Role of Porphyromonas gingivalis in oral and orodigestive squamous cell carcinoma.

ABSTRACT

Oral and esophageal squamous cell carcinomas harbor a diverse microbiome that differs compositionally from precancerous and healthy tissues. Though causality is yet to be definitively established, emerging trends implicate periodontal pathogens such as Porphyromonas gingivalis as associated with the cancerous state. Moreover, infection with P. gingivalis correlates with a poor prognosis, and P. gingivalis is oncopathogenic in animal models. Mechanistically, properties of P. gingivalis that have been established in vitro and could promote tumor development include induction of a dysbiotic inflammatory microenvironment, inhibition of apoptosis, increased cell proliferation, enhanced angiogenesis, activation of epithelial-to-mesenchymal transition, and production of carcinogenic metabolites. The microbial community context is also relevant to oncopathogenicity, and consortia of P. gingivalis and Fusobacterium nucleatum are synergistically pathogenic in oral cancer models in vivo. In contrast, oral streptococci, such as Streptococcus gordonii, can antagonize protumorigenic epithelial cell phenotypes induced by P. gingivalis, indicating functionally specialized roles for bacteria in oncogenic communities. Consistent with the notion of the bacterial community constituting the etiologic unit, metatranscriptomic data indicate that functional, rather than compositional, properties of the tumor-associated communities have more relevance to cancer development. A consistent association of P. gingivalis with oral and orodigestive carcinoma could have diagnostic potential for early detection of these conditions that have a high incidence and low survival rates.