Prognostic Biomarkers for Malignant Progression of Oral Epithelial Dysplasia: An Updated Systematic Review and Meta-Analysis

Oral Epithelial Dysplasia (OED) is a premalignant condition, which carries an appreciable risk of malignant progression. The current grading system for severity of OED, as defined by the World Health Organisation, is a valuable clinical tool but further work is required to improve the accuracy of predicting OED malignant progression. This systematic review aims to assess progress in prognostic biomarker discovery in OED over the past 16 years.The primary objective was to update the latest evidence on prognostic biomarkers that may predict malignant progression of OED – with strict inclusion criteria of studies with a longitudinal design and long-term follow-up data to enhance the robustness and clinical translational potential of the findings.Out of 2,829 studies identified through searching five databases, 20 met our inclusion criteria. These studies investigated a total of 32 biomarkers and 20 of which demonstrated significant potential in predicting malignant progression of OED. Meta-analysis demonstrated significant prognostic value of 4 biomarkers: Podoplanin, EGFR expression, p16 methylation and DNA aneuploidy.Our review identifies 20 reported biomarkers with prognostic potential for predicting malignant progression in OED, however the translation of these biomarkers into clinical practice remains elusive. Further research is required and should focus on validating promising biomarkers identified within this review in large cohort studies with adherence to standardised reporting guidelines