Molecular markers predicting the progression and prognosis of human papillomavirus-induced cervical lesions to cervical cancer.

Abstract

Persistent Human Papillomavirus (HPV) infection is linked to 99% of cervical cancer (CC) cases. HPV types 16 and 18 aloneresult in 75% of CC cases and thus are considered to be high-risk types (HR-HPV). CC is thethird most common cancer among women globally. Approximately, 7000 patients die from it yearly. It is worthy to note that not every patient with HPV precancerous lesions will progress to CC. The objectives of this review is to explore the utilization ofmolecular and viral biomarkers asa tool for early detection and prediction of HPV-induced cervical lesions that might progress to CC. The data basesPubMed, Google Scholar, EBSCO were searched using keywords CC screening, HPV, and recent molecular biomarkers. The search time frame was within the last 7years. Studies on HPV-induced cancers other than CC were excluded; a total of 200 eligible articles were retrieved. In this review we explored the current literature about HPV virology, virulence genes and early diagnostic/prognostic molecular biomarkers in CC. The oncogenic property of HPV is attributed to viral expression of various early proteins (E5, E6, E7). The interaction between viral oncoproteins and the cellular genetic apparatus alters the expression of many genes at different phases of the disease. There was an association between cervical lesions induced by HR-HPV andtheoverexpression of markers of oxidative DNA damage and other proteins. The markersp16INK4a, programmed cell death-1 (PD-1)/programmed cell death ligand 1, mismatch repair enzymes (MMR), miRNA-377, claudin family (CLDN)are dysregulated and are associated with high risk lesions. Furthermore, advanced older cervical lesions were associated with high methylation levels and higherrisk to progress to CC. Adding differentthe abovemarkers to the CC screening program scheme might offera triage for prioritizing patient management.