Introduction/Background Cervical cancer is the second most common cancer in women worldwide and is caused by a persistent infection with high-risk types of the human papillomavirus (hrHPV). The development of cervical squamous cell carcinomas occurs via well-recognizable premalignant precursor lesions (cervical intraepithelial neoplasia (CIN), graded 1–3), whereas less is known about the different precursor stages preceding cervical adenocarcinomas . Epigenetic mechanisms, including DNA methylation, can influence gene activity without changing the DNA sequence. DNA methylation is a stable, heritable, covalent modification to DNA, occurring mainly at CpG dinucleotides, but is also found at non-CpG sites. Methylation is associated with normal developmental processes, as well as the changes that are observable during oncogenesis and other pathological processes, such as gene silencing of tumor suppressor or DNA repair genes.
Methodology Cervical scrapings were obtained from from cervical cancer patients, 50 referred with an abnormal cervical smear (30 with high-grade cervical intraepithelial neoplasia (CIN2+), 5 with squamous cell carcinoma and 15 without CIN). All scrapings were analyzed by liquid based cytology (LBC) histologicaly confirmed, hr-HPV detection and DNA methylation analysis for detection (EPB41L3 and hsa-miR-124) using quantitative methylation-specific PCR(qMSP).
Results In CIN2+ patients methylation analysis was positive in hsa-miR-124 (19,5%) and EPB41L3 (25%), in SCCs patients hsa-miR-124 (91%) and EPB41L3 (93%). None of the normal samples scored positive for hsa-miR-124 or EPB41L3.
Conclusion This study shows that methylation of hsa-miR-124 and EPB41L3 is a frequent and functionally relevant event in cervical carcinogenesis. The high positivity rates in CIN2+ and carcinomas emphasize us that methylation is not directly related to the presence of of hrHPV. Our pilot study suggest that detection of cervical neoplasia by DNA methylation analysis either or not in combination with other promising methylation markers can improve future cervical screening strategies based on primary hrHPVtesting or triage in cervical pathology.
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