Salivary Biomarkers as a Diagnostic Tool for Oral Potentially Malignant Disorders: A Systematic Review

Background Oral potentially malignant disorders (OPMDs) are heterogeneous mucosal lesions with variable risk of malignant transformation. Early detection remains challenging due to reliance on invasive biopsy and subjective clinical assessment. Saliva has emerged as a promising noninvasive biofluid for molecular diagnosis.Types of studies reviewed A systematic review of the literature was conducted using PubMed, MEDLINE, EBSCOhost, and Google Scholar up to April 2025 in accordance with PRISMA 2020 guidelines. Studies evaluating the diagnostic accuracy of salivary biomarkers in OPMDs were included. Diagnostic parameters such as sensitivity, specificity, and area under the curve (AUC) were extracted, and methodological quality was assessed using the QUADAS-2 tool. Due to substantial clinical and methodological heterogeneity, findings were synthesized qualitatively.Results Twenty studies were included. Salivary transcriptomic, proteomic, metabolomic, and protease biomarkers demonstrated variable diagnostic performance across different OPMD subtypes. Several biomarkers showed high sensitivity and specificity; however, these findings were predominantly derived from small, single-center studies with limited external validation.Practical implications Salivary biomarkers offer a noninvasive approach for early OPMD detection and screening, potentially reducing biopsies and improving access; however, standardization, validation, and integration into clinical practice are essential before routine use.