New HIV Guidelines Recommend Screening to Mitigate Anal Cancer Risk

Managing high-grade squamous intraepithelial lesions may reduce the risk of anal cancer based on data from the phase 3 ANCHOR trial.

The U.S Department of Health and Human Services’ (HHS) Panel on the Prevention and Treatment of Opportunistic Infections in Adults and Adolescents with Human Immunodeficiency Virus (HIV) has issued the first federal guidelines containing recommendations for preventing anal cancer in people with HIV, according to a news release from the National Institutes of Health Office of Acquired Immunodeficiency Syndrome (AIDS).¹

Guideline provisions for patients with HIV include yearly assessment for anal abnormalities and a digital anorectal exam, standard anoscopy for those younger than 35 symptomatic or showing signs of anal cancer, and lab-based screening for older patients with HIV.

Supporting evidence for these guidelines came from the phase 3 ANCHOR trial (NCT02135419). Investigators found a reduced risk for anal cancer in patients with HIV 35 years or older with biopsy-proven anal high-grade squamous intraepithelial lesions (HSIL) undergoing HSIL treatment vs active monitoring, according to findings from the trial published in the New England Journal of Medicine.²

Trial data showed that at a median follow-up of 25.8 months, 9 of 2237 patients in the treatment group (173 per 100,000 person-years; 95% CI, 90-332) and 21 of 2222 in the active monitoring group (402 per 100,000 person-years; 95% CI, 262-616) had anal cancer diagnoses. Furthermore, the treatment group had a lower rate of progression to anal cancer than the active monitoring group by 57% (95% CI, 6%-80%; P = .03).

“The study had already affected clinical practice and now has been turned into policy,” Isabella Rosa-Cunha, MD, associate professor in the Division of Infectious Diseases at the University of Miami Miller School of Medicine and the initiator of the anal cancer prevention program at Sylvester and Jackson Memorial, said in a news release on the publication of these guidelines.³ “This really validates what we have been doing and changes the landscape for anal cancer prevention.”

Performed at 25 United States–based sites, investigators of the phase 3 study screened 10723 patients with HIV 35 years or older from September 24, 2014 to August 5, 2021. Patients were invited for HSIL screening, which included an anal swab for liquid-based anal cytologic analysis, as well as performance of complete physical examination and high-resolution anoscopy. HSIL- or cancer-suspicious lesions were biopsied.

Patients returned within 12 weeks of screening where blood samples were collected for plasma HIV-1 RNA and CD4 level measurement. Patients were then randomly assigned 1:1 to receive treatment or active monitoring, with stratification on the basis of trial site location, nadir CD4 count, and lesion size.

Patients assigned to treatment underwent ablative procedures, ablation or excision under anesthesia, and topical treatments with the aim of HSIL eradication. High-resolution anoscopy occurred every 6 months after randomization following full HSIL treatment.

Lesions were biopsied yearly; patients in either group who had cancer-suspicious lesions were eligible to undergo biopsy at any time. Patients in either group could be seen every 3 months with lesions arousing concern for imminent progression to cancer. Diagnoses of biopsy-confirmed cancer resulted in immediate removal from trial and referral to appropriate therapy.

The primary end point of the trial was time-to-event analysis for progression to anal cancer. The secondary end point was safety of HSIL treatment.

Biopsy review of patients revealed 4113 (96.6%) confirmed HSIL cases; those without confirmed cases remained on trial and were recorded in the intent-to-treat analysis. Of patients who remained on trial (n = 4151), office-based electrocautery was performed in 1862 of 2227 (83.6%), infrared coagulation in 107 (4.8%), topical fluorouracil in 100 (4.5%), as well as ablation or excision under anesthesia in 52 (2.3%) and topical imiquimod in 12 (0.5%). By data cutoff, 1921(86.3%), 233 (10.5%), 33 (1.5%), and 1 patient were treated with 1, 2, 3, and 4 or more therapies, respectively.

Overall, 32 cases of anal cancer were observed, with 30 cases analyzed after 2 were deemed ineligible. Median follow-up between groups was 25.3 months (IQR, 11.7-42.0) for the treatment group and 27.2 months (IQR, 12.0-42.1) for the active monitoring group.

Adverse events (AEs) were observed in 683 and 635 patients of the treatment and active-monitoring groups. Trial-related serious AEs occurred in 7 and 1, respectively. Serious AEs in the treatment group included single instances of skin ulceration due to fluorouracil, anal abscess due to electrocautery, pain due to electrocautery, pain due to treatment under anesthesia, and pain due to infrared coagulation.

References

1. HIV clinical guidelines now recommend high resolution anoscopy as part of anal cancer screening program for people with HIV. News release. National Institutes of Health Office of AIDS Research. July 9, 2024. Accessed August 8, 2024. https://tinyurl.com/3ndbz836
2. 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(24):2273-2282 doi:10.1056/NEJMoa2201048
3. Schubert C. New guidelines for anal cancer screening based partly on Sylvester data. News release. Miller School of Medicine. July 18, 2024. Accessed August 8, 2024. https://tinyurl.com/4rbpa88f