Cervical cancer screening: what role for methylation tests?

Cervical cancer is caused by persistent infection with high-risk human papillomaviruses (HR-HPV). Current screening programs rely on cytology and HR-HPV molecular detection. However, as most infections are transient, effective triage for HR-HPV positive women is crucial to identify those at high risk of progression to cancer. DNA methylation analysis, an epigenetic modification involved in HPV-induced oncogenesis, is emerging as a promising triage tool. This marker could stratify risk, thereby reducing invasive examinations (colposcopies) and unnecessary overtreatment (conizations), which may impact future pregnancies. Methylation tests, applicable to both cervical smears and self-collected vaginal samples, target viral genes (e.g., L1, L2) or host cell genes (e.g., FAM19A4, CADM1, MAL). While many markers show good performance, their optimal place in screening strategies and the choice of the most relevant test are still under investigation and require further comparative studies.