Learn about the medical, dental, pharmacy, behavioral, and voluntary benefits your employer may offer.
Note: A separate PDQ summary on Anal Cancer Treatment is also available.
Who Is at Risk?
Human papillomavirus (HPV) infection is the strongest risk factor for anal cancer and is accepted as a causal agent of squamous cell carcinoma of the anus and its precursor lesions.[
Factors Associated With Increased Risk of Anal Cancer
Anal HPV infection
Based on solid evidence, HPV infection causes squamous cell carcinoma of the anus.
Magnitude of Effect: About 90% of anal squamous cell cancers occur in individuals with detectable HPV infection.[
Study Design: Case series in men, women, heterosexuals, and homosexuals (HPV typing of tumor tissue). |
Internal Validity: Good. |
Consistency: Good. |
External Validity: Good. |
Behaviors or medical conditions associated with HPV infection
Based on solid evidence, behaviors or medical conditions that either indicate HPV infection or facilitate HPV transmission or persistence increase the risk or are associated with increased risk of anal cancer.
Magnitude of Effect: Risk varies by behavior and medical condition.
Study Design: Cohort, cancer registries, case-control studies. |
Internal Validity: Good. |
Consistency: Good. |
External Validity: Good. |
Cigarette smoking
Based on solid evidence, cigarette smoking increases the risk of anal cancer.
Magnitude of Effect: Risk is about twofold to threefold for ever-smokers; current smokers are at higher risk.[
Study Design: Cohort, case-control studies. |
Internal Validity: Good. |
Consistency: Good. |
External Validity: Good. |
Interventions Associated With a Decreased Risk of Anal Cancer
HPV vaccination
Based on solid evidence, HPV vaccination of men aged 16 to 26 years who have sex with men in the year before vaccination reduces anal intraepithelial neoplasia (AIN), a precursor lesion of anal cancer.
Magnitude of Effect: Vaccine efficacy against HPV-6, -11, -16, or -18–related AIN is between 50% and 75%.[
Study Design: Randomized controlled trial. |
Internal Validity: Good. |
Consistency: Not applicable (N/A)—only one study. |
External Validity: Good. |
Interventions With Inadequate Evidence as to Whether They Reduce the Risk of Anal Cancer
Condom use
In a study of HPV transmission, men who have sex with men (MSM), recently had anal sex, and never use condoms were more likely to be infected with oncogenic HPV strains than were those who always used condoms. However, the association was not statistically significant.
Magnitude of Effect: About twofold, but not statistically significant (odds ratio, 1.81; 95% confidence interval, 0.58–5.68).[
Study Design: Case-control study. |
Internal Validity: Fair. |
Consistency: N/A—only one study. |
External Validity: Fair. |
References:
United States
The Surveillance, Epidemiology, and End Results (SEER) Program age-adjusted annual incidence rate of anal cancer in the United States for the period from 2014 to 2018 was 2.0 cases per 100,000 persons per year, and the mortality rate was 0.3 cases per 100,000 persons per year. Incidence rates were slightly higher for women than for men (2.3 vs. 1.6 per 100,000 person-years, respectively), but mortality rates were about the same.[
World
An estimated 27,000 new cases of anal cancer were diagnosed worldwide in 2008.[
References:
About 85% of anal cancers in the United States have squamous cell histology or a histological variant.[
Precursor Lesions
Squamous cell cancer of the anus is preceded by grade 2 or 3 anal intraepithelial neoplasia (AIN), also referred to as high-grade AIN. Grade 1 AIN is not considered a precursor lesion of anal cancer but may precede high-grade AIN.[
One study reported that 11% of AIN cases progressed to invasive disease over an 8-year period.[
References:
Factors Associated With Increased Risk of Anal Cancer
Anal HPV infection
Human papillomavirus (HPV) infection is the strongest risk factor for anal cancer. About 90% of anal cancers occur in individuals with detectable HPV infection.[
HPVs are typically cleared rapidly in healthy individuals. Persistence of the oncogenic HPV strains is more likely in individuals with compromised immune systems; therefore, the risk of squamous cell anal cancer is much higher in these individuals. Behaviors that facilitate transmission of HPVs also increase risk.[
Given the paucity of cases of anal adenocarcinoma and other nonsquamous histological subtypes, it is unknown what role, if any, HPV plays in the development of these lesions.
Behaviors or medical conditions associated with HPV infection
History of cervical, vaginal, and vulvar cancer
Cancers of the cervix, vagina, and vulva are HPV-related cancers.[
Individuals with cancer of the oropharynx [
HIV infection/AIDS
The association between HIV infection and anal cancer is strong. One meta-analysis indicated a 30-fold increase in anal cancer in HIV-infected people, compared with the general population (SIR, 28.8; 95% CI, 21.6–38.3).[
Anal HPV infection is common in HIV-positive individuals. Studies suggest an HPV prevalence of 85% to 95% among HIV-positive MSM, 76% to 90% in HIV-positive women, and 60% in HIV-positive heterosexual men.[
In a cohort of almost 7,000 men with AIDS, 28 anal cancers occurred, and the odds ratios (OR) suggested relatively modest elevations (about twofold) in risk as the prevalence of high-risk behaviors increased. However, the only statistically significant OR relating to sexual practices was for seven or more unprotected anal receptive sexual partners during the time between study onset and the third study visit (OR, 4.0; 95% CI, 1.1–14.6).[
Anal cancer risk is positively associated with severity of immunosuppression in HIV-positive and AIDS patients.[
Investigators reported ORs for CD4+ counts 6 to 7 years before anal cancer diagnosis as follows:[
ORs for CD4+ counts in the 12 months before diagnosis were as follows:
Similar patterns were observed for CD8+ cell counts and for CD4+/CD8+ ratios.
Sexual practices associated with increased risk
Sexual practices that confer elevation in anal cancer risk include receptive anal intercourse, numerous sexual partners, and sex between men.[
Regardless of the underlying reason, MSM have the highest rates of anal cancer when compared with other men and women. As previously mentioned, HIV-positive MSM have the highest anal cancer rates (about 50 cases per 100,000 person-years),[
Chronic immunosuppressive states other than HIV infection
Chronic immunosuppression in general is thought to increase risk of anal cancer because of its impact on the ability to clear HPV infection.[
Cigarette smoking
Cigarette smoking was among the first risk factors for anal cancer to be identified. In 1987, a case-control study of 58 men and 90 women observed a ninefold increase in risk (relative risk [RR], 9.4; 95% CI, 2.3–38.5) for men and an eightfold increase in risk for women (RR, 7.7; 95% CI, 3.5–17.2) for current smokers after adjustment for number of sexual partners.[
References:
HPV Vaccination
Because human papillomavirus (HPV) is a causal condition for squamous cell anal cancer development, vaccination against the oncogenic strains of HPV before exposure may reduce the risk of anal cancer. Conducted from 2004 to 2008, a multicountry trial randomly assigned 4,065 boys and men to receive either the three-shot quadrivalent HPV vaccine regimen (for HPV-6, -11, -16, and -18) or a three-shot placebo injection regimen. Of the 4,065 patients, 602 reported having sex with male partners in the year before enrollment. Heterosexual participants were between the ages of 16 years and 23 years and had no more than five lifetime female partners. Patients who reported sex with male partners were between the ages of 16 years and 26 years and had no more than five lifetime male or female partners. Persistent infection was defined as detection of the same HPV type in anogenital swabs or biopsy specimens collected on two or more consecutive visits, with an interval of 6 months between visits. In the intent-to-treat analysis, which included participants regardless of their baseline HPV status, the efficacy against persistent HPV-6, -11, -16, and -18 infection was 48% (95% confidence interval [CI], 36.0%–57.6%). Among those who were negative for the four HPV strains of interest at baseline (per the protocol analysis, which included 1,397 intervention-arm and 1,408 control-arm participants), vaccine efficacy against persistent HPV-6, -11, -16, and -18 infection was 90% (95% CI, 69.2%–98.1%).[
Among the 602 patients who had sex with men, the vaccine efficacy against persistent HPV-6, -11, -16, and -18 infection was 59% (95% CI, 43.0%–71.4%) in the intent-to-treat analysis and 95% (95% CI, 80.4%–99.4%) in the per-protocol analysis. Efficacy against HPV-6, -11, -16 or -18–associated anal intraepithelial neoplasia (AIN) was 50% (95% CI, 25.7%–67.2%) in the intention-to-treat analysis and 77.5% (95% CI, 39.6%–93.9%) in the per-protocol analysis (275 intervention-arm and 276 control-arm participants). Efficacy against HPV-6, -11, -16, or -18–associated high-grade AIN was 54.2% (95% CI, 18.0%–75.3%) in the intent-to-treat analysis and 74.9% (95% CI, 8.8%–95.4%) in the per-protocol analysis (194 intervention-arm and 208 control-arm participants).[
Efficacy of the bivalent (HPV-16 and HPV-18) vaccine against anal infection was evaluated in the context of a randomized controlled trial of cervical cancer prevention. Conducted in 6,300 Costa Rican women aged 18 to 25 years at enrollment, the trial compared the efficacy of the three-dose bivalent vaccine with that of a control vaccine. Four years after vaccination, most women were offered the option of providing an anal specimen. Among the 2,103 intervention-arm and 2,107 control-arm participants who provided specimens, vaccine efficacy (i.e., absence of HPV-16 or -18 in the specimen) was 62% (95% CI, 47.1%–73.1%). Among the 1,003 intervention-arm and 986 control-arm participants who provided anal specimens, received the three doses, had no evidence of cervical HPV-16 or -18 infection before vaccination, and were seronegative before vaccination, vaccine efficacy was 84% (95% CI, 66.7%–92.8%).[
These data strongly suggest that vaccination against oncogenic HPV strains will lead to reductions in anal cancer. They also suggest that vaccination before exposure will provide the most benefit.
References:
Condom Use
Because human papillomavirus (HPV) can be transmitted through microabrasions, as well as through more pronounced exposures such as exchange of certain bodily fluids,[
In an Italian cohort of 258 HIV-negative men who have sex with men (MSM), the odds ratio (OR) for infection with high-risk HPV strains was 1.7 (95% confidence interval [CI], 0.52–6.3) for inconsistent or no use of condoms in receptive anal sex, compared with consistent condom use.[
References:
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, Mortality, and Survival
Updated statistics with estimated new cases and deaths for 2022 (cited American Cancer Society as reference 2).
Other editorial changes were made to this summary.
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® - NCI's Comprehensive Cancer Database pages.
Purpose of This Summary
This PDQ cancer information summary for health professionals provides comprehensive, peer-reviewed, evidence-based information about anal cancer prevention. It is intended as a resource to inform and assist clinicians in the care of their patients. It does not provide formal guidelines or recommendations for making health care decisions.
Reviewers and Updates
This summary is reviewed regularly and updated as necessary by the PDQ Screening and Prevention Editorial Board, which is editorially independent of the National Cancer Institute (NCI). The summary reflects an independent review of the literature and does not represent a policy statement of NCI or the National Institutes of Health (NIH).
Board members review recently published articles each month to determine whether an article should:
Changes to the summaries are made through a consensus process in which Board members evaluate the strength of the evidence in the published articles and determine how the article should be included in the summary.
Any comments or questions about the summary content should be submitted to Cancer.gov through the NCI website's Email Us. Do not contact the individual Board Members with questions or comments about the summaries. Board members will not respond to individual inquiries.
Levels of Evidence
Some of the reference citations in this summary are accompanied by a level-of-evidence designation. These designations are intended to help readers assess the strength of the evidence supporting the use of specific interventions or approaches. The PDQ Screening and Prevention Editorial Board uses a formal evidence ranking system in developing its level-of-evidence designations.
Permission to Use This Summary
PDQ is a registered trademark. Although the content of PDQ documents can be used freely as text, it cannot be identified as an NCI PDQ cancer information summary unless it is presented in its entirety and is regularly updated. However, an author would be permitted to write a sentence such as "NCI's PDQ cancer information summary about breast cancer prevention states the risks succinctly: [include excerpt from the summary]."
The preferred citation for this PDQ summary is:
PDQ® Screening and Prevention Editorial Board. PDQ Anal Cancer Prevention. Bethesda, MD: National Cancer Institute. Updated <MM/DD/YYYY>. Available at: https://www.cancer.gov/types/anal/hp/anal-prevention-pdq. Accessed <MM/DD/YYYY>. [PMID: 26389511]
Images in this summary are used with permission of the author(s), artist, and/or publisher for use within the PDQ summaries only. Permission to use images outside the context of PDQ information must be obtained from the owner(s) and cannot be granted by the National Cancer Institute. Information about using the illustrations in this summary, along with many other cancer-related images, is available in Visuals Online, a collection of over 2,000 scientific images.
Disclaimer
The information in these summaries should not be used as a basis for insurance reimbursement determinations. More information on insurance coverage is available on Cancer.gov on the Managing Cancer Care page.
Contact Us
More information about contacting us or receiving help with the Cancer.gov website can be found on our Contact Us for Help page. Questions can also be submitted to Cancer.gov through the website's Email Us.
Last Revised: 2022-03-04
This information does not replace the advice of a doctor. Healthwise, Incorporated, disclaims any warranty or liability for your use of this information. Your use of this information means that you agree to the
Healthwise, Healthwise for every health decision, and the Healthwise logo are trademarks of Healthwise, Incorporated.
Individual and family medical and dental insurance plans are insured by Cigna Health and Life Insurance Company (CHLIC), Cigna HealthCare of Arizona, Inc., Cigna HealthCare of Illinois, Inc., Cigna HealthCare of Georgia, Inc., Cigna HealthCare of North Carolina, Inc., Cigna HealthCare of South Carolina, Inc., and Cigna HealthCare of Texas, Inc. Group health insurance and health benefit plans are insured or administered by CHLIC, Connecticut General Life Insurance Company (CGLIC), or their affiliates (see
All insurance policies and group benefit plans contain exclusions and limitations. For availability, costs and complete details of coverage, contact a licensed agent or Cigna sales representative. This website is not intended for residents of New Mexico.