aCancer Centre Amsterdam, Department of Pathology, VU University Medical Centre, Amsterdam, The Netherlands bDepartment of Obstetrics and Gynaecology, Steve Biko Academic Hospital cDepartment of Medical Virology, University of Pretoria, and National Health Laboratory Service, Pretoria, South Africa dDepartment of Epidemiology and Biostatistics, VU University Medical Centre eSelf-screen B.V., Amsterdam, The Netherlands.
AIDS. 2017 Sep 10;31(14):1945-1953. doi: 10.1097/QAD.0000000000001583.
Cervical cancer is the leading cause of cancer-related death in women in South Africa. This study evaluates DNA methylation levels in cervical (pre)cancer and aims to assess the value of high-risk human papillomavirus (hrHPV) testing and methylation analysis, alone or in combination, on physician-taken cervical scrapes to detect cervical cancer, and cervical intraepithelial neoplasia grade 3 (CIN3) in an HIV-infected South African population.
Prospective observational multicentre cohort study.
Women from a cohort of women living with HIV (n = 355) and a referral cohort (n = 109, 60% HIV seropositive) were included. Cervical scrapes were collected for hrHPV testing and methylation analysis of cell adhesion molecule 1, T-lymphocyte maturation-associated protein, and microRNA124-2 genes. Histologic endpoints were available for all participants. Performance for detection of CIN3 or worse (CIN3+) was determined in the cohort of women living with HIV and different testing strategies were compared.
HrHPV and methylation positivity rates increased with severity of cervical disease in the two study cohorts, each reaching 100% in samples of women with carcinoma. HrHPV testing showed a sensitivity for CIN3+ of 83.6%, at a specificity of 67.7%. Methylation analysis showed a comparable CIN3+ sensitivity of 85.2%, but a significantly lower specificity of 49.6%. HrHPV testing with reflex methylation analysis showed a CIN3+ sensitivity of 73.8%, at a specificity of 81.5%.
In this HIV-infected South African population, stratifying hrHPV-positive women with reflex methylation analysis detects all cervical carcinomas and yields an acceptable sensitivity and specificity for CIN3+.
宫颈癌是南非女性癌症相关死亡的主要原因。本研究评估了宫颈癌（前）癌中的 DNA 甲基化水平，并旨在评估高危型人乳头瘤病毒（hrHPV）检测以及单独或联合使用基于医生采集的宫颈刮片的甲基化分析在检测宫颈癌和人免疫缺陷病毒（HIV）感染南非人群中宫颈上皮内瘤变 3 级（CIN3）方面的价值。
前瞻性观察性多中心队列研究。
从一个 HIV 感染者队列中的女性（n=355）和一个转诊队列（n=109，60% HIV 阳性）中纳入女性。收集宫颈刮片进行 hrHPV 检测和细胞黏附分子 1、T 淋巴细胞成熟相关蛋白和 microRNA124-2 基因的甲基化分析。所有参与者均有组织学终点。在 HIV 感染者队列中确定了不同检测策略在检测 CIN3 或更高级别病变（CIN3+）方面的性能。
在两个研究队列中，随着宫颈疾病的严重程度增加，hrHPV 和甲基化阳性率增加，在患有癌的女性样本中达到 100%。hrHPV 检测对 CIN3+的敏感性为 83.6%，特异性为 67.7%。甲基化分析显示出相当的 CIN3+敏感性为 85.2%，但特异性明显降低为 49.6%。hrHPV 检测加反射性甲基化分析对 CIN3+的敏感性为 73.8%，特异性为 81.5%。
在这个感染 HIV 的南非人群中，分层分析 hrHPV 阳性的女性并进行反射性甲基化分析可以检测到所有宫颈癌，并且对 CIN3+具有可接受的敏感性和特异性。
