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

Selection of women at risk for cervical cancer in an HIV-infected South African population.
Author Information (click to view)

Van Zummeren M, Kremer WW, Van Aardt MC, Breytenbach E, Richter KL, Rozendaal L, Witte BI, De Strooper LMA, Hesselink AT, Heideman DAM, Snijders PJF, Steenbergen RDM, Dreyer G, Meijer CJLM,


Van Zummeren M, Kremer WW, Van Aardt MC, Breytenbach E, Richter KL, Rozendaal L, Witte BI, De Strooper LMA, Hesselink AT, Heideman DAM, Snijders PJF, Steenbergen RDM, Dreyer G, Meijer CJLM, (click to view)

Van Zummeren M, Kremer WW, Van Aardt MC, Breytenbach E, Richter KL, Rozendaal L, Witte BI, De Strooper LMA, Hesselink AT, Heideman DAM, Snijders PJF, Steenbergen RDM, Dreyer G, Meijer CJLM,

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AIDS (London, England) 31(14) 1945-1953 doi 10.1097/QAD.0000000000001583

Abstract
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+.

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