Biomarkers in the Screening and Management of Cervical Cancer

Abstract

Cervical cancer is the fourth most frequent cancer in women globally. Nearly all cases occur due to human papillomavirus (HPV) infection, with majority regressing on their own and most precancerous resolving spontaneously. However, there is still a risk of persistent chronic infection that may progress to malignancy. Thus, efforts to improve screening methods and search for more cost effective, accessible biomarkers of proven efficacy are crucial to reducing the global impact. This review is aimed at summarizing the wide array of already available and upcoming biomarkers that hold potential in screening and management of cervical cancer. The wide range of biomarkers including the recently recognized cell free HPV deoxyribonucleic acid (DNA) were reviewed for their potential utility in clinical settings. Every biomarker has been evaluated for its significance in clinical settings beginning from screening, risk categorization to treatment response, and monitoring of tumor relapse. The World Health Organization recommends HPV DNA testing for cervical cancer screening, with high-risk genotyping and viral load assessment as triage markers. E6/E7 messenger ribonucleic acid (RNA)-based assays show higher specificity, complementing traditional screening methods for borderline/low grade lesions. Dual staining by P16/Ki-67 diagnoses cervical dysplasia and cancerous lesions. New biomarkers such as mini-chromosome maintenance protein 5/topoisomerase I and II alpha offer maximum specificity for cervical intraepithelial neoplasia (CIN 2) and CIN 3 lesions. Squamous cell carcinoma antigen is a prognostic and predictive biomarker for poor survival rates. Micro-RNAs provide prognostic information and insights into patient responses to treatment modalities. Liquid biopsy is an alternative, minimally invasive modality for cancer management. Programmed cell death (PD-1)/PD-ligand 1 inhibitors are valuable in treating advanced or recurrent cancer. This review aims to bridge the gap between current and potential new biomarkers in cervical cancer screening and management.