Genetic Predisposition to Cervical Cancer and Prevalence of Oncogenic HPV Types in Female Population of the Republic of Bashkortostan

BACKGROUND: Cervical cancer is a significant medical and social issue that greatly impacts women’s quality of life and life expectancy. The primary pathogenic factor is a persistent infection with a high-risk human papillomavirus (HPV) types. AIM: The study aimed to evaluate the prevalence and spectrum of HPV infections in the female population of the Republic of Bashkortostan, as well as to determine their molecular and genetic predisposition to cervical cancer. METHODS: The study included 219 randomly selected HPV-positive samples to evaluate the prevalence and spectrum of HPV types. Four years later, a follow-up screening was conducted in 70 HPV-positive women. The screening included an evaluation of their HPV and cervical statuses, an examination by an obstetrician/gynecologist, cytology, colposcopy, and biopsy for histology when indicated. In the third stage, we compared polymorphisms of the CLPTM1L (rs27069), PAX8 (rs10175462), and CDC42 (rs2268177) genes in patients with histologically confirmed cervical cancer and in apparently healthy women. RESULTS: No positive correlation was found between the number of HPV types per sample and viral load, nor between viral load and HPV clearance. Genome-wide association studies (GWAS) identified statistically significant associations between cervical cancer risk and the G allele of CLPTM1L rs27069 (χ2 = 4.098; p = 0.043), as well as with the T allele (χ2 = 16.99; p = 3.751e-5) and the TT genotype (χ2 = 17.35; p = 0.0002) of CDC42 rs2268177. No association was found for PAX8 (rs10175462). CONCLUSION: This was the first Russian study to replicate GWAS results for cervical cancer. Associations were identified for CLPTM1L (rs27069) and CDC42 (rs2268177), but not for PAX8 (rs10175462). The results highlight the need for further research to confirm these associations and improve our understanding of the molecular mechanisms associated with cervical cancer risk and HPV persistence.