Cervical Cancer in the Era of HPV: Translating Molecular Mechanisms into Preventive Public Health Action

Abstract

Cervical cancer remains a significant public health challenge, disproportionately affecting women in low- and middle-income countries (LMICs). Persistent infection with high-risk types of human papillomavirus (HPV), particularly HPV16 and HPV18, is the central cause of cervical carcinogenesis, driven by the viral oncoproteins E6 and E7, which disrupt the host tumor suppressors p53 and retinoblastoma protein (pRb). Advances in molecular understanding have catalyzed effective primary and secondary prevention strategies. Prophylactic HPV vaccination, especially the nonavalent formulation, has demonstrated high efficacy in reducing HPV infections and cervical precancer. Concurrently, HPV deoxyribonucleic acid (DNA) testing, self-sampling, and screen-and-treat protocols are transforming screening paradigms, particularly in resource-limited settings. However, global disparities in vaccine access, screening coverage, and health infrastructure persist, impeding progress toward the World Health Organization's (WHO) 90-70-90 elimination targets. By synthesizing recent advances in virology, prevention strategies, and implementation innovations, such as therapeutic vaccines, artificial-intelligence (AI)-driven diagnostics, and mobile health solutions, this review sheds light on their potential to narrow these equity gaps.

Keywords: HPV vaccination; cervical cancer; global health disparities; human papillomavirus; screening and prevention.

Figure 1

HPV: pathogenesis, prevention, and global health challenges. Conceptual mind map (figure created in BioRender). This mind map encapsulates the biological, clinical, and societal aspects of HPV. It not only covers viral pathogenesis and its link to cervical cancer but also integrates modern prevention strategies, such as vaccination and screening, while acknowledging global challenges like disparities in healthcare access and education. It is a valuable tool for health professionals, educators, and policymakers aiming to understand and communicate the comprehensive landscape of HPV control and cervical cancer elimination.

Figure 2

Molecular and clinical overview of human papillomavirus (HPV)-induced cervical carcinogenesis (figure created in BioRender). This schematic integrates molecular and clinical perspectives on HPV-mediated cervical cancer. Upon infection with high-risk types of HPV (16 and 18), the viral oncoproteins E6 and E7 are expressed and disrupt key tumor suppressor pathways. E6 promotes the degradation of p53, inhibiting apoptosis, while E7 inactivates retinoblastoma protein (pRb), driving uncontrolled cell proliferation. These alterations lead to the accumulation of genetic damage and progression from cervical intraepithelial neoplasia (CIN) to invasive cervical cancer. Clinically, understanding these mechanisms informs prevention and management strategies: HPV vaccination, high-performance screening, and novel therapeutic approaches targeting E6/E7 are reshaping cervical cancer control. Linking molecular pathways to public health interventions underscores the importance of translating biological insights into global elimination efforts.