How to reduce anal cancers in people with HIV

Anal cancers disproportionately affect people living with HIV, particularly men who have sex with men (MSM). However, it may be possible to curb the disease impact, particularly through widespread HPV vaccination.

“People living with HIV experience approximately 19 times the rate of anal cancer than the general population,” said Grant Ellsworth, MD, an assistant professor of medicine at Weill Cornell Medicine, in New York City, during a recent webinar hosted by the International Antiviral Society–USA. “While the rate is highest among MSM, we can’t discount women with HIV who experience about 10 times the rate of anal cancer compared with the general population.”

Among HIV-positive people, the rates of anal cancer rose through the mid-1990s, plateaued through the early 2000s and have tapered off in recent years. The increase seen in the 1990s was thought to be due to people with HIV living longer, “who were now surviving long enough to develop anal cancers,” Dr. Ellsworth said.

Although overall rates of anal cancer have fallen in recent years, the risk remains dire for people with HIV. Among MSM with HIV, rates of anal cancer are approximately as high as prostate or breast cancer, and much higher than other common cancers.

It is thought that the rates among HIV-positive MSM are driven by high levels of HPV exposure, combined with decreased cell-mediated immunity.

Preventing HPV-related cancers likely involves a balanced approach, including HPV immunization, so that initial HPV infection is not established, treating anal high-grade squamous intraepithelial lesion (HSIL) and finding ways to enhance cellular immunity among this patient population.

Emerging data show that early initiation of antiretroviral therapy (ART) among people with HIV may reduce cancer rates. Data from the SMART (Strategies for Management of Antiretroviral Therapy) trial found that immediate ART reduced infection-related cancers by as much as 76%, compared with individuals who delayed ART (AIDS 2007;21[14]:1957-1963).

“It’s thought that increases in ART coverage among PWH [people with HIV] have contributed to de-creases in anal cancer rates in recent years,” Dr. Ellsworth noted. “Clearly, effective ART is one strategy to prevent anal cancer in PWH.”

Screening also is an effective tool, and should be when a patient develops symptoms; some may need to be screened annually.

Determining who would benefit from screening and when remain unknown due a lack of well-established guidelines, according to Dr. Ellsworth. However, he noted, there are certain times when clinicians should certainly conduct testing.

“Given the higher rates of anal cancer among MSM with HIV, definitely screen that population,” Dr. Ellsworth said. In addition, he noted that women with HIV should be screened, as well as individuals with lower CD4 counts and a history of AIDS.

“They appear to be the group that most often advances to develop anal cancer,” Dr. Ellsworth said.

Symptomatic individuals with bleeding, pain with bowel movements or during receptive anal sex, anal warts or other lesions, and itching or irritation should be screened, as well as HIV-negative MSM.

“Less is known about anal cancer incidences in this population,” Dr. Ellsworth said. “However, they do have higher rates of HSIL and probably higher rates of anal cancer than the general population. And they may respond better to treatment of anal HSIL.”

Finally, immunosuppressed individuals should be regularly screened, as should HIV-negative women at least 45 years of age who have cervical HPV-16 infection.

“It’s been shown that 25% of this group can have prevalent HSIL,” Dr. Ellsworth said. “We believe about 70% of anal cancer is due to HPV-16, so the population that screens as HPV-16–positive should be more closely followed.”

Any abnormal findings should prompt referral for high-resolution or traditional anoscopy.

And one of the best tools available for the long-term prevention of anal cancers is the HPV vaccine.

Among people with HIV, it has been shown that the HPV vaccine is safe and immunogenic; however, they may develop fewer vaccine-specific antibodies than people without HIV infection.

A nested case–control study with real-world data among adults found that the HPV vaccine was more protective when administered at a younger age than when given to adults at least 21 years of age (Lancet Child Adolesc Health 2018;2[10]:707-714), the message being that early vaccination is effective, and vaccine efficacy decreases as age increases.

“This,” Dr. Ellsworth noted, “is probably due to HPV exposure via the onset of sexual activity.”

Current Advisory Committee on Immunization Practices recommendations for HPV vaccines focus vaccine efforts on adolescents, with catch-up vaccinations recommended up to age 26. Dr. Ellsworth agrees that wider adoption of the HPV vaccine and coverage of younger people are necessary. “The time to act is in adolescence,” he said.

“HPV vaccination at a young age is likely effective in preventing HPV-related disease, including anal cancer,” Dr. Ellsworth added.

By Ethan Covey