# HPV-Driven Cervical Carcinogenesis: Genetic and Epigenetic Mechanisms and Diagnostic Approaches

## TL;DR

This paper reviews how HPV causes cervical cancer through genetic and epigenetic changes and explores new diagnostic methods.

## Contribution

The paper highlights DNA methylation as a novel biomarker for detecting cervical cancer.

## Key findings

- Genetic loci in the HLA region are linked to HPV infection and cervical cancer progression.
- HPV oncoproteins E6 and E7 cause genetic instability and epigenetic changes.
- DNA methylation of specific host genes is a promising diagnostic biomarker.

## Abstract

Cervical cancer remains a major global public health concern, with persistent infection by high-risk human papillomavirus (hrHPV) types recognized as the primary etiological factor. This review explores the multifactorial nature of the disease, focusing on the complex interplay between host genetic susceptibility and epigenetic alterations that drive cervical carcinogenesis. Evidence from genome-wide association studies (GWAS) is discussed, highlighting the contribution of specific genetic loci, predominantly within the HLA region, to susceptibility to HPV infection and disease progression. In parallel, the review examines the molecular mechanisms by which the viral oncoproteins E6 and E7 promote genetic instability and epigenetic reprogramming, including histone modifications and dysregulation of non-coding RNAs. Particular emphasis is placed on DNA methylation, affecting both the viral genome and host genes such as FAM19A4, CADM1, PAX1, and MAL, as a promising biomarker for triage and detection of high-grade intraepithelial lesions (CIN2+). Finally, the review evaluates currently available methylation-based assays and self-sampling devices, highlighting their potential to enhance diagnostic accuracy and increase participation in cervical cancer screening programs.