Candida albicans is a context-dependent risk factor for malignant transformation of oral precancer lesions: a prospective cohort study of 734 Taiwanese patients

Background: Candida albicans has been implicated in oral carcinogenesis, but its role in the progression of oral potentially malignant disorders (OPMDs) remains unclear. We investigated whether high Candida burden in OPMD lesions predicts malignant transformation (MT) and whether this association varied by OPMD subtype. Patients and methods: In a multicenter prospective cohort study across seven hospitals in Taiwan, 734 OPMD patients were followed for a mean of 2.4 years. Oral lesion swabs were cultured on chromogenic agar to quantify Candida albicans level. Cox models were used to estimate hazard ratios (HRs) for MT to oral cancer. Results: MT occurred in 6.8% of patients. High Candida burden was independently associated with increased MT risk (aHR = 2.84; 95% CI: 1.40–5.75). Patients with oral submucous fibrosis (OSF) or verrucous hyperplasia (VH) also had elevated risk (aHR = 4.99; 95% CI: 1.54–10.38). Interaction analysis revealed strong individual risks for high Candida burden (aHR = 13.83) and OSF/VH (aHR = 13.67), with an attenuating interaction term (aHR = 0.11), yielding a substantial combined risk (HR ≈ 20.8). Stratified analysis showed the strongest effect in leukoplakia (HR = 12.19). Conclusions: High Candida albicans burden is a significant, subtype-dependent risk factor for malignant progression in OPMDs. These findings underline the role of fungal–host interactions in oral carcinogenesis and support the integration of fungal profiling into routine surveillance of OPMDs.