TY - JOUR
T1 - Selection of women at risk for cervical cancer in an HIV-infected South African population
AU - Van Zummeren, Marjolein
AU - Kremer, Wieke W.
AU - Van Aardt, Matthys C.
AU - Breytenbach, Erika
AU - Richter, Karin L.
AU - Rozendaal, Lawrence
AU - Witte, Birgit I.
AU - De Strooper, Lise M.A.
AU - Hesselink, Albertus T.
AU - Heideman, Daniëlle A.M.
AU - Snijders, Peter J.F.
AU - Steenbergen, Renske D.M.
AU - Dreyer, Greta
AU - Meijer, Chris J.L.M.
PY - 2017/9/10
Y1 - 2017/9/10
N2 - 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+.
AB - 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+.
KW - DNA methylation marker testing
KW - HIV
KW - cytology
KW - early detection of cancer
KW - high-grade cervical intraepithelial neoplasia
KW - human papillomavirus DNA test
KW - uterine cervical neoplasms
UR - http://www.scopus.com/inward/record.url?scp=85021924996&partnerID=8YFLogxK
U2 - https://doi.org/10.1097/QAD.0000000000001583
DO - https://doi.org/10.1097/QAD.0000000000001583
M3 - Article
C2 - 28692545
SN - 0269-9370
VL - 31
SP - 1945
EP - 1953
JO - AIDS
JF - AIDS
IS - 14
ER -