PAX1 methylation as an auxiliary biomarker for cervical cancer screening: a meta-analysis

Objective: Several studies have implicated PAX1 epigenetic regulation in cervical neoplasia. The aim of this meta-analysis was to assess PAX1 gene methylation as a potential biomarker in cervical cancer screening.

Methods: A systematical search of all major databases was performed, in order to include all relevant publications in English until December 31(st) 2014. Studies with insufficient data, conducted in experimental models or associated with other comorbidities were excluded from the meta-analysis. Summary receiver operating characteristics (SROC) for Cervical Intraepithelial Neoplasia grade 2 or worse (CIN2(+)) versus normal, and CIN grade 3 or worse (CIN3(+)) versus normal, were estimated using the bivariate model.

Results: Out of the 20 initially included studies, finally 7 (comprising of 1385 subjects with various stages of CIN and normal cervical pathology) met the inclusion criteria. The sensitivity of CIN2(+) versus normal was estimated to be 0.66 (CI 95%, 0.46-0.81) and the specificity 0.92 (CI 95%, 0.88-0.95). On the other hand, the sensitivity of CIN3(+) versus normal was 0.77 (CI 95%, 0.58-0.89) and the specificity 0.92 (CI 95%, 0.88-0.94). Moreover, the area under the curve (AUC) in the former case was 0.923, and in the latter 0.931.

Conclusion: The results of this meta-analysis support the utility of PAX1 methylation as an auxiliary biomarker in cervical cancer screening. PAX1 could be used effectively to increase the specificity of HPV DNA by detecting women with more advanced cervical abnormalities.