Abstract Body

The incidence of anal cancer is substantially higher among people living with HIV (PLWH) than the general population. Similar to cervical cancer, anal cancer is preceded by high-grade squamous intraepithelial lesions (HSIL). Treatment of cervical HSIL reduces cervical cancer incidence; however, there are no prospective studies of screening for and treatment of anal HSIL to prevent anal cancer.

Randomized controlled trial of anal HSIL treatment to reduce anal cancer incidence compared with active monitoring (AM). PLWH ?35-years-old were screened for anal HSIL using high-resolution anoscopy (HRA). Eligible PLWH with biopsy-proven anal HSIL were randomized 1:1 to AM without treatment or HSIL treatment using modality-specific algorithms with repeated treatment for recurrent or persistent HSIL until HSIL was completely resolved. All participants underwent HRA at least every six months with biopsies for suspected ongoing HSIL in the treatment arm, annually in the AM arm, or any time in either arm if there was concern for cancer. The primary endpoint was time-to-incident anal cancer. Sample size estimates required 31 cancer cases for the primary analysis.

10,723 PLWH were screened at 25 US sites. 2,237 PLWH were randomized to the treatment arm and 2,222 to the AM arm. 4,446 (99.7%) were included in the time-to-incident cancer analysis. There were no differences between arms in gender identity, race/ethnicity, CD4 count or HIV viral load at randomization (Table). Most participants were treated with office-based electrocautery (92.7%). 8.2% had topical 5-fuorouracil cream or imiquimod. 9 anal cancer cases were diagnosed in the treatment arm and 21 in the AM arm. With a median follow-up of 25.8 months, the observed cancer incidence in the treatment arm was 173/100,000 PY of follow-up, compared with 402/100,000 PY in the AM arm, a 57% reduction in anal cancer (95%CI 6%-80%, P=.029 by log-rank test). There were 7 study-related serious adverse events (3 pain, 3 abscess, 1 ulceration) in the treatment arm and 1 soft tissue infection in the AM arm.

Treatment of HSIL, primarily with office-based electrocautery led to a significant reduction in anal cancer incidence. Treatment was well-tolerated. Anal cancer incidence was higher than expected in the AM arm. These data support inclusion of screening and treating anal HSIL as standard of care for anal cancer prevention in PLWH ?35-years-old. Our data are also likely relevant for other groups at risk of anal cancer.