Screening of Precancerous Lesions in Women with Human Papillomavirus (HPV) Infection by Molecular Typing and MicroRNA Analysis

SIMPLE SUMMARY: Cervical cancer is the second most common cancer among women aged 15 to 44, affecting more than 500,000 women each year. Therefore, is important to implement preventive measures, based on screening programs, which allow precancerous lesions to be identified and treated early before they evolve into cancer. The aim of the proposed study is to implement the routine diagnostics of HPV precancerous cervical lesions by introducing new molecular diagnostic tools. The microRNA analysis panel can improve early diagnosis, understand the nature of the lesion and, consequently, improve the clinical management of patients with HPV precancerous cervical lesions. Genotyping, the determination of viral load, the evaluation of viral integration status and the expression profile of microRNAs were examined for this purpose. A characterization of lesions before diagnostic interventions allows to treat in a targeted way only lesions with a high risk of cancer progression, improving early diagnosis. The results allow the stratification of the risk of progression, the creation of personalized, therapeutic and follow-up protocols. ABSTRACT: Human papillomavirus (HPV) is causatively associated with cervical cancer, the fourth most common malignant disease of women worldwide: (1) The aim of the proposed study is to implement routine diagnostics of HPV precancerous cervical lesions by introducing new molecular diagnostic tools. (2) Methods: This is a retrospective cohort study with a total of twenty-two formalin-fixed paraffin-embedded (FFPE) cervical samples of various sample type (nine biopsy and thirteen conization) each patient had a previous abnormal results of pap test or HPV DNA test. Genotyping, viral load and co-infections were determined. For each patient, the individual expression of 2549 microRNAs were evaluated by microarray and qPCR. (3) Results: Our data demonstrates that the microRNAs were commonly expressed in tissues biopsies. miR 4485-5p, miR4485-3p and miR-4497 were highly down-regulated in tissue biopsies with HPV precancerous cervical lesions. (4) Conclusions: the introduction of a microRNA analysis panel can improve early diagnosis, understand the nature of the lesion and, consequently, improve the clinical management of patients with HPV precancerous cervical lesions.