Diagnostic Accuracy of DNA-Methylation in Detection of Cervical Dysplasia: Findings from a Population-Based Screening Program.

Simple Summary: The use of epigenetic biomarkers represents a promising tool in the diagnosis and prognosis of cancer. Several studies demonstrated the applicability and accuracy of DNA methylation analysis in the risk stratification of women with high-grade lesions, whereas lower evidence was reported in mild dyskaryosis and/or HPV-positive women. Particularly, the hypermethylation of host genes, FAM19A4 and miR124-2, is associated with an increase in the severity of cervical lesions and showed high accuracy in the detection of CIN2/3. These findings support the adoption of FAM19A4/miR124-2 as potential biomarkers for the prevention of cervical cancer and in reducing the over-referral to colposcopy examinations in a population-based screening program. Background: Epigenetic biomarkers in cancer have emerged as promising tools for early detection, prognosis, and treatment response prediction. In cervical cells, hypermethylation of the host and viral HPV-genome increases with the severity of lesions, providing a useful biomarker in the triage of hr-HPV-positive women and during treatment. The present study focuses on evaluating the clinical performance of the FAM19A4/miR124-2 methylation test in a population-based cervical screening program. Methods: Previously collected cervical samples, after bisulfite-converted DNA, were analyzed by PreCursor-M+ kit (distributed by Fujirebio Europe), for DNA methylation. The sensitivity, specificity, and negative/positive predictive values of DNA methylation were compared to histology, colposcopy, the HPV-DNA test, and cytology results. Results: Among the 61-sample set, the specificity of methylation vs. positive histology (≥CIN2) and colposcopy (≥G2) were 87% and 90%, whereas the sensitivity was 50% and 33.3%, respectively. The combination of methylation analysis with standard methods increases diagnostic accuracy. Conclusions: Overall, we found a good specificity of DNA methylation in comparison to currently used techniques. Further larger studies could support the use of FAM19A4/miR124-2 as reliable biomarkers in the prevention of cervical cancer as triage in the screening protocol. [ABSTRACT FROM AUTHOR]

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