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

INTRODUCTION

Persistent Human Papillomavirus (HPV) infection is linked to 99% of cervical cancer (CC) cases. HPV types 16 and 18 alone result in 75% of CC cases and thus are considered to be high-risk types (HR-HPV). CC is the third 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.

OBJECTIVES

The objectives of this review is to explore the utilization of molecular and viral biomarkers as a tool for early detection and prediction of HPV-induced cervical lesions that might progress to CC.

METHODS

The data bases PubMed, Google Scholar, EBSCO were searched using keywords CC screening, HPV, and recent molecular biomarkers. The search time frame was within the last 7 years. Studies on HPV-induced cancers other than CC were excluded; a total of 200 eligible articles were retrieved.

RESULTS

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 and the overexpression of markers of oxidative DNA damage and other proteins. The markers p16INK4a, 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 higher risk to progress to CC.

CONCLUSION

Adding different the above markers to the CC screening program scheme might offer a triage for prioritizing patient management.