The Kirby Institute, University of New South Wales, New South Wales, Australia.
Douglass Hanly Moir Pathology, New South Wales, Australia.
Clin Infect Dis. 2021 Mar 1;72(5):853-861. doi: 10.1093/cid/ciaa166.
Gay and bisexual men (GBM) are disproportionately affected by anal cancer. Prevention is hindered by incomplete understanding of the natural history of its precursor, anal high-grade squamous intraepithelial lesions (HSIL).
The Study of the Prevention of Anal Cancer, conducted between 2010 and 2018, enrolled human immunodeficiency virus (HIV)-positive and HIV-negative GBM aged ≥35 years. Anal cytology and high-resolution anoscopy (HRA) were performed at baseline and 3 annual visits. A composite HSIL diagnosis (cytology ± histology) was used. Cytological high-grade squamous intraepithelial lesions (cHSIL) incidence and clearance rates were calculated with 95% confidence intervals (CIs). Predictors were calculated using Cox regression with hazard ratios (HRs) and 95% CIs.
Among 617 men, 220 (35.7%) were HIV-positive, median age 49 years. And 124 incident cHSIL cases occurred over 1097.3 person-years (PY) follow-up (11.3, 95% CI 9.5-13.5 per 100 PY). Significant bivariate predictors of higher incidence included age <45 years (HR 1.64, 95% CI 1.11-2.41), HIV positivity (HR 1.43, 95% CI .99-2.06), prior SIL diagnosis (P-trend < .001) and human papillomavirus (HPV)16 (HR 3.39, 2.38-4.84). Over 695.3 PY follow-up, 153 HSIL cleared (clearance 22.0, 95% CI 18.8-25.8 per 100 PY). Predictors were age < 45 years (HR 1.52, 1.08-2.16), anal intraepithelial neoplasia (AIN)2 rather than AIN3 (HR 1.79, 1.29-2.49), smaller lesions (HR 1.62, 1.11-2.36) and no persistent HPV16 (HR 1.72, 1.23-2.41). There was 1 progression to cancer (incidence 0.224, 95% CI .006-1.25 per 100 PY).
These data strongly suggest that not all anal HSIL detected in screening requires treatment. Men with persistent HPV16 were less likely to clear HSIL and are more likely to benefit from effective HSIL treatments.
Australia New Zealand Clinical Trials Registry (ANZCTR365383).
男同性恋和双性恋者（GBM）受肛门癌影响的比例不成比例。由于对其前体——肛门高级别鳞状上皮内病变（HSIL）的自然史认识不完整，因此预防工作受到阻碍。
2010 年至 2018 年期间开展的“预防肛门癌研究”，纳入了年龄≥35 岁的 HIV 阳性和 HIV 阴性的 GBM。在基线和 3 次年度访视时进行肛门细胞学和高分辨率肛门镜检查（HRA）。采用细胞学和组织学综合 HSIL 诊断（cytology ± histology）。用 95%置信区间（CI）计算细胞学高级别鳞状上皮内病变（cytological high-grade squamous intraepithelial lesions，cHSIL）的发生率和清除率。使用 Cox 回归计算预测因子，包括风险比（hazard ratios，HRs）和 95%CI。
在 617 名男性中，220 名（35.7%）HIV 阳性，中位年龄 49 岁。在 1097.3 人年（person-years，PY）随访期间，共发生 124 例新发 cHSIL 病例（11.3，95%CI 9.5-13.5/100PY）。年龄<45 岁（HR 1.64，95%CI 1.11-2.41）、HIV 阳性（HR 1.43，95%CI.99-2.06）、既往 SIL 诊断（P 趋势<.001）和 HPV16（HR 3.39，2.38-4.84）是更高发生率的显著单变量预测因子。在 695.3 PY 随访期间，有 153 例 HSIL 清除（清除率 22.0，95%CI 18.8-25.8/100PY）。年龄<45 岁（HR 1.52，1.08-2.16）、AIN2 而不是 AIN3（HR 1.79，1.29-2.49）、较小病变（HR 1.62，1.11-2.36）和无持续 HPV16（HR 1.72，1.23-2.41）是清除 HSIL 的预测因子。有 1 例进展为癌症（发病率 0.224，95%CI 0.006-1.25/100PY）。
这些数据强烈表明，并非所有在筛查中检测到的肛门 HSIL 都需要治疗。持续性 HPV16 的男性更不可能清除 HSIL，更可能受益于有效的 HSIL 治疗。
澳大利亚和新西兰临床试验注册（ANZCTR365383）。
