Treatment of Anal High-Grade Squamous Intraepithelial Lesions to Prevent Anal Cancer

作者：Joel M. Palefsky, Jeannette Y. Lee, Naomi Jay, Stephen E. Goldstone, Teresa M. Darragh, Hillary A. Dunlevy, Isabella Rosa-Cunha, Abigail Arons, Julia C. Pugliese, Don Vena, Joseph A. Sparano, Timothy Wilkin, Gary Bucher, Elizabeth A. Stier, Maribel Tirado Gomez, Lisa Flowers, Luis F. Barroso, Ronald T. Mitsuyasu, Shelly Lensing, Jeffrey Logan, David M. Aboulafia, Jeffrey T. Schouten, Juan de la Ossa, Rebecca Levine, Jessica D. Korman, Michael Hagensee, Thomas M. Atkinson, Mark H. Einstein, Bernadette Cracchiolo, Dorothy J. Wiley, Grant Ellsworth, Cristina Brickman, J. Michael Berry-Lawhorn · 发表于：New England Journal of Medicine · 年份：2022 · DOI：10.1056/nejmoa2201048 · 被引用次数：484 · 研究领域：Cervical Cancer and HPV Research、Colorectal and Anal Carcinomas、Genital Health and Disease

BACKGROUND: The incidence of anal cancer is substantially higher among persons living with the human immunodeficiency virus (HIV) than in the general population. Similar to cervical cancer, anal cancer is preceded by high-grade squamous intraepithelial lesions (HSILs). Treatment for cervical HSIL reduces progression to cervical cancer; however, data from prospective studies of treatment for anal HSIL to prevent anal cancer are lacking. METHODS: We conducted a phase 3 trial at 25 U.S. sites. Persons living with HIV who were 35 years of age or older and who had biopsy-proven anal HSIL were randomly assigned, in a 1:1 ratio, to receive either HSIL treatment or active monitoring without treatment. Treatment included office-based ablative procedures, ablation or excision under anesthesia, or the administration of topical fluorouracil or imiquimod. The primary outcome was progression to anal cancer in a time-to-event analysis. Participants in the treatment group were treated until HSIL was completely resolved. All the participants underwent high-resolution anoscopy at least every 6 months; biopsy was also performed for suspected ongoing HSIL in the treatment group, annually in the active-monitoring group, or any time there was concern for cancer. RESULTS: Of 4459 participants who underwent randomization, 4446 (99.7%) were included in the analysis of the time to progression to cancer. With a median follow-up of 25.8 months, 9 cases were diagnosed in the treatment group (173 per 100,...