Childhood nasopharyngeal cancer is a rare type of cancer that forms in the tissue lining the nasopharynx. The nasopharynx is the upper part of the throat behind the nose. The nostrils allow air into the nasopharynx. Air and food pass through the pharynx on the way to the trachea or esophagus.

Nasopharyngeal cancer is more common in children aged 10 to 19 years than in children younger than 10 years.

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Childhood nasopharyngeal cancer is caused by certain changes in the way the cells in the nasal cavity and top part of the throat function, especially how they grow and divide into new cells. Often, the exact cause of these changes is unknown. Learn more about how cancer develops at What Is Cancer?

A risk factor is anything that increases the chance of getting a disease. A known risk factor for childhood nasopharyngeal cancer is infection from the Epstein-Barr virus (EBV). Not every child with this risk factor will develop nasopharyngeal cancer. And it will develop in some children who don’t have a known risk factor. Talk with your child’s doctor if you think your child may be at risk.

Children may not have symptoms of nasopharyngeal cancer until the tumor has grown bigger. It’s important to check with your child’s doctor if your child has:

These symptoms may be caused by problems other than nasopharyngeal cancer. The only way to know is for your child to see a doctor.

If your child has symptoms that suggest nasopharyngeal cancer, the doctor will need to find out if these are due to cancer or another problem. The doctor will ask when the symptoms started and how often your child has been having them. They will also ask about your child’s personal and family medical history and do a physical exam. Depending on these results, the doctor may recommend other tests. If your child is diagnosed with nasopharyngeal cancer, the results of these tests will help plan treatment.

You may want to get a second opinion to confirm your child’s cancer diagnosis and treatment plan. If you seek a second opinion, you will need to get medical test results and reports from the first doctor to share with the second doctor. The second doctor will review the pathology report, slides, and scans. This doctor may agree with the first doctor, suggest changes to the treatment plan, or provide more information about your child’s cancer.

To learn more about choosing a doctor and getting a second opinion, visit Finding Cancer Care. You can contact NCI’s Cancer Information Service via chat, email, or phone (both in English and Spanish) for help finding a doctor or hospital that can provide a second opinion. For questions you might want to ask at your child’s appointments, visit Questions to Ask Your Doctor about Cancer.

The cancer stage describes the extent of cancer in the body, such as the size of the tumor, whether it has spread, and how far it has spread from where it first formed. It is important to know the stage of nasopharyngeal cancer to plan the best treatment.

There are several staging systems for cancer. Nasopharyngeal cancer staging usually uses the TNM staging system. You may see your child’s cancer described by this staging system in the pathology report. Based on the TNM results, a stage (I, II, III, or IV, also written as 1, 2, 3, or 4) is assigned to your child’s cancer. When talking with you about your child’s cancer, your child’s doctor may describe it as one of these stages.

Learn more about Cancer Staging.

Learn about the tests and procedures used to determine the stage of nasopharyngeal cancer. 

Stage I nasopharyngeal cancer

In stage I, nasopharyngeal cancer has formed and is found in the nasopharynx only or has spread from the nasopharynx to the oropharynx and/or nasal cavity.

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If your child has been diagnosed with nasopharyngeal cancer, you likely have questions about how serious the cancer is and your child’s chances of survival. The likely outcome or course of a disease is called prognosis. The prognosis can be affected by whether the cancer has spread to other parts of the body at the time of diagnosis and whether the cancer has just been diagnosed or has recurred (come back). No two people are alike, and responses to treatment can vary greatly. Your child’s cancer care team is in the best position to talk with you about your child’s prognosis.

Cancer treatments can cause side effects. Which side effects your child might have depends on the type of treatment they receive, the dose, and how their body reacts. Talk with your child’s treatment team about which side effects to look for and ways to manage them.

To learn more about side effects that begin during treatment for cancer, visit Side Effects.

Problems from cancer treatment that begin 6 months or later after treatment and continue for months or years are called late effects. Late effects of cancer treatment may include:

Some late effects may be treated or controlled. It is important to talk with your child’s doctors about the possible late effects caused by some treatments. Learn more about Late Effects of Treatment for Childhood Cancer.

As your child goes through treatment, they will have follow-up tests or check-ups. Some tests that were done to diagnose or stage the cancer may be repeated to see how well the treatment is working. Decisions about whether to continue, change, or stop treatment may be based on the results of these tests.

Some of the tests will continue to be done from time to time after treatment has ended. The results of these tests can show if your child’s condition has changed or if the cancer has recurred (come back).

When your child has cancer, every member of the family needs support. Taking care of yourself during this difficult time is important. Reach out to your child’s treatment team and to people in your family and community for support. To learn more, visit Support for Families: Childhood Cancer and the booklet Children with Cancer: A Guide for Parents. 

For more childhood cancer information and other general cancer resources, visit:

Childhood laryngeal tumors form in the voice box, also called the larynx. These tumors may be benign (which means they are not cancer) or cancer. Most laryngeal tumors in children are not cancer and do not spread to other tissues. Both types of tumors need treatment.

The most common type of benign laryngeal tumor is papillomatosis of the larynx. In this condition, papillomas (benign tumors that look like warts) form in the lining of the larynx. These tumors may block the airway and cause trouble breathing. They often come back after treatment and, in rare cases, may turn into cancer in the larynx or the lung.

The larynx is a part of the throat, between the base of the tongue and the trachea (windpipe). The larynx contains the vocal cords, which vibrate and make sound when air is directed against them. The sound echoes through the pharynx, mouth, and nose to make a person’s voice.

There are three main parts of the larynx:

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Laryngeal cancer in children is caused by certain changes to the way cells in the larynx function, especially how they grow and divide into new cells. Often, the exact cause of these cell changes is unknown. Learn more about how cancer develops at What Is Cancer?

Laryngeal papillomatosis is caused by infection with low-risk HPV (human papillomavirus), most often types 6 and 11. Children can get the HPV infection that causes laryngeal papillomatosis from an infected mother during birth. Most children with an HPV infection do not develop laryngeal papillomatosis. Talk with your child’s doctor if you think your child may be at risk.

Getting the HPV vaccine can help protect against HPV infection and reduce the risk of transmitting it during childbirth. Learn more about HPV Vaccines.

Children may not have symptoms of a laryngeal tumor until the tumor has grown bigger. It’s important to check with your child’s doctor if your child has:

Infants and young children with these tumors may grow slowly and not eat well or meet developmental milestones such as sitting, walking, and talking in sentences.

These symptoms may be caused by problems other than a laryngeal tumor. The only way to know is to see your child’s doctor.

If your child has symptoms that suggest a laryngeal tumor, the doctor will need to find out if these are due to cancer or some other problem. The doctor will ask when the symptoms started and how often your child has been having them. They will also ask about your child’s personal and family medical history and do a physical exam. Depending on these results, they may recommend other tests. If your child is diagnosed with a laryngeal tumor, the results of these tests will help you and your child’s doctor plan treatment.

The tests used to diagnose laryngeal tumors may include:

CT scan

CT scan (CAT scan) uses a computer linked to an x-ray machine to make a series of detailed pictures of areas inside the body. The pictures are taken from different angles and are used to create 3-D views of tissues and organs. A dye may be injected into a vein or swallowed to help the organs or tissues show up more clearly. This procedure is also called computed tomography, computerized tomography, or computerized axial tomography. Learn more about Computed Tomography (CT) Scans and Cancer.

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PET scan

PET scan (positron emission tomography scan) uses a small amount of radioactive sugar (also called radioactive glucose) that is injected into a vein. The PET scanner rotates around the body and makes pictures of where sugar is being used by the body. Cancer cells show up brighter in the pictures because they are more active and take up more sugar than normal cells do.

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You may want to get a second opinion to confirm your child’s cancer diagnosis and treatment plan. If you seek a second opinion, you will need to get medical test results and reports from the first doctor to share with the second doctor. The second doctor will review the pathology report, slides, and scans. This doctor may agree with the first doctor, suggest changes to the treatment plan, or provide more information about your child’s cancer.

To learn more about choosing a doctor and getting a second opinion, visit Finding Cancer Care. You can contact NCI’s Cancer Information Service via chat, email, or phone (both in English and Spanish) for help finding a doctor or hospital that can provide a second opinion. For questions you might want to ask at your child’s appointments, visit Questions to Ask Your Doctor About Cancer.

There are different types of treatment for children with laryngeal tumors. You and your child’s care team will work together to decide on treatment. Many factors will be considered, such as your child’s overall health and whether the tumor is newly diagnosed or has come back.

Your child’s treatment plan will include information about the tumor, the goals of treatment, treatment options, and the possible side effects. It will be helpful to talk with your child’s care team before treatment begins about what to expect. For help every step of the way, see our booklet, Children with Cancer: A Guide for Parents.

For some children, joining a clinical trial may be an option. There are different types of clinical trials for childhood cancer. For example, a treatment trial tests new treatments or new ways of using current treatments. Supportive care and palliative care trials look at ways to improve quality of life, especially for those who have side effects from cancer and its treatment.

You can use the clinical trial search to find NCI-supported cancer clinical trials accepting participants. The search allows you to filter trials based on the type of cancer, your child’s age, and where the trials are being done. Clinical trials supported by other organizations can be found on the ClinicalTrials.gov website.

Learn more about clinical trials, including how to find and join one, at Clinical Trials Information for Patients and Caregivers.

As your child goes through treatment, they will have follow-up tests or check-ups. Some of the tests that were done to diagnose the cancer may be repeated to see how well the treatment is working. Decisions about whether to continue, change, or stop treatment may be based on the results of these tests.

Some of the tests will continue to be done from time to time after treatment has ended. The results of these tests can show if your child’s condition has changed or if the cancer has recurred (come back).

When your child has cancer, every member of the family needs support. Taking care of yourself during this difficult time is important. Reach out to your child’s treatment team and to people in your family and community for support. To learn more, visit Support for Families: Childhood Cancer and the booklet Children with Cancer: A Guide for Parents.

For more childhood cancer information and other general cancer resources, visit:

For information about the treatments listed below, see the Treatment Option Overview section.

Treatment of stage I paranasal sinus and nasal cavity cancer depends on where cancer is found in the paranasal sinuses and nasal cavity:

Use our clinical trial search to find NCI-supported cancer clinical trials that are accepting patients. You can search for trials based on the type of cancer, the age of the patient, and where the trials are being done. General information about clinical trials is also available.

For information about the treatments listed below, see the Treatment Option Overview section.

Treatment of stage II paranasal sinus and nasal cavity cancer depends on where cancer is found in the paranasal sinuses and nasal cavity:

Use our clinical trial search to find NCI-supported cancer clinical trials that are accepting patients. You can search for trials based on the type of cancer, the age of the patient, and where the trials are being done. General information about clinical trials is also available.

For information about the treatments listed below, see the Treatment Option Overview section.

Treatment of stage III paranasal sinus and nasal cavity cancer depends on where cancer is found in the paranasal sinuses and nasal cavity.

If cancer is in the maxillary sinus, treatment may include:

If cancer is in the ethmoid sinus, treatment may include:

If cancer is in the sphenoid sinus, treatment is the same as for nasopharyngeal cancer, usually radiation therapy with or without chemotherapy. For more information, see Nasopharyngeal Cancer Treatment.

If cancer is in the nasal cavity, treatment may include:

For inverting papillomas, treatment is usually surgery with or without radiation therapy.

For melanomas and sarcomas, treatment may include:

For midline granulomas, treatment is usually radiation therapy.

If cancer is in the nasal vestibule, treatment may include:

Use our clinical trial search to find NCI-supported cancer clinical trials that are accepting patients. You can search for trials based on the type of cancer, the age of the patient, and where the trials are being done. General information about clinical trials is also available.

For information about the treatments listed below, see the Treatment Option Overview section.

Treatment of stage IV paranasal sinus and nasal cavity cancer depends on where cancer is found in the paranasal sinuses and nasal cavity.

If cancer is in the maxillary sinus, treatment may include:

If cancer is in the ethmoid sinus, treatment may include:

If cancer is in the sphenoid sinus, treatment is the same as for nasopharyngeal cancer, usually radiation therapy with or without chemotherapy. For more information, see Nasopharyngeal Cancer Treatment.

If cancer is in the nasal cavity, treatment may include:

For inverting papillomas, treatment is usually surgery with or without radiation therapy.

For melanomas and sarcomas, treatment may include:

For midline granulomas, treatment is usually radiation therapy.

If cancer is in the nasal vestibule, treatment may include:

Use our clinical trial search to find NCI-supported cancer clinical trials that are accepting patients. You can search for trials based on the type of cancer, the age of the patient, and where the trials are being done. General information about clinical trials is also available.

For information about the treatments listed below, see the Treatment Option Overview section.

Treatment of recurrent paranasal sinus and nasal cavity cancer depends on where cancer is found in the paranasal sinuses and nasal cavity.

If cancer is in the maxillary sinus, treatment may include:

If cancer is in the ethmoid sinus, treatment may include:

If cancer is in the sphenoid sinus, treatment is the same as for nasopharyngeal cancer and may include radiation therapy with or without chemotherapy. For more information, see Nasopharyngeal Cancer Treatment.

If cancer is in the nasal cavity, treatment may include:

For inverting papillomas, treatment is usually surgery with or without radiation therapy.

For melanomas and sarcomas, treatment may include:

For midline granulomas, treatment is usually radiation therapy.

If cancer is in the nasal vestibule, treatment may include:

Use our clinical trial search to find NCI-supported cancer clinical trials that are accepting patients. You can search for trials based on the type of cancer, the age of the patient, and where the trials are being done. General information about clinical trials is also available.

For more information from the National Cancer Institute about paranasal sinus and nasal cavity cancer, see:

For general cancer information and other resources from the National Cancer Institute, visit:

For information about the treatments listed below, see the Treatment Option Overview section.

Treatment for stage I salivary gland cancer depends on whether the cancer is low-grade (slow growing) or high-grade (fast growing).

If the cancer is low-grade, treatment may include the following:

If the cancer is high-grade, treatment may include the following:

Use our clinical trial search to find NCI-supported cancer clinical trials that are accepting patients. You can search for trials based on the type of cancer, the age of the patient, and where the trials are being done. General information about clinical trials is also available.

For information about the treatments listed below, see the Treatment Option Overview section.

Treatment for stage II salivary gland cancer depends on whether the cancer is low-grade (slow growing) or high-grade (fast growing).

If the cancer is low-grade, treatment may include the following:

If the cancer is high-grade, treatment may include the following:

Use our clinical trial search to find NCI-supported cancer clinical trials that are accepting patients. You can search for trials based on the type of cancer, the age of the patient, and where the trials are being done. General information about clinical trials is also available.

For information about the treatments listed below, see the Treatment Option Overview section.

Treatment for stage III salivary gland cancer depends on whether the cancer is low-grade (slow growing) or high-grade (fast growing).

If the cancer is low-grade, treatment may include the following:

If the cancer is high-grade, treatment may include the following:

Use our clinical trial search to find NCI-supported cancer clinical trials that are accepting patients. You can search for trials based on the type of cancer, the age of the patient, and where the trials are being done. General information about clinical trials is also available.

For information about the treatments listed below, see the Treatment Option Overview section.

Treatment of stage IVA, stage IVB, and stage IVC salivary gland cancer may include the following:

Use our clinical trial search to find NCI-supported cancer clinical trials that are accepting patients. You can search for trials based on the type of cancer, the age of the patient, and where the trials are being done. General information about clinical trials is also available.

For information about the treatments listed below, see the Treatment Option Overview section.

Treatment of recurrent salivary gland cancer may include the following:

Use our clinical trial search to find NCI-supported cancer clinical trials that are accepting patients. You can search for trials based on the type of cancer, the age of the patient, and where the trials are being done. General information about clinical trials is also available.

For more information from the National Cancer Institute about salivary gland cancer, see the following:

For general cancer information and other resources from the National Cancer Institute, visit:

References

1. Mendenhall WM, Werning JW, Pfister DG: Treatment of head and neck cancer. In: DeVita VT Jr, Lawrence TS, Rosenberg SA: Cancer: Principles and Practice of Oncology. 9th ed. Lippincott Williams & Wilkins, 2011, pp 729-80.
2. Laramore GE, ed.: Radiation Therapy of Head and Neck Cancer. Springer-Verlag, 1989.
3. Thawley SE, Panje WR, Batsakis JG, et al., eds.: Comprehensive Management of Head and Neck Tumors. 2nd ed. WB Saunders, 1999.
4. Johns ME, Kaplan MJ: Advances in the management of paranasal sinus tumors. In: Wolf GT, ed.: Head and Neck Oncology. Martinus Nijhoff Publishers, 1984, pp 27-52.
5. Alos L, Moyano S, Nadal A, et al.: Human papillomaviruses are identified in a subgroup of sinonasal squamous cell carcinomas with favorable outcome. Cancer 115 (12): 2701-9, 2009. [PUBMED Abstract]

The most common cell type for paranasal sinus and nasal cavity cancers is squamous cell carcinoma. Minor salivary gland tumors comprise 10% to 15% of these neoplasms. Malignant melanoma presents in less than 1% of neoplasms in this region. Some 5% of cases are malignant lymphomas.[1,2]

Esthesioneuroepithelioma, sometimes confused with undifferentiated carcinoma or undifferentiated lymphoma, arises from the olfactory nerves.[3]

Chondrosarcoma, osteosarcoma, Ewing sarcoma, and most soft tissue sarcomas have been reported for this region.

Inverting papilloma is considered a low-grade benign tumor with a tendency to recur and, in a small percentage of cases, to transform into a malignant tumor.

Midline granuloma, a progressively destructive condition, also involves this region.

References

1. Mendenhall WM, Werning JW, Pfister DG: Treatment of head and neck cancer. In: DeVita VT Jr, Lawrence TS, Rosenberg SA: Cancer: Principles and Practice of Oncology. 9th ed. Lippincott Williams & Wilkins, 2011, pp 729-80.
2. Goldenberg D, Golz A, Fradis M, et al.: Malignant tumors of the nose and paranasal sinuses: a retrospective review of 291 cases. Ear Nose Throat J 80 (4): 272-7, 2001. [PUBMED Abstract]
3. Jethanamest D, Morris LG, Sikora AG, et al.: Esthesioneuroblastoma: a population-based analysis of survival and prognostic factors. Arch Otolaryngol Head Neck Surg 133 (3): 276-80, 2007. [PUBMED Abstract]

The staging systems are clinical estimates of the extent of disease. The assessment of the tumor is based on inspection, palpation, and direct endoscopy when necessary. The tumor must be confirmed histologically, and any other pathological data obtained on biopsy may be included. The appropriate nodal drainage areas are examined by careful palpation. Computed tomographic and/or magnetic resonance imaging studies are generally required to adequately evaluate tumor extent before surgical resection or definitive radiation therapy. If a patient’s disease relapses, complete restaging must be done to select the appropriate additional therapy.[1,2]

References

1. Mendenhall WM, Werning JW, Pfister DG: Treatment of head and neck cancer. In: DeVita VT Jr, Lawrence TS, Rosenberg SA: Cancer: Principles and Practice of Oncology. 9th ed. Lippincott Williams & Wilkins, 2011, pp 729-80.
2. Laramore GE, ed.: Radiation Therapy of Head and Neck Cancer. Springer-Verlag, 1989.
3. Nasal cavity and paranasal sinuses. In: Amin MB, Edge SB, Greene FL, et al., eds.: AJCC Cancer Staging Manual. 8th ed. Springer; 2017, pp 137-47.

Except for patients with T1 mucosal carcinomas, the accepted method of treatment is a combination of radiation therapy and surgery. The incidence of lymph node metastases is generally low (approximately 20% of cases). Thus, routine radical neck dissection or elective neck radiation therapy is recommended only for patients presenting with positive nodes.

For patients with operable tumors, radical surgery is generally performed first to remove the bulk of the tumor and to establish drainage of the affected sinus(es). This is followed by postoperative radiation therapy. Some institutions continue to give a full dose of radiation therapy preoperatively for all patients with stage II and stage III tumors and operate 4 to 6 weeks later.[1–3] A review of published clinical results of radical radiation therapy for head and neck cancer suggested a significant loss of local control with prolonged radiation therapy; therefore, lengthening of standard treatment schedules should be avoided whenever possible.[4]

References

1. Mendenhall WM, Werning JW, Pfister DG: Treatment of head and neck cancer. In: DeVita VT Jr, Lawrence TS, Rosenberg SA: Cancer: Principles and Practice of Oncology. 9th ed. Lippincott Williams & Wilkins, 2011, pp 729-80.
2. Laramore GE, ed.: Radiation Therapy of Head and Neck Cancer. Springer-Verlag, 1989.
3. Thawley SE, Panje WR, Batsakis JG, et al., eds.: Comprehensive Management of Head and Neck Tumors. 2nd ed. WB Saunders, 1999.
4. Fowler JF, Lindstrom MJ: Loss of local control with prolongation in radiotherapy. Int J Radiat Oncol Biol Phys 23 (2): 457-67, 1992. [PUBMED Abstract]
5. Ganly I, Patel SG, Singh B, et al.: Craniofacial resection for malignant paranasal sinus tumors: Report of an International Collaborative Study. Head Neck 27 (7): 575-84, 2005. [PUBMED Abstract]
6. Turner SL, Tiver KW, Boyages SC: Thyroid dysfunction following radiotherapy for head and neck cancer. Int J Radiat Oncol Biol Phys 31 (2): 279-83, 1995. [PUBMED Abstract]
7. Constine LS: What else don’t we know about the late effects of radiation in patients treated for head and neck cancer? Int J Radiat Oncol Biol Phys 31 (2): 427-9, 1995. [PUBMED Abstract]
8. Jacobs C, Lyman G, Velez-García E, et al.: A phase III randomized study comparing cisplatin and fluorouracil as single agents and in combination for advanced squamous cell carcinoma of the head and neck. J Clin Oncol 10 (2): 257-63, 1992. [PUBMED Abstract]
9. Schornagel JH, Verweij J, de Mulder PH, et al.: Randomized phase III trial of edatrexate versus methotrexate in patients with metastatic and/or recurrent squamous cell carcinoma of the head and neck: a European Organization for Research and Treatment of Cancer Head and Neck Cancer Cooperative Group study. J Clin Oncol 13 (7): 1649-55, 1995. [PUBMED Abstract]
10. Sharma BB, Rai K, Blunt H, et al.: Pathogenic DPYD Variants and Treatment-Related Mortality in Patients Receiving Fluoropyrimidine Chemotherapy: A Systematic Review and Meta-Analysis. Oncologist 26 (12): 1008-1016, 2021. [PUBMED Abstract]
11. Lam SW, Guchelaar HJ, Boven E: The role of pharmacogenetics in capecitabine efficacy and toxicity. Cancer Treat Rev 50: 9-22, 2016. [PUBMED Abstract]
12. Shakeel F, Fang F, Kwon JW, et al.: Patients carrying DPYD variant alleles have increased risk of severe toxicity and related treatment modifications during fluoropyrimidine chemotherapy. Pharmacogenomics 22 (3): 145-155, 2021. [PUBMED Abstract]
13. Amstutz U, Henricks LM, Offer SM, et al.: Clinical Pharmacogenetics Implementation Consortium (CPIC) Guideline for Dihydropyrimidine Dehydrogenase Genotype and Fluoropyrimidine Dosing: 2017 Update. Clin Pharmacol Ther 103 (2): 210-216, 2018. [PUBMED Abstract]
14. Henricks LM, Lunenburg CATC, de Man FM, et al.: DPYD genotype-guided dose individualisation of fluoropyrimidine therapy in patients with cancer: a prospective safety analysis. Lancet Oncol 19 (11): 1459-1467, 2018. [PUBMED Abstract]
15. Lau-Min KS, Varughese LA, Nelson MN, et al.: Preemptive pharmacogenetic testing to guide chemotherapy dosing in patients with gastrointestinal malignancies: a qualitative study of barriers to implementation. BMC Cancer 22 (1): 47, 2022. [PUBMED Abstract]
16. Brooks GA, Tapp S, Daly AT, et al.: Cost-effectiveness of DPYD Genotyping Prior to Fluoropyrimidine-based Adjuvant Chemotherapy for Colon Cancer. Clin Colorectal Cancer 21 (3): e189-e195, 2022. [PUBMED Abstract]
17. Baker SD, Bates SE, Brooks GA, et al.: DPYD Testing: Time to Put Patient Safety First. J Clin Oncol 41 (15): 2701-2705, 2023. [PUBMED Abstract]

Stage I disease includes small lesions.

References

1. Kraus DH, Sterman BM, Levine HL, et al.: Factors influencing survival in ethmoid sinus cancer. Arch Otolaryngol Head Neck Surg 118 (4): 367-72, 1992. [PUBMED Abstract]
2. Shah JP: Surgery of the anterior skull base for malignant tumors. Acta Otorhinolaryngol Belg 53 (3): 191-4, 1999. [PUBMED Abstract]
3. Cantù G, Solero CL, Mariani L, et al.: Anterior craniofacial resection for malignant ethmoid tumors–a series of 91 patients. Head Neck 21 (3): 185-91, 1999. [PUBMED Abstract]
4. Hawkins RB, Wynstra JH, Pilepich MV, et al.: Carcinoma of the nasal cavity–results of primary and adjuvant radiotherapy. Int J Radiat Oncol Biol Phys 15 (5): 1129-33, 1988. [PUBMED Abstract]
5. Ang KK, Jiang GL, Frankenthaler RA, et al.: Carcinomas of the nasal cavity. Radiother Oncol 24 (3): 163-8, 1992. [PUBMED Abstract]
6. Levendag PC, Pomp J: Radiation therapy of squamous cell carcinoma of the nasal vestibule. Int J Radiat Oncol Biol Phys 19 (6): 1363-7, 1990. [PUBMED Abstract]
7. Wong CS, Cummings BJ: The place of radiation therapy in the treatment of squamous cell carcinoma of the nasal vestibule. A review. Acta Oncol 27 (3): 203-8, 1988. [PUBMED Abstract]

Stage II disease includes small and moderately advanced lesions.

References

1. Kraus DH, Sterman BM, Levine HL, et al.: Factors influencing survival in ethmoid sinus cancer. Arch Otolaryngol Head Neck Surg 118 (4): 367-72, 1992. [PUBMED Abstract]
2. Cantù G, Solero CL, Mariani L, et al.: Anterior craniofacial resection for malignant ethmoid tumors–a series of 91 patients. Head Neck 21 (3): 185-91, 1999. [PUBMED Abstract]
3. Shah JP: Surgery of the anterior skull base for malignant tumors. Acta Otorhinolaryngol Belg 53 (3): 191-4, 1999. [PUBMED Abstract]
4. Hawkins RB, Wynstra JH, Pilepich MV, et al.: Carcinoma of the nasal cavity–results of primary and adjuvant radiotherapy. Int J Radiat Oncol Biol Phys 15 (5): 1129-33, 1988. [PUBMED Abstract]
5. Ang KK, Jiang GL, Frankenthaler RA, et al.: Carcinomas of the nasal cavity. Radiother Oncol 24 (3): 163-8, 1992. [PUBMED Abstract]
6. Levendag PC, Pomp J: Radiation therapy of squamous cell carcinoma of the nasal vestibule. Int J Radiat Oncol Biol Phys 19 (6): 1363-7, 1990. [PUBMED Abstract]
7. Wong CS, Cummings BJ: The place of radiation therapy in the treatment of squamous cell carcinoma of the nasal vestibule. A review. Acta Oncol 27 (3): 203-8, 1988. [PUBMED Abstract]

Stage III disease includes small and moderately advanced lesions.

References

1. Johnson CR, Schmidt-Ullrich RK, Wazer DE: Concomitant boost technique using accelerated superfractionated radiation therapy for advanced squamous cell carcinoma of the head and neck. Cancer 69 (11): 2749-54, 1992. [PUBMED Abstract]
2. Kraus DH, Sterman BM, Levine HL, et al.: Factors influencing survival in ethmoid sinus cancer. Arch Otolaryngol Head Neck Surg 118 (4): 367-72, 1992. [PUBMED Abstract]
3. Cantù G, Solero CL, Mariani L, et al.: Anterior craniofacial resection for malignant ethmoid tumors–a series of 91 patients. Head Neck 21 (3): 185-91, 1999. [PUBMED Abstract]
4. Shah JP: Surgery of the anterior skull base for malignant tumors. Acta Otorhinolaryngol Belg 53 (3): 191-4, 1999. [PUBMED Abstract]
5. Hawkins RB, Wynstra JH, Pilepich MV, et al.: Carcinoma of the nasal cavity–results of primary and adjuvant radiotherapy. Int J Radiat Oncol Biol Phys 15 (5): 1129-33, 1988. [PUBMED Abstract]
6. Ang KK, Jiang GL, Frankenthaler RA, et al.: Carcinomas of the nasal cavity. Radiother Oncol 24 (3): 163-8, 1992. [PUBMED Abstract]
7. Wong CS, Cummings BJ: The place of radiation therapy in the treatment of squamous cell carcinoma of the nasal vestibule. A review. Acta Oncol 27 (3): 203-8, 1988. [PUBMED Abstract]

Stage IV disease includes advanced lesions.

Neoadjuvant chemotherapy as used in clinical trials has been used to shrink tumors and to render them more definitively treatable with either surgery or radiation therapy. This chemotherapy is given before the other modalities; therefore, the designation of neoadjuvant is used to distinguish it from standard adjuvant therapy, which is given after or during definitive therapy with radiation or after surgery. Many drug combinations have been used in neoadjuvant chemotherapy.[6–8]

References

1. Johnson CR, Schmidt-Ullrich RK, Wazer DE: Concomitant boost technique using accelerated superfractionated radiation therapy for advanced squamous cell carcinoma of the head and neck. Cancer 69 (11): 2749-54, 1992. [PUBMED Abstract]
2. Kraus DH, Sterman BM, Levine HL, et al.: Factors influencing survival in ethmoid sinus cancer. Arch Otolaryngol Head Neck Surg 118 (4): 367-72, 1992. [PUBMED Abstract]
3. Cantù G, Solero CL, Mariani L, et al.: Anterior craniofacial resection for malignant ethmoid tumors–a series of 91 patients. Head Neck 21 (3): 185-91, 1999. [PUBMED Abstract]
4. Shah JP: Surgery of the anterior skull base for malignant tumors. Acta Otorhinolaryngol Belg 53 (3): 191-4, 1999. [PUBMED Abstract]
5. Hawkins RB, Wynstra JH, Pilepich MV, et al.: Carcinoma of the nasal cavity–results of primary and adjuvant radiotherapy. Int J Radiat Oncol Biol Phys 15 (5): 1129-33, 1988. [PUBMED Abstract]
6. Stupp R, Weichselbaum RR, Vokes EE: Combined modality therapy of head and neck cancer. Semin Oncol 21 (3): 349-58, 1994. [PUBMED Abstract]
7. Al-Sarraf M: Head and neck cancer: chemotherapy concepts. Semin Oncol 15 (1): 70-85, 1988. [PUBMED Abstract]
8. Dimery IW, Hong WK: Overview of combined modality therapies for head and neck cancer. J Natl Cancer Inst 85 (2): 95-111, 1993. [PUBMED Abstract]

Chemotherapy for recurrent head and neck squamous cell cancer has shown promise. Chemotherapy may be indicated when there is recurrence in either distant or local disease after primary surgery or radiation therapy, and when there is residual disease after primary treatment.[1,2] Survival may be improved in those achieving a complete response to chemotherapy.[3] Combined-modality therapy with platinum and radiation therapy has been used in clinical trials such as UMCC-8810.[4]

References

1. Kies MS, Levitan N, Hong WK: Chemotherapy of head and neck cancer. Otolaryngol Clin North Am 18 (3): 533-41, 1985. [PUBMED Abstract]
2. LoRusso P, Tapazoglou E, Kish JA, et al.: Chemotherapy for paranasal sinus carcinoma. A 10-year experience at Wayne State University. Cancer 62 (1): 1-5, 1988. [PUBMED Abstract]
3. Al-Kourainy K, Kish J, Ensley J, et al.: Achievement of superior survival for histologically negative versus histologically positive clinically complete responders to cisplatin combination in patients with locally advanced head and neck cancer. Cancer 59 (2): 233-8, 1987. [PUBMED Abstract]
4. Al-Sarraf M, Pajak TF, Marcial VA, et al.: Concurrent radiotherapy and chemotherapy with cisplatin in inoperable squamous cell carcinoma of the head and neck. An RTOG Study. Cancer 59 (2): 259-65, 1987. [PUBMED Abstract]
5. Brasnu D, Laccourreye O, Bassot V, et al.: Cisplatin-based neoadjuvant chemotherapy and combined resection for ethmoid sinus adenocarcinoma reaching and/or invading the skull base. Arch Otolaryngol Head Neck Surg 122 (7): 765-8, 1996. [PUBMED Abstract]
6. Licitra L, Locati LD, Cavina R, et al.: Primary chemotherapy followed by anterior craniofacial resection and radiotherapy for paranasal cancer. Ann Oncol 14 (3): 367-72, 2003. [PUBMED Abstract]
7. Kraus DH, Sterman BM, Levine HL, et al.: Factors influencing survival in ethmoid sinus cancer. Arch Otolaryngol Head Neck Surg 118 (4): 367-72, 1992. [PUBMED Abstract]
8. Cantù G, Solero CL, Mariani L, et al.: Anterior craniofacial resection for malignant ethmoid tumors–a series of 91 patients. Head Neck 21 (3): 185-91, 1999. [PUBMED Abstract]
9. Shah JP: Surgery of the anterior skull base for malignant tumors. Acta Otorhinolaryngol Belg 53 (3): 191-4, 1999. [PUBMED Abstract]

The PDQ cancer information summaries are reviewed regularly and updated as new information becomes available. This section describes the latest changes made to this summary as of the date above.

Treatment Option Overview for Paranasal Sinus and Nasal Cavity Cancer

Added Fluorouracil dosing as a new subsection.

This summary is written and maintained by the PDQ Adult Treatment Editorial Board, which is editorially independent of NCI. The summary reflects an independent review of the literature and does not represent a policy statement of NCI or NIH. More information about summary policies and the role of the PDQ Editorial Boards in maintaining the PDQ summaries can be found on the About This PDQ Summary and PDQ® Cancer Information for Health Professionals pages.

References

1. Surveillance Research Program, National Cancer Institute: SEER*Explorer: An interactive website for SEER cancer statistics. Bethesda, MD: National Cancer Institute. Available online. Last accessed December 30, 2024.
2. Speight PM, Barrett AW: Salivary gland tumours. Oral Dis 8 (5): 229-40, 2002. [PUBMED Abstract]
3. Mendenhall WM, Werning JW, Pfister DG: Treatment of head and neck cancer. In: DeVita VT Jr, Lawrence TS, Rosenberg SA: Cancer: Principles and Practice of Oncology. 9th ed. Lippincott Williams & Wilkins, 2011, pp 729-80.
4. Ellis GL, Auclair PL: Tumors of the Salivary Glands. Armed Forces Institute of Pathology, 1996. Atlas of Tumor Pathology, 3.
5. Wahlberg P, Anderson H, Biörklund A, et al.: Carcinoma of the parotid and submandibular glands–a study of survival in 2465 patients. Oral Oncol 38 (7): 706-13, 2002. [PUBMED Abstract]
6. Scanlon EF, Sener SF: Head and neck neoplasia following irradiation for benign conditions. Head Neck Surg 4 (2): 139-45, 1981 Nov-Dec. [PUBMED Abstract]
7. van der Laan BF, Baris G, Gregor RT, et al.: Radiation-induced tumours of the head and neck. J Laryngol Otol 109 (4): 346-9, 1995. [PUBMED Abstract]
8. Spiro RH, Thaler HT, Hicks WF, et al.: The importance of clinical staging of minor salivary gland carcinoma. Am J Surg 162 (4): 330-6, 1991. [PUBMED Abstract]
9. Gooden E, Witterick IJ, Hacker D, et al.: Parotid gland tumours in 255 consecutive patients: Mount Sinai Hospital’s quality assurance review. J Otolaryngol 31 (6): 351-4, 2002. [PUBMED Abstract]
10. Theriault C, Fitzpatrick PJ: Malignant parotid tumors. Prognostic factors and optimum treatment. Am J Clin Oncol 9 (6): 510-6, 1986. [PUBMED Abstract]
11. Brandwein MS, Ferlito A, Bradley PJ, et al.: Diagnosis and classification of salivary neoplasms: pathologic challenges and relevance to clinical outcomes. Acta Otolaryngol 122 (7): 758-64, 2002. [PUBMED Abstract]
12. Seifert G, Sobin LH: Histological Typing of Salivary Gland Tumours. 2nd ed. Springer-Verlag, 1991.
13. Guzzo M, Andreola S, Sirizzotti G, et al.: Mucoepidermoid carcinoma of the salivary glands: clinicopathologic review of 108 patients treated at the National Cancer Institute of Milan. Ann Surg Oncol 9 (7): 688-95, 2002. [PUBMED Abstract]
14. Goode RK, Auclair PL, Ellis GL: Mucoepidermoid carcinoma of the major salivary glands: clinical and histopathologic analysis of 234 cases with evaluation of grading criteria. Cancer 82 (7): 1217-24, 1998. [PUBMED Abstract]
15. Spiro RH, Huvos AG, Strong EW: Cancer of the parotid gland. A clinicopathologic study of 288 primary cases. Am J Surg 130 (4): 452-9, 1975. [PUBMED Abstract]
16. Parsons JT, Mendenhall WM, Stringer SP, et al.: Management of minor salivary gland carcinomas. Int J Radiat Oncol Biol Phys 35 (3): 443-54, 1996. [PUBMED Abstract]
17. Vander Poorten VL, Balm AJ, Hilgers FJ, et al.: The development of a prognostic score for patients with parotid carcinoma. Cancer 85 (9): 2057-67, 1999. [PUBMED Abstract]
18. Terhaard CH, Lubsen H, Van der Tweel I, et al.: Salivary gland carcinoma: independent prognostic factors for locoregional control, distant metastases, and overall survival: results of the Dutch head and neck oncology cooperative group. Head Neck 26 (8): 681-92; discussion 692-3, 2004. [PUBMED Abstract]
19. Spiro RH: Factors affecting survival in salivary gland cancers. In: McGurk M, Renehan AG, eds.: Controversies in the Management of Salivary Gland Disease. Oxford University Press, 2001, pp 143-50.
20. Gormley WB, Sekhar LN, Wright DC, et al.: Management and long-term outcome of adenoid cystic carcinoma with intracranial extension: a neurosurgical perspective. Neurosurgery 38 (6): 1105-12; discussion 1112-3, 1996. [PUBMED Abstract]
21. Hosokawa Y, Shirato H, Kagei K, et al.: Role of radiotherapy for mucoepidermoid carcinoma of salivary gland. Oral Oncol 35 (1): 105-11, 1999. [PUBMED Abstract]
22. Borthne A, Kjellevold K, Kaalhus O, et al.: Salivary gland malignant neoplasms: treatment and prognosis. Int J Radiat Oncol Biol Phys 12 (5): 747-54, 1986. [PUBMED Abstract]
23. Spiro RH: Salivary neoplasms: overview of a 35-year experience with 2,807 patients. Head Neck Surg 8 (3): 177-84, 1986 Jan-Feb. [PUBMED Abstract]
24. Licitra L, Cavina R, Grandi C, et al.: Cisplatin, doxorubicin and cyclophosphamide in advanced salivary gland carcinoma. A phase II trial of 22 patients. Ann Oncol 7 (6): 640-2, 1996. [PUBMED Abstract]
25. Wang CC, Goodman M: Photon irradiation of unresectable carcinomas of salivary glands. Int J Radiat Oncol Biol Phys 21 (3): 569-76, 1991. [PUBMED Abstract]
26. Buchholz TA, Laramore GE, Griffin BR, et al.: The role of fast neutron radiation therapy in the management of advanced salivary gland malignant neoplasms. Cancer 69 (11): 2779-88, 1992. [PUBMED Abstract]
27. Krüll A, Schwarz R, Engenhart R, et al.: European results in neutron therapy of malignant salivary gland tumors. Bull Cancer Radiother 83 (Suppl): 125-9s, 1996. [PUBMED Abstract]
28. Naumann M, Zellner M, Toyka KV, et al.: Treatment of gustatory sweating with botulinum toxin. Ann Neurol 42 (6): 973-5, 1997. [PUBMED Abstract]
29. Arad-Cohen A, Blitzer A: Botulinum toxin treatment for symptomatic Frey’s syndrome. Otolaryngol Head Neck Surg 122 (2): 237-40, 2000. [PUBMED Abstract]
30. von Lindern JJ, Niederhagen B, Bergé S, et al.: Frey syndrome: treatment with type A botulinum toxin. Cancer 89 (8): 1659-63, 2000. [PUBMED Abstract]

Salivary gland neoplasms are remarkable for their histological diversity. These neoplasms include benign and malignant tumors of epithelial, mesenchymal, and lymphoid origin. Salivary gland tumors pose a particular challenge to the surgical pathologist. Differentiating benign from malignant tumors may be difficult, primarily because of the complexity of the classification and the rarity of several entities, which may exhibit a broad spectrum of morphological diversity in individual lesions.[1] In some cases, hybrid lesions may be seen.[2] The key guiding principle to establish the malignant nature of a salivary gland tumor is the demonstration of an infiltrative margin.[1]

The following cellular classification scheme draws heavily from a scheme published by the Armed Forces Institute of Pathology (AFIP).[3] Malignant nonepithelial neoplasms are included in the scheme because these neoplasms comprise a significant proportion of salivary gland neoplasms seen in the clinical setting. For completeness, malignant secondary tumors are also included in the scheme.

Where AFIP statistics regarding the incidence, or relative frequency, of particular histopathologies are cited, some bias may exist because of the AFIP methods of case accrual as a pathology reference service. When possible, other sources are cited for incidence data. Notwithstanding the AFIP data, the incidence of a particular histopathology has been found to vary considerably depending upon the study cited. This variability in reporting may be partially caused by the rare incidence of many salivary gland neoplasms.

References

1. Speight PM, Barrett AW: Salivary gland tumours. Oral Dis 8 (5): 229-40, 2002. [PUBMED Abstract]
2. Seifert G, Donath K: Hybrid tumours of salivary glands. Definition and classification of five rare cases. Eur J Cancer B Oral Oncol 32B (4): 251-9, 1996. [PUBMED Abstract]
3. Ellis GL, Auclair PL: Tumors of the Salivary Glands. Armed Forces Institute of Pathology, 1996. Atlas of Tumor Pathology, 3.
4. Cheuk W, Chan JKC: Salivary gland tumors. In: Fletcher CDM, ed.: Diagnostic Histopathology of Tumors. 3rd ed. Churchill Livingstone, 2007, pp 239-326.
5. Spiro RH, Huvos AG, Berk R, et al.: Mucoepidermoid carcinoma of salivary gland origin. A clinicopathologic study of 367 cases. Am J Surg 136 (4): 461-8, 1978. [PUBMED Abstract]
6. Goode RK, Corio RL: Oncocytic adenocarcinoma of salivary glands. Oral Surg Oral Med Oral Pathol 65 (1): 61-6, 1988. [PUBMED Abstract]
7. Guzzo M, Di Palma S, Grandi C, et al.: Salivary duct carcinoma: clinical characteristics and treatment strategies. Head Neck 19 (2): 126-33, 1997. [PUBMED Abstract]
8. Stephen J, Batsakis JG, Luna MA, et al.: True malignant mixed tumors (carcinosarcoma) of salivary glands. Oral Surg Oral Med Oral Pathol 61 (6): 597-602, 1986. [PUBMED Abstract]
9. Auclair PL, Ellis GL, Gnepp DR, et al.: Salivary gland neoplasms: general considerations. In: Ellis GL, Auclair PL, Gnepp DR, eds.: Surgical Pathology of the Salivary Glands. Saunders, 1991, pp 135-64.
10. Eveson JW, Cawson RA: Salivary gland tumours. A review of 2410 cases with particular reference to histological types, site, age and sex distribution. J Pathol 146 (1): 51-8, 1985. [PUBMED Abstract]
11. Spitz MR, Batsakis JG: Major salivary gland carcinoma. Descriptive epidemiology and survival of 498 patients. Arch Otolaryngol 110 (1): 45-9, 1984. [PUBMED Abstract]
12. Goode RK, Auclair PL, Ellis GL: Mucoepidermoid carcinoma of the major salivary glands: clinical and histopathologic analysis of 234 cases with evaluation of grading criteria. Cancer 82 (7): 1217-24, 1998. [PUBMED Abstract]
13. Guzzo M, Andreola S, Sirizzotti G, et al.: Mucoepidermoid carcinoma of the salivary glands: clinicopathologic review of 108 patients treated at the National Cancer Institute of Milan. Ann Surg Oncol 9 (7): 688-95, 2002. [PUBMED Abstract]
14. Neville BW, Damm DD, Weir JC, et al.: Labial salivary gland tumors. Cancer 61 (10): 2113-6, 1988. [PUBMED Abstract]
15. Auclair PL, Goode RK, Ellis GL: Mucoepidermoid carcinoma of intraoral salivary glands. Evaluation and application of grading criteria in 143 cases. Cancer 69 (8): 2021-30, 1992. [PUBMED Abstract]
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19. El-Naggar AK, Lovell M, Killary AM, et al.: A mucoepidermoid carcinoma of minor salivary gland with t(11;19)(q21;p13.1) as the only karyotypic abnormality. Cancer Genet Cytogenet 87 (1): 29-33, 1996. [PUBMED Abstract]
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22. Brookstone MS, Huvos AG: Central salivary gland tumors of the maxilla and mandible: a clinicopathologic study of 11 cases with an analysis of the literature. J Oral Maxillofac Surg 50 (3): 229-36, 1992. [PUBMED Abstract]
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24. Batsakis JG, Luna MA, el-Naggar A: Histopathologic grading of salivary gland neoplasms: III. Adenoid cystic carcinomas. Ann Otol Rhinol Laryngol 99 (12): 1007-9, 1990. [PUBMED Abstract]
25. Tomich CE: Adenoid cystic carcinoma. In: Ellis GL, Auclair PL, Gnepp DR, eds.: Surgical Pathology of the Salivary Glands. Saunders, 1991, pp 333-49.
26. Perzin KH, Gullane P, Clairmont AC: Adenoid cystic carcinomas arising in salivary glands: a correlation of histologic features and clinical course. Cancer 42 (1): 265-82, 1978. [PUBMED Abstract]
27. Spiro RH: The controversial adenoid cystic carcinoma. Clinical considerations. In: McGurk M, Renehan AG, eds.: Controversies in the Management of Salivary Gland Disease. Oxford University Press, 2001, pp 207-11.
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29. Spiro RH, Huvos AG: Stage means more than grade in adenoid cystic carcinoma. Am J Surg 164 (6): 623-8, 1992. [PUBMED Abstract]
30. Hamper K, Lazar F, Dietel M, et al.: Prognostic factors for adenoid cystic carcinoma of the head and neck: a retrospective evaluation of 96 cases. J Oral Pathol Med 19 (3): 101-7, 1990. [PUBMED Abstract]
31. Lewis JE, Olsen KD, Weiland LH: Acinic cell carcinoma. Clinicopathologic review. Cancer 67 (1): 172-9, 1991. [PUBMED Abstract]
32. Waldron CA, el-Mofty SK, Gnepp DR: Tumors of the intraoral minor salivary glands: a demographic and histologic study of 426 cases. Oral Surg Oral Med Oral Pathol 66 (3): 323-33, 1988. [PUBMED Abstract]
33. Vincent SD, Hammond HL, Finkelstein MW: Clinical and therapeutic features of polymorphous low-grade adenocarcinoma. Oral Surg Oral Med Oral Pathol 77 (1): 41-7, 1994. [PUBMED Abstract]
34. Evans HL, Luna MA: Polymorphous low-grade adenocarcinoma: a study of 40 cases with long-term follow up and an evaluation of the importance of papillary areas. Am J Surg Pathol 24 (10): 1319-28, 2000. [PUBMED Abstract]
35. Spiro RH, Huvos AG, Strong EW: Adenocarcinoma of salivary origin. Clinicopathologic study of 204 patients. Am J Surg 144 (4): 423-31, 1982. [PUBMED Abstract]
36. Matsuba HM, Mauney M, Simpson JR, et al.: Adenocarcinomas of major and minor salivary gland origin: a histopathologic review of treatment failure patterns. Laryngoscope 98 (7): 784-8, 1988. [PUBMED Abstract]
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38. Ellis GL, Wiscovitch JG: Basal cell adenocarcinomas of the major salivary glands. Oral Surg Oral Med Oral Pathol 69 (4): 461-9, 1990. [PUBMED Abstract]
39. Simpson RH, Sarsfield PT, Clarke T, et al.: Clear cell carcinoma of minor salivary glands. Histopathology 17 (5): 433-8, 1990. [PUBMED Abstract]
40. Ogawa I, Nikai H, Takata T, et al.: Clear cell tumors of minor salivary gland origin. An immunohistochemical and ultrastructural analysis. Oral Surg Oral Med Oral Pathol 72 (2): 200-7, 1991. [PUBMED Abstract]
41. Milchgrub S, Gnepp DR, Vuitch F, et al.: Hyalinizing clear cell carcinoma of salivary gland. Am J Surg Pathol 18 (1): 74-82, 1994. [PUBMED Abstract]
42. Ellis GL, Auclair PL, Gnepp DR, et al.: Other malignant epithelial neoplasms. In: Ellis GL, Auclair PL, Gnepp DR, eds.: Surgical Pathology of the Salivary Glands. Saunders, 1991, pp 455-88.
43. Gnepp DR: Sebaceous neoplasms of salivary gland origin: a review. Pathol Annu 18 Pt 1: 71-102, 1983. [PUBMED Abstract]
44. Gnepp DR, Brannon R: Sebaceous neoplasms of salivary gland origin. Report of 21 cases. Cancer 53 (10): 2155-70, 1984. [PUBMED Abstract]
45. Linhartová A: Sebaceous glands in salivary gland tissue. Arch Pathol 98 (5): 320-4, 1974. [PUBMED Abstract]
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47. Delgado R, Klimstra D, Albores-Saavedra J: Low grade salivary duct carcinoma. A distinctive variant with a low grade histology and a predominant intraductal growth pattern. Cancer 78 (5): 958-67, 1996. [PUBMED Abstract]
48. Barnes L, Rao U, Krause J, et al.: Salivary duct carcinoma. Part I. A clinicopathologic evaluation and DNA image analysis of 13 cases with review of the literature. Oral Surg Oral Med Oral Pathol 78 (1): 64-73, 1994. [PUBMED Abstract]
49. Osaki T, Hirota J, Ohno A, et al.: Mucinous adenocarcinoma of the submandibular gland. Cancer 66 (8): 1796-801, 1990. [PUBMED Abstract]
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51. LiVolsi VA, Perzin KH: Malignant mixed tumors arising in salivary glands. I. Carcinomas arising in benign mixed tumors: a clinicopathologic study. Cancer 39 (5): 2209-30, 1977. [PUBMED Abstract]
52. Gnepp DR: Malignant mixed tumors of the salivary glands: a review. Pathol Annu 28 Pt 1: 279-328, 1993. [PUBMED Abstract]
53. Seifert G: [Diseases of the Salivary Glands: Pathology, Diagnosis, Treatment, Facial Nerve Surgery]; translated by Philip M. Stell. Thieme, 1986.
54. Brandwein MS, Ferlito A, Bradley PJ, et al.: Diagnosis and classification of salivary neoplasms: pathologic challenges and relevance to clinical outcomes. Acta Otolaryngol 122 (7): 758-64, 2002. [PUBMED Abstract]
55. Wenig BM, Hitchcock CL, Ellis GL, et al.: Metastasizing mixed tumor of salivary glands. A clinicopathologic and flow cytometric analysis. Am J Surg Pathol 16 (9): 845-58, 1992. [PUBMED Abstract]
56. Schneider AB, Favus MJ, Stachura ME, et al.: Salivary gland neoplasms as a late consequence of head and neck irradiation. Ann Intern Med 87 (2): 160-4, 1977. [PUBMED Abstract]
57. Shemen LJ, Huvos AG, Spiro RH: Squamous cell carcinoma of salivary gland origin. Head Neck Surg 9 (4): 235-40, 1987 Mar-Apr. [PUBMED Abstract]
58. Sterman BM, Kraus DH, Sebek BA, et al.: Primary squamous cell carcinoma of the parotid gland. Laryngoscope 100 (2 Pt 1): 146-8, 1990. [PUBMED Abstract]
59. Gaughan RK, Olsen KD, Lewis JE: Primary squamous cell carcinoma of the parotid gland. Arch Otolaryngol Head Neck Surg 118 (8): 798-801, 1992. [PUBMED Abstract]
60. Batsakis JG, el-Naggar AK, Luna MA: Epithelial-myoepithelial carcinoma of salivary glands. Ann Otol Rhinol Laryngol 101 (6): 540-2, 1992. [PUBMED Abstract]
61. Daley TD, Wysocki GP, Smout MS, et al.: Epithelial-myoepithelial carcinoma of salivary glands. Oral Surg Oral Med Oral Pathol 57 (5): 512-9, 1984. [PUBMED Abstract]
62. Collina G, Gale N, Visonà A, et al.: Epithelial-myoepithelial carcinoma of the parotid gland: a clinico-pathologic and immunohistochemical study of seven cases. Tumori 77 (3): 257-63, 1991. [PUBMED Abstract]
63. Simpson RH, Clarke TJ, Sarsfield PT, et al.: Epithelial-myoepithelial carcinoma of salivary glands. J Clin Pathol 44 (5): 419-23, 1991. [PUBMED Abstract]
64. Noel S, Brozna JP: Epithelial-myoepithelial carcinoma of salivary gland with metastasis to lung: report of a case and review of the literature. Head Neck 14 (5): 401-6, 1992 Sep-Oct. [PUBMED Abstract]
65. Koss LG, Spiro RH, Hajdu S: Small cell (oat cell) carcinoma of minor salivary gland origin. Cancer 30 (3): 737-41, 1972. [PUBMED Abstract]
66. Gnepp DR, Wick MR: Small cell carcinoma of the major salivary glands. An immunohistochemical study. Cancer 66 (1): 185-92, 1990. [PUBMED Abstract]
67. Perez-Ordonez B, Caruana SM, Huvos AG, et al.: Small cell neuroendocrine carcinoma of the nasal cavity and paranasal sinuses. Hum Pathol 29 (8): 826-32, 1998. [PUBMED Abstract]
68. Gnepp DR, Corio RL, Brannon RB: Small cell carcinoma of the major salivary glands. Cancer 58 (3): 705-14, 1986. [PUBMED Abstract]
69. Scher RL, Feldman PS, Levine PA: Small-cell carcinoma of the parotid gland with neuroendocrine features. Arch Otolaryngol Head Neck Surg 114 (3): 319-21, 1988. [PUBMED Abstract]
70. Hui KK, Luna MA, Batsakis JG, et al.: Undifferentiated carcinomas of the major salivary glands. Oral Surg Oral Med Oral Pathol 69 (1): 76-83, 1990. [PUBMED Abstract]
71. Spiro RH: Salivary neoplasms: overview of a 35-year experience with 2,807 patients. Head Neck Surg 8 (3): 177-84, 1986 Jan-Feb. [PUBMED Abstract]
72. Batsakis JG, Luna MA: Undifferentiated carcinomas of salivary glands. Ann Otol Rhinol Laryngol 100 (1): 82-4, 1991. [PUBMED Abstract]
73. Bosch JD, Kudryk WH, Johnson GH: The malignant lymphoepithelial lesion of the salivary glands. J Otolaryngol 17 (4): 187-90, 1988. [PUBMED Abstract]
74. Hamilton-Dutoit SJ, Therkildsen MH, Neilsen NH, et al.: Undifferentiated carcinoma of the salivary gland in Greenlandic Eskimos: demonstration of Epstein-Barr virus DNA by in situ nucleic acid hybridization. Hum Pathol 22 (8): 811-5, 1991. [PUBMED Abstract]
75. Leung SY, Chung LP, Yuen ST, et al.: Lymphoepithelial carcinoma of the salivary gland: in situ detection of Epstein-Barr virus. J Clin Pathol 48 (11): 1022-7, 1995. [PUBMED Abstract]
76. Borg MF, Benjamin CS, Morton RP, et al.: Malignant lympho-epithelial lesion of the salivary gland: a case report and review of the literature. Australas Radiol 37 (3): 288-91, 1993. [PUBMED Abstract]
77. Saw D, Lau WH, Ho JH, et al.: Malignant lymphoepithelial lesion of the salivary gland. Hum Pathol 17 (9): 914-23, 1986. [PUBMED Abstract]
78. Cleary KR, Batsakis JG: Undifferentiated carcinoma with lymphoid stroma of the major salivary glands. Ann Otol Rhinol Laryngol 99 (3 Pt 1): 236-8, 1990. [PUBMED Abstract]
79. Savera AT, Sloman A, Huvos AG, et al.: Myoepithelial carcinoma of the salivary glands: a clinicopathologic study of 25 patients. Am J Surg Pathol 24 (6): 761-74, 2000. [PUBMED Abstract]
80. Kassan SS, Thomas TL, Moutsopoulos HM, et al.: Increased risk of lymphoma in sicca syndrome. Ann Intern Med 89 (6): 888-92, 1978. [PUBMED Abstract]
81. Abbondanzo SL: Extranodal marginal-zone B-cell lymphoma of the salivary gland. Ann Diagn Pathol 5 (4): 246-54, 2001. [PUBMED Abstract]
82. Ihrler S, Baretton GB, Menauer F, et al.: Sjögren’s syndrome and MALT lymphomas of salivary glands: a DNA-cytometric and interphase-cytogenetic study. Mod Pathol 13 (1): 4-12, 2000. [PUBMED Abstract]
83. Harris NL: Lymphoid proliferations of the salivary glands. Am J Clin Pathol 111 (1 Suppl 1): S94-103, 1999. [PUBMED Abstract]
84. DiGiuseppe JA, Corio RL, Westra WH: Lymphoid infiltrates of the salivary glands: pathology, biology and clinical significance. Curr Opin Oncol 8 (3): 232-7, 1996. [PUBMED Abstract]
85. Harris NL: Extranodal lymphoid infiltrates and mucosa-associated lymphoid tissue (MALT). A unifying concept. Am J Surg Pathol 15 (9): 879-84, 1991. [PUBMED Abstract]
86. Burke JS: Waldeyer’s ring, sinonasal region, salivary gland, thyroid gland, central nervous system, and other extranodal lymphomas and lymphoid hyperplasias. In: Knowles DM, ed.: Neoplastic Hematopathology. Williams & Wilkins, 1992, pp 1047-79.
87. Salhany KE, Pietra GG: Extranodal lymphoid disorders. Am J Clin Pathol 99 (4): 472-85, 1993. [PUBMED Abstract]
88. Schmid U, Helbron D, Lennert K: Primary malignant lymphomas localized in salivary glands. Histopathology 6 (6): 673-87, 1982. [PUBMED Abstract]
89. Gleeson MJ, Bennett MH, Cawson RA: Lymphomas of salivary glands. Cancer 58 (3): 699-704, 1986. [PUBMED Abstract]
90. Seifert G, Oehne H: [Mesenchymal (non-epithelial) salivary gland tumors. Analysis of 167 tumor cases of the salivary gland register] Laryngol Rhinol Otol (Stuttg) 65 (9): 485-91, 1986. [PUBMED Abstract]
91. Auclair PL, Ellis GL, Gnepp DR, et al.: Salivary gland neoplasms: general considerations. In: Ellis GL, Auclair PL, Gnepp DR, eds.: Surgical Pathology of the Salivary Glands. Saunders, 1991, pp 135-64.
92. Auclair PL, Ellis GL: Nonlymphoid sarcomas of the major salivary glands. In: Ellis GL, Auclair PL, Gnepp DR, eds.: Surgical Pathology of the Salivary Glands. Saunders, 1991, pp 514-27.
93. Luna MA, Tortoledo ME, Ordóñez NG, et al.: Primary sarcomas of the major salivary glands. Arch Otolaryngol Head Neck Surg 117 (3): 302-6, 1991. [PUBMED Abstract]
94. Auclair PL, Langloss JM, Weiss SW, et al.: Sarcomas and sarcomatoid neoplasms of the major salivary gland regions. A clinicopathologic and immunohistochemical study of 67 cases and review of the literature. Cancer 58 (6): 1305-15, 1986. [PUBMED Abstract]
95. Weiss SW, Goldblum JR: Enzinger and Weiss’s Soft Tissue Tumors. 4th ed. Mosby, 2001.
96. Cantera JM, Hernandez AV: Bilateral parotid gland metastasis as the initial presentation of a small cell lung carcinoma. J Oral Maxillofac Surg 47 (11): 1199-201, 1989. [PUBMED Abstract]
97. Gnepp DR: Metastatic disease to the major salivary glands. In: Ellis GL, Auclair PL, Gnepp DR, eds.: Surgical Pathology of the Salivary Glands. Saunders, 1991, pp 560-9.
98. Seifert G, Hennings K, Caselitz J: Metastatic tumors to the parotid and submandibular glands–analysis and differential diagnosis of 108 cases. Pathol Res Pract 181 (6): 684-92, 1986. [PUBMED Abstract]
99. Batsakis JG, Bautina E: Metastases to major salivary glands. Ann Otol Rhinol Laryngol 99 (6 Pt 1): 501-3, 1990. [PUBMED Abstract]

In general, tumors of the major salivary glands are staged according to size, extraparenchymal extension, lymph node involvement (in parotid tumors, whether or not the facial nerve is involved), and presence of metastases.[1–4] Tumors arising in the minor salivary glands are staged according to the anatomical site of origin (e.g., oral cavity and sinuses).

Clinical stage, particularly tumor size, may be the critical factor in determining the outcome of salivary gland cancer and may be more important than histological grade.[5,6] Diagnostic imaging studies may be used in staging. With excellent spatial resolution and superior soft tissue contrast, magnetic resonance imaging (MRI) offers advantages over computed tomographic scanning in the detection and localization of head and neck tumors. Overall, MRI is the preferred modality for evaluation of suspected neoplasms of the salivary glands.[7]

References

1. Spiro RH, Huvos AG, Strong EW: Cancer of the parotid gland. A clinicopathologic study of 288 primary cases. Am J Surg 130 (4): 452-9, 1975. [PUBMED Abstract]
2. Fu KK, Leibel SA, Levine ML, et al.: Carcinoma of the major and minor salivary glands: analysis of treatment results and sites and causes of failures. Cancer 40 (6): 2882-90, 1977. [PUBMED Abstract]
3. Levitt SH, McHugh RB, Gómez-Marin O, et al.: Clinical staging system for cancer of the salivary gland: a retrospective study. Cancer 47 (11): 2712-24, 1981. [PUBMED Abstract]
4. Kuhel W, Goepfert H, Luna M, et al.: Adenoid cystic carcinoma of the palate. Arch Otolaryngol Head Neck Surg 118 (3): 243-7, 1992. [PUBMED Abstract]
5. Major salivary glands. In: Amin MB, Edge SB, Greene FL, et al., eds.: AJCC Cancer Staging Manual. 8th ed. Springer; 2017, pp. 95–101.
6. Spiro RH: Factors affecting survival in salivary gland cancers. In: McGurk M, Renehan AG, eds.: Controversies in the Management of Salivary Gland Disease. Oxford University Press, 2001, pp 143-50.
7. Shah GV: MR imaging of salivary glands. Magn Reson Imaging Clin N Am 10 (4): 631-62, 2002. [PUBMED Abstract]

The minimum therapy for patients with low-grade malignancies of the superficial portion of the parotid gland is a superficial parotidectomy. For all other lesions, a total parotidectomy is often indicated. The facial nerve or its branches should be resected if involved by tumor; repair can be done simultaneously. Evidence suggests that postoperative radiation therapy augments surgical resection, particularly for the high-grade neoplasms, when margins are close or involved, when tumors are large, or when histological evidence of lymph node metastases is present.[1–8] Clinical trials in the United States and England indicated that fast neutron-beam radiation therapy improves disease-free survival and overall survival in patients with unresectable tumors or for patients with recurrent neoplasms.[9–12] The availability of facilities with fast neutron-beam radiation therapy is limited in the United States. Accelerated hyperfractionated photon-beam radiation therapy has also resulted in high rates of long-term local regional controls.[13,14] The use of chemotherapy for malignant salivary gland tumors remains under evaluation.[15–19]

References

1. Myers EN, Suen JY, eds.: Cancer of the Head and Neck. 3rd ed. Saunders, 1996.
2. Freund HR: Principles of Head and Neck Surgery. 2nd ed. Appleton-Century-Crofts, 1979.
3. Lore JM: An Atlas of Head and Neck Surgery. 3rd ed. Saunders, 1988.
4. Million RR, Cassisi NJ, eds.: Management of Head and Neck Cancer: A Multidisciplinary Approach. Lippincott, 1994.
5. Wang CC, ed.: Radiation Therapy for Head and Neck Neoplasms. 3rd ed. Wiley-Liss, 1997.
6. Cummings CW, Fredrickson JM, Harker LA, et al.: Otolaryngology – Head and Neck Surgery. Mosby-Year Book, Inc., 1998.
7. Garden AS, el-Naggar AK, Morrison WH, et al.: Postoperative radiotherapy for malignant tumors of the parotid gland. Int J Radiat Oncol Biol Phys 37 (1): 79-85, 1997. [PUBMED Abstract]
8. Chen AM, Granchi PJ, Garcia J, et al.: Local-regional recurrence after surgery without postoperative irradiation for carcinomas of the major salivary glands: implications for adjuvant therapy. Int J Radiat Oncol Biol Phys 67 (4): 982-7, 2007. [PUBMED Abstract]
9. Buchholz TA, Laramore GE, Griffin BR, et al.: The role of fast neutron radiation therapy in the management of advanced salivary gland malignant neoplasms. Cancer 69 (11): 2779-88, 1992. [PUBMED Abstract]
10. Krüll A, Schwarz R, Engenhart R, et al.: European results in neutron therapy of malignant salivary gland tumors. Bull Cancer Radiother 83 (Suppl): 125-9s, 1996. [PUBMED Abstract]
11. Douglas JG, Lee S, Laramore GE, et al.: Neutron radiotherapy for the treatment of locally advanced major salivary gland tumors. Head Neck 21 (3): 255-63, 1999. [PUBMED Abstract]
12. Douglas JG, Laramore GE, Austin-Seymour M, et al.: Treatment of locally advanced adenoid cystic carcinoma of the head and neck with neutron radiotherapy. Int J Radiat Oncol Biol Phys 46 (3): 551-7, 2000. [PUBMED Abstract]
13. Wang CC, Goodman M: Photon irradiation of unresectable carcinomas of salivary glands. Int J Radiat Oncol Biol Phys 21 (3): 569-76, 1991. [PUBMED Abstract]
14. Douglas JG, Koh WJ, Austin-Seymour M, et al.: Treatment of salivary gland neoplasms with fast neutron radiotherapy. Arch Otolaryngol Head Neck Surg 129 (9): 944-8, 2003. [PUBMED Abstract]
15. Kaplan MJ, Johns ME, Cantrell RW: Chemotherapy for salivary gland cancer. Otolaryngol Head Neck Surg 95 (2): 165-70, 1986. [PUBMED Abstract]
16. Eisenberger MA: Supporting evidence for an active treatment program for advanced salivary gland carcinomas. Cancer Treat Rep 69 (3): 319-21, 1985. [PUBMED Abstract]
17. Spiro RH: Salivary neoplasms: overview of a 35-year experience with 2,807 patients. Head Neck Surg 8 (3): 177-84, 1986 Jan-Feb. [PUBMED Abstract]
18. Theriault C, Fitzpatrick PJ: Malignant parotid tumors. Prognostic factors and optimum treatment. Am J Clin Oncol 9 (6): 510-6, 1986. [PUBMED Abstract]
19. Licitra L, Cavina R, Grandi C, et al.: Cisplatin, doxorubicin and cyclophosphamide in advanced salivary gland carcinoma. A phase II trial of 22 patients. Ann Oncol 7 (6): 640-2, 1996. [PUBMED Abstract]

References

1. Byers RM, Jesse RH, Guillamondegui OM, et al.: Malignant tumors of the submaxillary gland. Am J Surg 126 (4): 458-63, 1973. [PUBMED Abstract]
2. Mendenhall WM, Werning JW, Pfister DG: Treatment of head and neck cancer. In: DeVita VT Jr, Lawrence TS, Rosenberg SA: Cancer: Principles and Practice of Oncology. 9th ed. Lippincott Williams & Wilkins, 2011, pp 729-80.
3. Woods JE, Chong GC, Beahrs OH: Experience with 1,360 primary parotid tumors. Am J Surg 130 (4): 460-2, 1975. [PUBMED Abstract]
4. Guillamondegui OM, Byers RM, Luna MA, et al.: Aggressive surgery in treatment for parotid cancer: the role of adjunctive postoperative radiotherapy. Am J Roentgenol Radium Ther Nucl Med 123 (1): 49-54, 1975. [PUBMED Abstract]
5. Krüll A, Schwarz R, Engenhart R, et al.: European results in neutron therapy of malignant salivary gland tumors. Bull Cancer Radiother 83 (Suppl): 125-9s, 1996. [PUBMED Abstract]
6. Douglas JG, Lee S, Laramore GE, et al.: Neutron radiotherapy for the treatment of locally advanced major salivary gland tumors. Head Neck 21 (3): 255-63, 1999. [PUBMED Abstract]
7. Douglas JG, Laramore GE, Austin-Seymour M, et al.: Treatment of locally advanced adenoid cystic carcinoma of the head and neck with neutron radiotherapy. Int J Radiat Oncol Biol Phys 46 (3): 551-7, 2000. [PUBMED Abstract]
8. Hosokawa Y, Shirato H, Kagei K, et al.: Role of radiotherapy for mucoepidermoid carcinoma of salivary gland. Oral Oncol 35 (1): 105-11, 1999. [PUBMED Abstract]
9. Garden AS, el-Naggar AK, Morrison WH, et al.: Postoperative radiotherapy for malignant tumors of the parotid gland. Int J Radiat Oncol Biol Phys 37 (1): 79-85, 1997. [PUBMED Abstract]
10. Mendenhall WM, Morris CG, Amdur RJ, et al.: Radiotherapy alone or combined with surgery for salivary gland carcinoma. Cancer 103 (12): 2544-50, 2005. [PUBMED Abstract]
11. Chen AM, Granchi PJ, Garcia J, et al.: Local-regional recurrence after surgery without postoperative irradiation for carcinomas of the major salivary glands: implications for adjuvant therapy. Int J Radiat Oncol Biol Phys 67 (4): 982-7, 2007. [PUBMED Abstract]
12. Kaplan MJ, Johns ME, Cantrell RW: Chemotherapy for salivary gland cancer. Otolaryngol Head Neck Surg 95 (2): 165-70, 1986. [PUBMED Abstract]
13. Eisenberger MA: Supporting evidence for an active treatment program for advanced salivary gland carcinomas. Cancer Treat Rep 69 (3): 319-21, 1985. [PUBMED Abstract]

References

1. Spiro RH: Salivary neoplasms: overview of a 35-year experience with 2,807 patients. Head Neck Surg 8 (3): 177-84, 1986 Jan-Feb. [PUBMED Abstract]
2. Theriault C, Fitzpatrick PJ: Malignant parotid tumors. Prognostic factors and optimum treatment. Am J Clin Oncol 9 (6): 510-6, 1986. [PUBMED Abstract]
3. Byers RM, Jesse RH, Guillamondegui OM, et al.: Malignant tumors of the submaxillary gland. Am J Surg 126 (4): 458-63, 1973. [PUBMED Abstract]
4. Mendenhall WM, Werning JW, Pfister DG: Treatment of head and neck cancer. In: DeVita VT Jr, Lawrence TS, Rosenberg SA: Cancer: Principles and Practice of Oncology. 9th ed. Lippincott Williams & Wilkins, 2011, pp 729-80.
5. Woods JE, Chong GC, Beahrs OH: Experience with 1,360 primary parotid tumors. Am J Surg 130 (4): 460-2, 1975. [PUBMED Abstract]
6. Guillamondegui OM, Byers RM, Luna MA, et al.: Aggressive surgery in treatment for parotid cancer: the role of adjunctive postoperative radiotherapy. Am J Roentgenol Radium Ther Nucl Med 123 (1): 49-54, 1975. [PUBMED Abstract]
7. Hosokawa Y, Shirato H, Kagei K, et al.: Role of radiotherapy for mucoepidermoid carcinoma of salivary gland. Oral Oncol 35 (1): 105-11, 1999. [PUBMED Abstract]
8. Garden AS, el-Naggar AK, Morrison WH, et al.: Postoperative radiotherapy for malignant tumors of the parotid gland. Int J Radiat Oncol Biol Phys 37 (1): 79-85, 1997. [PUBMED Abstract]
9. Mendenhall WM, Morris CG, Amdur RJ, et al.: Radiotherapy alone or combined with surgery for salivary gland carcinoma. Cancer 103 (12): 2544-50, 2005. [PUBMED Abstract]
10. Chen AM, Granchi PJ, Garcia J, et al.: Local-regional recurrence after surgery without postoperative irradiation for carcinomas of the major salivary glands: implications for adjuvant therapy. Int J Radiat Oncol Biol Phys 67 (4): 982-7, 2007. [PUBMED Abstract]
11. Krüll A, Schwarz R, Engenhart R, et al.: European results in neutron therapy of malignant salivary gland tumors. Bull Cancer Radiother 83 (Suppl): 125-9s, 1996. [PUBMED Abstract]
12. Wang CC, Goodman M: Photon irradiation of unresectable carcinomas of salivary glands. Int J Radiat Oncol Biol Phys 21 (3): 569-76, 1991. [PUBMED Abstract]
13. Douglas JG, Lee S, Laramore GE, et al.: Neutron radiotherapy for the treatment of locally advanced major salivary gland tumors. Head Neck 21 (3): 255-63, 1999. [PUBMED Abstract]
14. Douglas JG, Laramore GE, Austin-Seymour M, et al.: Treatment of locally advanced adenoid cystic carcinoma of the head and neck with neutron radiotherapy. Int J Radiat Oncol Biol Phys 46 (3): 551-7, 2000. [PUBMED Abstract]
15. Suen JY, Johns ME: Chemotherapy for salivary gland cancer. Laryngoscope 92 (3): 235-9, 1982. [PUBMED Abstract]
16. Posner MR, Ervin TJ, Weichselbaum RR, et al.: Chemotherapy of advanced salivary gland neoplasms. Cancer 50 (11): 2261-4, 1982. [PUBMED Abstract]

References

1. Krüll A, Schwarz R, Engenhart R, et al.: European results in neutron therapy of malignant salivary gland tumors. Bull Cancer Radiother 83 (Suppl): 125-9s, 1996. [PUBMED Abstract]
2. Catterall M, Errington RD: The implications of improved treatment of malignant salivary gland tumors by fast neutron radiotherapy. Int J Radiat Oncol Biol Phys 13 (9): 1313-8, 1987. [PUBMED Abstract]
3. Kaplan MJ, Johns ME, Cantrell RW: Chemotherapy for salivary gland cancer. Otolaryngol Head Neck Surg 95 (2): 165-70, 1986. [PUBMED Abstract]
4. Eisenberger MA: Supporting evidence for an active treatment program for advanced salivary gland carcinomas. Cancer Treat Rep 69 (3): 319-21, 1985. [PUBMED Abstract]
5. Byers RM, Jesse RH, Guillamondegui OM, et al.: Malignant tumors of the submaxillary gland. Am J Surg 126 (4): 458-63, 1973. [PUBMED Abstract]
6. Mendenhall WM, Werning JW, Pfister DG: Treatment of head and neck cancer. In: DeVita VT Jr, Lawrence TS, Rosenberg SA: Cancer: Principles and Practice of Oncology. 9th ed. Lippincott Williams & Wilkins, 2011, pp 729-80.
7. Woods JE, Chong GC, Beahrs OH: Experience with 1,360 primary parotid tumors. Am J Surg 130 (4): 460-2, 1975. [PUBMED Abstract]
8. Guillamondegui OM, Byers RM, Luna MA, et al.: Aggressive surgery in treatment for parotid cancer: the role of adjunctive postoperative radiotherapy. Am J Roentgenol Radium Ther Nucl Med 123 (1): 49-54, 1975. [PUBMED Abstract]
9. Spiro RH: Salivary neoplasms: overview of a 35-year experience with 2,807 patients. Head Neck Surg 8 (3): 177-84, 1986 Jan-Feb. [PUBMED Abstract]
10. Theriault C, Fitzpatrick PJ: Malignant parotid tumors. Prognostic factors and optimum treatment. Am J Clin Oncol 9 (6): 510-6, 1986. [PUBMED Abstract]
11. Hosokawa Y, Shirato H, Kagei K, et al.: Role of radiotherapy for mucoepidermoid carcinoma of salivary gland. Oral Oncol 35 (1): 105-11, 1999. [PUBMED Abstract]
12. Garden AS, el-Naggar AK, Morrison WH, et al.: Postoperative radiotherapy for malignant tumors of the parotid gland. Int J Radiat Oncol Biol Phys 37 (1): 79-85, 1997. [PUBMED Abstract]
13. Mendenhall WM, Morris CG, Amdur RJ, et al.: Radiotherapy alone or combined with surgery for salivary gland carcinoma. Cancer 103 (12): 2544-50, 2005. [PUBMED Abstract]
14. Chen AM, Granchi PJ, Garcia J, et al.: Local-regional recurrence after surgery without postoperative irradiation for carcinomas of the major salivary glands: implications for adjuvant therapy. Int J Radiat Oncol Biol Phys 67 (4): 982-7, 2007. [PUBMED Abstract]
15. Wang CC, Goodman M: Photon irradiation of unresectable carcinomas of salivary glands. Int J Radiat Oncol Biol Phys 21 (3): 569-76, 1991. [PUBMED Abstract]
16. Douglas JG, Lee S, Laramore GE, et al.: Neutron radiotherapy for the treatment of locally advanced major salivary gland tumors. Head Neck 21 (3): 255-63, 1999. [PUBMED Abstract]
17. Douglas JG, Laramore GE, Austin-Seymour M, et al.: Treatment of locally advanced adenoid cystic carcinoma of the head and neck with neutron radiotherapy. Int J Radiat Oncol Biol Phys 46 (3): 551-7, 2000. [PUBMED Abstract]
18. Suen JY, Johns ME: Chemotherapy for salivary gland cancer. Laryngoscope 92 (3): 235-9, 1982. [PUBMED Abstract]
19. Posner MR, Ervin TJ, Weichselbaum RR, et al.: Chemotherapy of advanced salivary gland neoplasms. Cancer 50 (11): 2261-4, 1982. [PUBMED Abstract]

References

1. Wang CC, Goodman M: Photon irradiation of unresectable carcinomas of salivary glands. Int J Radiat Oncol Biol Phys 21 (3): 569-76, 1991. [PUBMED Abstract]
2. Laramore GE, Krall JM, Griffin TW, et al.: Neutron versus photon irradiation for unresectable salivary gland tumors: final report of an RTOG-MRC randomized clinical trial. Radiation Therapy Oncology Group. Medical Research Council. Int J Radiat Oncol Biol Phys 27 (2): 235-40, 1993. [PUBMED Abstract]
3. Krüll A, Schwarz R, Engenhart R, et al.: European results in neutron therapy of malignant salivary gland tumors. Bull Cancer Radiother 83 (Suppl): 125-9s, 1996. [PUBMED Abstract]
4. Douglas JG, Lee S, Laramore GE, et al.: Neutron radiotherapy for the treatment of locally advanced major salivary gland tumors. Head Neck 21 (3): 255-63, 1999. [PUBMED Abstract]
5. Douglas JG, Laramore GE, Austin-Seymour M, et al.: Treatment of locally advanced adenoid cystic carcinoma of the head and neck with neutron radiotherapy. Int J Radiat Oncol Biol Phys 46 (3): 551-7, 2000. [PUBMED Abstract]
6. Eisenberger MA: Supporting evidence for an active treatment program for advanced salivary gland carcinomas. Cancer Treat Rep 69 (3): 319-21, 1985. [PUBMED Abstract]
7. Venook AP, Tseng A, Meyers FJ, et al.: Cisplatin, doxorubicin, and 5-fluorouracil chemotherapy for salivary gland malignancies: a pilot study of the Northern California Oncology Group. J Clin Oncol 5 (6): 951-5, 1987. [PUBMED Abstract]
8. Rentschler R, Burgess MA, Byers R: Chemotherapy of malignant major salivary gland neoplasms: a 25-year review of M. D. Anderson Hospital experience. Cancer 40 (2): 619-24, 1977. [PUBMED Abstract]
9. Posner MR, Ervin TJ, Weichselbaum RR, et al.: Chemotherapy of advanced salivary gland neoplasms. Cancer 50 (11): 2261-4, 1982. [PUBMED Abstract]
10. Suen JY, Johns ME: Chemotherapy for salivary gland cancer. Laryngoscope 92 (3): 235-9, 1982. [PUBMED Abstract]
11. Catterall M, Errington RD: The implications of improved treatment of malignant salivary gland tumors by fast neutron radiotherapy. Int J Radiat Oncol Biol Phys 13 (9): 1313-8, 1987. [PUBMED Abstract]
12. Ono M, Watanabe A, Matsumoto Y, et al.: Methamphetamine modifies the photic entraining responses in the rodent suprachiasmatic nucleus via serotonin release. Neuroscience 72 (1): 213-24, 1996. [PUBMED Abstract]
13. Saroja KR, Mansell J, Hendrickson FR, et al.: An update on malignant salivary gland tumors treated with neutrons at Fermilab. Int J Radiat Oncol Biol Phys 13 (9): 1319-25, 1987. [PUBMED Abstract]
14. Licitra L, Cavina R, Grandi C, et al.: Cisplatin, doxorubicin and cyclophosphamide in advanced salivary gland carcinoma. A phase II trial of 22 patients. Ann Oncol 7 (6): 640-2, 1996. [PUBMED Abstract]
15. Sharma BB, Rai K, Blunt H, et al.: Pathogenic DPYD Variants and Treatment-Related Mortality in Patients Receiving Fluoropyrimidine Chemotherapy: A Systematic Review and Meta-Analysis. Oncologist 26 (12): 1008-1016, 2021. [PUBMED Abstract]
16. Lam SW, Guchelaar HJ, Boven E: The role of pharmacogenetics in capecitabine efficacy and toxicity. Cancer Treat Rev 50: 9-22, 2016. [PUBMED Abstract]
17. Shakeel F, Fang F, Kwon JW, et al.: Patients carrying DPYD variant alleles have increased risk of severe toxicity and related treatment modifications during fluoropyrimidine chemotherapy. Pharmacogenomics 22 (3): 145-155, 2021. [PUBMED Abstract]
18. Amstutz U, Henricks LM, Offer SM, et al.: Clinical Pharmacogenetics Implementation Consortium (CPIC) Guideline for Dihydropyrimidine Dehydrogenase Genotype and Fluoropyrimidine Dosing: 2017 Update. Clin Pharmacol Ther 103 (2): 210-216, 2018. [PUBMED Abstract]
19. Henricks LM, Lunenburg CATC, de Man FM, et al.: DPYD genotype-guided dose individualisation of fluoropyrimidine therapy in patients with cancer: a prospective safety analysis. Lancet Oncol 19 (11): 1459-1467, 2018. [PUBMED Abstract]
20. Lau-Min KS, Varughese LA, Nelson MN, et al.: Preemptive pharmacogenetic testing to guide chemotherapy dosing in patients with gastrointestinal malignancies: a qualitative study of barriers to implementation. BMC Cancer 22 (1): 47, 2022. [PUBMED Abstract]
21. Brooks GA, Tapp S, Daly AT, et al.: Cost-effectiveness of DPYD Genotyping Prior to Fluoropyrimidine-based Adjuvant Chemotherapy for Colon Cancer. Clin Colorectal Cancer 21 (3): e189-e195, 2022. [PUBMED Abstract]
22. Baker SD, Bates SE, Brooks GA, et al.: DPYD Testing: Time to Put Patient Safety First. J Clin Oncol 41 (15): 2701-2705, 2023. [PUBMED Abstract]

The prognosis for any patient with progressing or relapsing salivary gland cancer is poor, regardless of cell type or stage. Selecting further treatment depends on many factors, including the specific cancer, prior treatment, site of recurrence, and individual patient considerations. Fast neutron-beam radiation therapy is superior to conventional radiation therapy using x-rays and may be curative in selected patients with recurrent disease.[1]

Patients with inoperable, unresectable, or recurrent malignant salivary gland tumors treated with fast neutron-beam radiation therapy have better disease-free survival and overall survival than patients treated with conventional x-ray radiation therapy.[2–5] Clinical trials are appropriate and should be considered when possible.

References

1. Laramore GE, Krall JM, Griffin TW, et al.: Neutron versus photon irradiation for unresectable salivary gland tumors: final report of an RTOG-MRC randomized clinical trial. Radiation Therapy Oncology Group. Medical Research Council. Int J Radiat Oncol Biol Phys 27 (2): 235-40, 1993. [PUBMED Abstract]
2. Laramore GE: Fast neutron radiotherapy for inoperable salivary gland tumors: is it the treatment of choice? Int J Radiat Oncol Biol Phys 13 (9): 1421-3, 1987. [PUBMED Abstract]
3. Saroja KR, Mansell J, Hendrickson FR, et al.: An update on malignant salivary gland tumors treated with neutrons at Fermilab. Int J Radiat Oncol Biol Phys 13 (9): 1319-25, 1987. [PUBMED Abstract]
4. Buchholz TA, Laramore GE, Griffin BR, et al.: The role of fast neutron radiation therapy in the management of advanced salivary gland malignant neoplasms. Cancer 69 (11): 2779-88, 1992. [PUBMED Abstract]
5. Krüll A, Schwarz R, Engenhart R, et al.: European results in neutron therapy of malignant salivary gland tumors. Bull Cancer Radiother 83 (Suppl): 125-9s, 1996. [PUBMED Abstract]

The PDQ cancer information summaries are reviewed regularly and updated as new information becomes available. This section describes the latest changes made to this summary as of the date above.

General Information About Salivary Gland Cancer

Revised text about the incidence and mortality rates of salivary gland cancer in the United States (cited National Cancer Institute as reference 1).

This summary is written and maintained by the PDQ Adult Treatment Editorial Board, which is editorially independent of NCI. The summary reflects an independent review of the literature and does not represent a policy statement of NCI or NIH. More information about summary policies and the role of the PDQ Editorial Boards in maintaining the PDQ summaries can be found on the About This PDQ Summary and PDQ® Cancer Information for Health Professionals pages.

Oral cavity, oropharyngeal, hypopharyngeal, and laryngeal cancers may be referred to as head and neck squamous cell cancers. Oral cavity squamous cell cancers most commonly arise from the mucosal surfaces lining the oral cavity. Pharyngeal squamous cell cancers can be categorized into nasopharyngeal, oropharyngeal, and hypopharyngeal cancers on the basis of anatomical landmarks. Figure 1 shows the anatomy of the pharynx.

Enlarge

Note: The Overview section summarizes the published evidence on this topic. The rest of the summary describes the evidence in more detail.

Other PDQ summaries on Oral Cavity, Oropharyngeal, Hypopharyngeal, and Laryngeal Cancers Prevention and Lip and Oral Cavity Cancer Treatment are also available.

An estimated 59,660 new cases of oral cavity and oropharynx cancers will be diagnosed in the United States in 2025, and an estimated 12,770 people will die of these diseases.[1] The overall annual incidence in the United States is about 11 cases per 100,000 men and women; the incidence rate is highest in individuals aged 75 to 84 years.[2]

Between 2012 and 2021, incidence rates increased by 0.7% per year.[1] The incidence has been increasing for oral cavity and oropharyngeal cancers related to human papillomavirus (HPV) infection. About 60% of oral/pharyngeal cancers are moderately advanced (regional stage) or metastatic at the time of diagnosis.[2] The 5-year relative survival rate is 69%.[1]

The estimated annual worldwide number of cases of oral cavity and oropharyngeal cancers is about 275,000, with an approximate 20-fold variation geographically.[3] South and Southeast Asia (India, Sri Lanka, Pakistan, and Bangladesh), France, and Brazil have particularly high rates. In most countries, men have higher rates of oral cavity cancer than women (caused by tobacco use) and higher rates of lip cancer (caused by sunlight exposure from outdoor occupations).[3]

Nasopharyngeal cancers are rare in the United States, with an annual incidence rate of 0.7 cases per 100,000 persons.[4] However, there are marked geographic differences, with an overall incidence in China that is 40- to 380-fold higher than that in the United States.[4] There are elevated rates of nasopharyngeal cancers in the Cantonese population of southern China (including Hong Kong), and intermediate rates are observed in several indigenous populations in Southeast Asia and in natives of the Arctic region, North Africa, and the Middle East. First-generation Chinese immigrants to the United States maintain a high incidence rate, while their descendants born in the United States show a decreased incidence. The 5-year survival rate for keratinizing squamous cell carcinoma, the most common subtype of nasopharyngeal cancer in the United States, is 46%.[5]

References

1. American Cancer Society: Cancer Facts and Figures 2025. American Cancer Society, 2025. Available online. Last accessed January 16, 2025.
2. Surveillance Research Program, National Cancer Institute: SEER*Explorer: An interactive website for SEER cancer statistics. Bethesda, MD: National Cancer Institute. Available online. Last accessed December 30, 2024.
3. Warnakulasuriya S: Global epidemiology of oral and oropharyngeal cancer. Oral Oncol 45 (4-5): 309-16, 2009 Apr-May. [PUBMED Abstract]
4. Richey LM, Olshan AF, George J, et al.: Incidence and survival rates for young blacks with nasopharyngeal carcinoma in the United States. Arch Otolaryngol Head Neck Surg 132 (10): 1035-40, 2006. [PUBMED Abstract]
5. Ou SH, Zell JA, Ziogas A, et al.: Epidemiology of nasopharyngeal carcinoma in the United States: improved survival of Chinese patients within the keratinizing squamous cell carcinoma histology. Ann Oncol 18 (1): 29-35, 2007. [PUBMED Abstract]

The primary risk factors for oral cavity cancers in American men and women are tobacco (including smokeless tobacco) use, alcohol use, betel-quid chewing, and human papillomavirus infection (HPV).

Risk factors for nasopharyngeal cancer include Epstein-Barr virus (EBV) persistent infection.[1]

For more information about factors associated with an increased or decreased risk of oral cavity squamous cell cancers, see Oral Cavity, Oropharyngeal, Hypopharyngeal, and Laryngeal Cancers Prevention and Lip and Oral Cavity Cancer Treatment.

References

1. IARC Working Group on the Evaluation of Carcinogenic Risks to Humans: Biological agents. Volume 100 B. A review of human carcinogens. IARC Monogr Eval Carcinog Risks Hum 100 (Pt B): 1-441, 2012. [PUBMED Abstract]
2. Henle W, Henle G, Ho HC, et al.: Antibodies to Epstein-Barr virus in nasopharyngeal carcinoma, other head and neck neoplasms, and control groups. J Natl Cancer Inst 44 (1): 225-31, 1970. [PUBMED Abstract]
3. Chien YC, Chen JY, Liu MY, et al.: Serologic markers of Epstein-Barr virus infection and nasopharyngeal carcinoma in Taiwanese men. N Engl J Med 345 (26): 1877-82, 2001. [PUBMED Abstract]
4. Lin JC, Wang WY, Chen KY, et al.: Quantification of plasma Epstein-Barr virus DNA in patients with advanced nasopharyngeal carcinoma. N Engl J Med 350 (24): 2461-70, 2004. [PUBMED Abstract]
5. Chang ET, Adami HO: The enigmatic epidemiology of nasopharyngeal carcinoma. Cancer Epidemiol Biomarkers Prev 15 (10): 1765-77, 2006. [PUBMED Abstract]

No population-based screening programs for oral cavity squamous cell cancers have been implemented in developed countries, although opportunistic screening or screening as part of a periodic health examination has been advocated for the oral cavity, which is the only site accessible without endoscopy.[1,2]

References

1. Opportunistic oral cancer screening: a management strategy for dental practice. BDA Occasional Paper 6: 1-36, 2000. Also available online. Last accessed April 14, 2025.
2. Smith RA, Cokkinides V, Brooks D, et al.: Cancer screening in the United States, 2011: A review of current American Cancer Society guidelines and issues in cancer screening. CA Cancer J Clin 61 (1): 8-30, 2011 Jan-Feb. [PUBMED Abstract]
3. Kerr AR, Changrani JG, Gany FM, et al.: An academic dental center grapples with oral cancer disparities: current collaboration and future opportunities. J Dent Educ 68 (5): 531-41, 2004. [PUBMED Abstract]
4. Warnakulasuriya S, Johnson NW, van der Waal I: Nomenclature and classification of potentially malignant disorders of the oral mucosa. J Oral Pathol Med 36 (10): 575-80, 2007. [PUBMED Abstract]
5. Brocklehurst P, Kujan O, Glenny AM, et al.: Screening programmes for the early detection and prevention of oral cancer. Cochrane Database Syst Rev (11): CD004150, 2010. [PUBMED Abstract]
6. Poh CF, Zhang L, Anderson DW, et al.: Fluorescence visualization detection of field alterations in tumor margins of oral cancer patients. Clin Cancer Res 12 (22): 6716-22, 2006. [PUBMED Abstract]
7. Poh CF, Zhang L, Lam WL, et al.: A high frequency of allelic loss in oral verrucous lesions may explain malignant risk. Lab Invest 81 (4): 629-34, 2001. [PUBMED Abstract]
8. Screening for oral cancer. In: Fisher M, Eckhart C, eds.: Guide to Clinical Preventive Services: an Assessment of the Effectiveness of 169 Interventions. Report of the U.S. Preventive Services Task Force. Williams & Wilkins, 1989, pp 91-94.
9. Antunes JL, Biazevic MG, de Araujo ME, et al.: Trends and spatial distribution of oral cancer mortality in São Paulo, Brazil, 1980-1998. Oral Oncol 37 (4): 345-50, 2001. [PUBMED Abstract]
10. U.S. Preventive Services Task Force: Screening for Oral Cancer: Recommendation Statement. Rockville, Md: U.S. Preventive Services Task Force, 2013. Available online. Last accessed April 14, 2025.
11. Scattoloni J: Screening for Oral Cancer: Brief Evidence Update. Rockville, Md: U.S. Preventive Services Task Force, 2004. Available online. Last accessed April 14, 2025.
12. Sankaranarayanan R, Mathew B, Jacob BJ, et al.: Early findings from a community-based, cluster-randomized, controlled oral cancer screening trial in Kerala, India. The Trivandrum Oral Cancer Screening Study Group. Cancer 88 (3): 664-73, 2000. [PUBMED Abstract]
13. Ramadas K, Sankaranarayanan R, Jacob BJ, et al.: Interim results from a cluster randomized controlled oral cancer screening trial in Kerala, India. Oral Oncol 39 (6): 580-8, 2003. [PUBMED Abstract]
14. Sankaranarayanan R, Ramadas K, Thomas G, et al.: Effect of screening on oral cancer mortality in Kerala, India: a cluster-randomised controlled trial. Lancet 365 (9475): 1927-33, 2005 Jun 4-10. [PUBMED Abstract]
15. Sankaranarayanan R, Ramadas K, Thara S, et al.: Long term effect of visual screening on oral cancer incidence and mortality in a randomized trial in Kerala, India. Oral Oncol 49 (4): 314-21, 2013. [PUBMED Abstract]
16. Lingen MW, Kalmar JR, Karrison T, et al.: Critical evaluation of diagnostic aids for the detection of oral cancer. Oral Oncol 44 (1): 10-22, 2008. [PUBMED Abstract]
17. Su WW, Yen AM, Chiu SY, et al.: A community-based RCT for oral cancer screening with toluidine blue. J Dent Res 89 (9): 933-7, 2010. [PUBMED Abstract]
18. Patton LL, Epstein JB, Kerr AR: Adjunctive techniques for oral cancer examination and lesion diagnosis: a systematic review of the literature. J Am Dent Assoc 139 (7): 896-905; quiz 993-4, 2008. [PUBMED Abstract]
19. Chan KCA, Woo JKS, King A, et al.: Analysis of Plasma Epstein-Barr Virus DNA to Screen for Nasopharyngeal Cancer. N Engl J Med 377 (6): 513-522, 2017. [PUBMED Abstract]
20. Cao SM, Simons MJ, Qian CN: The prevalence and prevention of nasopharyngeal carcinoma in China. Chin J Cancer 30 (2): 114-9, 2011. [PUBMED Abstract]
21. Zeng Y, Zhang LG, Li HY, et al.: Serological mass survey for early detection of nasopharyngeal carcinoma in Wuzhou City, China. Int J Cancer 29 (2): 139-41, 1982. [PUBMED Abstract]
22. Zeng Y, Zhong JM, Li LY, et al.: Follow-up studies on Epstein-Barr virus IgA/VCA antibody-positive persons in Zangwu County, China. Intervirology 20 (4): 190-4, 1983. [PUBMED Abstract]

Harms associated with screening for oral cavity squamous cell cancers are poorly studied in any quantifiable way.[1] However, there are some unavoidable harms that would be associated with routine screening, including:

An additional potential harm is misdiagnosis and resulting under- or overtreatment, given the subjective pathology judgments in the reading of biopsies of oral lesions. When 87 biopsy diagnoses of oral lesions were compared between 21 local pathologists and double-reading by two of three central pathologists in a multicenter study of patients with prior upper aerodigestive tract cancers, agreement was only fair to good (kappa-weighted statistic, 0.59; 95% confidence interval [CI], 0.45–0.72).[3] In a bivariate categorization of carcinoma in situ plus carcinoma versus less serious lesions, the agreement was poor, but with very wide CIs (kappa statistic, 0.39; 95% CI, -0.12 to -0.97). The investigators in the same study analyzed an agreement between the local and central pathologists on clinically normal tissue adjacent to 67 biopsied, clinically suspicious lesions. The agreement on clinically normal tissue was better than for visibly abnormal lesions, but still not in the excellent range (kappa-weighted statistic, 0.75; 95% CI, 0.64–0.86).[4]

References

1. Scattoloni J: Screening for Oral Cancer: Brief Evidence Update. Rockville, Md: U.S. Preventive Services Task Force, 2004. Available online. Last accessed April 14, 2025.
2. Speight PM, Zakrzewska J, Downer MC: Screening for oral cancer and precancer. Eur J Cancer B Oral Oncol 28B (1): 45-8, 1992. [PUBMED Abstract]
3. Fischer DJ, Epstein JB, Morton TH, et al.: Interobserver reliability in the histopathologic diagnosis of oral pre-malignant and malignant lesions. J Oral Pathol Med 33 (2): 65-70, 2004. [PUBMED Abstract]
4. Fischer DJ, Epstein JB, Morton TH, et al.: Reliability of histologic diagnosis of clinically normal intraoral tissue adjacent to clinically suspicious lesions in former upper aerodigestive tract cancer patients. Oral Oncol 41 (5): 489-96, 2005. [PUBMED Abstract]

The PDQ cancer information summaries are reviewed regularly and updated as new information becomes available. This section describes the latest changes made to this summary as of the date above.

Incidence and Mortality

Updated statistics with estimated new cases and deaths for 2025 (cited American Cancer Society as reference 1).

Revised text to state that between 2012 and 2021, incidence rates increased by 0.7% per year.

This summary is written and maintained by the PDQ Screening and Prevention Editorial Board, which is editorially independent of NCI. The summary reflects an independent review of the literature and does not represent a policy statement of NCI or NIH. More information about summary policies and the role of the PDQ Editorial Boards in maintaining the PDQ summaries can be found on the About This PDQ Summary and PDQ® Cancer Information for Health Professionals pages.

Note: The Overview section summarizes the published evidence on this topic. The rest of the summary describes the evidence in more detail.

Oral cavity, oropharyngeal, hypopharyngeal, and laryngeal cancers may be referred to as head and neck squamous cell cancers. Head and neck squamous cell cancers most commonly arise from the mucosal surfaces lining the oral cavity, oropharynx, hypopharynx, and larynx. Anatomically, the pharynx includes the nasopharynx, oropharynx, and hypopharynx, but cancers in these sites have distinct clinical and epidemiologic characteristics. Thus, it is inappropriate to group them together.[1] For more information, see the following PDQ summaries:

Figure 1 shows the anatomy of the pharynx.

Enlarge

References

1. IARC Working Group on the Evaluation of Carcinogenic Risks to Humans: Personal habits and indoor combustions. Volume 100 E. A review of human carcinogens. IARC Monogr Eval Carcinog Risks Hum 100 (Pt E): 1-538, 2012. [PUBMED Abstract]
2. Castellsagué X, Alemany L, Quer M, et al.: HPV Involvement in Head and Neck Cancers: Comprehensive Assessment of Biomarkers in 3680 Patients. J Natl Cancer Inst 108 (6): djv403, 2016. [PUBMED Abstract]
3. Song H, Wan Y, Xu YY: Betel quid chewing without tobacco: a meta-analysis of carcinogenic and precarcinogenic effects. Asia Pac J Public Health 27 (2): NP47-57, 2015. [PUBMED Abstract]
4. Guha N, Warnakulasuriya S, Vlaanderen J, et al.: Betel quid chewing and the risk of oral and oropharyngeal cancers: a meta-analysis with implications for cancer control. Int J Cancer 135 (6): 1433-43, 2014. [PUBMED Abstract]
5. Atienza JA, Dasanu CA: Incidence of second primary malignancies in patients with treated head and neck cancer: a comprehensive review of literature. Curr Med Res Opin 28 (12): 1899-909, 2012. [PUBMED Abstract]
6. Kreimer AR, Johansson M, Waterboer T, et al.: Evaluation of human papillomavirus antibodies and risk of subsequent head and neck cancer. J Clin Oncol 31 (21): 2708-15, 2013. [PUBMED Abstract]
7. U.S. Department of Health and Human Services: The Health Consequences of Smoking—50 Years of Progress: A Report of the Surgeon General. U.S. Department of Health and Human Services, CDC, National Center for Chronic Disease Prevention and Health Promotion, Office on Smoking and Health, 2014. Also available online. Last accessed December 30, 2024.
8. Vineis P, Alavanja M, Buffler P, et al.: Tobacco and cancer: recent epidemiological evidence. J Natl Cancer Inst 96 (2): 99-106, 2004. [PUBMED Abstract]
9. Hashibe M, Brennan P, Benhamou S, et al.: Alcohol drinking in never users of tobacco, cigarette smoking in never drinkers, and the risk of head and neck cancer: pooled analysis in the International Head and Neck Cancer Epidemiology Consortium. J Natl Cancer Inst 99 (10): 777-89, 2007. [PUBMED Abstract]
10. IARC Working Group on the Evaluation of Carcinogenic Risks to Humans: Smokeless tobacco and some tobacco-specific N-nitrosamines. IARC Monogr Eval Carcinog Risks Hum 89: 1-592, 2007. [PUBMED Abstract]
11. Purdue MP, Hashibe M, Berthiller J, et al.: Type of alcoholic beverage and risk of head and neck cancer–a pooled analysis within the INHANCE Consortium. Am J Epidemiol 169 (2): 132-42, 2009. [PUBMED Abstract]
12. Islami F, Tramacere I, Rota M, et al.: Alcohol drinking and laryngeal cancer: overall and dose-risk relation–a systematic review and meta-analysis. Oral Oncol 46 (11): 802-10, 2010. [PUBMED Abstract]
13. Hashibe M, Brennan P, Chuang SC, et al.: Interaction between tobacco and alcohol use and the risk of head and neck cancer: pooled analysis in the International Head and Neck Cancer Epidemiology Consortium. Cancer Epidemiol Biomarkers Prev 18 (2): 541-50, 2009. [PUBMED Abstract]
14. Lubin JH, Purdue M, Kelsey K, et al.: Total exposure and exposure rate effects for alcohol and smoking and risk of head and neck cancer: a pooled analysis of case-control studies. Am J Epidemiol 170 (8): 937-47, 2009. [PUBMED Abstract]
15. Mello FW, Melo G, Pasetto JJ, et al.: The synergistic effect of tobacco and alcohol consumption on oral squamous cell carcinoma: a systematic review and meta-analysis. Clin Oral Investig 23 (7): 2849-2859, 2019. [PUBMED Abstract]
16. Hobbs CG, Sterne JA, Bailey M, et al.: Human papillomavirus and head and neck cancer: a systematic review and meta-analysis. Clin Otolaryngol 31 (4): 259-66, 2006. [PUBMED Abstract]
17. D’Souza G, Kreimer AR, Viscidi R, et al.: Case-control study of human papillomavirus and oropharyngeal cancer. N Engl J Med 356 (19): 1944-56, 2007. [PUBMED Abstract]
18. Steinau M, Saraiya M, Goodman MT, et al.: Human papillomavirus prevalence in oropharyngeal cancer before vaccine introduction, United States. Emerg Infect Dis 20 (5): 822-8, 2014. [PUBMED Abstract]
19. Marron M, Boffetta P, Zhang ZF, et al.: Cessation of alcohol drinking, tobacco smoking and the reversal of head and neck cancer risk. Int J Epidemiol 39 (1): 182-96, 2010. [PUBMED Abstract]
20. Herrero R, Quint W, Hildesheim A, et al.: Reduced prevalence of oral human papillomavirus (HPV) 4 years after bivalent HPV vaccination in a randomized clinical trial in Costa Rica. PLoS One 8 (7): e68329, 2013. [PUBMED Abstract]
21. Chaturvedi AK, Graubard BI, Broutian T, et al.: Effect of Prophylactic Human Papillomavirus (HPV) Vaccination on Oral HPV Infections Among Young Adults in the United States. J Clin Oncol 36 (3): 262-267, 2018. [PUBMED Abstract]

Oral cavity and oropharynx cancers

From 2017 to 2021, the estimated age-adjusted incidence rate for cancers of the oral cavity and oropharynx in the United States was 11.5 cases per 100,000 persons per year.[1] Cancers of the tongue, oropharynx, and tonsil comprise the majority of cases (30% tongue and 24% oropharynx and tonsil). The estimated age-adjusted mortality rate for cancers of the oral cavity and oropharynx from 2018 to 2022 was 2.6 per 100,000 persons per year. U.S. incidence rates are about 1.7 times higher in men than in women. However, mortality rates are about 1.9 times higher in men than in women.[1] It is estimated that there will be 59,660 new cases of oral cavity and oropharynx cancer diagnosed in the United States in 2025 and 12,770 deaths due to these diseases.[2] Rates of oral cavity cancer vary greatly across the world, primarily because of differences in alcohol use, tobacco use, and betel-quid chewing and the products chewed.[3]

Although localized cancers of the oral cavity and oropharynx have an excellent anticipated 5-year survival rate of about 87.5%, only 26.4% of these cancer cases are diagnosed at this stage.[1] The overall 5-year relative survival rate for patients with cancers of the oral cavity and oropharynx combined is only 69%.[2] However, the 5-year relative survival rate is much lower in Black patients (57%) than in White patients (71%).[2] Additionally, the 5-year survival rate varies greatly by cancer site, with 52.1% survival among patients with cancer on the floor of the mouth and 73.8% survival among patients with cancer in the oropharynx and tonsil.[4]

Hypopharyngeal cancer

Hypopharyngeal cancers are rare, with approximately 2,500 new cases diagnosed in the United States each year and an annual incidence of 0.6 cases per 100,000 persons.[5] The 5-year survival rate for hypopharyngeal cancer is 35%.[5] New cases have been falling an average of 2% per year over the last 20 years.[5] This has been attributed to a reduction in cigarette smoking.

Laryngeal cancer

Laryngeal cancers are less common, with an annual incidence of 2.6 cases per 100,000 persons.[6] It is estimated that 13,020 new cases of laryngeal cancer will be diagnosed in the United States in 2025, and an estimated 3,910 individuals will die of this disease.[2] The 5-year relative survival rate for laryngeal cancer is 62%.[2] Age-adjusted death rates have been falling on average 1.6% each year from 2013 to 2022.[6] This has been attributed to a reduction in cigarette smoking.

References

1. National Cancer Institute: SEER Cancer Stat Facts: Oral Cavity and Pharynx Cancer. National Cancer Institute. Available online. Last accessed December 30, 2024.
2. American Cancer Society: Cancer Facts and Figures 2025. American Cancer Society, 2025. Available online. Last accessed January 16, 2025.
3. Shield KD, Ferlay J, Jemal A, et al.: The global incidence of lip, oral cavity, and pharyngeal cancers by subsite in 2012. CA Cancer J Clin 67 (1): 51-64, 2017. [PUBMED Abstract]
4. Surveillance Research Program, National Cancer Institute: SEER*Explorer: An interactive website for SEER cancer statistics. Bethesda, MD: National Cancer Institute. Available online. Last accessed December 30, 2024.
5. Kuo P, Chen MM, Decker RH, et al.: Hypopharyngeal cancer incidence, treatment, and survival: temporal trends in the United States. Laryngoscope 124 (9): 2064-9, 2014. [PUBMED Abstract]
6. National Cancer Institute: SEER Cancer Stat Facts: Laryngeal Cancer. National Cancer Institute. Available online. Last accessed April 14, 2025.

References

1. IARC Working Group on the Evaluation of Carcinogenic Risks to Humans: Personal habits and indoor combustions. Volume 100 E. A review of human carcinogens. IARC Monogr Eval Carcinog Risks Hum 100 (Pt E): 1-538, 2012. [PUBMED Abstract]
2. U.S. Department of Health and Human Services: The Health Consequences of Smoking—50 Years of Progress: A Report of the Surgeon General. U.S. Department of Health and Human Services, CDC, National Center for Chronic Disease Prevention and Health Promotion, Office on Smoking and Health, 2014. Also available online. Last accessed December 30, 2024.
3. Vineis P, Alavanja M, Buffler P, et al.: Tobacco and cancer: recent epidemiological evidence. J Natl Cancer Inst 96 (2): 99-106, 2004. [PUBMED Abstract]
4. IARC Working Group on the Evaluation of Carcinogenic Risks to Humans: Betel-quid and areca-nut chewing and some areca-nut derived nitrosamines. IARC Monogr Eval Carcinog Risks Hum 85: 1-334, 2004. [PUBMED Abstract]
5. Hashibe M, Brennan P, Benhamou S, et al.: Alcohol drinking in never users of tobacco, cigarette smoking in never drinkers, and the risk of head and neck cancer: pooled analysis in the International Head and Neck Cancer Epidemiology Consortium. J Natl Cancer Inst 99 (10): 777-89, 2007. [PUBMED Abstract]
6. Purdue MP, Hashibe M, Berthiller J, et al.: Type of alcoholic beverage and risk of head and neck cancer–a pooled analysis within the INHANCE Consortium. Am J Epidemiol 169 (2): 132-42, 2009. [PUBMED Abstract]
7. Goldstein BY, Chang SC, Hashibe M, et al.: Alcohol consumption and cancers of the oral cavity and pharynx from 1988 to 2009: an update. Eur J Cancer Prev 19 (6): 431-65, 2010. [PUBMED Abstract]
8. Hashibe M, Brennan P, Chuang SC, et al.: Interaction between tobacco and alcohol use and the risk of head and neck cancer: pooled analysis in the International Head and Neck Cancer Epidemiology Consortium. Cancer Epidemiol Biomarkers Prev 18 (2): 541-50, 2009. [PUBMED Abstract]
9. Lubin JH, Purdue M, Kelsey K, et al.: Total exposure and exposure rate effects for alcohol and smoking and risk of head and neck cancer: a pooled analysis of case-control studies. Am J Epidemiol 170 (8): 937-47, 2009. [PUBMED Abstract]
10. Mello FW, Melo G, Pasetto JJ, et al.: The synergistic effect of tobacco and alcohol consumption on oral squamous cell carcinoma: a systematic review and meta-analysis. Clin Oral Investig 23 (7): 2849-2859, 2019. [PUBMED Abstract]
11. Blot WJ, McLaughlin JK, Winn DM, et al.: Smoking and drinking in relation to oral and pharyngeal cancer. Cancer Res 48 (11): 3282-7, 1988. [PUBMED Abstract]
12. Guha N, Warnakulasuriya S, Vlaanderen J, et al.: Betel quid chewing and the risk of oral and oropharyngeal cancers: a meta-analysis with implications for cancer control. Int J Cancer 135 (6): 1433-43, 2014. [PUBMED Abstract]
13. Kreimer AR, Johansson M, Waterboer T, et al.: Evaluation of human papillomavirus antibodies and risk of subsequent head and neck cancer. J Clin Oncol 31 (21): 2708-15, 2013. [PUBMED Abstract]
14. Hobbs CG, Sterne JA, Bailey M, et al.: Human papillomavirus and head and neck cancer: a systematic review and meta-analysis. Clin Otolaryngol 31 (4): 259-66, 2006. [PUBMED Abstract]
15. D’Souza G, Kreimer AR, Viscidi R, et al.: Case-control study of human papillomavirus and oropharyngeal cancer. N Engl J Med 356 (19): 1944-56, 2007. [PUBMED Abstract]
16. Kreimer AR, Ferreiro-Iglesias A, Nygard M, et al.: Timing of HPV16-E6 antibody seroconversion before OPSCC: findings from the HPVC3 consortium. Ann Oncol 30 (8): 1335-1343, 2019. [PUBMED Abstract]
17. Sonawane K, Suk R, Chiao EY, et al.: Oral Human Papillomavirus Infection: Differences in Prevalence Between Sexes and Concordance With Genital Human Papillomavirus Infection, NHANES 2011 to 2014. Ann Intern Med 167 (10): 714-724, 2017. [PUBMED Abstract]
18. Steinau M, Saraiya M, Goodman MT, et al.: Human papillomavirus prevalence in oropharyngeal cancer before vaccine introduction, United States. Emerg Infect Dis 20 (5): 822-8, 2014. [PUBMED Abstract]

References

1. Marron M, Boffetta P, Zhang ZF, et al.: Cessation of alcohol drinking, tobacco smoking and the reversal of head and neck cancer risk. Int J Epidemiol 39 (1): 182-96, 2010. [PUBMED Abstract]

References

1. Marron M, Boffetta P, Zhang ZF, et al.: Cessation of alcohol drinking, tobacco smoking and the reversal of head and neck cancer risk. Int J Epidemiol 39 (1): 182-96, 2010. [PUBMED Abstract]
2. Herrero R, Quint W, Hildesheim A, et al.: Reduced prevalence of oral human papillomavirus (HPV) 4 years after bivalent HPV vaccination in a randomized clinical trial in Costa Rica. PLoS One 8 (7): e68329, 2013. [PUBMED Abstract]
3. Chaturvedi AK, Graubard BI, Broutian T, et al.: Effect of Prophylactic Human Papillomavirus (HPV) Vaccination on Oral HPV Infections Among Young Adults in the United States. J Clin Oncol 36 (3): 262-267, 2018. [PUBMED Abstract]

The PDQ cancer information summaries are reviewed regularly and updated as new information becomes available. This section describes the latest changes made to this summary as of the date above.

Incidence and Mortality

Updated statistics with estimated new cases and deaths for oral cavity and pharynx cancer for 2025 (cited American Cancer Society as reference 2).

Updated statistics with estimated new cases and deaths for laryngeal cancer for 2025.

This summary is written and maintained by the PDQ Screening and Prevention Editorial Board, which is editorially independent of NCI. The summary reflects an independent review of the literature and does not represent a policy statement of NCI or NIH. More information about summary policies and the role of the PDQ Editorial Boards in maintaining the PDQ summaries can be found on the About This PDQ Summary and PDQ® Cancer Information for Health Professionals pages.

The following types of treatment are used:

Surgery

Surgery to remove the tumor is a common treatment for all stages of oropharyngeal cancer. A surgeon may remove the cancer and some of the healthy tissue around the cancer. After the surgeon removes all the cancer that can be seen at the time of the surgery, some people may be given chemotherapy or radiation therapy after surgery to kill any cancer cells that are left. Treatment given after the surgery, to lower the risk that the cancer will come back, is called adjuvant therapy.

New types of surgery, including transoral robotic surgery, are being studied for the treatment of oropharyngeal cancer. Transoral robotic surgery may be used to remove cancer from hard-to-reach areas of the mouth and throat. Cameras attached to a robot give a 3-dimensional (3D) image that a surgeon can see. Using a computer, the surgeon guides very small tools at the ends of the robot arms to remove the cancer. This procedure may also be done using an endoscope.

Learn more about Surgery to Treat Cancer.

Radiation therapy

Radiation therapy uses high-energy x-rays or other types of radiation to kill cancer cells or keep them from growing by damaging their DNA. External radiation therapy uses a machine outside the body to send radiation toward the area of the body with cancer.

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Certain ways of giving radiation therapy can help keep radiation from damaging nearby healthy tissue. These types of radiation therapy include:

• Intensity-modulated radiation therapy (IMRT): IMRT is a type of 3-dimensional (3-D) radiation therapy that uses a computer to make pictures of the size and shape of the tumor. Thin beams of radiation of different intensities (strengths) are aimed at the tumor from many angles.
• Stereotactic body radiation therapy: Stereotactic body radiation therapy is a type of external radiation therapy. Special equipment is used to place the person in the same position for each radiation treatment. Once a day for several days, a radiation machine aims a larger than usual dose of radiation directly at the tumor. By having the person in the same position for each treatment, there is less damage to nearby healthy tissue. This procedure is also called stereotactic external-beam radiation therapy and stereotaxic radiation therapy.

In advanced oropharyngeal cancer, dividing the daily dose of radiation into smaller-dose treatments improves the way the tumor responds to treatment. This is called hyperfractionated radiation therapy.

Radiation therapy may work better in people who have stopped smoking before beginning treatment.

If the thyroid or pituitary gland are part of the radiation treatment area, the person has an increased risk of hypothyroidism (too little thyroid hormone). A blood test to check the thyroid hormone level in the body should be done before and after treatment.

Learn more about External Beam Radiation Therapy for Cancer and Radiation Therapy Side Effects.

Chemotherapy

Chemotherapy uses drugs to stop the growth of cancer cells, either by killing the cells or by stopping them from dividing. Chemotherapy for oropharyngeal cancer is usually systemic, meaning it is taken by mouth or injected into a vein or muscle. When given this way, the drugs enter the bloodstream and can reach cancer cells throughout the body.

Chemotherapy drugs used to treat oropharyngeal cancer include:

• cisplatin
• docetaxel
• fluorouracil
• paclitaxel

Combinations of these drugs may be used. Other chemotherapy drugs not listed here may also be used.

Chemotherapy may be combined with other types of treatment, such as radiation therapy.

To learn more about how chemotherapy works, how it is given, common side effects, and more, visit Chemotherapy to Treat Cancer and Chemotherapy and You: Support for People With Cancer.

Targeted therapy

Targeted therapy uses drugs or other substances to identify and attack specific cancer cells. Cetuximab is a type of targeted therapy used to treat recurrent and metastatic oropharyngeal cancer.

Learn more about Targeted Therapy to Treat Cancer. 

Immunotherapy

Immunotherapy is a treatment that uses a person’s immune system to fight cancer. Your doctor may suggest biomarker tests to help predict your response to certain immunotherapy drugs. Learn more about Biomarker Testing for Cancer Treatment.   

Pembrolizumab and nivolumab are types of immunotherapy used to treat metastatic or recurrent oropharyngeal cancer.

Learn more about Immunotherapy to Treat Cancer.

After treatment is complete, it is important to have head and neck exams to look for signs that the cancer has come back. Check-ups will be done every 6 to 12 weeks in the first year, every 3 months in the second year, every 3 to 4 months in the third year, and every 6 months thereafter.

For information about the treatments listed below, see the Treatment Option Overview section.

Treatment of newly diagnosed stage I and stage II oropharyngeal cancer may include:

Use our clinical trial search to find NCI-supported cancer clinical trials that are accepting patients. You can search for trials based on the type of cancer, the age of the patient, and where the trials are being done. General information about clinical trials is also available.

For information about the treatments listed below, see the Treatment Option Overview section.

Treatment of newly diagnosed stage III oropharyngeal cancer and stage IV oropharyngeal cancer may include:

Use our clinical trial search to find NCI-supported cancer clinical trials that are accepting patients. You can search for trials based on the type of cancer, the age of the patient, and where the trials are being done. General information about clinical trials is also available.

For information about the treatments listed below, see the Treatment Option Overview section.

Treatment of oropharyngeal cancer that has metastasized or recurred in the oropharynx may include:

Use our clinical trial search to find NCI-supported cancer clinical trials that are accepting patients. You can search for trials based on the type of cancer, the age of the patient, and where the trials are being done. General information about clinical trials is also available.

For more information from the National Cancer Institute about oropharyngeal cancer, visit:

For general cancer information and other resources from the National Cancer Institute, visit:

Anatomy

Anatomically, the oropharynx is located between the soft palate superiorly and the hyoid bone inferiorly. It is continuous with the oral cavity anteriorly and communicates with the nasopharynx superiorly and the supraglottic larynx and hypopharynx inferiorly.

The oropharynx is divided into the following parts:[4]

• Base of the tongue, which includes the pharyngoepiglottic folds and the glossoepiglottic folds.
• Vallecula.
• Tonsillar region, which includes the fossa and the anterior and posterior pillars.
• Soft palate, which includes the uvula.
• Posterior and lateral pharyngeal walls.

Regional lymph node anatomy of the head and neck

The regional lymph nodes of the head and neck include the lymph nodes that run parallel to the jugular veins, spinal accessory nerve, and facial artery and into the submandibular triangle. An understanding of regional anatomy and the status of regional lymph nodes is critical to the care of patients with head and neck cancer.[3,5,6] To facilitate communication regarding lymph node anatomy, the regions of the neck are described as levels I to V and retropharyngeal:

• Level I contains the submental and submandibular lymph nodes.
• Level II contains the upper jugular lymph nodes, which are above the digastric muscle.
• Level III contains the midjugular lymph nodes, which are between the omohyoid muscle and the digastric muscle.
• Level IV contains the lower jugular lymph nodes.
• Level V contains the lymph nodes of the posterior triangle.
• Retropharyngeal lymph nodes.

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The retropharyngeal lymph nodes are a possible site for nodal spread in oropharyngeal cancer. A large retrospective cohort study from the MD Anderson Cancer Center described the clinical features of 981 patients with oropharyngeal cancer who underwent primary radiation therapy.[7][Level of evidence C1][Level of evidence C2]

• The base of the tongue (47%) and the tonsil (46%) were the most common primary sites.
• Most patients had stage T1 to T2 primary tumors (64%) and stage III to IVB disease (94%).
• The incidence of radiographic retropharyngeal node involvement was 10% and was highest for the pharyngeal wall (23%) and lowest for the base of the tongue (6%).
• Retropharyngeal lymph node involvement was associated with inferior 5-year local control and inferior recurrence-free survival, distant metastases−free survival, and overall survival on multivariate analysis.

References

1. American Cancer Society: Cancer Facts and Figures 2025. American Cancer Society, 2025. Available online. Last accessed January 16, 2025.
2. Bray F, Laversanne M, Sung H, et al.: Global cancer statistics 2022: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA Cancer J Clin 74 (3): 229-263, 2024. [PUBMED Abstract]
3. Mendenhall WM, Werning JW, Pfister DG: Treatment of head and neck cancer. In: DeVita VT Jr, Lawrence TS, Rosenberg SA: Cancer: Principles and Practice of Oncology. 9th ed. Lippincott Williams & Wilkins, 2011, pp 729-80.
4. Choi WH, Hu KS, Culliney B, et al.: Cancer of the oropharynx. In: Harrison LB, Sessions RB, Hong WK, eds.: Head and Neck Cancer: A Multidisciplinary Approach. 3rd ed. Lippincott, William & Wilkins, 2009, pp 285-335.
5. HPV-Mediated (p16+) Oropharyngeal Cancer. In: Amin MB, Edge SB, Greene FL, et al., eds.: AJCC Cancer Staging Manual. 8th ed. Springer; 2017, pp. 113-21.
6. Oropharynx (p16-) and Hypopharynx. In: Amin MB, Edge SB, Greene FL, et al., eds.: AJCC Cancer Staging Manual. 8th ed. Springer; 2017, pp. 123-35.
7. Gunn GB, Debnam JM, Fuller CD, et al.: The impact of radiographic retropharyngeal adenopathy in oropharyngeal cancer. Cancer 119 (17): 3162-9, 2013. [PUBMED Abstract]
8. Neville BW, Day TA: Oral cancer and precancerous lesions. CA Cancer J Clin 52 (4): 195-215, 2002 Jul-Aug. [PUBMED Abstract]
9. Mendenhall WM, Werning JW, Pfister DG: Treatment of head and neck cancer. In: DeVita VT Jr, Lawrence TS, Rosenberg SA: Cancer: Principles and Practice of Oncology. 9th ed. Lippincott Williams & Wilkins, 2011, pp 729-80.
10. Licitra L, Bernier J, Grandi C, et al.: Cancer of the oropharynx. Crit Rev Oncol Hematol 41 (1): 107-22, 2002. [PUBMED Abstract]
11. Mork J, Lie AK, Glattre E, et al.: Human papillomavirus infection as a risk factor for squamous-cell carcinoma of the head and neck. N Engl J Med 344 (15): 1125-31, 2001. [PUBMED Abstract]
12. Gillison ML, Koch WM, Capone RB, et al.: Evidence for a causal association between human papillomavirus and a subset of head and neck cancers. J Natl Cancer Inst 92 (9): 709-20, 2000. [PUBMED Abstract]
13. D’Souza G, Kreimer AR, Viscidi R, et al.: Case-control study of human papillomavirus and oropharyngeal cancer. N Engl J Med 356 (19): 1944-56, 2007. [PUBMED Abstract]
14. Chaturvedi AK, Engels EA, Pfeiffer RM, et al.: Human papillomavirus and rising oropharyngeal cancer incidence in the United States. J Clin Oncol 29 (32): 4294-301, 2011. [PUBMED Abstract]
15. Ringström E, Peters E, Hasegawa M, et al.: Human papillomavirus type 16 and squamous cell carcinoma of the head and neck. Clin Cancer Res 8 (10): 3187-92, 2002. [PUBMED Abstract]
16. Schwartz SR, Yueh B, McDougall JK, et al.: Human papillomavirus infection and survival in oral squamous cell cancer: a population-based study. Otolaryngol Head Neck Surg 125 (1): 1-9, 2001. [PUBMED Abstract]
17. Ang KK, Harris J, Wheeler R, et al.: Human papillomavirus and survival of patients with oropharyngeal cancer. N Engl J Med 363 (1): 24-35, 2010. [PUBMED Abstract]
18. Khuri FR, Lippman SM, Spitz MR, et al.: Molecular epidemiology and retinoid chemoprevention of head and neck cancer. J Natl Cancer Inst 89 (3): 199-211, 1997. [PUBMED Abstract]
19. León X, Quer M, Diez S, et al.: Second neoplasm in patients with head and neck cancer. Head Neck 21 (3): 204-10, 1999. [PUBMED Abstract]
20. Do KA, Johnson MM, Doherty DA, et al.: Second primary tumors in patients with upper aerodigestive tract cancers: joint effects of smoking and alcohol (United States). Cancer Causes Control 14 (2): 131-8, 2003. [PUBMED Abstract]
21. Khuri FR, Kim ES, Lee JJ, et al.: The impact of smoking status, disease stage, and index tumor site on second primary tumor incidence and tumor recurrence in the head and neck retinoid chemoprevention trial. Cancer Epidemiol Biomarkers Prev 10 (8): 823-9, 2001. [PUBMED Abstract]
22. Day GL, Blot WJ, Shore RE, et al.: Second cancers following oral and pharyngeal cancers: role of tobacco and alcohol. J Natl Cancer Inst 86 (2): 131-7, 1994. [PUBMED Abstract]
23. Slaughter DP, Southwick HW, Smejkal W: Field cancerization in oral stratified squamous epithelium: clinical implications of multicentric origin. Cancer 6 (5): 963-8, 1953. [PUBMED Abstract]
24. Braakhuis BJ, Tabor MP, Leemans CR, et al.: Second primary tumors and field cancerization in oral and oropharyngeal cancer: molecular techniques provide new insights and definitions. Head Neck 24 (2): 198-206, 2002. [PUBMED Abstract]
25. Braakhuis BJ, Tabor MP, Kummer JA, et al.: A genetic explanation of Slaughter’s concept of field cancerization: evidence and clinical implications. Cancer Res 63 (8): 1727-30, 2003. [PUBMED Abstract]
26. Tabor MP, Brakenhoff RH, van Houten VM, et al.: Persistence of genetically altered fields in head and neck cancer patients: biological and clinical implications. Clin Cancer Res 7 (6): 1523-32, 2001. [PUBMED Abstract]
27. Tabor MP, Brakenhoff RH, Ruijter-Schippers HJ, et al.: Multiple head and neck tumors frequently originate from a single preneoplastic lesion. Am J Pathol 161 (3): 1051-60, 2002. [PUBMED Abstract]
28. Ha PK, Califano JA: The molecular biology of mucosal field cancerization of the head and neck. Crit Rev Oral Biol Med 14 (5): 363-9, 2003. [PUBMED Abstract]
29. Gan SJ, Dahlstrom KR, Peck BW, et al.: Incidence and pattern of second primary malignancies in patients with index oropharyngeal cancers versus index nonoropharyngeal head and neck cancers. Cancer 119 (14): 2593-601, 2013. [PUBMED Abstract]
30. Ho PS, Ko YC, Yang YH, et al.: The incidence of oropharyngeal cancer in Taiwan: an endemic betel quid chewing area. J Oral Pathol Med 31 (4): 213-9, 2002. [PUBMED Abstract]
31. Yokoyama A, Watanabe H, Fukuda H, et al.: Multiple cancers associated with esophageal and oropharyngolaryngeal squamous cell carcinoma and the aldehyde dehydrogenase-2 genotype in male Japanese drinkers. Cancer Epidemiol Biomarkers Prev 11 (9): 895-900, 2002. [PUBMED Abstract]
32. Tremmel SC, Götte K, Popp S, et al.: Intratumoral genomic heterogeneity in advanced head and neck cancer detected by comparative genomic hybridization. Cancer Genet Cytogenet 144 (2): 165-74, 2003. [PUBMED Abstract]
33. Brieger J, Jacob R, Riazimand HS, et al.: Chromosomal aberrations in premalignant and malignant squamous epithelium. Cancer Genet Cytogenet 144 (2): 148-55, 2003. [PUBMED Abstract]
34. Forastiere A, Koch W, Trotti A, et al.: Head and neck cancer. N Engl J Med 345 (26): 1890-900, 2001. [PUBMED Abstract]
35. Lindberg R: Distribution of cervical lymph node metastases from squamous cell carcinoma of the upper respiratory and digestive tracts. Cancer 29 (6): 1446-9, 1972. [PUBMED Abstract]
36. Tahari AK, Alluri KC, Quon H, et al.: FDG PET/CT imaging of oropharyngeal squamous cell carcinoma: characteristics of human papillomavirus-positive and -negative tumors. Clin Nucl Med 39 (3): 225-31, 2014. [PUBMED Abstract]

Most oropharyngeal cancers are squamous cell carcinomas (SCCs).[1–3] SCCs may be noninvasive or invasive. For noninvasive SCC, the term carcinoma in situ is used. Histologically, invasive carcinomas are classified as well differentiated, moderately differentiated, poorly differentiated, or undifferentiated. SCCs are usually moderately or poorly differentiated.[4] Grading the deep invasive margins (i.e., invasive front) of SCC may provide better prognostic information than grading the entire tumor.[5] Human papillomavirus (HPV)-positive oropharyngeal cancers arising from the lingual and palatine tonsils are a distinct molecular-pathological entity that is linked to infection with HPV, especially HPV-16. Compared with HPV-negative tumors, HPV-positive tumors are more frequently poorly differentiated and nonkeratinizing. They are strongly associated with basaloid morphology and less likely to have TP53 variants.[6]

Immunohistochemical examination of tissues for the expression of the biomarker Ki-67, a proliferation antigen, may complement histological grading. As a molecular indicator of epithelial dysplasia of the oropharynx, Ki-67 expression appears to correlate well with loss of heterozygosity (LOH) in tumor cells. In a retrospective study involving 43 tissue samples from 25 patients, the assessment of proliferation with Ki-67 was a better surrogate for LOH than was histological grading.[7]

Other types of oropharyngeal cancer include:

For more information, see Salivary Gland Cancer Treatment, Hodgkin Lymphoma Treatment, Indolent B-Cell Non-Hodgkin Lymphoma Treatment, Aggressive B-Cell Non-Hodgkin Lymphoma Treatment, and Peripheral T-Cell Non-Hodgkin Lymphoma Treatment.

References

1. Mendenhall WM, Werning JW, Pfister DG: Treatment of head and neck cancer. In: DeVita VT Jr, Lawrence TS, Rosenberg SA: Cancer: Principles and Practice of Oncology. 9th ed. Lippincott Williams & Wilkins, 2011, pp 729-80.
2. HPV-Mediated (p16+) Oropharyngeal Cancer. In: Amin MB, Edge SB, Greene FL, et al., eds.: AJCC Cancer Staging Manual. 8th ed. Springer; 2017, pp. 113-21.
3. Oropharynx (p16-) and Hypopharynx. In: Amin MB, Edge SB, Greene FL, et al., eds.: AJCC Cancer Staging Manual. 8th ed. Springer; 2017, pp. 123-35.
4. Oral cavity and oropharynx. In: Rosai J, ed.: Rosai and Ackerman’s Surgical Pathology. Vol. 1. 10th ed. Mosby Elsevier, 2011, pp. 237-264.
5. Bryne M, Boysen M, Alfsen CG, et al.: The invasive front of carcinomas. The most important area for tumour prognosis? Anticancer Res 18 (6B): 4757-64, 1998 Nov-Dec. [PUBMED Abstract]
6. Gillison ML, Koch WM, Capone RB, et al.: Evidence for a causal association between human papillomavirus and a subset of head and neck cancers. J Natl Cancer Inst 92 (9): 709-20, 2000. [PUBMED Abstract]
7. Tabor MP, Braakhuis BJ, van der Wal JE, et al.: Comparative molecular and histological grading of epithelial dysplasia of the oral cavity and the oropharynx. J Pathol 199 (3): 354-60, 2003. [PUBMED Abstract]

The staging system for oropharyngeal cancer is clinical rather than pathological. It is based on the best estimate of the extent of disease before treatment.

Clinical anatomical staging of oropharyngeal cancer involves the following clinical assessment and imaging techniques:

PET has been investigated as an imaging modality for recurrent oropharyngeal cancer.[3]

References

1. Weber AL, Romo L, Hashmi S: Malignant tumors of the oral cavity and oropharynx: clinical, pathologic, and radiologic evaluation. Neuroimaging Clin N Am 13 (3): 443-64, 2003. [PUBMED Abstract]
2. Oropharynx (p16-) and Hypopharynx. In: Amin MB, Edge SB, Greene FL, et al., eds.: AJCC Cancer Staging Manual. 8th ed. Springer; 2017, pp. 123-35.
3. Wong RJ, Lin DT, Schöder H, et al.: Diagnostic and prognostic value of [(18)F]fluorodeoxyglucose positron emission tomography for recurrent head and neck squamous cell carcinoma. J Clin Oncol 20 (20): 4199-208, 2002. [PUBMED Abstract]
4. HPV-Mediated (p16+) Oropharyngeal Cancer. In: Amin MB, Edge SB, Greene FL, et al., eds.: AJCC Cancer Staging Manual. 8th ed. Springer; 2017, pp. 113-21.

An optimal approach for the treatment of oropharyngeal cancer is not easily defined because no single regimen offers a distinct superior-survival advantage. The literature reports various therapeutic options but does not present any valid comparative studies of these options. Treatment considerations should account for functional and performance status, including speech and swallowing outcomes.

References

1. Iyer NG, Tan DS, Tan VK, et al.: Randomized trial comparing surgery and adjuvant radiotherapy versus concurrent chemoradiotherapy in patients with advanced, nonmetastatic squamous cell carcinoma of the head and neck: 10-year update and subset analysis. Cancer 121 (10): 1599-607, 2015. [PUBMED Abstract]
2. Mehanna H, Wong WL, McConkey CC, et al.: PET-CT Surveillance versus Neck Dissection in Advanced Head and Neck Cancer. N Engl J Med 374 (15): 1444-54, 2016. [PUBMED Abstract]
3. Parsons JT, Mendenhall WM, Stringer SP, et al.: Squamous cell carcinoma of the oropharynx: surgery, radiation therapy, or both. Cancer 94 (11): 2967-80, 2002. [PUBMED Abstract]
4. Harrison LB, Zelefsky MJ, Armstrong JG, et al.: Performance status after treatment for squamous cell cancer of the base of tongue–a comparison of primary radiation therapy versus primary surgery. Int J Radiat Oncol Biol Phys 30 (4): 953-7, 1994. [PUBMED Abstract]
5. Mendenhall WM, Morris CG, Amdur RJ, et al.: Definitive radiotherapy for squamous cell carcinoma of the base of tongue. Am J Clin Oncol 29 (1): 32-9, 2006. [PUBMED Abstract]
6. Chen AM, Daly ME, Luu Q, et al.: Comparison of functional outcomes and quality of life between transoral surgery and definitive chemoradiotherapy for oropharyngeal cancer. Head Neck 37 (3): 381-5, 2015. [PUBMED Abstract]
7. Cooper JS, Pajak TF, Forastiere AA, et al.: Postoperative concurrent radiotherapy and chemotherapy for high-risk squamous-cell carcinoma of the head and neck. N Engl J Med 350 (19): 1937-44, 2004. [PUBMED Abstract]
8. Bernier J, Domenge C, Ozsahin M, et al.: Postoperative irradiation with or without concomitant chemotherapy for locally advanced head and neck cancer. N Engl J Med 350 (19): 1945-52, 2004. [PUBMED Abstract]
9. Bernier J, Cooper JS, Pajak TF, et al.: Defining risk levels in locally advanced head and neck cancers: a comparative analysis of concurrent postoperative radiation plus chemotherapy trials of the EORTC (#22931) and RTOG (# 9501). Head Neck 27 (10): 843-50, 2005. [PUBMED Abstract]
10. Cooper JS, Zhang Q, Pajak TF, et al.: Long-term follow-up of the RTOG 9501/intergroup phase III trial: postoperative concurrent radiation therapy and chemotherapy in high-risk squamous cell carcinoma of the head and neck. Int J Radiat Oncol Biol Phys 84 (5): 1198-205, 2012. [PUBMED Abstract]
11. Fowler JF, Lindstrom MJ: Loss of local control with prolongation in radiotherapy. Int J Radiat Oncol Biol Phys 23 (2): 457-67, 1992. [PUBMED Abstract]
12. Allal AS, de Pree C, Dulguerov P, et al.: Avoidance of treatment interruption: an unrecognized benefit of accelerated radiotherapy in oropharyngeal carcinomas? Int J Radiat Oncol Biol Phys 45 (1): 41-5, 1999. [PUBMED Abstract]
13. Browman GP, Wong G, Hodson I, et al.: Influence of cigarette smoking on the efficacy of radiation therapy in head and neck cancer. N Engl J Med 328 (3): 159-63, 1993. [PUBMED Abstract]
14. Eisbruch A, Harris J, Garden AS, et al.: Multi-institutional trial of accelerated hypofractionated intensity-modulated radiation therapy for early-stage oropharyngeal cancer (RTOG 00-22). Int J Radiat Oncol Biol Phys 76 (5): 1333-8, 2010. [PUBMED Abstract]
15. Leclerc M, Maingon P, Hamoir M, et al.: A dose escalation study with intensity modulated radiation therapy (IMRT) in T2N0, T2N1, T3N0 squamous cell carcinomas (SCC) of the oropharynx, larynx and hypopharynx using a simultaneous integrated boost (SIB) approach. Radiother Oncol 106 (3): 333-40, 2013. [PUBMED Abstract]
16. Buettner F, Miah AB, Gulliford SL, et al.: Novel approaches to improve the therapeutic index of head and neck radiotherapy: an analysis of data from the PARSPORT randomised phase III trial. Radiother Oncol 103 (1): 82-7, 2012. [PUBMED Abstract]
17. Gulliford SL, Miah AB, Brennan S, et al.: Dosimetric explanations of fatigue in head and neck radiotherapy: an analysis from the PARSPORT Phase III trial. Radiother Oncol 104 (2): 205-12, 2012. [PUBMED Abstract]
18. Kohler RE, Sheets NC, Wheeler SB, et al.: Two-year and lifetime cost-effectiveness of intensity modulated radiation therapy versus 3-dimensional conformal radiation therapy for head-and-neck cancer. Int J Radiat Oncol Biol Phys 87 (4): 683-9, 2013. [PUBMED Abstract]
19. Gupta T, Agarwal J, Jain S, et al.: Three-dimensional conformal radiotherapy (3D-CRT) versus intensity modulated radiation therapy (IMRT) in squamous cell carcinoma of the head and neck: a randomized controlled trial. Radiother Oncol 104 (3): 343-8, 2012. [PUBMED Abstract]
20. Nutting CM, Morden JP, Harrington KJ, et al.: Parotid-sparing intensity modulated versus conventional radiotherapy in head and neck cancer (PARSPORT): a phase 3 multicentre randomised controlled trial. Lancet Oncol 12 (2): 127-36, 2011. [PUBMED Abstract]
21. Fu KK, Pajak TF, Trotti A, et al.: A Radiation Therapy Oncology Group (RTOG) phase III randomized study to compare hyperfractionation and two variants of accelerated fractionation to standard fractionation radiotherapy for head and neck squamous cell carcinomas: first report of RTOG 9003. Int J Radiat Oncol Biol Phys 48 (1): 7-16, 2000. [PUBMED Abstract]
22. Beitler JJ, Zhang Q, Fu KK, et al.: Final results of local-regional control and late toxicity of RTOG 9003: a randomized trial of altered fractionation radiation for locally advanced head and neck cancer. Int J Radiat Oncol Biol Phys 89 (1): 13-20, 2014. [PUBMED Abstract]
23. Baujat B, Bourhis J, Blanchard P, et al.: Hyperfractionated or accelerated radiotherapy for head and neck cancer. Cochrane Database Syst Rev (12): CD002026, 2010. [PUBMED Abstract]
24. Turner SL, Tiver KW, Boyages SC: Thyroid dysfunction following radiotherapy for head and neck cancer. Int J Radiat Oncol Biol Phys 31 (2): 279-83, 1995. [PUBMED Abstract]
25. Constine LS: What else don’t we know about the late effects of radiation in patients treated for head and neck cancer? Int J Radiat Oncol Biol Phys 31 (2): 427-9, 1995. [PUBMED Abstract]
26. Murthy V, Narang K, Ghosh-Laskar S, et al.: Hypothyroidism after 3-dimensional conformal radiotherapy and intensity-modulated radiotherapy for head and neck cancers: prospective data from 2 randomized controlled trials. Head Neck 36 (11): 1573-80, 2014. [PUBMED Abstract]
27. O’Sullivan B, Warde P, Grice B, et al.: The benefits and pitfalls of ipsilateral radiotherapy in carcinoma of the tonsillar region. Int J Radiat Oncol Biol Phys 51 (2): 332-43, 2001. [PUBMED Abstract]
28. Denis F, Garaud P, Bardet E, et al.: Final results of the 94-01 French Head and Neck Oncology and Radiotherapy Group randomized trial comparing radiotherapy alone with concomitant radiochemotherapy in advanced-stage oropharynx carcinoma. J Clin Oncol 22 (1): 69-76, 2004. [PUBMED Abstract]
29. Mendenhall WM, Werning JW, Pfister DG: Treatment of head and neck cancer. In: DeVita VT Jr, Lawrence TS, Rosenberg SA: Cancer: Principles and Practice of Oncology. 9th ed. Lippincott Williams & Wilkins, 2011, pp 729-80.
30. Adelstein DJ: Oropharyngeal cancer: the role of chemotherapy. Curr Treat Options Oncol 4 (1): 3-13, 2003. [PUBMED Abstract]
31. Pignon JP, le Maître A, Maillard E, et al.: Meta-analysis of chemotherapy in head and neck cancer (MACH-NC): an update on 93 randomised trials and 17,346 patients. Radiother Oncol 92 (1): 4-14, 2009. [PUBMED Abstract]
32. Lacas B, Carmel A, Landais C, et al.: Meta-analysis of chemotherapy in head and neck cancer (MACH-NC): An update on 107 randomized trials and 19,805 patients, on behalf of MACH-NC Group. Radiother Oncol 156: 281-293, 2021. [PUBMED Abstract]
33. Kiyota N, Tahara M, Mizusawa J, et al.: Weekly Cisplatin Plus Radiation for Postoperative Head and Neck Cancer (JCOG1008): A Multicenter, Noninferiority, Phase II/III Randomized Controlled Trial. J Clin Oncol 40 (18): 1980-1990, 2022. [PUBMED Abstract]
34. Patil VM, Noronha V, Menon N, et al.: Results of Phase III Randomized Trial for Use of Docetaxel as a Radiosensitizer in Patients With Head and Neck Cancer, Unsuitable for Cisplatin-Based Chemoradiation. J Clin Oncol 41 (13): 2350-2361, 2023. [PUBMED Abstract]
35. Bonner JA, Harari PM, Giralt J, et al.: Radiotherapy plus cetuximab for squamous-cell carcinoma of the head and neck. N Engl J Med 354 (6): 567-78, 2006. [PUBMED Abstract]
36. Curran D, Giralt J, Harari PM, et al.: Quality of life in head and neck cancer patients after treatment with high-dose radiotherapy alone or in combination with cetuximab. J Clin Oncol 25 (16): 2191-7, 2007. [PUBMED Abstract]
37. Trotti A, Harris J, Gillison M, et al.: NRG-RTOG 1016: phase III trial comparing radiation/cetuximab to radiation/cisplatin in HPV-related cancer of the oropharynx. [Abstract] Int J Radiat Oncol Biol Phys 102 (5): A-LBA4, 1604-5, 2018. Also available online. Last accessed November 18, 2024.
38. Gillison ML, Trotti AM, Harris J, et al.: Radiotherapy plus cetuximab or cisplatin in human papillomavirus-positive oropharyngeal cancer (NRG Oncology RTOG 1016): a randomised, multicentre, non-inferiority trial. Lancet 393 (10166): 40-50, 2019. [PUBMED Abstract]
39. Mehanna H, Robinson M, Hartley A, et al.: Radiotherapy plus cisplatin or cetuximab in low-risk human papillomavirus-positive oropharyngeal cancer (De-ESCALaTE HPV): an open-label randomised controlled phase 3 trial. Lancet 393 (10166): 51-60, 2019. [PUBMED Abstract]
40. Budach W, Bölke E, Kammers K, et al.: Induction chemotherapy followed by concurrent radio-chemotherapy versus concurrent radio-chemotherapy alone as treatment of locally advanced squamous cell carcinoma of the head and neck (HNSCC): A meta-analysis of randomized trials. Radiother Oncol 118 (2): 238-43, 2016. [PUBMED Abstract]
41. Marur S, Li S, Cmelak AJ, et al.: E1308: Phase II Trial of Induction Chemotherapy Followed by Reduced-Dose Radiation and Weekly Cetuximab in Patients With HPV-Associated Resectable Squamous Cell Carcinoma of the Oropharynx- ECOG-ACRIN Cancer Research Group. J Clin Oncol 35 (5): 490-497, 2017. [PUBMED Abstract]
42. Haddad R, O’Neill A, Rabinowits G, et al.: Induction chemotherapy followed by concurrent chemoradiotherapy (sequential chemoradiotherapy) versus concurrent chemoradiotherapy alone in locally advanced head and neck cancer (PARADIGM): a randomised phase 3 trial. Lancet Oncol 14 (3): 257-64, 2013. [PUBMED Abstract]
43. Cohen EE, Karrison TG, Kocherginsky M, et al.: Phase III randomized trial of induction chemotherapy in patients with N2 or N3 locally advanced head and neck cancer. J Clin Oncol 32 (25): 2735-43, 2014. [PUBMED Abstract]
44. Hitt R, Grau JJ, López-Pousa A, et al.: A randomized phase III trial comparing induction chemotherapy followed by chemoradiotherapy versus chemoradiotherapy alone as treatment of unresectable head and neck cancer. Ann Oncol 25 (1): 216-25, 2014. [PUBMED Abstract]
45. Driessen CM, de Boer JP, Gelderblom H, et al.: Induction chemotherapy with docetaxel/cisplatin/5-fluorouracil followed by randomization to two cisplatin-based concomitant chemoradiotherapy schedules in patients with locally advanced head and neck cancer (CONDOR study) (Dutch Head and Neck Society 08-01): A randomized phase II study. Eur J Cancer 52: 77-84, 2016. [PUBMED Abstract]
46. Sharma BB, Rai K, Blunt H, et al.: Pathogenic DPYD Variants and Treatment-Related Mortality in Patients Receiving Fluoropyrimidine Chemotherapy: A Systematic Review and Meta-Analysis. Oncologist 26 (12): 1008-1016, 2021. [PUBMED Abstract]
47. Lam SW, Guchelaar HJ, Boven E: The role of pharmacogenetics in capecitabine efficacy and toxicity. Cancer Treat Rev 50: 9-22, 2016. [PUBMED Abstract]
48. Shakeel F, Fang F, Kwon JW, et al.: Patients carrying DPYD variant alleles have increased risk of severe toxicity and related treatment modifications during fluoropyrimidine chemotherapy. Pharmacogenomics 22 (3): 145-155, 2021. [PUBMED Abstract]
49. Amstutz U, Henricks LM, Offer SM, et al.: Clinical Pharmacogenetics Implementation Consortium (CPIC) Guideline for Dihydropyrimidine Dehydrogenase Genotype and Fluoropyrimidine Dosing: 2017 Update. Clin Pharmacol Ther 103 (2): 210-216, 2018. [PUBMED Abstract]
50. Henricks LM, Lunenburg CATC, de Man FM, et al.: DPYD genotype-guided dose individualisation of fluoropyrimidine therapy in patients with cancer: a prospective safety analysis. Lancet Oncol 19 (11): 1459-1467, 2018. [PUBMED Abstract]
51. Lau-Min KS, Varughese LA, Nelson MN, et al.: Preemptive pharmacogenetic testing to guide chemotherapy dosing in patients with gastrointestinal malignancies: a qualitative study of barriers to implementation. BMC Cancer 22 (1): 47, 2022. [PUBMED Abstract]
52. Brooks GA, Tapp S, Daly AT, et al.: Cost-effectiveness of DPYD Genotyping Prior to Fluoropyrimidine-based Adjuvant Chemotherapy for Colon Cancer. Clin Colorectal Cancer 21 (3): e189-e195, 2022. [PUBMED Abstract]
53. Baker SD, Bates SE, Brooks GA, et al.: DPYD Testing: Time to Put Patient Safety First. J Clin Oncol 41 (15): 2701-2705, 2023. [PUBMED Abstract]

The management of stage III and stage IV carcinomas of the oropharynx is complex and requires multidisciplinary input to establish the optimal treatment. For more information, see the Treatment Option Overview for Oropharyngeal Cancer section.

References

1. Bernier J, Cooper JS, Pajak TF, et al.: Defining risk levels in locally advanced head and neck cancers: a comparative analysis of concurrent postoperative radiation plus chemotherapy trials of the EORTC (#22931) and RTOG (# 9501). Head Neck 27 (10): 843-50, 2005. [PUBMED Abstract]
2. Cooper JS, Zhang Q, Pajak TF, et al.: Long-term follow-up of the RTOG 9501/intergroup phase III trial: postoperative concurrent radiation therapy and chemotherapy in high-risk squamous cell carcinoma of the head and neck. Int J Radiat Oncol Biol Phys 84 (5): 1198-205, 2012. [PUBMED Abstract]
3. Cooper JS, Pajak TF, Forastiere AA, et al.: Postoperative concurrent radiotherapy and chemotherapy for high-risk squamous-cell carcinoma of the head and neck. N Engl J Med 350 (19): 1937-44, 2004. [PUBMED Abstract]
4. Bernier J, Domenge C, Ozsahin M, et al.: Postoperative irradiation with or without concomitant chemotherapy for locally advanced head and neck cancer. N Engl J Med 350 (19): 1945-52, 2004. [PUBMED Abstract]
5. Horiot JC, Le Fur R, N’Guyen T, et al.: Hyperfractionation versus conventional fractionation in oropharyngeal carcinoma: final analysis of a randomized trial of the EORTC cooperative group of radiotherapy. Radiother Oncol 25 (4): 231-41, 1992. [PUBMED Abstract]
6. Bourhis J, Lapeyre M, Tortochaux J, et al.: Phase III randomized trial of very accelerated radiation therapy compared with conventional radiation therapy in squamous cell head and neck cancer: a GORTEC trial. J Clin Oncol 24 (18): 2873-8, 2006. [PUBMED Abstract]
7. Overgaard J, Hansen HS, Specht L, et al.: Five compared with six fractions per week of conventional radiotherapy of squamous-cell carcinoma of head and neck: DAHANCA 6 and 7 randomised controlled trial. Lancet 362 (9388): 933-40, 2003. [PUBMED Abstract]
8. Overgaard J, Mohanti BK, Begum N, et al.: Five versus six fractions of radiotherapy per week for squamous-cell carcinoma of the head and neck (IAEA-ACC study): a randomised, multicentre trial. Lancet Oncol 11 (6): 553-60, 2010. [PUBMED Abstract]
9. Fu KK, Pajak TF, Trotti A, et al.: A Radiation Therapy Oncology Group (RTOG) phase III randomized study to compare hyperfractionation and two variants of accelerated fractionation to standard fractionation radiotherapy for head and neck squamous cell carcinomas: first report of RTOG 9003. Int J Radiat Oncol Biol Phys 48 (1): 7-16, 2000. [PUBMED Abstract]
10. Bonner JA, Harari PM, Giralt J, et al.: Radiotherapy plus cetuximab for squamous-cell carcinoma of the head and neck. N Engl J Med 354 (6): 567-78, 2006. [PUBMED Abstract]
11. Curran D, Giralt J, Harari PM, et al.: Quality of life in head and neck cancer patients after treatment with high-dose radiotherapy alone or in combination with cetuximab. J Clin Oncol 25 (16): 2191-7, 2007. [PUBMED Abstract]
12. Denis F, Garaud P, Bardet E, et al.: Final results of the 94-01 French Head and Neck Oncology and Radiotherapy Group randomized trial comparing radiotherapy alone with concomitant radiochemotherapy in advanced-stage oropharynx carcinoma. J Clin Oncol 22 (1): 69-76, 2004. [PUBMED Abstract]
13. Olmi P, Crispino S, Fallai C, et al.: Locoregionally advanced carcinoma of the oropharynx: conventional radiotherapy vs. accelerated hyperfractionated radiotherapy vs. concomitant radiotherapy and chemotherapy–a multicenter randomized trial. Int J Radiat Oncol Biol Phys 55 (1): 78-92, 2003. [PUBMED Abstract]
14. Semrau R, Mueller RP, Stuetzer H, et al.: Efficacy of intensified hyperfractionated and accelerated radiotherapy and concurrent chemotherapy with carboplatin and 5-fluorouracil: updated results of a randomized multicentric trial in advanced head-and-neck cancer. Int J Radiat Oncol Biol Phys 64 (5): 1308-16, 2006. [PUBMED Abstract]
15. Pignon JP, le Maître A, Maillard E, et al.: Meta-analysis of chemotherapy in head and neck cancer (MACH-NC): an update on 93 randomised trials and 17,346 patients. Radiother Oncol 92 (1): 4-14, 2009. [PUBMED Abstract]

References

1. Wong LY, Wei WI, Lam LK, et al.: Salvage of recurrent head and neck squamous cell carcinoma after primary curative surgery. Head Neck 25 (11): 953-9, 2003. [PUBMED Abstract]
2. Vikram B, Strong EW, Shah JP, et al.: Intraoperative radiotherapy in patients with recurrent head and neck cancer. Am J Surg 150 (4): 485-7, 1985. [PUBMED Abstract]
3. Spencer SA, Harris J, Wheeler RH, et al.: RTOG 96-10: reirradiation with concurrent hydroxyurea and 5-fluorouracil in patients with squamous cell cancer of the head and neck. Int J Radiat Oncol Biol Phys 51 (5): 1299-304, 2001. [PUBMED Abstract]
4. Vargo JA, Ferris RL, Ohr J, et al.: A prospective phase 2 trial of reirradiation with stereotactic body radiation therapy plus cetuximab in patients with previously irradiated recurrent squamous cell carcinoma of the head and neck. Int J Radiat Oncol Biol Phys 91 (3): 480-8, 2015. [PUBMED Abstract]
5. Cohen EEW, Soulières D, Le Tourneau C, et al.: Pembrolizumab versus methotrexate, docetaxel, or cetuximab for recurrent or metastatic head-and-neck squamous cell carcinoma (KEYNOTE-040): a randomised, open-label, phase 3 study. Lancet 393 (10167): 156-167, 2019. [PUBMED Abstract]
6. Ferris RL, Blumenschein G, Fayette J, et al.: Nivolumab for Recurrent Squamous-Cell Carcinoma of the Head and Neck. N Engl J Med 375 (19): 1856-1867, 2016. [PUBMED Abstract]
7. Burtness B, Harrington KJ, Greil R, et al.: Pembrolizumab alone or with chemotherapy versus cetuximab with chemotherapy for recurrent or metastatic squamous cell carcinoma of the head and neck (KEYNOTE-048): a randomised, open-label, phase 3 study. Lancet 394 (10212): 1915-1928, 2019. [PUBMED Abstract]
8. Harrington KJ, Burtness B, Greil R, et al.: Pembrolizumab With or Without Chemotherapy in Recurrent or Metastatic Head and Neck Squamous Cell Carcinoma: Updated Results of the Phase III KEYNOTE-048 Study. J Clin Oncol 41 (4): 790-802, 2023. [PUBMED Abstract]
9. Tortochaux J, Tao Y, Tournay E, et al.: Randomized phase III trial (GORTEC 98-03) comparing re-irradiation plus chemotherapy versus methotrexate in patients with recurrent or a second primary head and neck squamous cell carcinoma, treated with a palliative intent. Radiother Oncol 100 (1): 70-5, 2011. [PUBMED Abstract]
10. Vermorken JB, Mesia R, Rivera F, et al.: Platinum-based chemotherapy plus cetuximab in head and neck cancer. N Engl J Med 359 (11): 1116-27, 2008. [PUBMED Abstract]
11. Mesía R, Rivera F, Kawecki A, et al.: Quality of life of patients receiving platinum-based chemotherapy plus cetuximab first line for recurrent and/or metastatic squamous cell carcinoma of the head and neck. Ann Oncol 21 (10): 1967-73, 2010. [PUBMED Abstract]
12. Licitra L, Mesia R, Rivera F, et al.: Evaluation of EGFR gene copy number as a predictive biomarker for the efficacy of cetuximab in combination with chemotherapy in the first-line treatment of recurrent and/or metastatic squamous cell carcinoma of the head and neck: EXTREME study. Ann Oncol 22 (5): 1078-87, 2011. [PUBMED Abstract]
13. Machiels JP, Haddad RI, Fayette J, et al.: Afatinib versus methotrexate as second-line treatment in patients with recurrent or metastatic squamous-cell carcinoma of the head and neck progressing on or after platinum-based therapy (LUX-Head & Neck 1): an open-label, randomised phase 3 trial. Lancet Oncol 16 (5): 583-94, 2015. [PUBMED Abstract]
14. Haddad RI, Harrington K, Tahara M, et al.: Nivolumab Plus Ipilimumab Versus EXTREME Regimen as First-Line Treatment for Recurrent/Metastatic Squamous Cell Carcinoma of the Head and Neck: The Final Results of CheckMate 651. J Clin Oncol 41 (12): 2166-2180, 2023. [PUBMED Abstract]
15. Burtness B: First-Line Nivolumab Plus Ipilimumab in Recurrent/Metastatic Head and Neck Cancer-What Happened? J Clin Oncol 41 (12): 2134-2137, 2023. [PUBMED Abstract]
16. Harrington KJ, Ferris RL, Gillison M, et al.: Efficacy and Safety of Nivolumab Plus Ipilimumab vs Nivolumab Alone for Treatment of Recurrent or Metastatic Squamous Cell Carcinoma of the Head and Neck: The Phase 2 CheckMate 714 Randomized Clinical Trial. JAMA Oncol 9 (6): 779-789, 2023. [PUBMED Abstract]
17. Patil VM, Noronha V, Menon N, et al.: Low-Dose Immunotherapy in Head and Neck Cancer: A Randomized Study. J Clin Oncol 41 (2): 222-232, 2023. [PUBMED Abstract]
18. Mitchell AP, Goldstein DA: Cost Savings and Increased Access With Ultra-Low-Dose Immunotherapy. J Clin Oncol 41 (2): 170-172, 2023. [PUBMED Abstract]

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