DNA Methylation Testing in Cervical Cancer: A Triage Tool for HPV-Based Screening and Post-Treatment Surveillance.

BACKGROUND: High-risk HPV screening achieves high sensitivity but low specificity, resulting in excessive colposcopy referrals. DNA methylation biomarkers could refine risk stratification across the cervical cancer care continuum. OBJECTIVE: To evaluate the diagnostic performance and clinical implementation of DNA methylation testing in HPV-positive triage and post-treatment surveillance. METHODS: Narrative review of prospective cohorts and randomized trials (2013-2024) evaluating methylation markers in cervical cancer screening and monitoring. RESULTS: The FAM19A4/miR124-2 panel demonstrated sensitivity/specificity of 0.83/0.90 for CIN3+ in HPV-positive women, reducing colposcopy referrals by 45% while maintaining < 3% missed CIN3+. In post-treatment surveillance, plasma cell-free DNA (cfDNA) methylation may enable earlier recurrence detection than imaging (sensitivity 0.81, specificity 0.93, based on limited prospective data). A proposed three-step conceptual framework integrating methylation testing across screening, postoperative assessment, and recurrence monitoring is presented as a hypothesis-generating model requiring prospective validation. CONCLUSIONS: DNA methylation testing shows promise for clinical implementation in HPV triage and post-treatment surveillance. Evidence remains fragmented across separate studies. Standardization of thresholds and cost reduction are priorities for guideline inclusion.