Prediction of the risk and progression of cervical intraepithelial neoplasias associated with papillomavirus infection

Objective. To reveal the specific features of a change in human mRNA gene expression in patients with human papillomavirus (HPV)-associated diseases of the cervix uteri for the prediction of the risk and progression of cervical intraepithelial neoplasias. Subjects and methods. The prospective investigation enrolled 225 women aged 18 to 60 years. The examination included collection of complaints, history data, gynecological status determination, expanded colposcopy, and molecular biological and morphological studies. The molecular biological studies involved real-time multiplex PCR assay with the detection of results for the quantification and typing of HPV 21 and the determination of the mRNA expression of the genes MKI 67 (KI67), CTSL2, CDKN2A (P16), ESR1, PGR, BCL2, BAX, BAG1, CD68, SCUBE2, and PTEN. Results. There were 5 groups: 1) 45 (20%) HPV-negative patients (a control group); 180 (80%) HPV-positive patients divided into 4 groups: 2) 56 (24.9%) with latent and subclinical papillomavirus infection (PVI); 3) 50 (22.2%) with low-grade squamous intraepithelial lesion (LSIL); 4) 55 (24.4%) with high-grade squamous intraepithelial lesion; 5) 19 (8.5%) with cancer of the cervix uteri (CCU). Conclusion. The investigation showed differences in the mRNA expression level of potential cervical epithelial tumor markers in patients with cervical neoplasias of varying degrees or CCU and in healthy women. The increased mRNA expression of the genes MKI67 (KI67) and CDKN2A (P16), the decreased expression of PGR, BCL2 in combination with high-risk HPV types, and an abnormal colposcopic pattern correlate with the outcomes of LSIL and may be regarded as possible biomarkers for the prediction of the course of already developed neoplasia; in HPV carriage as possible biomarkers for the prediction of evolving neoplastic transformation of the cervical epithelium. The comprehensive analysis of clinical and anamnestic parameters and the identification of molecular genetic markers increase the risk of disease progression.

human papilloma virus, cervical intraepithelial neoplasia, cancer of the cervix uteri, mRNA expression