Selection of women at risk for cervical cancer in an HIV-infected South African population
Van Zummeren, Marjolein; Kremer, Wieke W.; Van Aardt, M.C. (Matthys Cornelis); Breytenbach, Erika; Richter, Karin Louise; Rozendaal, Lawrence; Witte, Birgit I.; De Strooper, Lise M.A.; Hesselink, Albertus T.; Heideman, Danielle A.M.; Snijders, Peter J.F.; Steenbergen, Renske D.M.; Dreyer, Greta; Meijer, Chris J.L.M.
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+.
Data presented previously at 31st International Papillomavirus Conference, HPV 2017, South Africa, and published as abstract in the conference abstract book.