Anal cancer (AC) is still rare in the general population. It accounts for about 2% of all gastrointestinal tract malignancies. It is nearly always caused by the persistent infection of anal cells with cancer-causing types of human papillomavirus (HPV), particularly HPV16, and is preceded by a high-grade squamous intraepithelial lesion (HSIL), a precancerous growth that is also known as anal intraepithelial neoplasia (AIN) 2 or 3. Squamous cell cancer constitutes more than 90% of all anal cancers (ASCC) Certain groups are known to have higher than average anal cancer risk, namely persons living with HIV, men who have sex with men, women with a history of vulvar or cervical HSIL or cancer. Other high-risk groups include persons with immunosuppression for solid-organ transplantation, history of genital warts, anal fissures or fistulas, and smoking.
The AMA estimates for anal cancer in the US for 2024 are about 10,540 new cases (3,360 in men and 7,180 in women) and about 2,190 deaths (1,000 in men and 1,190 in women). It is rare in individuals younger than 35 and is found mainly in older adults, with an average age being in the early 60s. It is also more common in White women and Black men.
In 2022, a large NCI-sponsored randomized clinical trial demonstrated that detecting and treating precancerous growths in the anus substantially reduced a person’s risk of developing anal cancer. The trial, called Anal Cancer–HSIL Outcomes Research trial (ANCHOR), included people with HIV aged 35 or older. The ANCHOR results provided a strong rationale for screening people with HIV for the presence of precancerous anal lesions. In March 2024, an international group of experts representing the International Anal Neoplasia Society released consensus guidelines on anal cancer screening. The guidelines focus on screening individuals who have an increased risk of the disease. Last month, a panel of experts in HIV care released new recommendations to prevent anal cancer for people with HIV, the first U.S. federal guidelines on the topic. The recommendations, which include a screening program to detect and treat precancer and prevent anal cancer for people with HIV, were also based in part on results from the ANCHOR trial.
These guidelines recommend that anal cancer screening start at age 35 for some people who are living with HIV, particularly men who have sex with men and transgender women. For other people with HIV and for men who have sex with men and transgender women who are not living with HIV, they recommend starting screening at age 45. Screening often starts with an anal Pap test followed by a digital anal rectal examination (DARE). As with a cervical Pap test, a swab is used to collect cells from the anus. The cells are examined by a pathologist for abnormalities that can indicate precancer or cancer. Abnormal findings with either test will require a high-resolution anoscopy. If abnormalities or precancers in the anal canal and perianus are found, a biopsy may be taken during the procedure to further pathological analysis. Another screening strategy may include testing anal cells for infection with cancer-causing types of HPV. Most HPV infections are transient, meaning that the body may clear the virus over time. As such, HPV testing will often be performed in combination with an anal Pap test either at the same time (“co-testing”) or sequentially.
Although HPV vaccines were initially developed to prevent cervical cancer, the vaccines also help protect against other HPV-related cancers, including anal cancer. HPV vaccination effectively prevents the initial acquisition of anal HPV and the development of anal HSIL in young persons living with HIV. Gardasil, for instance, has FDA approval for anal cancer prevention. If anal HSIL is documented, treatment may involve the use of office-based electrocautery ablation (primarily hyfrecation) or excision under anesthesia, or the administration of topical fluorouracil or imiquimod.
