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Clinically, oral fungating lesions frequently occur in cancer patients following radiation and chemotherapy. However, their role in carcinogenesis has not been fully understood. Our previous finding showed that defective IKKα-mediated autoreactive T cells promote fungal infection and esophageal malignancy, but whether IKKα-mediated altered epithelial properties regulate fungal colonization and carcinogenesis remains to be tested. To investigate whether IKKα-mediated altered epithelial properties regulate fungal colonization and carcinogenesis, we orally infected mice lacking Ikkα (IkkαΔSOE) or both Ikkα and Stat3 (IkkαΔSOEStat3ΔSOE) in the stem cells of the skin and mouth with fungi. We found that oral fungal infection enhanced Ikkα ablation-mediated skin and oral carcinogenesis in association with increased oral and skin bacteria counts and altered oral bacteria phylum from gram-positive to gram-negative …