Faria Faiza, Hawes Stephen E, Lin John, Schouten Jeffrey, Stankiewicz Karita Helen Cristina, Cherne Stephen, Vasavada Anjali, Barnabas Ruanne V, Wasserheit Judith N, Feng Qinghua, Winer Rachel L
University of Washington, United States.
University of Washington, Seattle, WA, United States.
Cancer Epidemiol Biomarkers Prev. 2025 Jul 11. doi: 10.1158/1055-9965.EPI-25-0327.
Molecular biomarkers could enhance anal cancer screening accuracy in people living with HIV (PLWH). We assessed the performance of human papillomavirus (HPV)-16/18 E6 oncoprotein in detecting anal high-grade squamous intraepithelial lesions (HSIL) in men living with HIV (MLWH).
We analyzed clinical data from 125 clinic visits of 82 MLWH who underwent high-resolution anoscopy in Seattle, Washington (2015-2016), including presence and extent of HSIL. Anal brush specimens were tested for high-risk (hr)HPV DNA, with HPV-16/18-positive samples further tested for E6 oncoprotein. Sensitivity, specificity, positive predictive value (PPV) and negative predictive value (NPV) of HPV-16/18 E6 oncoprotein for HSIL were calculated, plus prevalence ratios (PR) with 95% confidence intervals (CIs).
Forty-eight samples (38.4%) were HPV-16/18 positive, including three also E6 positive. Forty-nine (39.2%) had corresponding HSIL. Specificity and PPV of HPV-16/18 E6 for HSIL was 100% and the PR was 7.33 (95%CI:2.44-22.07) for HPV-16/18 E6 positive versus hrHPV-negative samples. Sensitivity for HSIL, however, was only 6.1%, with moderate NPV (62.3%). Two of four persons with HSILs with >75% disease extent had corresponding HPV-16/18 E6 positive samples, whereas none of 30 persons with <25% extent did.
The HPV-16/18 E6 oncoprotein has potential utility as a triage biomarker for identifying and prioritizing lesions at highest risk for progression.
PLWH are at increased risk of anal cancer and would benefit from improved screening methods. Further research may elucidate the role of HPV-16/18 E6 oncoprotein in anal cancer prevention, alone or combined with other biomarkers.
分子生物标志物可提高艾滋病病毒感染者（PLWH）肛门癌筛查的准确性。我们评估了人乳头瘤病毒（HPV）-16/18 E6癌蛋白在检测男性艾滋病病毒感染者（MLWH）肛门高级别鳞状上皮内病变（HSIL）中的性能。
我们分析了华盛顿州西雅图市82名接受高分辨率肛门镜检查的MLWH的125次门诊临床数据（2015 - 2016年），包括HSIL的存在情况和范围。对肛门刷检标本进行高危（hr）HPV DNA检测，HPV-16/18阳性样本进一步检测E6癌蛋白。计算HPV-16/18 E6癌蛋白对HSIL的敏感性、特异性、阳性预测值（PPV）和阴性预测值（NPV），以及95%置信区间（CI）的患病率比（PR）。
48个样本（38.4%）HPV-16/18呈阳性，其中3个样本E6也呈阳性。49个样本（39.2%）有相应的HSIL。HPV-16/18 E6对HSIL的特异性和PPV为100%，HPV-16/18 E6阳性与hrHPV阴性样本的PR为7.33（95%CI：2.44 - 22.07）。然而，对HSIL的敏感性仅为6.1%，NPV中等（62.3%）。4名疾病范围>75%的HSIL患者中有2人有相应的HPV-16/18 E6阳性样本，而30名疾病范围<25%的患者中无人有相应样本。
HPV-16/18 E6癌蛋白作为一种分流生物标志物，在识别和优先处理进展风险最高的病变方面具有潜在应用价值。
PLWH患肛门癌的风险增加，将从改进的筛查方法中受益。进一步的研究可能会阐明HPV-16/18 E6癌蛋白在肛门癌预防中的作用，单独或与其他生物标志物联合使用时的作用。
