Dutch researchers at the NKI Cancer Center Amsterdam report that the absence of DNA methylation at the gene FAM19A4 and microRNA miR124-2 is associated with clinical regression in grade 2/3 cervical intra-epithelial neoplasia (CIN). The findings of this study were recently published in the Journal of Clinical Oncology.
Some of the grade2/3 CINs can progress to cervical cancer; thus, predicting clinical regression can help avoid overtreatment for these patients.
The multicentre, longitudinal, CONCERVE study enrolled 114 females (80 with CIN2 and 34 with CIN3) at three clinics across the Netherlands. These participants were observed for 24 months in a “wait-and-see” policy. They were tested for human papillomavirus (HPV) every six months, along with cytology and colonoscopy examination to exclude disease progression. Finally, two biopsies were taken at the final study visit.
Clinical regression and progression were seen during the follow-up period in 67 and 25 patients. Interestingly, clinical regression was seen in 74.7% (95% confidence interval [CI] = 65.7%–81.7%) of patients with a negative FAM19A4/miR124-2 methylation test as compared to those with a positive result (51.4%, 95% CI = 34.6%–65.9%, P = .013). Clinical regression in patients with an unmethylated FAM19A4/miR124-2 status was highest among patients with atypical squamous cells of undetermined significance/low-grade intraepithelial lesion (88.4%), or HPV16 was negative (85.1%).
The investigators concluded, “Most women with untreated CIN2/3 and a negative baseline FAM19A4/miR124-2 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.”