Chapter 2 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 HPV-positive cervical samples of controls (≤CIN1; n = 352) and women diagnosed with CIN3 (n = 175) or cervical cancer (n = 50) were analysed for methylation of ASCL1, LHX8, ST6GALNAC5, GHSR, SST and ZIC1. RESULTS Methylation levels increased significantly with disease severity (all markers p value < 0.001). Three markers (ASCL1, LHX8 and 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 a specificity of 82.4%. CONCLUSION All six methylation markers showed an equivalent, high performance for the triage of HPV-positive women using cervical samples with complementarity between markers.
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