Comparative evaluation of two DNA methylation assays for triage of hrHPV E6/E7 mRNA–positive women
Background
The low specificity of high-risk human papillomavirus (hrHPV) testing necessitates effective triage strategies to avoid unnecessary colposcopy. DNA methylation testing shows promise, but its performance specifically in hrHPV E6/E7 mRNA-positive women, a population with active oncogenic activity, requires further evaluation.
Methods
This study evaluated the clinical performance of two commercial methylation-specific PCR assays, GynTect ® and CISCER ® , as triage tools for detecting high-grade cervical intraepithelial neoplasia (CIN) and cervical cancer in hrHPV E6/E7 mRNA-positive women. A total of 119 women were categorized into five groups based on colposcopy results: cervicitis, CIN1, CIN2, CIN3, and cervical cancer.
Results
Both GynTect ® and CISCER ® showed increasing detection rates with disease severity, reaching 90.91 and 86.36% in cervical cancer cases, respectively. For CIN2 + lesions, GynTect ® demonstrated a detection rate of 59.49%, while CISCER ® showed 63.29%, with both assays achieving a specificity of 95.00%. For CIN3 + lesions, GynTect ® demonstrated a sensitivity of 73.21%, specificity of 87.30%, a positive predictive value (PPV) of 83.7%, and a negative predictive value (NPV) of 78.6%, whereas CISCER ® showed a sensitivity of 76.79%, specificity of 85.71%, a PPV of 82.7%, and an NPV of 80.6%. No statistically significant differences in diagnostic performance were observed between the two assays. Both tests also demonstrated comparable performance across different cytological grades and HPV genotypes, with higher detection rates for HPV 16/18-associated lesions compared to non-16/18 types.
Conclusion
Overall, although limited by its single-center design and modest sample size, GynTect ® and CISCER ® demonstrated comparable clinical performance for the identification of high-grade CIN in hrHPV E6/E7 mRNA–positive women, supporting their potential role as effective triage tools in HPV-based cervical cancer screening.