About 90% of anal cancers are caused by human papillomavirus, or HPV. The remaining cases are linked to a combination of smoking, immune suppression, and genetic mutations unrelated to the virus. Anal cancer is uncommon, accounting for roughly 0.5% of all new cancer diagnoses in the U.S., with an estimated 11,270 new cases expected in 2026.
HPV Is the Primary Cause
HPV is a group of more than 200 related viruses, most of which are harmless. A handful of high-risk strains can trigger cancer, and two in particular drive the vast majority of anal cancer cases. Among the 90% of anal squamous cell cancers tied to HPV, strains HPV-16 and HPV-18 are detectable in over 90% of them. HPV-16 is by far the more common of the two.
HPV is extremely widespread. Most sexually active people will contract at least one strain at some point, and the immune system usually clears the infection within a year or two without any symptoms. The problem starts when a high-risk strain persists for years or decades. During that time, the virus produces two proteins that hijack normal cell behavior. One disables the body’s ability to repair damaged DNA or trigger the self-destruction of abnormal cells. The other forces cells to divide more rapidly than they should, creating genomic instability. Together, these two mechanisms gradually transform healthy anal tissue into precancerous lesions and, eventually, invasive cancer.
The long gap between initial HPV infection and cancer development explains why the median age at diagnosis is 65, even though most people acquire HPV much earlier in life.
Who Is at Higher Risk
Having HPV is necessary for most anal cancers but not sufficient on its own. Several factors increase the likelihood that a persistent infection progresses to cancer.
Receptive anal intercourse. This is the strongest behavioral risk factor because it directly exposes the cells of the anal canal to HPV. Both men and women who engage in receptive anal sex have elevated risk, though anal cancer can also develop in people who have never had anal intercourse.
HIV and immune suppression. A weakened immune system makes it harder to clear HPV naturally. People living with HIV face substantially higher rates of anal cancer, and the risk climbs as immune function declines. Research tracking people with HIV found that those whose immune cell counts dropped to very low levels had a 13-fold higher risk of anal cancer compared to those who maintained healthy counts. Even periods of moderate immune suppression years in the past contribute to long-term risk. Organ transplant recipients who take immune-suppressing medications also face elevated risk.
Multiple sexual partners. More partners means more opportunities for HPV exposure, including exposure to multiple high-risk strains simultaneously.
History of other HPV-related cancers. If you’ve had cervical, vulvar, or vaginal cancer or precancerous changes in those areas, your risk of anal cancer is higher because it signals persistent high-risk HPV infection.
How Smoking Increases Risk
Cigarette smoking roughly doubles the odds of developing anal cancer. The relationship is partly direct and partly about how smoking interacts with HPV. Tobacco suppresses the local immune response in tissue, increases the rate at which cells divide, triggers inflammation, and damages DNA. All of these changes make it more likely that an HPV infection will persist rather than clear.
Studies have found that current smokers are 36% more likely to have an active anal HPV infection and 74% more likely to acquire a new one compared to people who have never smoked. They are also 67% more likely to have a persistent infection lasting 12 months or longer. In practical terms, smoking makes HPV harder for your body to fight off and gives the virus more time to do damage.
Anal Cancer Without HPV
Roughly 10% of anal cancers develop without any detectable HPV involvement. These HPV-negative cancers appear to follow a different biological pathway, one more closely resembling how tobacco and alcohol drive certain head and neck cancers. Instead of viral proteins disabling the body’s tumor suppression systems, the damage comes from environmental carcinogens that directly mutate key protective genes. Studies have found that 80% of HPV-negative anal tumors carry disruptive mutations in TP53, a critical tumor suppressor gene, compared to only 6% of HPV-positive tumors.
HPV-negative anal cancer is more common in men and tends to respond less well to standard treatment. It remains rare overall, but its existence means that anal cancer can develop even without HPV exposure.
Age and Gender Patterns
Anal cancer is primarily a disease of middle and older age. Nearly 60% of diagnoses occur between ages 55 and 74, and cases before age 35 are extremely rare, making up just 1% of the total. Women are diagnosed at a higher rate than men (2.4 versus 1.6 per 100,000), which may partly reflect higher rates of persistent anal HPV infection in women. However, among certain subgroups, particularly men who have sex with men and especially those living with HIV, the incidence is dramatically higher than the general population averages suggest.
HPV Vaccination and Prevention
The HPV vaccine is the most effective tool for preventing anal cancer. It works by generating antibodies against the high-risk HPV strains before a person is ever exposed to them. In a clinical trial of young men who have sex with men, vaccination reduced precancerous anal lesions caused by vaccine-targeted HPV strains by about 75% among participants who hadn’t previously been infected. Even in the broader study group, which included some people already exposed to HPV, the reduction was 54%.
The current vaccine covers nine HPV strains, including the HPV-16 and HPV-18 responsible for the overwhelming majority of anal cancers, plus five additional high-risk strains. It is most effective when given before sexual debut, which is why vaccination is routinely recommended starting at ages 11 to 12. Adults up to age 26, and in some cases up to 45, can also benefit, though the protection is less complete if prior HPV exposure has already occurred.
For people already living with persistent HPV, vaccination won’t clear an existing infection, but there is evidence it can reduce recurrence of precancerous lesions after treatment. A study of older men who had been treated for high-grade anal precancer found that those who received the vaccine had roughly half the rate of recurrence compared to unvaccinated patients over a three-year follow-up period.
Screening for High-Risk Groups
Because anal cancer develops slowly from precancerous changes, screening can catch problems early. Current guidelines recommend annual screening for adults with HIV starting at age 35, particularly men who have sex with men and transgender women. For other people with HIV, screening is recommended starting at age 45. Screening typically involves an anal Pap test (similar in concept to a cervical Pap smear), testing for high-risk HPV strains, or both. If results are abnormal, a closer examination called high-resolution anoscopy allows clinicians to identify and treat precancerous tissue before it progresses.
For people who test negative for both high-risk HPV and abnormal cells on two consecutive screenings, the interval can be extended to every three years. Outside of the HIV-positive population, there are no widely adopted screening guidelines for the general public, largely because anal cancer remains uncommon enough that routine screening of everyone isn’t considered cost-effective.