Medical Research: What is the background for this study?
Response: Epigenetic changes are part of the natural history of cervical neoplasia. Tracking these changes at the molecular level is necessary for understanding disease progression, response to treatment and prognosis. Epigenetic biomarkers can potentially assess the stage of cervical intraepithelial neoplasia (CIN). This information can be used for screening purposes, to improve the overall quality of cervical cancer diagnostics.
Medical Research: What are the main findings?
Response: Paired boxed 1 (PAX1) gene methylation status has been widely used as a biomarker for cervical cancer screening. We have conducted a meta-analysis of the diagnostic test accuracy of PAX1 methylation, on moderate cervical dysplasia or worse (CIN2+) versus normal epithelium, and severe cervical dysplasia or worse (CIN3+) versus normal epithelium, for a total population of 1385 women. The results of this assay were generally satisfactory for CIN2+ vs normal, and extremely satisfactory for CIN3+ vs normal (Sensitivity=0.77, Specificity=0.92, AUC=0.931). This raises the possibility of utilizing this biomarker to improve current diagnostic protocols.
Medical Research: What should clinicians and patients take away from your report?
Response: The incorporation of HPV-DNA analysis into clinical practice has greatly improved cervical cancer screening. However, despite its higher sensitivity, a notable compromise in specificity is often observed, due to the transient nature of most HPV infections. Currently, most patients with second (CIN2) or third degree (CIN3) lesions undergo corrective surgery by ablation or excision of the intraepithelial anomaly. Being able to accurately distinguish between benign infections, and those requiring more intensive treatment is of paramount importance. Numerous unnecessary referrals could be avoided, preventing iatrogenic discomfort to patients and significantly reducing healthcare costs.
Medical Research: What recommendations do you have for future research as a result of this study?
Response: The fact that certain genes are found methylated at precancerous stages, suggests that methylation-specific biomarkers have an important role to play in secondary cancer prevention. Research in the field of cancer epigenetics can greatly improve diagnostic practices in the near future. Further studies are required, in order to identify the best candidate gene/s for clinical application and test their efficacy.
PAX1 methylation as an auxiliary biomarker for cervical cancer screening: A meta-analysis
Nikolaidis, Christos et al.
Cancer Epidemiology Published Online: July 30, 2015
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Christos Nikolaidis Ph.D. (2015). Epigenetic Biomarker May Improve Cervical Cancer Screening