Immunological Biomarkers in Oral Leukoplakia According to Oral Intraepithelial Neoplasia (OIN) Classification: A Comparative Analysis of Salivary and Plasma Cytokines.

BACKGROUND

Oral leukoplakia (OL) is the most common oral potentially malignant disorder, defined as a white patch or plaque not attributable to other causes. While OL carries an inherent risk of malignant transformation, the underlying immunological changes remain poorly characterized. This study aimed to profile a broad panel of cytokines in saliva and plasma of OL patients in comparison to healthy controls, in order to elucidate local and systemic immunoinflammatory alterations associated with OL.

METHODS

Thirty patients with clinically and histopathologically confirmed OL and 30 age- and gender-matched healthy controls were enrolled. Detailed clinical examinations were performed, including lesion characterization and psychosocial assessments. Unstimulated whole saliva and peripheral blood samples were collected, and concentrations of 13 cytokines/chemokines (IL-1β, IL-6, IL-8/CXCL8, IL-10, IL-12p70, IL-17A, IL-18, IL-23, IL-33, TNF-α, IFN-γ, IFN-α2, and MCP-1/CCL2) were measured using a multiplex bead-based immunoassay. Group comparisons were performed using appropriate statistical tests (χ2/Fisher's exact test for categorical variables and t-test or Mann-Whitney U test for continuous variables), with statistical significance set at p < 0.05.

RESULTS

OL patients (mean age 52.4 ± 10.7 years) and controls (59.9 ± 12.8 years) showed no significant differences in gender, socioeconomic status, or psychological scores. Salivary levels of IL-1β, TNF-α, MCP-1, IL-8, and IL-18 were significantly lower in OL patients compared to controls (p < 0.01 for all), whereas other salivary cytokines (IFN-α2, IFN-γ, IL-6, IL-10, IL-12p70, IL-17A, IL-23, IL-33) showed no significant differences. In contrast, plasma levels of IFN-α2, IL-6, IL-12p70, IL-17A, IL-18, and IL-33 were significantly higher in OL patients than in controls (p < 0.05), indicating systemic inflammation, while plasma IL-1β, IFN-γ, TNF-α, MCP-1, IL-8, IL-10, and IL-23 did not differ. No significant differences in salivary cortisol, liver enzymes, or hepatitis viral markers were observed between groups. Across histopathological subgroups, cytokine concentrations did not significantly differ between lesions graded as hyperkeratosis, OIN1, OIN2, or OIN3, although a trend toward higher plasma IL-6, IL-17A, and IL-18 levels was observed in cases with higher OIN grades.

CONCLUSION

These findings shed light on the inflammatory profile of OL. The decrease in salivary IL-1β, IL-8, TNF-α, and MCP-1 may indicate a more suppressed local immune response, whereas the higher plasma levels of IL-6, IL-17A, IL-18, and IL-33 tend to be seen in lesions showing greater degrees of dysplasia. In particular, patients with higher OIN grades often display this systemic inflammatory shift, which may signal an increased risk of progression.