Changes in gene expression and mechanisms underlying activation of tumor invasion and spread at the early steps of squamous cervical carcinoma progression.

The development of an HPV-associated cervical cancer usually takes a long time (years, decades) and comprises stepwise change of intraepithelial (preclinical) neoplastic forms, but after invasive carcinoma is established it demonstrates extremely aggressive behavior and heterogenic molecular profile. Women with pre-invasive neoplastic lesions or early-stage invasive cervical cancer who underwent treatment in the Republican Oncological Dispensary were enrolled in our study (all were HPV-positive). Tissue samples were excised during surgery before any other treatment. Comparative transcriptomic analysis of invasive cancers (with an emphasis to the earliest stages) versus non-invasive precursor lesions was performed by means of RNA sequencing. Using RNA-seq we profiled 16 surgically obtained tissue samples, which comprised high-risk HPV(+) cervical intraepithelial neoplasia grades 1-3 (including carcinoma in situ, n=5), invasive squamous cell carcinoma at FIGO IA1-IIB stages (n=9, including 4 cases of microinvasive carcinoma), and morphologically normal epithelium (n=2).