The Thai Red Cross AIDS Research Centre, Bangkok, Thailand ; SEARCH, Bangkok, Thailand.
PLoS One. 2013 Nov 12;8(11):e78291. doi: 10.1371/journal.pone.0078291. eCollection 2013.
Men who have sex with men (MSM) are at high risk of having anal cancer. Anal high-grade squamous intraepithelial lesion (HSIL) is the precursor of anal cancer. We explored the use of different biomarkers associated with human papillomavirus (HPV) infection and HPV-mediated cell transformation to detect and predict HSIL among HIV-positive and HIV-negative MSM.
METHODOLOGY/PRINCIPAL FINDINGS: A total of 123 HIV-positive and 123 HIV-negative MSM were enrolled and followed for 12 months. High-resolution anoscopy (HRA) with biopsies were performed at every visit along with anal sample collection for cytology, high-risk HPV DNA genotyping, HPV E6/E7 mRNA, and p16 immunocytochemistry. Performance characteristics and area under the receiver operator characteristics curve were calculated for these biomarkers at baseline, and Cox regression compared the usefulness of these biomarkers in predicting incident HSIL. High-risk HPV DNA, E6/E7 mRNA, and p16 immunocytochemistry each identified 43-46% of MSM whose baseline test positivity would trigger HRA referral. E6/E7 mRNA had the highest sensitivity (64.7%) and correctly classified the highest number of prevalent HSIL cases. With the exception of p16 immunochemistry, most tests showed significant increases in sensitivity but decreases specificity versus anal cytology, while the overall number of correctly classified cases was not significantly different. Baseline or persistent type 16 and/or 18 HPV DNA was the only test significantly predicting incident histologic HSIL within 12 months in models adjusted for HIV status and low-grade squamous intraepithelial lesions at baseline.
CONCLUSIONS/SIGNIFICANCE: Countries with a high HIV prevalence among MSM and limited HRA resources may consider using biomarkers to identify individuals at high risk of HSIL. E6/E7 mRNA had the highest sensitivity for prevalent HSIL detection regardless of HIV status, whereas type 16 and/or 18 HPV DNA performed best in predicting development of incident HSIL within 12 months.
男男性行为者（MSM）患肛门癌的风险很高。肛门高级别鳞状上皮内病变（HSIL）是肛门癌的前身。我们探讨了使用与人类乳头瘤病毒（HPV）感染和 HPV 介导的细胞转化相关的不同生物标志物来检测和预测 HIV 阳性和 HIV 阴性 MSM 中的 HSIL。
方法/主要发现：共纳入 123 名 HIV 阳性和 123 名 HIV 阴性 MSM ，并随访 12 个月。每次就诊时均进行高分辨率肛门镜检查（HRA）和活检，并采集肛门样本进行细胞学、高危 HPV DNA 基因分型、HPV E6/E7 mRNA 和 p16 免疫细胞化学检查。在基线时计算这些生物标志物的性能特征和接收者操作特征曲线下面积，并通过 Cox 回归比较这些生物标志物在预测新发 HSIL 中的有用性。高危 HPV DNA、E6/E7 mRNA 和 p16 免疫细胞化学检查均能识别出 43-46%的 MSM，其基线检查阳性结果将触发 HRA 转诊。E6/E7 mRNA 的敏感性最高（64.7%），并且正确分类的现患 HSIL 病例最多。除了 p16 免疫细胞化学检查外，大多数检查的敏感性均显著增加，但特异性均低于肛门细胞学检查，而正确分类的病例总数无显著差异。在调整基线时的 HIV 状态和低级别鳞状上皮内病变后，只有基线时存在 16 型和/或 18 型 HPV DNA 是唯一预测 12 个月内发生组织学 HSIL 的测试。
结论/意义：在 HIV 流行率较高的 MSM 国家和 HRA 资源有限的情况下，可能会考虑使用生物标志物来识别 HSIL 风险较高的个体。E6/E7 mRNA 对现患 HSIL 的检测具有最高的敏感性，无论 HIV 状态如何，而 16 型和/或 18 型 HPV DNA 在预测 12 个月内发生新发 HSIL 方面表现最佳。
