The Role of the Oral Microbiota in the Etiopathogenesis of Oral Squamous Cell Carcinoma

Abstract

Dysbiosis in the oral environment may play a role in the etiopathogenesis of oral squamous cell carcinoma (OSCC). This review aims to summarize the current knowledge about the association of oral microbiota with OSCC and to describe possible etiopathogenetic mechanisms involved in processes of OSCC development and progression. Association studies included in this review were designed as case–control/case studies, analyzing the bacteriome, mycobiome, and virome from saliva, oral rinses, oral mucosal swabs, or oral mucosal tissue samples (deep and superficial) and comparing the results in healthy individuals to those with OSCC and/or with premalignant lesions. Changes in relative abundances of specific bacteria (e.g., Porphyromonas gingivalis, Fusobacterium nucleatum, Streptococcus sp.) and fungi (especially Candida sp.) were associated with OSCC. Viruses can also play a role; while the results of studies investigating the role of human papillomavirus in OSCC development are controversial, Epstein–Barr virus was positively correlated with OSCC. The oral microbiota has been linked to tumorigenesis through a variety of mechanisms, including the stimulation of cell proliferation, tumor invasiveness, angiogenesis, inhibition of cell apoptosis, induction of chronic inflammation, or production of oncometabolites. We also advocate for the necessity of performing a complex analysis of the microbiome in further studies and of standardizing the sampling procedures by establishing guidelines to support future meta-analyses.

Oral microbiota in human systematic diseases

“… 92 P. gingivalis inhibits activation of caspase-3 by activating Akt and Jak/Stat dual signaling pathways, blocking the increase of mitochondrial membrane permeability caused by caspase-3, and triggering inherent mitochondrial apoptosis. 93 , 94 At the same time, P. gingivalis can also activate the Jak/Akt/Stat3 signaling pathway to upregulate the anti-apoptotic protein Bcl-2, the tumor formation-related gene c-Myc, and the apoptosis-inhibiting gene Survivin, inhibiting the inherent apoptosis of mitochondria and cell apoptosis. 95 P. gingivalis can also activate the classical signaling pathway-phosphatidylinositol 3-hydroxy kinase (PI3K)/Akt signaling pathway, and activate the expression of NF-κB, participate in a series of processes such as anti-apoptosis, promote angiogenesis and tumor cell invasion, and can further promote anti-apoptosis factor expression.…”

MicroRNA-21 Expression as a Prognostic Biomarker in Oral Cancer: Systematic Review and Meta-Analysis

“…The most important risk factors for the development of oral cancer are tobacco and alcohol use, and it is estimated that approximately 80% of oral cancers occur due to these factors [ 7 , 8 ]. Other risk factors have been identified concomitantly with other pathologies, such as the presence of oral precancerous diseases (leukoplakia, erythroplakia, and lichen planus) and infectious agents (HPV, HCV, and EBV) [ 9 , 10 , 11 , 12 ]. Moreover, traumatic events may contribute to the pathogenesis of oral cancer, along with nutritional factors, genetic factors, ultraviolet radiation, and immunosuppression [ 1 ].…”

Prophyromonas gingivalis promoted the progression of oral squamous cell carcinoma by activating the neutrophil chemotaxis in the tumor microenvironment

“…The oral microbiota plays an important role in promoting the development of OSCC through mediating the direct metabolism of chemical carcinogens and the systemic in ammatory response [23]. Oral microbiota such as P. gingivalis can destroy the local immune response by establishing chronic in ammation and can lead to the immune escape of tumour cells [24].…”