A Randomized Clinical Trial of Infrared Coagulation Ablation Versus Active Monitoring of Intra-anal High-grade Dysplasia in Adults With Human Immunodeficiency Virus Infection: An AIDS Malignancy Consortium Trial

Abstract

Background: Anal high-grade squamous intraepithelial lesions (HSILs) ablation may reduce the incidence of invasive cancer, but few data exist on treatment efficacy and natural regression without treatment.

Methods: An open-label, randomized, multisite clinical trial of human immunodeficiency virus (HIV)-infected adults aged ≥27 years with 1-3 biopsy-proven anal HSILs (index HSILs) without prior history of HSIL treatment with infrared coagulation (IRC). Participants were randomized 1:1 to HSIL ablation with IRC (treatment) or no treatment (active monitoring [AM]). Participants were followed every 3 months with high-resolution anoscopy. Treatment participants underwent anal biopsies of suspected new or recurrent HSILs. The AM participants underwent biopsies only at month 12. The primary end point was complete clearance of index HSIL at month 12.

Results: We randomized 120 participants. Complete index HSIL clearance occurred more frequently in the treatment group than in the AM (62% vs 30%; risk difference, 32%; 95% confidence interval [CI], 13%-48%; P < .001). Complete or partial clearance (clearance of ≥1 index HSIL) occurred more commonly in the treatment group (82% vs 47%; risk difference, 35%; 95% CI, 16%-50%; P < .001). Having a single index lesion, compared with having 2-3 lesions, was significantly associated with complete clearance (relative risk, 1.96; 95% CI, 1.22-3.10). The most common adverse events related to treatment were mild or moderate anal pain and bleeding. No serious adverse events were deemed related to treatment or study participation.

Conclusion: IRC ablation of anal HSILs results in more clearance of HSILs than observation alone.

Trial registration: ClinicalTrials.gov NCT01164722.

Keywords: HSIL; ablation; anal cancer; high-grade dysplasia; human papillomavirus.

© The Author(s) 2018. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved. For permissions, e-mail: journals.permissions@oup.com.

Figures

Figure 1.

Participant disposition flow diagram. The modified intention-to-treat (ITT) analysis included all participants who attended the baseline visit. Both participants categorized as not evaluable had 2 index lesions at enrollment, and at 12 months, 1 biopsy site was benign and 1 was not evaluable; for both participants, the result was considered a failure for the primary outcome. Abbreviations: HSILs, high-grade squamous intraepithelial lesions; IRC, infrared coagulation.

Figure 2.

Kaplan-Meir Probability of high-grade squamous intraepithelial lesion (HSIL) diagnosis after initial infrared coagulation (IRC) treatment for IRC arm and active monitoring (AM) arm after crossover to IRC treatment. Those in the AM arm were not treated for the first 12 months. Those with HSILs at month 12 could then be treated and followed up for recurrence for an additional 12 months.