Diagnostic Value of Serum and Salivary Podoplanin as Clinical Biomarkers for Distinguishing Oral Cancer from Oral Leukoplakia

<b>Objective:</b> This study aimed to evaluate serum and salivary podoplanin (PDPN) levels in patients with oral cancer (OC) and oral leukoplakia (OL) and to investigate their potential role as diagnostic biomarkers in distinguishing between these conditions. <b>Materials and Method:</b> Ninety participants were enrolled: 30 healthy controls, 30 patients with OL, and 30 patients with histopathologically confirmed OC. All cases were recruited from the Department of Otorhinolaryngology, Cerrahpaşa Medical Faculty and Istanbul Atlas University Hospital. Demographic characteristics, comorbidities, and biochemical parameters were recorded. Serum and salivary PDPN levels were measured using the ELISA method. <b>Results:</b> Serum PDPN levels were significantly higher in the OC group (3.25 ± 0.80 ng/mL) compared with both OL (1.85 ± 0.56 ng/mL) and controls (0.98 ± 0.42 ng/mL) (<i>p</i> < 0.001). Salivary PDPN levels showed a similar pattern, being highest in OC (2.65 ± 0.75 ng/mL), followed by leukoplakia (1.40 ± 0.45 ng/mL), and controls (0.72 ± 0.30 ng/mL) (<i>p</i> < 0.001). Importantly, both serum and salivary PDPN concentrations increased progressively with increasing epithelial dysplasia severity among patients with OL (one-way ANOVA, <i>p</i> < 0.001). ROC analysis demonstrated excellent diagnostic accuracy for OC: AUC = 0.976 for serum PDPN (cut-off: 2.0 ng/mL; sensitivity 93.3%, specificity 100%) and AUC = 0.987 for salivary PDPN (cut-off 1.24 ng/mL; sensitivity 93.3%, specificity 95%). <b>Conclusions:</b> Serum and salivary PDPN levels were significantly elevated in patients with OC and demonstrated excellent diagnostic performance in distinguishing malignant lesions from OL and healthy controls. The observed stepwise increase in PDPN levels with dysplasia severity further supports its role in malignant transformation. Notably, salivary PDPN represents a non-invasive, practical, and reproducible biomarker that may aid in early detection and risk stratification of high-risk oral premalignant lesions. PDPN assessment could therefore complement clinical and histopathological evaluation, although larger prospective studies are warranted to validate its diagnostic and prognostic utility.