The Microbiome of Oral Squamous Cell Carcinomas: a Functional Perspective

This decade has witnessed increasing interest in the potential role of the oral microbiome in head and neck cancers, particularly oral squamous cell carcinoma (OSCC). Most studies have focused on the bacterial component of the microbiome (bacteriome), but the fungal component (mycobiome) is also receiving attention. In this review, we provide an overview of mechanisms by which the microbiome can contribute to oral carcinogenesis, and summarize results from clinical studies, especially focusing on those reporting functional microbiome analysis. Synthesizing and illustrating the evidence, we also suggest a new “passenger-turning-driver” functional model for the role of the microbiome in oral cancer. In vitro studies provide convincing evidence for the carcinogenicity of the periodontal bacteria Fusobacterium nucleatum and Porphyromonas gingivalis. However, results from clinical studies are inconsistent, with significant variations in composition of the microbiome associated with oral cancer. Methodological differences may partially explain the differing conclusion. However, variations observed may also reflect functional redundancy: the phenomenon that different species may be enriched in different samples, but still serve the same functions. Indeed, functional analyses of the bacteriome associated with oral cancer have revealed more consistent results, namely enrichment of a virulent, inflammatory bacteriome in the tumors. Apart from oncoviruses associated with a special entity of oral cancer, no consistent evidence implicates specific microbial species in OSCC etiology. Instead, the disturbed function of an initially “passenger” microbiome within the tumor microenvironment likely contributes to tumor progression by sustaining chronic inflammation.