Screening, early treatment cut anal cancer risk

  • by Liz Highleyman, BAR Contributor
  • Wednesday June 22, 2022
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UCSF researcher Dr. Joel Palefsky. Photo: Courtesy UCSF
UCSF researcher Dr. Joel Palefsky. Photo: Courtesy UCSF

Screening people with HIV for precancerous anal cell changes and treating them early cuts the risk of anal cancer by more than half, according to results from the ANCHOR study published June 16 in the New England Journal of Medicine.

"It is great news that we now have the possibility to reduce the risk of developing anal cancer," lead investigator Dr. Joel Palefsky, who established the world's first clinic devoted to anal cancer prevention at UCSF in 1991, told the Bay Area Reporter.

"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," he added. "We are working on detailed guidelines for anal screening in people with HIV now, and we hope these will be out in the very near future."

Anal cancer, like cervical cancer, is caused by the human papillomavirus, one of the most common sexually transmitted infections. The virus triggers abnormal cell growth that can progress to precancerous dysplasia (known as high-grade squamous intraepithelial lesions, or HSIL) and invasive cancer. HPV vaccines, which are recommended for girls and boys at age 11 or 12, can prevent anal, cervical, and oral cancer.

While anal cancer is uncommon in the general population, rates have been rising for both men and women since the 1970s, Dr. Robert Yarchoan, director of the National Cancer Institute's Office of HIV and AIDS Malignancy, said during a June 15 media briefing. HIV-positive people, especially gay and bisexual men, are at greater risk for developing anal cancer even if they are on effective antiretroviral treatment. In fact, anal cancer is the fourth most common cancer among people living with HIV.

Widespread Pap smear screening and early treatment of precancerous lesions has dramatically reduced cervical cancer since the 1950s. But this is not yet the standard of care for people at risk for anal cancer because — until now — there was no direct evidence that it would work.

The ANCHOR study was designed to address this question. The trial, funded by the NCI's AIDS Malignancy Consortium, enrolled nearly 11,000 HIV-positive men and women ages 35 and older at 25 sites across the United States, including UCSF. Most of the men were gay or bisexual, and the median age was 51. More than 80% were on antiretroviral treatment with an undetectable viral load, and the median CD4 count was high, at approximately 600 cells.

At study entry, the participants were screened for HSIL using anal Pap smears and a technique called high-resolution anoscopy, which uses a magnifying scope to examine the anal canal. If HSIL was suspected, a biopsy sample was collected for further analysis.

More than half (53% of men, 46% of women, and 67% of transgender people) were found to have HSIL at study entry. The prevalence of HSIL was about what was expected for men, but was higher than expected for women, Palefsky said when he presented the study findings at this year's Conference on Retroviruses and Opportunistic Infections in February.

The 4,459 participants found to have HSIL were then evenly randomized to receive either immediate treatment or active monitoring (the current standard of care) at least every six months. The most common treatment was office-based electrocautery, a method that uses electricity to burn off abnormal lesions.

The trial was halted ahead of schedule in October 2021 after an interim analysis showed that screening and early treatment confers a clear benefit. Detecting and removing precancerous lesions significantly reduced the likelihood of progression to anal cancer.

Nine people in the immediate treatment arm and 21 people in the active monitoring arm were diagnosed with invasive anal cancer, meaning screening and treatment reduced the risk by 57%. Most people diagnosed with anal cancer in both the treatment and monitoring groups were at an early stage.

Treatment was generally safe and well tolerated, although there were "more treatment failures than we would have liked," Palefsky said during the media briefing. Seven people in the immediate treatment group and one in the active monitoring group experienced serious adverse events related to biopsy or treatment procedures.

These findings support the inclusion of routine anal screening and early treatment as part of the standard of care for people living with HIV, the researchers concluded. What's more, having results from a randomized trial should encourage insurers to cover these procedures.

"Until now, you had to be lucky or privileged enough to live someplace with progressive and knowledgeable HIV providers willing to perform these procedures and have insurance that would pay for it," said Jeff Taylor, a longtime HIV advocate who has had anal cancer himself.

However, the lack of clinicians who are trained to perform high-resolution anoscopy remains a barrier, and there is "room for improvement" in the treatment of anal HSIL, according to Palefsky.

"Anal cancer will increase as the HIV population ages," he said at the retrovirus conference. "This is a great time to train the workforce and get them ready for when that inevitable increase happens."

When availability of the procedure is limited, first priority should go to people who have symptoms of anal HSIL or cancer, such as anal bleeding, pain, or lumps, followed by older individuals and those with a low current or past CD4 count, according to Palefsky.

"This trial provides the groundwork to change practice for the treatment of HSIL and the screening of it in persons living with HIV and possibly other high-risk groups," Yarchoan said in a UCSF news release. "It will certainly have an impact on reducing the pain and suffering from anal cancer."

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