Van Zummeren, MarjoleinKremer, Wieke W.Van Aardt, M.C. (Matthys Cornelis)Breytenbach, ErikaRichter, Karin LouiseRozendaal, LawrenceWitte, Birgit I.De Strooper, Lise M.A.Hesselink, Albertus T.Heideman, Danielle A.M.Snijders, Peter J.F.Steenbergen, Renske D.M.Dreyer, GretaMeijer, Chris J.L.M.2017-12-012017-09Van Zummeren, M., Kremer , W., Van Aardt, M.C. ... et al. 2017, 'Selection of women at risk for cervical cancer in an HIV-infected South African population', Aids, vol. 31, pp. 1945-1953.0269-9370 (print)1473-5571 (online)10.1097/QAD.0000000000001583http://hdl.handle.net/2263/63413Data presented previously at 31st International Papillomavirus Conference, HPV 2017, South Africa, and published as abstract in the conference abstract book.OBJECTIVE : 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. DESIGN : Prospective observational multicentre cohort study. METHODS : 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. RESULTS : 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%. CONCLUSION : 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+.en© 2017 Wolters Kluwer Health / Lippincott Williams & Wilkins. This is a non-final version of an article published in final form in AIDS, vol. 31, pp. 1945-1953, 2017, doi : 10.1097/QAD.0000000000001583.Cervical cancerHigh-risk human papillomavirus (hrHPV)Uterine cervical neoplasmsCytologyDNA methylation marker testingEarly detection of cancerHigh-grade cervical intraepithelial neoplasiaHuman immunodeficiency virus (HIV)Human papillomavirus DNA testPostprint Article