Evaluation of Six Methylation Markers Derived from Genome-Wide Screens for Detection of Cervical Precancer and Cancer
Stèfanie Dick, Lisanne Verhoef, Lise M.A. De Strooper, Iuliana Ciocănea‐Teodorescu, G. Bea A. Wisman, Chris J.L.M. Meijer, Maaike C.G. Bleeker, Renske D.M. Steenbergen, Daniëlle A.M. Heideman
Abstract
Aim: To evaluate the triage performance of six host-cell DNA methylation markers derived from two genome-wide discovery screens for detection of cervical precancer (cervical intraepithelial neoplasia 3 [CIN]) and cancer. Materials & methods: Human papillomavirus-positive cervical scrapes of controls (≤CIN1; n = 352) and women diagnosed with CIN3 (n = 175) or cervical cancer (n = 50) were analyzed for methylation of ASCL1, LHX8, ST6GALNAC5, GHSR, SST and ZIC1. Results: Methylation levels increased significantly with disease severity (all markers p < 0.001). Three markers (ASCL1, LHX8, ZIC1) showed receiver operating characteristic curves with area under the curve >0.800 after leave-one-out cross-validation. Bi-marker panel ASCL1/LHX8 had highest area under the curve (0.882), and detected 83.4% of CIN3 and all cervical cancers at specificity of 82.4%. Conclusion: All six methylation markers showed an equivalent, high performance for the triage of human papillomavirus-positive women using cervical scrapes with complementarity between markers.