For the first time, updated national guidelines for the management of opportunistic infections now include recommendations on anal cancer prevention for people living with HIV. According to the new guidelines, older HIV-positive adults should be regularly assessed for signs of anal cancer, and those with symptoms or abnormalities should receive more intensive screening.

Anal cancer, like cervical cancer, is caused by the human papillomavirus (HPV), one of the most common sexually transmitted infections. The virus triggers abnormal cell growth (dysplasia), which can progress to precancerous intraepithelial neoplasia and, ultimately, invasive cancer. The more advanced stage of neoplasia is known as high-grade squamous intraepithelial lesions, or HSIL.

 
Anal cancer is uncommon among the general population, but people with HIV are at greater risk, even if they are on effective antiretroviral treatment. HIV-positive people tend to have more cancer-causing HPV types, are less likely to clear the virus and experience more rapid progression from neoplasia to cancer.

Cervical cancer is considered an AIDS-defining illness, and guidelines have long recommended that women with HIV should receive cytology screening—better known as a Pap test—to detect precancerous abnormal cell growth an early stage. But until now, guidelines did not include recommendations for anal cancer screening.

The ANCHOR study provided the evidence needed to support the new recommendations. More than 10,700 HIV-positive men and women ages 35 and older received anal cytology screening and high-resolution anoscopy (HRA), which uses a magnifying scope to examine the anal canal. More than half were found to have HSIL, and they were randomly assigned to receive either immediate treatment or regular monitoring.

As reported at the 2022 Conference on Retroviruses and Opportunistic Infections and in The New England Journal of Medicine, the trial showed that screening for precancerous lesions and treating them promptly lowered the risk of progression to anal cancer by more than half. What’s more, most cases of anal cancer were diagnosed at an early stage.

“We believe that screening for anal cancer precursors and treating them should become the standard of care for people with HIV over the age of 35 years,” lead investigator Joel Palefsky, MD, of the University of California at San Francisco, told POZ at the time.

Results from a randomized clinical trial should lead to more insurers covering anal cancer screening, but the shortage of clinicians trained to perform high-resolution anoscopy remains a barrier. HRA, which involves magnification and staining cells, is more precise and better able to identify flat lesions than standard anoscopy.


Screening Algorithm

The Department of Health and Human Services’ Panel on the Prevention and Treatment of Opportunistic Infections in Adults and Adolescents with HIV reviewed the latest research to develop recommendations for cervical cancer, anal cancer, oral cancer and other manifestations of HPV disease.

For anal cancer, the panel recommends that HIV-positive men who have sex with men and transgender women should undergo routine anal screening starting at age 35, and all other HIV-positive people should start at age 45. This should include assessment of symptoms (such as pain or palpable lumps) and a digital anal-rectal exam, in which a doctor inserts a finger to feel for abnormal growths. If HRA is available, a specimen is collected for cytology and HPV testing. 

  • If HRA is unavailable, people with no symptoms or digital exam abnormalities should be assessed again in one year. Those with any symptoms or abnormalities should receive standard anoscopy, followed by a biopsy if lesions are found.
  • If HRA is available but HPV testing is not done, people with normal cytology should be tested again in one year; if cytology is normal for three consecutive years, the testing interval can be extended to every three years. Those with an abnormal cytology test should receive HRA.
  • If HPV testing is done, people with normal cytology should repeat testing in six months to three years, depending on their HPV test results. Those who test positive for high-risk HPV types 16 or 18 should receive HRA.
  • If cytology testing shows atypical squamous cell of undetermined significance (mild abnormality), people who test negative for high-risk HPV types should receive another cytology test in one year. People who test positive for high-risk HPV should receive HRA.
  • If cytology testing shows low-grade squamous intraepithelial lesions or further progression, people should receive HRA regardless of HPV test results.

Source: Guidelines for the Prevention and Treatment of Opportunistic Infections in Adults and Adolescents With HIVDepartment of Health and Human Services

Source: Guidelines for the Prevention and Treatment of Opportunistic Infections in Adults and Adolescents With HIVDepartment of Health and Human Services

The guidelines do not recommend routine anal screening for asymptomatic gay or bisexual men and transgender women younger than 35 or for other HIV-positive people under 45. However, those who have potential symptoms of anal cancer should receive a digital exam and standard anoscopy. Because ANCHOR did not include younger adults, there is not enough evidence for the benefits of regular screening in these age groups, and more research is needed.


Older people, those with a history of AIDS, those with a longer duration of HIV infection and immune suppression, those who test positive for HPV types 16 or 18—which most often cause cancer—and smokers are at increased risk for anal cancer and should be screened and referred for HRA as soon as feasible, according to the guidelines.

While screening and prompt treatment can prevent progression to invasive cancer, HPV vaccination can prevent infection in the first place. The Gardasil 9 vaccine protects against nine high-risk HPV types, including 16 and 18. The Centers for Disease Control and Prevention recommends the vaccine for girls and boys at ages 11 or 12, with catch-up vaccination through age 26, but the Food and Drug Administration has approved it for people up to age 45. Although vaccination is most effective before people become sexually active, older people can discuss with their doctor whether they might still benefit.

Click here for the full DHHS guidelines for HPV disease.
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