Molecular Insights into HPV-Driven Cervical Cancer: Oncoproteins, Immune Evasion, and Epigenetic Modifications

Abstract

Cervical cancer ranks third in mortality and fourth in incidence among women worldwide as one of the leading causes of death from cancer in females. The main reason behind cervical carcinogenesis is long-term infection with high-risk human papillomavirus (HPV) genotypes, particularly HPV16 and HPV18. This review investigates HPV distribution across the world, along with cervical cancer molecular development mechanisms and current treatment strategies. Epidemiological data show that disease patterns vary significantly between different geographic regions because underdeveloped nations bear a higher disease burden. The molecular mechanisms of oncogenes E6 and E7 disrupt tumor suppressor pathways, while epigenetic modifications through DNA methylation and miRNA dysregulation promote malignant cell transformation. The reduction in HPV infection through prophylactic vaccination has shown promise, yet barriers related to accessibility and coverage still exist. The therapeutic technologies of gene expression inhibitors together with immunotherapies and epigenetic targeting agents show promise but require optimization to achieve specific targeting while minimizing off-target effects. A combined approach that integrates HPV vaccination with early diagnosis and molecular-specific therapies represents the most effective method to manage cervical cancer impact. The future care of patients will require increased translational research along with better immunization programs to drive prevention and therapeutic outcomes.

Keywords: DNA methylation; HPV; cervical cancer; early proteins; exosomes; miRNA.

Figure 1

World map with the prevalence of the predominant high-risk HPV subtypes by continent or region in healthy women (Adapted from: https://www.cancer.gov/about-nci/organization/cgh/blog/2018/world-report, accessed on 1 February 2025).

Figure 2

The mechanisms of oncoproteins in carcinogenesis.