Assessment of Interleukin-6 (IL-6) and Cotinine Levels in the Saliva of Patients with Precancerous Lesions and Oral Mucosa Cancer

Background/Objectives: Oral squamous cell carcinoma (OSCC) and oral potentially malignant disorders (OPMDs) remain major clinical challenges due to late diagnosis and limited prognostic markers. This study evaluated salivary interleukin-6 (IL-6) and cotinine as potential biomarkers for oral epithelial transformation and exposure to risk factors. Methods: From 267 individuals with histopathologically confirmed OPMDs or OSCC, 47 patients met the inclusion criteria and were enrolled (18 OPMDs, 29 OSCC). A control group comprised 40 individuals without oral mucosal pathology. Unstimulated saliva samples were collected and analyzed for IL-6 and cotinine concentrations. Biomarker levels were compared among groups and evaluated in relation to smoking exposure, alcohol use, and clinicopathological parameters. Results: Salivary IL-6 and cotinine levels differed significantly among groups (p < 0.05), with the highest concentrations observed in OSCC patients, intermediate levels in OPMDs, and the lowest levels in controls. Cotinine levels were significantly higher in smokers and individuals with greater tobacco exposure in both study groups, whereas IL-6 concentrations were not significantly associated with smoking or alcohol consumption. No correlation between IL-6 and cotinine was found in OPMDs or OSCC; however, a moderate negative correlation was observed in controls. Conclusions: Salivary IL-6 and cotinine demonstrate potential as complementary, non-invasive biomarkers for assessing oral epithelial transformation and tobacco exposure. Their combined evaluation may support risk stratification and early detection in patients with OPMDs.