Activity is rapidly increasing in this field. Critical considerations/caveats include: association does not prove cause and effect; composition is significantly different by sample type [saliva, surface swab, tissue within the neoplasm]; nature of control sample [contralateral mucosa, matched subject with benign mucosal lesion; matched healthy subject – with/without tobacco/other risk factors]; fungi, bacteria, archaea, viruses are all relevant; stage is important [do oral potentially malignant disorders harbour an oncogenic flora?, are associated organisms of primary importance or only secondary invaders?]; laboratory techniques are critical; 16s or shotgun sequencing; contamination is a significant confounder. The functional metabolome of the microbiota is what matters.
Candida species are heavily involved, as well as bacteria capable of metabolizing alcohol to acetaldehyde, which adducts DNA. High-risk Human Papillomaviruses drive the majority of squamous cell carcinomas of the oropharynx and a minority of oral cavity SCC. No consistent small group of bacteria emerge: phyla Firmicutes, Bacteroides and Spirochaetes are enriched in our Indian cases, and at species level Fusobacterium nucleatum and Porphyromonas gingivalis are abundant in several studies: these are described in other gastrointestinal cancers and are oncogenic in vitro. These are keystone pathogens of destructive periodontitis, and there is strong epidemiological evidence of association between severity of periodontal disease and risk of oral cancer.
What is consistent is the function of the microbiota: most consortia described are pro-inflammatory. We propose < https://link.springer.com/article/10.1007/s40496-019-0215-5> a “passenger turned driver” scenario whereby organisms initially colonise cancer tissues, including the deep invading front, and consortia are selected by the anerobic and acid environment of the tissues. As they flourish, their metabolic products are strongly pro-inflammatory, favouring tumour progression.
Maintaining a health-associated oral microbiome [by sensible diet and reasonable oral hygiene], and treatment of periodontal disease, should contribute to risk mitigation. Might probiotics have a role? Might antibiotics be a treatment component? As always, avoidance of tobacco and areca nut, mimimal alcohol intake, and diets rich in antioxidant macro- and micro-nutrients are the mainstay of prevention.