Oral Microbiota and Oral Squamous Cell Carcinoma: a Review of Their Relation and Carcinogenic Mechanisms

Abstract

Oral Squamous Cell Carcinoma (OSCC) is among the most prevalent malignancies of the oral cavity, representing a significant global health burden due to its high morbidity and mortality rates. Recent research has revealed that beyond conventional etiological factors such as tobacco, alcohol consumption, and human papillomavirus infection, alterations in the oral microbiota play a pivotal role in oral carcinogenesis. The oral cavity hosts a complex and dynamic microbial ecosystem, comprising bacteria, fungi, and viruses that coexist in a delicate balance with the host. Disruption of this equilibrium, known as dysbiosis, has been increasingly associated with inflammatory and neoplastic processes within the oral mucosa. Emerging evidence suggests that specific bacterial species, including Fusobacterium nucleatum, Porphyromonas gingivalis, and Prevotella intermedia, may contribute to the initiation and progression of OSCC through mechanisms involving chronic inflammation, immune modulation, and the production of carcinogenic metabolites. These pathogens promote a pro-tumorigenic microenvironment by inducing cytokine release, activating oncogenic signaling pathways such as NF-κB and STAT3, and interfering with cell cycle regulation and apoptosis. Furthermore, microbial metabolites such as acetaldehyde, lipopolysaccharides, and reactive oxygen species contribute to DNA damage, genomic instability, and epigenetic modifications that accelerate malignant transformation. The interplay between host immunity and microbial activity further exacerbates these effects, fostering conditions conducive to cancer development. Advances in metagenomic sequencing and bioinformatics have enhanced our understanding of microbial diversity and its correlation with tumor biology, offering new diagnostic and prognostic biomarkers for early OSCC detection. This review comprehensively explores the intricate association between oral microbiota and OSCC, emphasizing microbial-driven carcinogenic mechanisms, host-microbe interactions, and potential therapeutic strategies targeting oral dysbiosis. By elucidating these complex relationships, this study underscores the importance of integrating microbiome analysis into oral cancer research and clinical management. Understanding the microbial contribution to oral oncogenesis may pave the way for innovative preventive and therapeutic interventions, including microbiota modulation, antimicrobial therapy, and probiotic-based approaches aimed at restoring microbial homeostasis and reducing OSCC risk.