A protocol in which high-grade squamous intraepithelial lesions (HSIL) of the anal canal were immediately treated was more effective for preventing incidence of anal cancer in people with HIV, a randomized trial found.

In the study involving nearly 4,500 individuals with anal HSIL detected by screening, nine of those assigned to aggressive therapy — mostly office-based electrocautery — went on to develop anal cancer compared with 21 of those in an active monitoring group, representing a 57% decrease in relative risk over the median 25.8-month follow-up period (P=0.029), reported Joel Palefsky, MD, of the University of California San Francisco.

Anal cancer incidence was 173 vs 402 per 100,000 patient-years in the two respective arms, he said during a special session at the virtual Conference on Retroviruses and Opportunistic Infections.

The trial was truncated early for efficacy on the recommendation of the data monitoring and safety committee, said Palefsky.

“Treatment of anal HSIL is effective in reducing the incidence of anal cancer,” he said, adding that the findings support screening for and treating anal HSIL as standard of care for people living with HIV.

Palefsky said he and his colleagues were “not entirely happy with the high rate of cancer in the treatment arm, so there is room for improvement. There were some treatment failures as also happens when treating HSIL in cervical cancer.”

He told MedPage Today that none of the patients in the study died from anal cancer. “About one-third of the patients in each group had advanced cancer when it was diagnosed, so that was disappointing that it occurred within the treatment group.”

Palefsky said the ANCHOR trial was initiated because doctors recognized that HSIL should be treated similarly to cervical cancer, but no large randomized controlled trial had been done to prove the point.

“Both cervical cancer and anal cancer are preceded by HSIL,” Palefsky said. “The treatment of cervical HSIL is proven to reduce the incidence of cervical cancer, so why do we not routinely screen for and treat anal HSIL? Because there is a lack of evidence that it will work.”

He noted that among people living with HIV, anal cancer is the fourth most common malignancy.

“This was an amazingly well-thought-out study,” said Elizabeth Chiao, MD, of the University of Texas MD Anderson Cancer Center in Houston, during a panel discussion following the presentation. “I think this answers definitively about whether we should be treating the HSIL that we find.”

Chiao noted that only people over the age of 35 were included in the study. “That helps us as clinicians to target who we should be looking at,” she said.

But Palefsky acknowledged that screening the entire population of people living with HIV for anal HSIL could prove challenging if close to half of these individuals had such lesions, as the numbers required to treat would be overwhelming. In the study, 52.2% of the total screened group had biopsy-proven HSIL — 53.3% of men, 35.8% of women, and 62.5% of the transgender individuals.

“We clearly need biomarkers that can tell us which HSIL are likely to progress and which will not,” he said.

Also, patients underwent high-resolution anoscopy with biopsy, and Palefsky noted that the number of pathologists with such expertise is limited, which may make implementing the ANCHOR study findings slow to roll out.

“High-resolution anoscopy is a challenging technique, and it takes a while to get good at it,” he said.

Study Details

From September 2014 through August 2021, the researchers screened 10,723 people living with HIV at 15 sites in the U.S. If a screening biopsy came back positive for HSIL, the patients returned for randomization. The patients were also randomized by study site, CD4-positive cell counts, and lesion size.

During the screening process, 17 individuals were found to have anal cancer and were excluded from randomization.

Overall, participants were about 51 years old on average and had been living with an HIV diagnosis for a mean 17 years. About 80% of the participants were men, 16% were women, and 3.8% identified as transgender.

Immediate treatment (n=2,237) most often consisted of office-based electrocautery ablation of the HSIL (93% of cases). These patients were then biopsied if there was a suspicion that the HSIL was still present. Anal cytology was performed every 6 months after HSIL cleared. The time frame was shortened if there was suspicion of cancer, and biopsies could be performed at any visit if there was a suspicion of cancer.

In the active monitoring group (n=2,222), patients had anal cytology every 6 months and underwent annual biopsies to confirm persistent HSIL — but returned every 3 months if the clinician was concerned about development of cancer. Again, biopsies were done at any visit at which there was a cancer concern.

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