Comprehensive cross-sectional study of CIN prevalence, HPV genotyping, genetic alterations, and microbiota as molecular biomarkers for early cervical cancer detection: A pilot clinical study among women in Russia.

Objective: To explore the relationships between HPV genotypes, vaginal microbiota, oncogenic mutations, and cervical intraepithelial neoplasia (CIN) to develop a risk assessment model for predicting CIN.

Methods: A cross-sectional analysis was conducted on 264 women living in the Kaliningrad region, assessing CIN presence, HPV genotypes, vaginal microbiota composition, and mutations in key oncogenes.

Results: HPV genotypes 16, 31, 33, 35, 58, and 66 were identified as the most prevalent among patients with HPV infections. However, in a multifactorial model, only HPV genotypes 16 and 58 demonstrated a significant association with high-grade squamous intraepithelial lesions and above. Genetic analysis revealed mutations in TP53 and ERBB2 genes in 20 and 17 patients, respectively, with TP53 mutations showing a notable correlation with CIN progression. Two patients with diagnoses of "Negative for Intraepithelial Lesion or Malignancy" carried the TP53 R248W mutation, a well-established neoplasia-related variant, highlighting its potential as a predictor of precancerous conditions. Increased copy numbers of human DNA and Enterobacteriaceae DNA correlated with low-grade squamous intraepithelial lesions, though many DNA-derived features displayed instability in logistic regression models, suggesting the need for further validation.

Conclusion: These findings suggest that although HPV genotypes, genetic mutations, and microbiota profiles may serve as markers for CIN, their predictive reliability requires further investigation. The present study represents the first large-scale exploration of these factors conducted within the Russian female population.