Background:  Anal cancer is an increasing problem among HIV⁺ men-who-have-sex-with-men (MSM). Screening for its precursor lesion, anal intraepithelial neoplasia (AIN), is subject of discussion. Current treatment options are suboptimal and have not been compared in a prospective trial. In this randomized clinical trial we compared efficacy and side effects of imiquimod, topical 5-fluoruracil (5-FU), and electrocautery for the treatment of AIN.

Methods:  We randomized 148 HIV⁺ MSM with histologically confirmed AIN among 16 weeks of imiquimod (3 times a week), 5-FU (twice a week), and monthly electrocautery for 4 months. Participants were evaluated by high-resolution anoscopy with biopsies 4 weeks and 6 months after treatment. Response rates were compared by c² analysis.

Results:  Of all patients, 57% had high-grade (HG) AIN. In an intent-to-treat analysis, imiquimod showed a response rate of 39% (95%CI 27 to 52), 5-FU of 29% (95%CI 18 to 43), and electrocautery of 48% (95%CI 34 to 62). Complete response was seen in 26% (95%CI 16 to 39), 17% (95%CI 8 to 30), and 41% (95%CI 28 to 56), respectively (p = 0.03), of which 25%, 57%, and 17% recurred 6 months after treatment. In a multivariate logistic regression, HGAIN, peri-anal AIN and high plasma CD4 cell count were significantly associated with response to treatment, with odds ratios of 3.5 (p = 0.003), 31.9 (p = 0.003), and 1.003 (per cell/µL; p = 0.002), respectively. Severe side effects were seen in 43% (imiquimod), 27% (5-FU), and 18% (ECA) (p = 0.02).

Conclusions: This study showed that regarding both efficacy and side effects electrocautery is superior to imiquimod and 5-FU in treatment of AIN, but recurrence rates are substantial.