Yes. People infected with HIV have a substantially higher risk of some types of cancer compared with uninfected people of the same age (1). The general term for these cancers is “HIV-associated cancers.” Three of these cancers are known as “acquired immunodeficiency syndrome (AIDs)-defining cancers” or “AIDS-defining malignancies”: Kaposi sarcoma, aggressive B-cell non-Hodgkin lymphoma, and cervical cancer. A diagnosis of any of these cancers in someone infected with HIV confirms a diagnosis of AIDS.

Compared with the general population, people infected with HIV are currently about 500 times more likely to be diagnosed with Kaposi sarcoma, 12 times more likely to be diagnosed with non-Hodgkin lymphoma, and, among women, 3 times more likely to be diagnosed with cervical cancer (2).

In addition, people infected with HIV are at higher risk of several other types of cancer (collectively called “non–AIDS-defining cancers“) (1, 2). These other malignancies include cancers of the anus, liver, oral cavity/pharynx, and lung, and Hodgkin lymphoma (3, 4).

People infected with HIV are 19 times more likely to be diagnosed with anal cancer, 3 times as likely to be diagnosed with liver cancer, 2 times as likely to be diagnosed with lung cancer, about 2 times as likely to be diagnosed with oral cavity/pharynx cancer, and about 8 times more likely to be diagnosed with Hodgkin lymphoma compared with the general population (2).

In addition to being linked to an increased risk of cancer, HIV infection is associated with an increased risk of dying from cancer. HIV-infected people with a range of cancer types are more likely to die of their cancer than HIV-uninfected people with these cancers (5, 6).

Infection with HIV weakens the immune system and reduces the body’s ability to fight viral infections that may lead to cancer (2, 7, 8). The viruses that are most likely to cause cancer in people with HIV are (9):

• Kaposi sarcoma-associated herpesvirus (KSHV), also known as human herpesvirus 8 (HHV-8), which causes Kaposi sarcoma and some subtypes of lymphoma
• Epstein-Barr virus (EBV), which causes some subtypes of non-Hodgkin and Hodgkin lymphoma
• Human papillomaviruses (HPV), high-risk types of which cause cervical cancer, most anal cancers, and oropharyngeal, penile, vaginal, and vulvar cancer
• Hepatitis B virus (HBV) and hepatitis C virus (HCV), which both cause liver cancer

HIV-infected persons are more likely to be infected with these viruses than people in the general population (10–13).

In addition, the prevalence of some traditional risk factors for cancer, especially smoking (a known cause of lung and other cancers) and heavy alcohol use (which can increase the risk of liver cancer), is higher among people infected with HIV (12, 14). Also, because people infected with HIV have compromised immune systems, both immunosuppression and inflammation may have direct or indirect roles in the development of some cancers that are elevated in people infected with HIV (2, 9).

The poorer cancer survival of HIV-infected people may result, at least in part, from the weakened immune system in such individuals. The increased risk of death could also result from the cancer being more advanced at diagnosis, delays in cancer treatment, or poorer access to appropriate cancer treatment.

The introduction of highly active antiretroviral therapy (HAART), also called combination antiretroviral therapy (cART), starting in the mid-1990s greatly reduced the incidence of certain cancers in HIV-infected patients, especially Kaposi sarcoma and non-Hodgkin lymphoma (2). The likely explanation for this reduced incidence is that cART lowers the amount of HIV circulating in the blood, thereby allowing partial restoration of immune system function to fight the viruses that cause many of these cancers.

Although the risk of these AIDS-defining cancers among people infected with HIV is lower than in the past, it is still much higher than among people in the general population (15). This persistently high risk may reflect the fact that cART does not completely restore immune system functioning. Also, many people infected with HIV are not aware they are infected, have had difficulty in accessing medical care, or for other reasons are not receiving adequate antiretroviral therapy.

The introduction of cART has not reduced the incidence of all HIV-related cancers, and in fact there has been an increase in non–AIDS-defining cancers. For example, the incidence of liver and anal cancer may be increasing among HIV-infected individuals (2, 15).

An important factor contributing to the increase in non–AIDS-defining cancers is that as cART has reduced the number of deaths from AIDS, the HIV-infected population has grown in size and become older. The fastest growing proportion of HIV-infected individuals is the over-40 age group. These individuals are now developing cancers common in older age and also have an increased cumulative risk of developing HIV-associated cancers.

Taking cART as indicated based on current HIV treatment guidelines lowers the risk of Kaposi sarcoma and non-Hodgkin lymphoma and increases overall survival.

The risk of lung, oral, and other cancers can be reduced by quitting smoking. Because HIV-infected people have a higher risk of lung cancer, it is especially important that they do not smoke. Help with quitting smoking is available through the National Cancer Institute’s (NCI’s) smoking quitline at 1–877–448–7848 (1–877–44U–QUIT) and other NCI resources, which are listed on the Tobacco page.

The higher incidence of liver cancer among HIV-infected people appears to be related to more frequent infection with hepatitis virus (particularly HCV in the United States) than among HIV-uninfected people (12, 16). Therefore, HIV-infected individuals should know their hepatitis status.

In addition, if HIV-infected people currently have viral hepatitis, they should discuss with their health care provider whether antiviral treatment is an option for them (9, 16–19). Some drugs may be used for both HBV-suppressing therapy and cART (16).

Because HIV-infected women have a higher risk of cervical cancer, it is important that they be screened regularly for this disease. In addition, the Centers for Disease Control and Prevention (CDC) recommends vaccination against human papillomavirus (HPV) for women and men with HIV infection up to age 26 years. Cervical cancer screening guidelines that incorporate results of a Pap test and an HPV DNA test are evolving, and women should discuss screening options with their healthcare provider (20).

Some researchers recommend anal Pap test screening to detect and treat early lesions before they progress to anal cancer (21). However, it is not clear if this type of screening benefits all HIV-infected people or if treating such lesions prevents anal cancer. These questions are being addressed in an NCI-funded trial called the Anal Cancer/HSIL Outcomes Research (ANCHOR) Study. This study is currently enrolling men and women with HIV to undergo anal Pap testing and then be randomly assigned to receive either treatment or observation (no treatment). The goal is to determine whether treatment of anal lesions prevents anal cancer in HIV-infected people with anal lesions.

KSHV is secreted in saliva, and transmission of this virus may occur through deep kissing, through the use of saliva as a lubricant in sex, or through oral–anal sex. Reducing contact through these routes may reduce the chance of being infected with KSHV.

The Office of HIV and AIDS Malignancy (OHAM) coordinates and oversees NCI-sponsored research on AIDS-related cancers and HIV/AIDS. OHAM also acts as a point of contact for the National Institutes of Health (NIH) Office of AIDS Research (OAR).

OHAM has two programs:

• The AIDS Malignancy Program, which has primary responsibility for identifying new initiatives; for sponsoring international activities, such as the Strengthening Capacity for Research for HIV-Associated Malignancies in Africa initiative; and for overseeing programs that NCI co-manages with other NIH institutes, such as the Centers for AIDS Research, the Multicenter AIDS Cohort Study, the Women’s Interagency HIV Study, and the International Epidemiology Databases to Evaluate AIDS.

• The AIDS Cancer Clinical Program, which has primary responsibility for overseeing clinical programs in OHAM, including the AIDS Malignancy Consortium and the AIDS and Cancer Specimen Resource.

The two intramural divisions of NCI, the Center for Cancer Research (CCR) and the Division of Cancer Epidemiology and Genetics (DCEG), conduct research on both HIV and HIV/AIDS-associated cancer. For example, DCEG is conducting the HIV/AIDS Cancer Match Study, which uses data previously collected by public health agencies to examine cancer risk in people with HIV. Nearly all other NCI divisions, offices, and centers also support HIV/AIDS research.

HPV vaccines protect against infection with human papillomaviruses (HPV). HPV is a group of more than 200 related viruses, of which more than 40 are spread through direct sexual contact. Among these, two HPV types cause genital warts, and about a dozen HPV types can cause certain types of cancer—cervical, anal, oropharyngeal, penile, vulvar, and vaginal.

Three vaccines that prevent infection with disease-causing HPV have been licensed in the United States: Gardasil, Gardasil 9, and Cervarix. Gardasil 9 has, since 2016, been the only HPV vaccine used in the United States. It prevents infection with the following nine HPV types:

• HPV types 6 and 11, which cause 90% of genital warts (1)
• HPV types 16 and 18, two high-risk HPVs that cause about 70% of cervical cancers and an even higher percentage of some of the other HPV-caused cancers (2–4) 
• HPV types 31, 33, 45, 52, and 58, high-risk HPVs that account for an additional 10% to 20% of cervical cancers 

Cervarix prevents infection with types 16 and 18, and Gardasil prevents infection with types 6, 11, 16, and 18. Both vaccines are still used in some other countries.

The Centers for Disease Control and Prevention’s (CDC) Advisory Committee on Immunization Practices (ACIP) develops recommendations regarding all vaccination in the United States, including HPV vaccination. The current ACIP recommendations for HPV vaccination are (5):

• Children and adults ages 9 through 26 years. HPV vaccination is routinely recommended at age 11 or 12 years; vaccination can be started at age 9 years. HPV vaccination is recommended for all persons through age 26 years who were not adequately vaccinated earlier. 
• Adults ages 27 through 45 years. Although the HPV vaccine is Food and Drug Administration (FDA) approved to be given through age 45 years, HPV vaccination is not recommended for all adults ages 27 through 45 years. Instead, ACIP recommends that clinicians consider discussing with their patients in this age group who were not adequately vaccinated earlier whether HPV vaccination is right for them. HPV vaccination in this age range provides less benefit because more people have already been exposed to the virus. 
• Persons who are pregnant. HPV vaccination should be delayed until after pregnancy, but pregnancy testing is not required before vaccination. There is no evidence that vaccination will affect a pregnancy or harm a fetus. 

The HPV vaccine is given as a series of shots. ACIP specifies different dosing schedules, depending on the age when the vaccination series is started (6). Children who start the vaccine series before their 15th birthday need only two doses to be fully protected. People who start the series at age 15 or older and people who have certain conditions that weaken the immune system need three doses to be fully protected. 

Researchers are currently investigating whether a single dose of HPV vaccine might be effective. See What research is being done on strategies to prevent HPV infection?

Clinical trials have shown that HPV vaccines are highly effective in preventing cervical infection with the types of HPV they target when given before first exposure to the virus—that is, before individuals begin to engage in sexual activity. HPV vaccines have also been found to reduce infections in other tissues that HPV infects, including the anus (7) and oral region (8, 9).

Because the cell changes and cancers caused by HPV take years to develop, it has only recently been confirmed that the vaccines reduce the risk of these outcomes as well. Trials and real-world data from population-based studies have now demonstrated that the vaccines greatly reduce the risk of precancers and cancers of the cervix, vagina, and vulva in vaccinated women (10–13). A clinical trial of Gardasil in men indicated that it can prevent anal cell changes caused by persistent infection (14). The trials that led to approval of Gardasil 9 found it to be nearly 100% effective in preventing cervical, vulvar, and vaginal infections and precancers caused by all seven cancer-causing HPV types (16, 18, 31, 33, 45, 52, and 58) that it targets (10).

Although Cervarix and Gardasil prevent infection with just two high-risk HPV types, HPV16 and HPV18, these two HPV types are responsible for most HPV-caused cancers. In a 2017 position paper, the World Health Organization stated that the HPV vaccines have comparable efficacy (15). In addition, Cervarix has been found to provide substantial protection against a few additional cancer-causing HPV types, a phenomenon called cross-protection (16). Women who received three doses of Cervarix experienced strong protection against new infections with HPV types 31, 33, and 45 (17). 

To date, protection against infections with the targeted HPV types has been found to last for at least 10 years with Gardasil (18), up to 11 years with Cervarix (17), and at least 6 years with Gardasil 9 (19). Long-term studies of vaccine efficacy that are still in progress will help scientists better understand how long protection lasts (20).

Like other immunizations that guard against viral infection, HPV vaccines stimulate the body to produce antibodies that, in future encounters with HPV, bind to the virus and prevent it from infecting cells.

The current HPV vaccines are based on virus-like particles (VLPs) that are formed by HPV surface components. VLPs are not infectious because they lack the virus’s DNA. However, they closely resemble the natural virus, and antibodies against the VLPs also have activity against the natural virus. The VLPs have been found to be strongly immunogenic, which means that they induce high levels of antibody production by the body. This makes the vaccines highly effective.

The vaccines do not prevent other sexually transmitted diseases, nor do they treat existing HPV infections or HPV-caused disease.

The combination of HPV vaccination and cervical screening can provide the greatest protection against cervical cancer. Also, HPV vaccination reduces the risk of developing cancers caused by HPV at sites other than the cervix.

Not only does vaccination protect vaccinated individuals against infection by the HPV types targeted by the vaccine that is used (and possibly other types, depending on the extent of cross protection), but vaccination can also reduce the prevalence of the vaccine-targeted HPV types in the population, thereby reducing infection in individuals who are not vaccinated (a phenomenon called herd protection, or herd immunity). For example, in Australia, where a high proportion of girls are vaccinated with Gardasil, the incidence of genital warts went down during the first 4 years of the vaccination program among young males—who were not being vaccinated at the time—as well as among young females (21).

Further evidence that large-scale HPV vaccination confers protection for unvaccinated individuals comes from a 2019 meta-analysis of girls-only HPV vaccination programs in 14 high-income countries that included 60 million vaccinated people (22). That analysis showed that, up to 8 years after the start of vaccination, diagnoses of anogenital warts decreased by 31% among women aged 25–29 years, by 48% among boys aged 15–19 years, and by 32% among men aged 20–24 years, compared with the period before vaccination began.

Similarly, a study of women aged 20–29 years in one US region found that within about 10 years of vaccine introduction, the prevalence of HPV types targeted by the vaccine decreased in both vaccinated and unvaccinated women, providing evidence of both direct and herd protection (23).

Widespread HPV vaccination has the potential to reduce cervical cancer incidence around the world by as much as 90% (16, 19). In addition, the vaccines may reduce the need for screening and subsequent medical care, biopsies, and invasive procedures associated with follow-up from abnormal cervical screening, thus helping to reduce health care costs and anxieties related to follow-up procedures (24).

As the incidence of cervical cancer has declined in the United States, due mainly to cervical cancer screening, the incidence of HPV-associated oropharyngeal, vulvar, and anal cancers has been increasing (25). Indeed, analyses of data for 2012–2016 found that HPV caused more oropharyngeal cancers than cervical cancers in the United States (2). There are no formal screening programs for the non-cervical cancers, so universal HPV vaccination could have a large public health impact.

Yes. More than 12 years of safety monitoring show that the vaccines have caused no serious side effects. The most common problems have been brief soreness and other local symptoms at the injection site. These problems are similar to those commonly experienced with other vaccines.

The FDA and the CDC conducted a safety review of adverse side effect s related to Gardasil immunization that have been reported to the Vaccine Adverse Events Reporting System since the vaccine was licensed (26–28). The rates of adverse side effects were consistent with what was seen in safety studies carried out before the vaccine was approved and were similar to those seen with other vaccines. The most recent safety data review for HPV vaccines continues to indicate that these vaccines are safe (29, 30).

Syncope (fainting) is sometimes observed with Gardasil, as with other vaccines. Falls after fainting may sometimes cause serious injuries, such as head injuries. These can largely be prevented by keeping the person seated for up to 15 minutes after vaccination. The FDA and CDC have reminded health care providers that, to prevent falls and injuries, all vaccine recipients should remain seated or lying down and be closely observed for 15 minutes after vaccination. More information is available from the CDC on its HPV Vaccine page.

ACIP recommends that people who have an HPV infection and/or an abnormal Pap test result that may indicate an HPV infection should still receive the HPV vaccine if they are in the appropriate age group (9 through 26 years) because the vaccine may protect them against high-risk HPV types that they have not yet acquired. However, these people should be told that the vaccination will not cure them of current HPV infections or treat the abnormal results of their Pap test (31).

Although HPV vaccines have been found to be safe when given to people who are already infected with HPV, the vaccines provide maximum benefit if a person receives them before he or she is sexually active (32, 33).

It is likely that someone previously infected with HPV will still get some residual benefit from vaccination, even if he or she has already been infected with one or more of the HPV types included in the vaccines.

Yes. Because HPV vaccines do not protect against all HPV types that can cause cancer, women who have been vaccinated are advised to follow the same screening recommendations as unvaccinated women. There could be future changes in screening recommendations for vaccinated women.

Most private insurance plans cover HPV vaccination. The federal Affordable Care Act requires most private insurance plans to cover recommended preventive services (including HPV vaccination) with no copay or deductible.

Medicaid covers HPV vaccination in accordance with ACIP recommendations, and immunizations are a mandatory service under Medicaid for eligible individuals under age 21. In addition, the federal Vaccines for Children Program provides immunization services for children younger than 19 years who are Medicaid eligible, uninsured, underinsured, or Native American or Alaska Native.

Merck, the manufacturer of Gardasil 9, offers the Merck Vaccine Patient Assistance Program, which provides Gardasil 9 for free to people aged 19 to 45 years who live in the United States, do not have health insurance, and have an annual household income less than a certain amount.

If a single dose of HPV vaccine were effective, that would be an important advance. A large observational study using national data from women across Australia found that one dose of HPV vaccine was as effective as two or three doses in preventing high-grade cervical lesions (34). An analysis of data from a community-based clinical trial of Cervarix in Costa Rica, found that even one dose of the vaccine caused the body to produce approximately nine times more antibodies against HPV than the body produces in response to a natural HPV infection, and those antibody levels persisted for 11 years (35). In addition, the rates of HPV infection remained low for at least 10 years (35). 

Two NCI-led clinical trials have been launched in Costa Rica to confirm and extend these findings. The ESCUDDO study, a randomized double-blind controlled trial involving 20,000 girls ages 12–16 years, is testing whether one dose of either Cervarix or Gardasil 9 is as effective as two doses at preventing persistent cervical infection with HPV. PRIMAVERA-ESCUDDO, a non-randomized open-label trial, will provide earlier and complementary results to ESCUDDO about the immunogenicity of one dose of Cervarix in girls ages 9–14 years compared with three doses of Gardasil in women ages 18–25 years.

Another prevention strategy that is being explored is topical microbicides. Carrageenan, a compound that is extracted from a type of seaweed and used widely in foods and other products, has been found to inhibit HPV infection in laboratory studies. An interim analysis of data from a randomized clinical trial showed that consistent use of a lubricant gel that contains carrageenan reduced the risk of genital HPV infection in healthy women (36). 

Researchers are working to develop therapeutic HPV vaccines, which instead of preventing HPV infection would prevent cancer from developing among women previously infected with HPV (37–40). These vaccines work by stimulating the immune system to specifically target and kill infected cells. Ongoing clinical trials are testing the safety and efficacy of a therapeutic DNA vaccine to treat HPV-related cervical and vulvar lesions.  

Yes. Although H. pylori infection does not itself cause illness, chronic infection causes long-lasting inflammation in the stomach (called non-atrophic gastritis) in most people. This inflammation can lead to several possible conditions, including atrophic gastritis (thinning of the stomach lining caused by long-term inflammation) and certain types of stomach (gastric) cancer, particularly gastric adenocarcinoma and gastric mucosa-associated lymphoid tissue (MALT) lymphoma, which is a rare type of non-Hodgkin lymphoma. 

Because of its role in causing stomach cancer, in 1994 H. pylori was classified as a human carcinogen, or cancer-causing agent, by the World Health Organization’s International Agency for Research on Cancer (5). In 2021, the National Toxicology Program’s 15th Report on Carcinogens added chronic infection with H. pylori to its list of substances that are known or reasonably anticipated to cause cancer in humans. 

It remains unclear whether chronic H. pylori infection is associated with an increased risk of other cancers. Although some studies have found a possible association between H. pylori infection and an increased risk of pancreatic cancer, a 2023 meta-analysis of observational studies found insufficient evidence to support such an association (6). Growing evidence suggests a link between H. pylori infection and an increased risk of colorectal cancer (7–9).

However, infection with H. pylori is also associated with a reduced risk of esophageal adenocarcinoma, a type of esophageal cancer that is associated with Barrett esophagus and gastroesophageal reflux disease. 

Chronic H. pylori infection can also cause peptic ulcers (ulcers of the stomach and upper small intestine). More information about peptic ulcers is available from the National Institute of Diabetes and Digestive and Kidney Diseases.

According to the Centers for Disease Control and Prevention, people with an active gastric or duodenal ulcers or a documented history of ulcers should be tested for H. pylori, and, if they have an infection, should be treated. Testing for and treating H. pylori infection is also recommended after surgery for early gastric cancer or low-grade gastric MALT lymphoma (52–54). However, most experts agree that the available evidence does not support widespread testing for and eradication of H. pylori infection (52, 55). Unnecessary or inappropriate eradication treatment may be contributing to the increase in H. pylori resistance to several antibiotics in the United States (56).

Physical activity is defined as any movement that uses skeletal muscles and requires more energy than resting. Physical activity can include walking, running, dancing, biking, swimming, performing household chores, exercising, and engaging in sports activities.

A measure called the metabolic equivalent of task, or MET, is used to characterize the intensity of physical activity. One MET is the rate of energy expended by a person sitting at rest. Light-intensity activities expend less than 3 METs, moderate-intensity activities expend 3 to 6 METs, and vigorous activities expend 6 or more METs (1).

Sedentary behavior is any waking behavior characterized by an energy expenditure of 1.5 or fewer METs while sitting, reclining, or lying down (1). Examples of sedentary behaviors include most office work, driving a vehicle, and sitting while watching television.

A person can be physically active and yet spend a substantial amount of time being sedentary.

Evidence linking higher physical activity to lower cancer risk comes mainly from observational studies, in which individuals report on their physical activity and are followed for years for diagnoses of cancer. Although observational studies cannot prove a causal relationship, when studies in different populations have similar results and when a possible mechanism for a causal relationship exists, this provides evidence of a causal connection. 

There is strong evidence that higher levels of physical activity are linked to lower risk of several types of cancer (2–4). 

• Bladder cancer: In a 2014 meta-analysis of 11 cohort studies and 4 case-control studies, the risk of bladder cancer was 15% lower for individuals with the highest level of recreational or occupational physical activity than in those with the lowest level (5). A pooled analysis of over 1 million individuals found that leisure-time physical activity was linked to a 13% reduced risk of bladder cancer (6).
• Breast cancer: Many studies have shown that physically active women have a lower risk of breast cancer than inactive women. In a 2016 meta-analysis that included 38 cohort studies, the most physically active women had a 12–21% lower risk of breast cancer than those who were least physically active (7). Physical activity has been associated with similar reductions in risk of breast cancer among both premenopausal and postmenopausal women (7, 8). Women who increase their physical activity after menopause may also have a lower risk of breast cancer than women who do not (9, 10).
• Colon cancer: In a 2016 meta-analysis of 126 studies, individuals who engaged in the highest level of physical activity had a 19% lower risk of colon cancer than those who were the least physically active (11). 
• Endometrial cancer: Several meta-analyses and cohort studies have examined the relationship between physical activity and the risk of endometrial cancer (cancer of the lining of the uterus) (12–15). In a meta-analysis of 33 studies, highly physically active women had a 20% lower risk of endometrial cancer than women with low levels of physical activity (12). There is some evidence that the association is indirect, in that physical activity would have to reduce obesity for the benefits to be observed. Obesity is a strong risk factor for endometrial cancer (12–14).
• Esophageal cancer: A 2014 meta-analysis of nine cohort and 15 case–control studies found that the individuals who were most physically active had a 21% lower risk of esophageal adenocarcinoma than those who were least physically active (16). 
• Kidney (renal cell) cancer: In a 2013 meta-analysis of 11 cohort studies and 8 case–control studies, individuals who were the most physically active had a 12% lower risk of renal cancer than those who were the least active (17). A pooled analysis of over 1 million individuals found that leisure-time physical activity was linked to a 23% reduced risk of kidney cancer (6).
• Stomach (gastric) cancer: A 2016 meta-analysis of 10 cohort studies and 12 case–control studies reported that individuals who were the most physically active had a 19% lower risk of stomach cancer than those who were least active (18).

There is some evidence that physical activity is associated with a reduced risk of lung cancer (2, 4). However, it is possible that differences in smoking, rather than in physical activity, are what explain the association of physical activity with reduced risk of lung cancer. In a 2016 meta-analysis of 25 observational studies, physical activity was associated with reduced risk of lung cancer among former and current smokers but was not associated with risk of lung cancer among never smokers (19). 

For several other cancers, there is more limited evidence of an association. These include certain cancers of the blood, as well as cancers of the pancreas, prostate, ovaries, thyroid, liver, and rectum (2, 6). 

Exercise has many biological effects on the body, some of which have been proposed to explain associations with specific cancers. These include:

• Lowering the levels of sex hormones, such as estrogen, and growth factors that have been associated with cancer development and progression (20) [breast, colon]
• Preventing high blood levels of insulin, which has been linked to cancer development and progression (20) [breast, colon]
• Reducing inflammation
• Improving immune system function
• Altering the metabolism of bile acids, decreasing exposure of the gastrointestinal tract to these suspected carcinogens (21, 22) [colon]
• Reducing the time it takes for food to travel through the digestive system, which decreases gastrointestinal tract exposure to possible carcinogens [colon] 
• Helping to prevent obesity, which is a risk factor for many cancers

Although there are fewer studies of sedentary behavior and cancer risk than of physical activity and cancer risk, sedentary behavior—sitting, reclining, or lying down for extended periods of time (other than sleeping)—is a risk factor for developing many chronic conditions and premature death (4, 23, 24). It may also be associated with increased risk for certain cancers (23, 25).

The U.S. Department of Health and Human Services Physical Activity Guidelines for Americans, 2nd edition, released in 2018 (1), recommends that, for substantial health benefits and to reduce the risk of chronic diseases, including cancer, adults engage in

• 150 to 300 minutes of moderate-intensity aerobic activity, 75 to 100 minutes of vigorous aerobic activity, or an equivalent combination of each intensity each week. This physical activity can be done in episodes of any length.
• muscle-strengthening activities at least 2 days a week
• balance training, in addition to aerobic and muscle-strengthening activity

Yes. A report of the 2018 American College of Sports Medicine International Multidisciplinary Roundtable on Physical Activity and Cancer Prevention and Control (26) concluded that exercise training and testing are generally safe for cancer survivors and that every survivor should maintain some level of physical activity. 

The Roundtable also found

• strong evidence that moderate-intensity aerobic training and/or resistance exercise during and after cancer treatment can reduce anxiety, depressive symptoms, and fatigue and improve health-related quality of life and physical function 
• strong evidence that exercise training is safe in persons who have or might develop breast-cancer–related lymphedema
• some evidence that exercise is beneficial for bone health and sleep quality 
• insufficient evidence that physical activity can help prevent cardiotoxicity or chemotherapy-induced peripheral neuropathy or improve cognitive function, falls, nausea, pain, sexual function, or treatment tolerance

In addition, research findings have raised the possibility that physical activity may have beneficial effects on survival for patients with breast, colorectal, and prostate cancers (26, 27). 

• Breast cancer: In a 2019 systematic review and meta-analysis of observational studies, breast cancer survivors who were the most physically active had a 42% lower risk of death from any cause and a 40% lower risk of death from breast cancer than those who were the least physically active (28). 
• Colorectal cancer: Evidence from multiple epidemiologic studies suggests that physical activity after a colorectal cancer diagnosis is associated with a 30% lower risk of death from colorectal cancer and a 38% lower risk of death from any cause (4). 
• Prostate cancer: Limited evidence from a few epidemiologic studies suggests that physical activity after a prostate cancer diagnosis is associated with a 33% lower risk of death from prostate cancer and a 45% lower risk of death from any cause (4). 

There is very limited evidence for beneficial effects of physical activity on survival for other cancers, including non-Hodgkin lymphoma, stomach cancer, and malignant glioma (4). 

Findings from observational studies provide much evidence for a link between higher levels of physical activity and lower risk of cancer. However, these studies cannot fully rule out the possibility that active people have lower cancer risk because they engage in other healthy lifestyle behaviors. For this reason, clinical trials that randomly assign participants to exercise interventions provide the strongest evidence because they eliminate bias caused by pre-existing illness and attendant physical inactivity. 

To confirm the observational evidence and define the potential magnitude of the effect, several large clinical trials are examining physical activity and/or exercise interventions in cancer patients and survivors. These include the Breast Cancer Weight Loss (BWEL) trial in newly diagnosed breast cancer patients, the CHALLENGE trial in colon cancer patients who have recently completed chemotherapy (29), and the INTERVAL-GAP4 trial in men with metastatic, castrate-resistant prostate cancer (30). 

Many additional questions have yet to be answered in several broad areas of research on physical activity and cancer:

• What are the mechanisms by which physical activity reduces cancer risk? 
• What is the optimal time in life, intensity, duration, and/or frequency of physical activity needed to reduce the risk of cancer, both overall and for specific sites?
• Is sedentary behavior associated with increased risk of cancer?
• Does the association between physical activity and cancer differ by age or race/ethnicity?
• Does physical activity reduce the risk of cancer in people who have inherited a genetic variant that increases cancer risk?

Obesity is a disease in which a person has an unhealthy amount and/or distribution of body fat (1). Compared with people of healthy weight, those with overweight or obesity are at greater risk for many diseases, including diabetes, high blood pressure, cardiovascular disease, stroke, and at least 13 types of cancer, as well as having an elevated risk of death from all causes (2–5). 

To determine if someone has obesity, researchers commonly use a measure known as the body mass index (BMI). BMI is calculated by dividing a person’s weight (in kilograms) by their height (in meters) squared (commonly expressed as kg/m²). BMI provides a more accurate measure of obesity than weight alone, and for most people it is a good (although imperfect) indicator of body fatness. 

The National Heart Lung and Blood Institute has a BMI calculator for adults. The standard weight categories based on BMI for adults ages 20 years or older are:

The Centers for Disease Control and Prevention (CDC) has a BMI percentile calculator for children and teens. Overweight and obesity for people younger than 20 years old, whose BMI can change significantly as they grow, are based on CDC’s BMI-for-age growth charts. 

Measurements that reflect the distribution of body fat are sometimes used along with BMI as indicators of obesity and disease risks. These measurements include waist circumference, waist-to-hip ratio (the waist circumference divided by the hip circumference), waist-to-height ratio, and fat distribution as measured by dual-energy X-ray absorptiometry (DXA or DEXA) or imaging with CT or PET.

These measures are used because the distribution of fat is increasingly understood to be relevant to disease risks. In particular, visceral fat—fat that surrounds internal organs—seems to be more dangerous, in terms of disease risks, than overall fat or subcutaneous fat (the layer just under the skin). 
 

Obesity and severe obesity have become more common in the United States in recent years (7). 

• In 2011, 27.4% of adults ages 18 or older had obesity or severe obesity.
• By contrast, in 2020, 31.9% of adults ages 18 or older had obesity or severe obesity. 

The percentage of children and adolescents ages 2–19 years with obesity or severe obesity has also increased (6). 

• In 2011–2012, 16.9% of 2–19-year-olds had obesity and 5.6% had severe obesity.
• By contrast, in 2017–2018, 19.3% of 2–19-year-olds had obesity and 6.1% had severe obesity. 

According to the CDC, the prevalence of obesity in the United States differs among racial and ethnic groups (7). In 2020, the proportions of adults ages 18 years or older with obesity or severe obesity were:

• Non-Hispanic Black, 41.6% 
• American Indian/Alaska Native, 38.8%
• Hawaiian/Pacific Islander, 38.5%
• Hispanic, 36.6% 
• Non-Hispanic White, 30.7%
• Asian, 11.8% 

In 2017–2018, the proportions of obesity among children and adolescents ages 2–19 years were (6):

• Mexican American, 26.9%
• Hispanic, 25.6%
• Non-Hispanic Black, 24.2%
• Non-Hispanic White, 16.1%
• Non-Hispanic Asian, 8.7%

The prevalence of obesity has increased more quickly recently, possibly due to the COVID-19 pandemic (8). CDC has state-level estimates of adult obesity prevalence in the United States. 

Nearly all of the evidence linking obesity to cancer risk comes from large cohort studies, a type of observational study. However, data from observational studies cannot definitively establish that obesity causes cancer. That is because people with obesity or overweight may differ from people without these conditions in ways other than their body fat, and it is possible that these other differences—rather than their body fat—explain their increased cancer risk.

An International Agency for Research on Cancer (IARC) Working Group concluded that there is consistent evidence that higher amounts of body fat are associated with an increased risk of a number of cancers. The table below shows the risks reported in representative studies. 

People who have a higher BMI at the time their cancer is diagnosed (29) or who have survived cancer (30, 31) have higher risks of developing a second, unrelated cancer (a second primary cancer).

Several possible mechanisms have been suggested to explain how obesity might increase the risks of some cancers (32, 33).

• Fat tissue (also called adipose tissue) produces excess amounts of estrogen, high levels of which have been associated with increased risks of breast, endometrial, ovarian, and some other cancers.
• People with obesity often have increased blood levels of insulin and insulin-like growth factor-1 (IGF-1). High levels of insulin, a condition known as hyperinsulinemia, is due to insulin resistance and precedes the development of type 2 diabetes, another known cancer risk factor. High levels of insulin and IGF-1 may promote the development of colon, kidney, prostate, and endometrial cancers (34).
• People with obesity often have chronic inflammatory conditions such as gallstones or non-alcoholic fatty liver disease. These conditions can cause oxidative stress, which leads to DNA damage (35) and increases the risk of biliary tract and other cancers (36).
• Fat cells produce hormones called adipokines that can stimulate or inhibit cell growth. For example, the level of an adipokine called leptin in the blood increases with increasing body fat, and high levels of leptin can promote aberrant cell proliferation. Another adipokine, adiponectin, is less abundant in people with obesity than in people with a healthy weight and may have antiproliferative effects that protect against tumor growth.
• Fat cells may also have direct and indirect effects on other cell growth and metabolic regulators, including mammalian target of rapamycin (mTOR) and AMP-activated protein kinase.

Other possible mechanisms by which obesity could affect cancer risk include impaired tumor immunity and changes in the mechanical properties of the scaffolding tissue that surrounds developing tumors (37).

In addition to biological effects, obesity can lead to difficulties in screening and management. For example, women with overweight or obesity have an increased risk of cervical cancer compared with women of healthy weight, likely due to less effective cervical cancer screening in these individuals (38).

A nationwide cross-sectional study using BMI and cancer incidence data from the US Cancer Statistics database estimated that each year in 2011 to 2015 among people ages 30 and older, about 37,670 new cancer cases in men (4.7%) and 74,690 new cancer cases in women (9.6%) were due to excess body weight (overweight, obesity, or severe obesity) (39). The percentage of cases attributed to excess body weight varied widely across cancer types and was as high as 51% for liver or gallbladder cancer and 49.2% for endometrial cancer in women and 48.8% for liver or gallbladder cancer and 30.6% for esophageal adenocarcinoma in men.

Globally, a 2019 study found that in 2012, excess body weight accounted for approximately 3.9% of all cancers (544,300 cases), with the burden of these cancer cases higher for women (368,500 cases) than for men (175,800 cases) (40). The proportion of cancers due to excess body weight varied from less than 1% in low-income countries to 7% or 8% in some high-income Western countries and in Middle Eastern and Northern African countries.

Most of the data about whether losing weight reduces cancer risk comes from cohort and case–control studies. Observational studies of obesity and cancer risk should be interpreted with caution because they cannot definitively establish that obesity causes cancer and people who lose weight may differ in other ways from people who do not.

Some of these studies have found decreased risks of breast, endometrial, colon, and prostate cancers among people with obesity who had lost weight. For example, in one large prospective study of postmenopausal women, intentional loss of more than 5% of body weight was associated with lower risk of obesity-related cancers, especially endometrial cancer (41). However, unintentional weight loss was not associated with cancer risk in this study. 

A follow-up study of weight and breast cancer in the Women’s Health Initiative (42) found that, for women who were already overweight or obese at the beginning of the study, weight change (either gain or loss) was not associated with breast cancer risk during follow-up. However, in a study that pooled data from 10 cohorts, sustained weight loss was associated with lower breast cancer risk among women 50 years and older (43).

To better understand the relationship between weight loss among people with obesity and cancer risk, some researchers are examining cancer risk in people with obesity who have undergone bariatric surgery (surgery performed on the stomach or intestines to provide maximum and sustained weight loss). Studies have found that bariatric surgery among people with obesity, particularly women, is associated with reduced risks of cancer overall (44); of hormone-related cancers, such as breast, endometrial, and prostate cancers (45); and of obesity-related cancers, such as postmenopausal breast cancer, endometrial cancer, and colon cancer (46).

Most of the evidence about obesity in cancer survivors comes from people who were diagnosed with breast, prostate, or colorectal cancer. Research indicates that obesity may worsen several aspects of cancer survivorship, including quality of life, cancer recurrence, cancer progression, prognosis (survival), and risk of certain second primary cancers (29, 30, 47, 48).

For example, obesity is associated with increased risks of treatment-related lymphedema in breast cancer survivors (49) and of incontinence in prostate cancer survivors treated with radical prostatectomy (50). In a large clinical trial of patients with stage II and stage III rectal cancer, those with a higher baseline BMI (particularly men) had an increased risk of local recurrence (51). Death from multiple myeloma is 50% more likely for people with the highest levels of obesity compared with people at healthy weight (52).

Most studies of this question have focused on breast cancer. Several randomized clinical trials in breast cancer survivors have reported weight loss interventions that resulted in both weight loss and beneficial changes in biomarkers that have been linked to the association between obesity and prognosis (53, 54). 

However, there is little evidence about whether weight loss reduces the risk of breast cancer recurrence or death (55). The NCI-sponsored Breast Cancer WEight Loss (BWEL) Study, an ongoing randomized phase III trial, is examining whether participating in a weight loss program after breast cancer diagnosis affects invasive disease-free survival and recurrence in overweight and obese women (56).

Many studies are exploring mechanisms that link obesity and cancer (34, 57). One research area involves understanding the role of the microbes that live in the human gastrointestinal tract (collectively called the gut microbiota, or microbiome) in both type 2 diabetes and obesity. Both diseases are associated with dysbiosis, an imbalance in the community of these microbes. For example, the gut microbiomes of people with obesity differ from and are less diverse than those of people of healthy weight. Imbalances in the gut microbiota are associated with inflammation, altered metabolism, and genotoxicity, which may in turn be related to cancer. 

Researchers are also studying how obesity alters the tumor microenvironment, which may play a role in cancer progression. For example, studies in mouse models show that obesity (induced by feeding mice a high-fat diet) creates a competition for lipids between tumor cells and T cells that makes the T cells less effective at fighting the cancer (58). 

Another area of investigation is the role of insulin receptor signaling in cancer. Many cancer cells express elevated levels of IR-A, a form of the insulin receptor that has a high affinity for insulin and related growth factors. Researchers are investigating how these factors contribute to metabolic disease and cancer and whether they may be useful targets for therapeutic interventions to prevent obesity-related cancers.

Investigators are also exploring whether the associations of obesity with cancer risk and outcomes vary by race or ethnicity (59). Also, researchers are investigating whether different cutoffs for overweight and obesity should be used for different racial/ethnic groups. For example, the World Health Organization (WHO) has suggested the alternate thresholds of 23.0 and 27.5 kg/m² for overweight and obesity for people of Asian ancestry (60).

The NCI Cohort Consortium is an extramural–intramural partnership that combines more than 50 prospective cohort studies from around the world with more than seven million participants. The studies are gathering information on body mass index, waist circumference, and other measures of adiposity from each cohort. The large size of the consortium will allow researchers to get a better sense of how obesity-related factors relate to less common cancers, such as cancers of the thyroid, gallbladder, head and neck, and kidney.

Another area of study is focused on developing more precise and effective interventions to prevent weight gain and weight regain after weight loss. This area of research includes two NIH-based initiatives—the Accumulating Data to Optimally Predict Obesity Treatment (ADOPT) Core Measures (61) and the Trans-NIH Consortium of Randomized Controlled Trials of Lifestyle Weight Loss Interventions (62)—both of which aim to identify predictors of successful weight loss and maintenance and to incorporate information on genetic, psychosocial, behavioral, biological, and environmental factors into predictive profiles to enable more precise and, ultimately, more effective weight loss interventions.

NCI supports research on obesity and cancer risk through a variety of activities, including large cooperative initiatives, web and data resources, epidemiologic and basic science studies, and dissemination and implementation resources. For example, the Transdisciplinary Research on Energetics and Cancer (TREC) initiative supports ongoing training workshops for postdocs and early career investigators to enhance the ability to produce innovative and impactful transdisciplinary research in energetics and cancer and clinical care. The Trans-NCI Obesity and Cancer Working Group promotes the exchange of information and cross-cutting interests in obesity and cancer research within NCI by identifying and sharing state-of-the-science knowledge about obesity and cancer to document what is known and what is needed to move the science forward.