Department of Pathology, Cancer Center Amsterdam, Amsterdam UMC, Vrije Universiteit Amsterdam, Amsterdam, The Netherlands.
Department of Internal Medicine, Division of Infectious Diseases, Amsterdam Institute for Infection and Immunity, Amsterdam UMC, University of Amsterdam, Amsterdam, The Netherlands.
Mol Oncol. 2021 Nov;15(11):3024-3036. doi: 10.1002/1878-0261.12926. Epub 2021 Mar 16.
Anal cancer has increasing incidence and is preceded by high-grade anal intraepithelial neoplasia (HGAIN; AIN2-3). Previously, we identified and validated several methylation markers for accurate detection of anal cancer and HGAIN with cancer risk in HIV-positive (HIV+) men who have sex with men (MSM). This study aimed to evaluate these markers in HIV-negative risk groups. A cross-sectional series of 176 tissue samples of anal cancer, AIN3, AIN2, AIN1 and control biopsies obtained in HIV-negative women and men was tested for six methylation markers (ASCL1, LHX8, SST, WDR17, ZIC1 and ZNF582). Accuracy for detection of AIN3 and cancer (AIN3+) was determined by univariable and multivariable mixed-effect ordinal logistic regression. Methylation levels of all markers increased with increasing severity of disease (P < 0.0001) and were comparable to results in HIV+ MSM. All markers showed high accuracy for AIN3+ detection [area under the curve (AUC): 0.83-0.86]. The optimal marker panel (ASCL1 and ZIC1; AUC = 0.85 for AIN3+) detected 98% of cancers at 79% specificity. In conclusion, DNA methylation markers show a high diagnostic performance for AIN3+ detection in HIV+ and HIV-negative risk groups, justifying broad application of methylation analysis for anal cancer prevention programmes.
肛门癌的发病率不断上升，其前期为高级别肛门上皮内瘤变（HGAIN；AIN2-3）。此前，我们已经鉴定并验证了一些甲基化标记物，可用于准确检测 HIV 阳性（HIV+）男男性行为者（MSM）中肛门癌和 HGAIN 及其癌症风险。本研究旨在评估这些标记物在 HIV 阴性风险群体中的表现。我们对 176 例来自 HIV 阴性的男性和女性的肛门癌、AIN3、AIN2、AIN1 和对照活检组织样本进行了横断面研究，检测了六个甲基化标记物（ASCL1、LHX8、SST、WDR17、ZIC1 和 ZNF582）。采用单变量和多变量混合效应有序逻辑回归确定了用于检测 AIN3 和癌症（AIN3+）的准确性。所有标记物的甲基化水平随着疾病严重程度的增加而增加（P<0.0001），与 HIV+MSM 的结果相当。所有标记物在检测 AIN3+方面均具有较高的准确性[曲线下面积（AUC）：0.83-0.86]。最佳标记物组合（ASCL1 和 ZIC1；AUC 为 0.85 用于检测 AIN3+）在 79%特异性时可检测到 98%的癌症。总之，DNA 甲基化标记物在 HIV+和 HIV 阴性风险群体中对 AIN3+检测具有较高的诊断性能，这为肛门癌预防计划中的甲基化分析的广泛应用提供了依据。
