Epigenetic Regulation and Gene Expression Profiles in Cervical Swabs: Toward Non-Invasive Biomarkers of Cervical Lesion Progression

<b>Background/Objectives</b>: Cervical cancer is a common malignancy in women worldwide, closely associated with persistent human papillomavirus (HPV) infection. Epigenetic mechanisms, particularly promoter methylation, may contribute to tumour progression. This pilot study aimed to analyse the promoter methylation patterns and gene expression of selected genes (<i>DNMT</i>, <i>BCL2</i>, <i>CDH1</i>, <i>CD8A</i>, <i>MUC1</i>, <i>ALCAM</i>). The goal was to identify associations between promoter hypermethylation, gene expression, and HPV infection in cervical swab specimens obtained from patients with low-grade squamous intraepithelial lesions (SILs), high-grade SILs, or squamous cell carcinomas. <b>Methods</b>: A total of 81 cervical swab samples from Slovak participants were included in the study. DNA methylation and gene expression profiling was performed using real-time PCR (qPCR) and pyrosequencing. <b>Results</b>: <i>BCL2</i> expression was significantly reduced across all lesion grades. <i>CD8A</i> expression was slightly elevated in low- and high-grade SILs, particularly in HPV-positive samples. <i>MUC1</i> showed variability with lesion grade. No statistically significant differences in DNA methylation were observed across groups stratified by HPV status, community state type, and lesion grade. <b>Conclusions</b>: Our findings suggest that <i>BCL2</i> downregulation and gene activity variability influenced by the vaginal microbiome may play a role in cervical lesion progression. These results highlight potential non-invasive biomarkers for monitoring cervical lesions.