The Role of Methylation Marker FAM19A4/mir124-2 and HPV Genotype in Active Surveillance of Women With Cervical Intraepithelial Neoplasia Grade 2 (CIN2).

A substantial proportion of cervical intraepithelial neoplasia grade 2 (CIN2) spontaneously regress, supporting the use of active surveillance over immediate treatment. Identification of prognostic factors associated with higher rates of spontaneous regression could enable better selection of patients in whom such approach would be safe. We evaluated the prognostic value of FAM19A4/miR124-2 methylation status, HPV genotype, and baseline cytology for predicting spontaneous regression of CIN2. Women aged 18-40 years with CIN2 were prospectively enroled and followed for 2 years. At baseline, HPV genotyping was performed together with FAM19A4/miR124-2 methylation analysis. Among 119 enroled patients, the rate of spontaneous regression of CIN2 was 61.3% (73/119). Regression of CIN2 was significantly associated with HPV genotype (χ2 = 19.374; p = 0.002) and negative methylation result (χ2 = 10.945; p = 0.012). Negative methylation in combination with low-grade cytology and non-HPV16 genotype was associated with regression rates of 71.4% and 70.4%, respectively. Spontaneous regression of CIN2 is more frequent in women with non-HPV16 infection and negative FAM19A4/miR124-2 methylation. A combination of these markers improves identification of women with lower risk of disease progression and supports safer implementation of active surveillance and conservative management. CLINICAL TRIAL REGISTRATION: The study was registered at ClinicalTrials.gov as NCT05624827.