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AIDS. 2017 Sep 10;31(14):1945-1953. doi: 10.1097/QAD.0000000000001583.

Selection of women at risk for cervical cancer in an HIV-infected South African population.

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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.



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 (nā€Š=ā€Š355) and a referral cohort (nā€Š=ā€Š109, 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+.

[Indexed for MEDLINE]

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