Candida albicans in oral squamous cell carcinoma: a review of mechanistic pathways and clinical translational strategies.

Authors

Peining Zheng, Qin Xie, Kenneth K Y Cheng, Jordy Evan Sulaiman, Xiaojing Huang, Guowu Gan

Published in

Frontiers in cellular and infection microbiology. Volume 16. Pages 1923618. Epub Sep 28, 2026.

Abstract

Oral squamous cell carcinoma (OSCC) develops within a complex mucosal ecosystem in which microbial dysbiosis, epithelial injury, inflammation, and immune remodeling interact with established carcinogenic exposures. Although Candida albicans has repeatedly been associated with OSCC and oral potentially malignant disorders (OPMDs), its causal and translational significance remains uncertain. This review critically evaluates clinical, microbiological, mechanistic, and translational evidence, with particular attention to the distinction between association, biological plausibility, and causal inference. Current evidence is more consistent with context-dependent tumor-promoting activity than with independent carcinogenicity. Proposed mechanisms include acetaldehyde- and nitrosamine-related genotoxicity, inflammatory and immune-microenvironment remodeling, virulence factor-mediated epithelial injury, and biofilm-associated persistence; however, no single mechanism has been established as necessary or sufficient for Candida-associated tumor promotion. Longitudinal human evidence supports an association between increased fungal burden and malignant transformation in OPMDs, but no validated fungal-burden, virulence, or immune-cell threshold currently distinguishes colonization from pathological amplification. Candidate biomarkers, risk-stratification approaches, and fungal-directed interventions therefore remain investigational. Future studies should integrate standardized longitudinal sampling, spatially resolved fungal-bacterial-host analysis, and functional perturbation to determine whether C. albicans provides reproducible incremental value for clinical risk assessment or therapeutic targeting.

PMID:
42865781
Bibliographic data and abstract were imported from PubMed on 13 Oct 2026.

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