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.