DNA methylation for the triage of HPV-positive clinician-collected cervical samples 83 3 ASCL1 LHX8 ST6GALNAC5 GHSR ZIC1 SST 0.860 0.801 0.737 0.723 0.695 0.668 (0.816-0.904) (0.741-0.861) (0.672-0.803) (0.661-0.785) (0.829-0.760) (0.597-0.739) AUC 95% CI Cytology HPV16/18 genotyping ASCL1/LHX8 methylation Trainingset10 AUC = 0.882 (95% CI 0.859-0.920) Validationset (n = 695) AUC = 0.860 (95% CI 0.816-0.903) CIN3+ (A) 0.0 0.0 0.2 0.2 0.4 0.4 0.6 0.6 0.8 0.8 1.0 1.0 1 − Specificity Sensitivity CIN3+ (B) 0.0 0.0 0.2 0.2 0.4 0.4 0.6 0.6 0.8 0.8 1.0 1.0 1 − Specificity Sensitivity Supplementary Figure 3.2 Diagnostic accuracy – subgroup with revision diagnosis. ROC curves and corresponding AUC for CIN3+ detection for (A) single marker classifiers ASCL1, LHX8, ST6GALNAC5, GHSR, ZIC1, SST; and (B) bi-marker panel ASCL1/LHX8 (solid line), including point estimates of cytology (darkest pink circle), HPV16/18 genotyping (middle pink circle) and bi-marker panel ASCL1/LHX8 with the predefined threshold calibrated at 70% clinical specificity (lightest pink circle). For comparison, the cross-validated ROC curve and corresponding AUC, as obtained in the hrHPV-positive training series is projected (dotted line) 10. Abbreviations: AUC, area under the curve; CIN, cervical intraepithelial neoplasia; ROC, receiver operating characteristic
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