Clinical Regression of High-Grade Cervical Intraepithelial Neoplasia Is Associated With Absence of <i>FAM19A4/miR124-2</i> DNA Methylation (CONCERVE Study).

Abstract

Cervical screening can prevent cancer by detection and treatment of cervical intraepithelial neoplasia grade 2 or 3 (CIN2/3). Screening also results in considerable overtreatment because many CIN2/3 lesions show spontaneous regression when left untreated. In this multicenter longitudinal cohort study of women with untreated CIN2/3, the prognostic value of <i>FAM19A4/miR124-2</i> methylation was evaluated for clinical regression. Women with CIN2/3 were prospectively followed for 24 months. Surgical excision was replaced by a wait-and-see policy. <i>FAM19A4/miR124-2</i> methylation was evaluated on all clinician-collected samples and self-collected samples collected at baseline. Every 6 months, human papillomavirus (HPV) testing and cytology were conducted on a clinician-collected sample, and a colposcopic examination was performed by a gynecologist to exclude progression. At the final study visit, two biopsies were taken. Clinical regression was defined as histologically confirmed absence of CIN2+ or an HPV-negative clinician-collected sample with normal cytology. Regression incidences were estimated using the Kaplan-Meier method. One hundred fourteen women (median age, 30 years; range, 20-53 years) were included, 80 of whom were diagnosed with CIN2 and 34 with CIN3. During the study, 65.8% of women (75/114) did not receive surgical treatment. Women with a <i>negative FAM19A4/miR124-2</i> result on the baseline clinician-collected sample showed more clinical regression (74.7%) than women with a <i>positive</i> methylation result (51.4%, <i>P</i> = .013). Regression in women with a negative <i>FAM19A4/miR124-2</i> methylation test was highest when cytology was atypical squamous cells of undetermined significance/low-grade squamous intraepithelial lesion (88.4%) or HPV16 was negative (85.1%). Most women with untreated CIN2/3 and a negative baseline <i>FAM19A4/miR124-2</i> methylation test showed clinical regression. Methylation, in combination with cytology or HPV genotyping, can be used to support a wait-and-see policy in women with CIN2/3.