TY - JOUR
T1 - Treatment of Anal High-Grade Squamous Intraepithelial Lesions to Prevent Anal Cancer
AU - Palefsky, Joel M.
AU - Lee, Jeannette Y.
AU - Jay, Naomi
AU - Goldstone, Stephen E.
AU - Darragh, Teresa M.
AU - Dunlevy, Hillary A.
AU - Rosa-Cunha, Isabella
AU - Arons, Abigail
AU - Pugliese, Julia C.
AU - Vena, Don
AU - Sparano, Joseph A.
AU - Wilkin, Timothy J.
AU - Bucher, Gary
AU - Stier, Elizabeth A.
AU - Gomez, Maribel Tirado
AU - Flowers, Lisa
AU - Barroso, Luis F.
AU - Mitsuyasu, Ronald T.
AU - Lensing, Shelly Y.
AU - Logan, Jeffrey
AU - Aboulafia, David M.
AU - Schouten, Jeffrey T.
AU - de la Ossa, Juan
AU - Levine, Rebecca
AU - Korman, Jessica D.
AU - Hagensee, Michael
AU - Atkinson, Thomas M.
AU - Einstein, Mark H.
AU - Cracchiolo, Bernadette M.
AU - Wiley, Dorothy
AU - Ellsworth, Grant B.
AU - Brickman, Cristina
AU - Berry-Lawhorn, J. Michael
N1 - Publisher Copyright:
Copyright © 2022 Massachusetts Medical Society.
PY - 2022/6/16
Y1 - 2022/6/16
N2 - 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 100,000 person-years; 95% confidence interval [CI], 90 to 332) and 21 cases in the active-monitoring group (402 per 100,000 person-years; 95% CI, 262 to 616). The rate of progression to anal cancer was lower in the treatment group than in the active-monitoring group by 57% (95% CI, 6 to 80; P=0.03 by log-rank test). CONCLUSIONS Among participants with biopsy-proven anal HSIL, the risk of anal cancer was significantly lower with treatment for anal HSIL than with active monitoring.
AB - 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 100,000 person-years; 95% confidence interval [CI], 90 to 332) and 21 cases in the active-monitoring group (402 per 100,000 person-years; 95% CI, 262 to 616). The rate of progression to anal cancer was lower in the treatment group than in the active-monitoring group by 57% (95% CI, 6 to 80; P=0.03 by log-rank test). CONCLUSIONS Among participants with biopsy-proven anal HSIL, the risk of anal cancer was significantly lower with treatment for anal HSIL than with active monitoring.
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U2 - 10.1056/NEJMoa2201048
DO - 10.1056/NEJMoa2201048
M3 - Article
C2 - 35704479
AN - SCOPUS:85132200636
SN - 0028-4793
VL - 386
SP - 2273
EP - 2282
JO - New England Journal of Medicine
JF - New England Journal of Medicine
IS - 24
ER -
