The Role of the Microbiome in Oral Squamous Cell Carcinoma with Insight into the Microbiome–Treatment Axis

Abstract

Oral squamous cell carcinoma (OSCC) is one of the leading presentations of head and neck cancer (HNC). The first part of this review will describe the highlights of the oral microbiome in health and normal development while demonstrating how both the oral and gut microbiome can map OSCC development, progression, treatment and the potential side effects associated with its management. We then scope the dynamics of the various microorganisms of the oral cavity, including bacteria, mycoplasma, fungi, archaea and viruses, and describe the characteristic roles they may play in OSCC development. We also highlight how the human immunodeficiency viruses (HIV) may impinge on the host microbiome and increase the burden of oral premalignant lesions and OSCC in patients with HIV. Finally, we summarise current insights into the microbiome–treatment axis pertaining to OSCC, and show how the microbiome is affected by radiotherapy, chemotherapy, immunotherapy and also how these therapies are affected by the state of the microbiome, potentially determining the success or failure of some of these treatments.

Distinct microbial communities colonize tonsillar squamous cell carcinoma

“…31 The Gram-negative and invasive bacteria Fusobacterium (F.) nucleatum and Porphyromonas (P.) gingivalis are frequently discussed to be causally involved in the induction of squamous cell carcinoma in the oropharynx. 32,33 F. nucleatum and P. gingivalis have been shown to promote tumor progression in an oropharyngeal squamous cell carcinoma mouse model 34 and F. nucleatum subspecies polymorphum has been found to be significantly increased in oral squamous cell carcinoma biopsies. 35 Moreover, an elevated abundance in oral wash and surface swabs of oral squamous cell carcinoma has been described for the genus Fusobacterium.…”

Crosstalk between the oral microbiota, mucosal immunity, and the epithelial barrier regulates oral mucosal disease pathogenesis

“…112 In addition, several damaging metabolic end products, such as volatile sulfur compounds, organic acids, and aldehydes, and nitrosatable compounds are reported to be associated with the development of oral cancer. 27 Many oral microbiota, including the Streptococcus species (S. gordonii, S. mitis, S. oralis, S. salivarius, and S. sanguinis), Rothia species, P. gingivalis and C. albicans, 113 produce ACH, which has the ability to exert DNA damage and cause excess proliferation in the epithelium. Bacteria and fungi also can catalyze nitrosatable compounds to form N-nitroso compounds through nitridation pathways.…”

“…[20][21][22][23][24] An increasing body of evidence suggests that perturbations of the mucosal microbiota can modulate innate and adaptive immune responses, with inflammation arising due to a reduction in the number of symbiont microorganisms and/or an increase in the number of pathobiont microorganisms (commensal bacteria with pathogenic potential). [25][26][27][28] For example, one mechanism by which these microbes regulate immunity is by controlling regulatory T cells (Tregs) and T helper 17 (Th17) cells. [29][30][31] In addition, the epithelium recognizes and responds to the microbiota, and in turn, microbial dysbiosis and associated metabolite alterations destroy the integrity of the mucosal epithelium and its barrier functions.…”

Distinct Microbial Communities Colonize Tonsillar Squamous Cell Carcinoma

“…Localized chronic in ammation is thought to be one of the major drivers of carcinogenesis [31]. The Gram-negative and invasive bacteria Fusobacterium (F.) nucleatum and Porphyromonas (P.) gingivalis are frequently discussed to be causally involved in the induction of squamous cell carcinoma in the oropharynx [32,33]. F. nucleatum and P. gingivalis have been shown to promote tumor progression in an oropharyngeal squamous cell carcinoma mouse model [34] and F. nucleatum subspecies polymorphum has been found to be signi cantly increased in oral squamous cell carcinoma biopsies [35].…”