Comparative Evaluation of Salivary Inflammatory Cytokines and microRNA Biomarkers Across the Spectrum of Oral Carcinogenesis

Background Oral potentially malignant disorders (OPMDs) represent precursor conditions that carry an elevated probability of progressing to oral squamous cell carcinoma (OSCC). Despite ongoing research efforts, identifying dependable, non-invasive markers that can detect early molecular changes linked to malignant conversion continues to present a significant clinical obstacle. Objective To evaluate the diagnostic utility of salivary inflammatory cytokines (IL-10 and IL-17) and microRNAs (miR-21, miR-138, and miR-184) in healthy individuals, patients with OPMDs, and patients with OSCC, and to assess the performance of a combined biomarker panel for oral cancer clinical stratification. Methods A cross-sectional analytical study was conducted involving 150 participants categorized into healthy controls (n=50), OPMD patients (n=50), and histopathologically confirmed OSCC patients (n=50). Salivary IL-10 and IL-17 concentrations were quantified using enzyme-linked immunosorbent assay (ELISA), whereas miR-21, miR-138, and miR-184 expression levels were measured using quantitative reverse-transcription polymerase chain reaction (qRT-PCR). Relative miRNA expression was calculated using the 2^−ΔΔCt method. Diagnostic performance was evaluated using receiver operating characteristic (ROC) curve analysis. Results Significant alterations in salivary cytokine and microRNA expression were observed across the disease spectrum. miR-21 and miR-184 demonstrated progressive upregulation, whereas miR-138 showed progressive downregulation from healthy controls to OPMD and OSCC patients (all p<0.001). Both IL-10 and IL-17 were significantly elevated in OPMD and OSCC patients compared with healthy controls (both p<0.001). Biomarker expression profiles were significantly associated with dysplasia severity and tumor stage. Among individual biomarkers, miR-138 demonstrated the highest diagnostic accuracy (AUC=0.84), followed by IL-17 (AUC=0.82), miR-21 (AUC=0.80), miR-184 (AUC=0.76), and IL-10 (AUC=0.74). The combined cytokine-microRNA panel achieved superior performance, with an AUC of 0.93, sensitivity of 90%, and specificity of 88%. Conclusions The findings support the potential utility of integrated salivary biomarker profiling as a non-invasive approach for early detection, clinical stratification, and disease monitoring in oral carcinogenesis. The combined biomarker panel highlights the potential of integrated salivary diagnostics for improving the non-invasive detection and clinical assessment of OPMDs and OSCC.