ZNF582 methylation as a potential biomarker to predict cervical intraepithelial neoplasia type III/worse

Abstract

Objective: DNA methylation markers have been assessed as potential biomarkers for early cervical cancer detection. Herein, we evaluated the diagnostic performance of zinc finger protein 582 (ZNF582) methylation for cervical cancer detection. Methods: Eligible studies were systematically searched from the electronic databases. The quality of enrolled studies was evaluated using the second version of the check list for Quality Assessment of Diagnostic Accuracy Studies (QUADAS-2). The bivariate meta-analysis model was employed to plot the summary receiver operator characteristic (SROC) curve using Stata 14.0 software. Cochran s Q test and I2 statistics were applied to assess heterogeneity among studies. Publication bias was evaluated by the Deeks’ funnel plot asymmetry test. Results: Seven studies composed of 1749 patients were eventually included. The pooled sensitivity of ZNF582 methylation was estimated to be 0.71 [95% confidence interval (CI): 0.67–0.75] in differentiating patients with cervical intraepithelial neoplasia type III/worse (CIN3+), corresponding to a specificity of 0.81 (95% CI: 0.79–0.83) and area under the curve (AUC) of 0.85. Our stratified analysis suggested that sequential combined of HPV DNA and ZNF582 methylation test (AUC, sensitivity, and specificity of 0.876, 0.75, and 0.87, respectively) achieved higher diagnostic accuracy than single HPV DNA testing test (AUC, sensitivity and specificity of 0.669, 0.96, and 0.41, respectively). Conclusions: ZNF582 methylation has a prospect to be an auxiliary biomarker for cervical cancer screening. A new strategy of co-testing HPV DNA and ZNF582 methylation test in cervical scrapings confers an improved diagnostic accuracy than single HPV DNA testing.