Association of Candida and fluconazole therapy with proinflammatory cytokines in oral leukoplakia: a pilot study

Objectives Chronic inflammation caused by infection may lead to the production of proinflammatory cytokines (PICs) that can cause DNA damage and cell proliferation, thus playing a role in carcinogenesis. Candida infection has been reported to be increased in oral leukoplakia (OL) and is associated with an increased rate of malignant transformation into oral squamous cell carcinoma (OSCC). In vitro studies have demonstrated that the interactions between Candida and the oral epithelium lead to the release of PICs (interleukin [IL]-6, IL-8. IL-17, tumor necrosis factor [TNF]-α) that have also been found to be upregulated in OSCC and OL. This study aims to determine the correlation between Candida infection and PICs and their response to fluconazole therapy in OL. Methods Immunocompetent adult patients with OL (30 homogenous leukoplakia [HL], 30 nonhomogenous leukoplakia [NHL]) and 30 age- and sex-matched healthy control subjects (C) with no predisposing factors for oral candidal infection were recruited. Sterile cotton swabs and polyvinyl alcohol ophthalmic sponges were used to take samples from the lesional surface in OL and from the buccal mucosa in C for direct microscopy and culture for Candida and to determine levels of PICs (IL-6, IL-8, IL-17, TNF-α) by enzyme-linked immunosorbent assay, respectively. Sampling for PICs was repeated from the same sites in OL after treatment with tablet fluconazole 100 mg (oral rinse for 2 minutes and swallow) once daily for 14 days. Chi-square and Mann-Whitney U tests were used to estimate the difference between the groups. Results Forty percent of patients with NHL and 30% of patients with HL had positive findings for Candida albicans. Levels of IL-6, IL-8, and IL-17 were observed to be significantly higher (P Conclusions Candidal infection is common in OL and causes release of PICs. There is a decrease in levels of these PICs and clinical improvement after fluconazole therapy in both NHL and HL. Hence, antifungal therapy in the management of OL can reduce the inflammatory milieu in which carcinogenesis can occur.