Article Text
Abstract
Introduction/Background Historically, Cervical Intraepithelial Neoplasia grade 2 (CIN2) has been the cut-off to proceed to local surgical treatment of the cervix. However, treatment has been shown to increase the risk of poor future reproductive outcomes, and there is increasing evidence to suggest that a large number of CIN2 lesions will regress. DNA methylation has recently been proposed as a novel molecular technique, which may be accurate for both diagnosis and prediction of future oncological outcomes.
Methodology DNA was extracted from liquid-based cytology samples in a subset of 58 women aged 16–24 managed conservatively for histologically-confirmed CIN2, with known outcomes (12 progressors, 31 regressors, and 15 late regressors). Extracted DNA underwent bisulphite conversion and an Illumina 850k EPIC Methylation array. Data were processed using R; minfi package and a bespoke statistical pipeline.
Results Quality control was met for all 58 samples. Data were adjusted for principal components, previous pregnancy, and smoking status. Beta values were compared between groups using linear regression. In progressors (n=12) as compared to regressors (n=46) one CpG was statistically significantly differentially methylated (FDR <0.1).
Conclusion Previous work with DNA methylation in prediction of CIN2 progression has typically focused on known CpG sites. We have identified a novel CpG site which may assist in predicting progression of CIN2. This CpG site is within the promoter region of a gene involved in immune regulation, and thus biological plausibility exists for its role in malignant development. Larger prospective cohort studies are needed to validate these findings.
Disclosures n/a.