Integrating Biomarkers into Cervical Cancer Screening—Advances in Diagnosis and Risk Prediction: A Narrative Review

Background: Cervical cancer remains a major global health challenge, ranking fourth among malignancies in women, with an estimated 660,000 new cases and 350,000 deaths in 2022. Despite advances in vaccination and screening, incidence and mortality remain disproportionately high in low- and middle-income countries. The disease is strongly linked to persistent infection with high-risk human papillomavirus (HPV) types, predominantly HPV 16 and 18, whose E6 and E7 oncoproteins drive cervical intraepithelial neoplasia (CIN) and invasive cancer. This review summarizes current evidence on clinically relevant biomarkers in HPV-associated CIN and cervical cancer, emphasizing their role in screening, risk stratification, and disease management. Methods: We analyzed the recent literature focusing on validated and emerging biomarkers with potential clinical applications in HPV-related cervical disease. Results: Biomarkers are essential tools for improving early detection, assessment of progression risk, and personalized management. Established markers such as p16 immunostaining, p16/Ki-67 dual staining, and HPV E6/E7 mRNA assays increase diagnostic accuracy and reduce overtreatment. Prognostic indicators, including squamous cell carcinoma antigen (SCC-Ag) and telomerase activity, provide information on tumor burden and recurrence risk. Novel approaches—such as DNA methylation panels, HPV viral load quantification, ncRNAs, and cervico-vaginal microbiota profiling—show promise in refining risk assessment and supporting non-invasive follow-up strategies. Conclusions: The integration of validated biomarkers into clinical practice facilitates more effective triage, individualized treatment decisions, and optimal use of healthcare resources. Emerging biomarkers, once validated, could further improve precision in predicting lesion outcomes, ultimately reducing the global burden of cervical cancer and improving survival.