A key study from 2022, the ANCHOR Study, proved that treatment of high-grade precursors to anal cancer can prevent the development of anal cancer in people with HIV (PWH).
Rates of anal cancer are substantially higher in PWH (both women and men) than in people without HIV. In a process analogous to that with cervical cancer, anal cancer develops from progression of high-grade squamous intraepithelial lesions (HSIL), which is largely driven by infection with human papillomavirus (HPV). While much evidence shows that screening and treatment for cervical HSIL can prevent cervical cancer, no previous prospective studies had investigated the impact of anal HSIL treatment on anal cancer rates.
The ANCHOR Study is a large Phase 3 multisite trial in PWH age ≥35 who had biopsy-proven anal HSIL (persons with anal cancer or a history of anal cancer were excluded). Subjects were randomized to receive treatment for HSIL or active monitoring (without treatment).
4446 subjects were enrolled. The median age was 51, the two study groups were well matched for baseline variables, and overall, about 80% were male, 16% female, 4% transgender; 42% were black, 32% white, 16% Hispanic, 1% Asian or Pacific Islander. HIV was generally well controlled - 90% had HIV RNA <200 copies/mL (83% had HIV RNA <50 copies/mL), and the median CD4 was 605 cells/mm3. About 60% were current or former cigarette smokers.
All study participants underwent high-resolution anoscopy (HRA) of the anus at the time of randomization. In the treatment arm, subjects received immediate treatment intended to eradicate HSIL. Treatments were determined by the treating clinician among specified options (ablation procedures or excision or topical agents [fluorouracil or imiquimod]); the great majority of treatments (>80%) were office-based electrocautery procedures. After initial treatment, these subjects were reevaluated with HRA at least every 6 months (more frequently if indicated), suspected HSIL lesions were biopsied, and any recurrent HSIL was treated.
In the active monitoring group, HRA was done every 6 months, and suspected HSIL lesions were biopsied yearly. In both groups, more frequent monitoring was allowed if there was concern for impending progression to cancer, and a biopsy could be done at any time if cancer was suspected. Persons whose biopsies showed cancer were immediately referred for cancer treatment.
Results
After a median follow up time of 26 months, anal cancer was diagnosed in 9 persons in the treatment group and 21 persons in the active monitoring group, demonstrating a 57% reduction in rate of progression to cancer with treatment of HSIL versus active monitoring; these differences were statistically significant. Time to progression to anal cancer was significantly associated with lesion size but not with nadir CD4 count. Serious adverse events related to study interventions occurred in 7 and 1 subjects in the treatment and monitoring groups, respectively.
Clinical Bottom Line
This study demonstrates strongly that treatment of HSIL can prevent anal cancer in the high-risk population of PWH. It raises the urgency of screening for HPV-related anal disease and of scaling up services for further evaluation (eg, HRA) for those with abnormal screening test results, and treatment for those with HSIL; more clinicians trained in HRA and treatment of HSIL will be needed. It should be noted, though, no national guidelines define the method or frequency of screening for anal dysplasia or cancer. Some HIV care systems, such as the New York State Department of Health AIDS Institute have developed recommendations for anal cytology, HPV testing, and digital anorectal exam. In general, screening for anal dysplasia should be done only if HRA is available for further evaluation of abnormal screening tests.
The ANCHOR Study is also a reminder to practice primary prevention through HPV vaccination of eligible individuals (the HPV vaccine series is recommended for all up to age 26 and may be offered on an individual basis for those age 27-45).
The HPV material in the US national guidelines on opportunistic infections is currently being updated to include recommendations stemming from the ANCHOR Study results.
References
- Palefsky JM, Lee JY, Jay, N, et al. Treatment of Anal High-Grade Squamous Intraepithelial Lesions to Prevent Anal Cancer. N Engl J Med 2022;386:2273-82. DOI: 10.1056/NEJMoa2201048
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About Susa Coffey, MD
Susa Coffey is medical editor of the NCRC. She is a Professor of Medicine at UCSF in the Division of HIV, Infectious Diseases and Global Medicine. Also, she is a longtime clinician and educator in HIV at San Francisco General Hospital clinic (“Ward 86”). She is also the Medical Editor of HIV InSite. Dr. Coffey is Co-Lead of the RAPID clinical program at Ward 86, San Francisco General Hospital and the Chair of the RAPID Committee of San Francisco's Getting to Zero campaign.