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Treating Anal Lesions in HIV+ Cuts Anal
Cancer Rate 57% in Randomized Trial
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2022 CROI, February 12-16 and 22-24, 2022
Mark Mascolini
Finding and treating precancerous high-grade squamous intraepithelial lesions (HSIL) lowered the anal cancer rate 57% in people with HIV when compared with steady monitoring of HSIL [1]. The 4446-person ANCHOR Study stopped early when it became clear that removing precursor HSIL significantly cut anal cancer risk compared with regular observation [2].
Human papillomavirus (HPV) causes both anal cancer and cervical cancer, and HSIL precedes both cancers. Studies show that treating cervical HSIL lowers cervical cancer incidence. Women are advised to have regular Pap tests to detect cervical lesions that may lead to cervical cancer. The American Cancer Society says “the Pap test has been more successful than any other screening test in preventing a cancer” [4].
But regular screening for anal HSIL has not become a routine part of anal cancer prevention in people at high risk, mainly because the medical community lacks evidence that looking for and removing these precursor lesions will prevent anal cancer. The ANCHOR Study aimed to fill this evidence gap in a randomized trial. Participants had to be at least 35 years old and have HIV infection; both men and women were eligible. They could not have had earlier treatment of HSIL, could not have signs of anal cancer, and could not have a history of anal, penile, vulvar, vaginal, or cervical cancer.
ANCHOR candidates got screened for HSIL with high-resolution anoscopy. If screening detected HSIL, that candidate got randomized to receive topical or ablative therapy or to receive active monitoring (clinical observation every 6 months and biopsy of observed lesions every 12 months). The primary outcome was time from randomization to diagnosis of anal cancer during up to 5 years of assessment. People randomized to HSIL treatment got treated immediately-at the randomization visit-and 93% received office-based electrocautery ablation of their lesion.
Researchers screened 10,723 people with HIV from September 2014 to August 2021. Just over half, 52.2% had biopsy-proved HSIL, including 53.3% of men, 45.8% of women, and 62.5% of transgender individuals. Seventeen people (0.16%) got diagnosed with anal cancer at the screening visit.
ANCHOR randomized 2227 people to treatment and 2219 to active monitoring. At randomization, both groups had a median age of 51 and a median of 17 years since HIV diagnosis. Median follow-up reached 25.3 months in the treatment arm and 27.2 months in the active monitoring arm. Men made up about 80% of the whole randomized group, women about 16%, and transgender people about 3.5%. Non-Hispanic whites accounted for about one third of each study arm, African Americans 42%, Hispanics about 16%, and Asian/Pacific Islanders about 1.2%. More than three quarters in each trial group (78%) identified themselves as homosexual. About one third in each study arm currently smoked, and over 80% in each arm had a viral load below 50 copies. HSIL size did not differ between the two trial arms (about 13% occupied more than 50% of the anal canal/perianal region).
Among 30 invasive anal cancers diagnosed during follow-up, 9 occurred in the treatment arm and 21 in the active monitoring arm. Through a median follow-up of 25.8 months, HSIL treatment conferred a 57% reduction in anal cancer incidence (95% confidence interval 6% to 80%, P = 0.029). Anal cancer incidence came to 173 cases per 100,000 person-years in the treatment arm versus 402 per 100,000 in the active monitoring arm. With these results in hand, the data and safety monitoring board recommended stopping the trial because of greater efficacy with HSIL treatment and advised treating everyone in the monitoring arm.
Serious adverse events numbered 586 in the treatment arm and 568 in the active monitoring arm. The treatment group had more study-related adverse events (43 versus 4) and more study-related serious adverse events (7 versus 1). These serious events in the treatment group included infection or abscess due to anal biopsy in 2, and in 1 each, skin ulceration due to 5-fluorouracil, anal abscess due to electrocautery, pain due to electrocautery, pain due to treatment under anesthesia, and pain due to infrared coagulation.
The ANCHOR investigators, led by Joel Palefsky of the University of California, San Francisco, recommended including these findings in an “overall assessment for inclusion of screening for and treating anal HSIL as standard of care.” They also see a need to define biomarkers of HSIL progression or regression and for broad scale-up of high-resolution anoscopy training programs to make wider use of this approach feasible.
References
1. Palefsky J, Lee J, Darragh T, et al. Treatment of anal high-grade squamous intraepithelial lesions to prevent anal cancer. 2022 CROI, February 12-16 and 22-24, 2022. Abstract 106.
2. theANCHORstudy.org. Treating anal cancer precursor lesions reduces cancer risk for people living with HIV. https://anchorstudy.org/
3. ClinicalTrials.gov. Topical or ablative treatment in preventing anal cancer in patients with HIV and anal high-grade squamous intraepithelial lesions (ANCHOR). ClinicalTrials.gov identifier NCT02135419. https://clinicaltrials.gov/ct2/show/NCT02135419
4. American Cancer Society. Cervical cancer. The Pap (Papanicolaou) test. https://www.cancer.org/cancer/cervical-cancer/detection-diagnosis-staging/screening-tests/pap-test.html
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