FIGURE 6.

Predicted probabilities plot of binarized cytological outcomes using HPV carcinogenicity as a singular or integrated predictor variable. (A) HPV carcinogenicity as a one-dimensional predictor of 3 sequentially binarized cytological outcomes (NILM vs. ASC-US/LSIL/HSIL, NILM/ASCUS vs. LSIL/HSIL, and NILM/ASC-US/LSIL vs. HSIL) is shown with respective cut-off values of ≥0.680, 0.5222, and 0.3321 (dashed lines) as determined by Youden’s index. (B) HPV carcinogenicity and host loci-specific methylation as predictors of cytological outcome. Top left, comparison of predicted probabilities for abnormal cytology (NILM vs. ASC-US/LSIL/HSIL) by HPV carcinogenicity and binarized ZNF582 and ADCY8 methylation status. Top right, comparison of predicted probabilities for NILM/ASC-US vs. LSIL/HSIL permuted by binarized methylation values of ADCY8, CDH8, and ZNF582 at the CpG sites noted in the text. Bottom, comparison of predicted probabilities for <HSIL vs. HSIL permuted by binarized methylation values of ADCY8, CDH8, and ZNF582 at the CpG sites noted in the text. The cut-off values for predicting a positive binarized cytological outcomes (NILM vs. ASC-US/LSIL/HSIL, NILM/ASC-US vs. LSIL/HSIL, and NILM/ASC-US/LSIL vs. HSIL) were ≥0.6503, 0.4533, and 0.2645 (dashed lines) as determined by Youden’s index. Definitions: For loci-specific CpG methylation levels (%), the 95th percentile value for each CpG derived from HPV-negative. NILM cytology was used as the cut-off for normal methylation (coded as 0); >95th percentile was deemed hypermethylated (coded as 1). AUC, area under the curve; mC, 5-methylcytosine at CpG sites; mC = 0, unmethylated cytosine; mC = 1, methylated cytosine; Pr, probability; ROC, Receiver operating characteristic; Se, sensitivity.