MicroRNA Expressions in HPV-induced Cervical Dysplasia and Cancer

Background/aim: The role of oncogenic or high-risk human papillomavirus (HPV) in cervical carcinogenesis is inevitable, yet not fully understood. Detailed analysis of microRNA (miRNA) alterations occurring during high-risk HPV transformation will increase our current understanding over cervical carcinogenesis. The two main aims of the study were: (i) finding association between HPV infection characteristics and socio-demographic variables, (ii) finding an predictors of clinical outcome.

Materials And Methods: The expression levels of different microRNAs (miR-21, miR-27a, miR-34a, miR-155, miR-196a, miR-203) were determined in formalin-fixed paraffin-embedded (FFPE) human HPV-positive cervical dysplastic and tumorous tissue samples using quantitative real-time PCR (qPCR). Sociodemographic and life-style factors were also analyzed.

Results: The expression of miR-27a was significantly higher in cervical intraepithelial neoplasia (CIN)2-3 compared to CIN1 (p=0.023) and in squamous cell carcinoma (SCC) compared to CIN2-3 (p=0.033). Moreover, significantly lower levels of miR-34a were detected in CIN2-3 than in CIN1 (p=0.041) and in SCC than in CIN2-3 (p=0.021). Furthermore, we found significant differences in subjects with multiple HPV in miR-27a (p=0.015) and miR-203 (p=0.025) in CIN2-3 compared to CIN1 and miR-21 (p=0.002), mir-27a (p=0.001) and miR-34a (p=0.001) in SCC/CIN2-3. Expression of miR-27a, showing up-regulation in CIN2-3 compared to CIN1 (p=0.028) and miR-34a (down-regulated), correlated with HPV 16 positivity (CIN2-3/CIN1: p=0.027 and SCC/CIN2-3: p=0.036). MiR-34a expression was also significantly altered in connection to smoking status and presence of HPV 16.

Conclusion: The demand for additional, alternative molecular biomarkers with prognostic potential is strong. Evaluation of miRNA expression might be helpful to distinguish different cervical lesions and might be able to help in the prediction of HPV infection outcome.