The microbiome landscape of oral cancer in young patients

The incidence of oral squamous cell carcinoma (OSCC) is rising in patients under the age of 50, without smoking or alcohol abuse. Viruses are not a causative factor of OSCC in younger patients. The oral microbiome has not been evaluated in this unique patient cohort for a potential bacterial etiology.

We report the bacterial diversity and composition of the largest cohort of OSCC patients with whole genome sequencing (n = 72) and compare it with oral mucosa from healthy controls (n = 10) using the Strengthening the Organization and Reporting of Microbiome Studies guidelines.

The microbial diversity between tumor, normal mucosa from cancer patients and healthy control mucosa is significantly different, with specific species (Streptococcus mitis, Haemophilus haemolyticus, and Cutibacterium acnes) reduced in normal mucosa of cancer patients as compared with healthy controls (adjusted P < .05). The microbial diversity is significantly higher in younger patients as compared with older patients (P < .001), with a reduced abundance of anaerobes in older patients (Aggregatibacter segnis, Gemella morbillorum, Peptostreptococcus stomatis, Filifactor alocis, and Porphyromonas endodontalis; adjusted P < .05).

The OSCC tissue of younger patients is significantly more polymicrobial, and their OSCC microbiomes harbor more anaerobic bacteria as compared with older patients. This compositional difference builds the hypothesis that the oral microbiome of younger OSCC patients may have a more hypoxic, immunosuppressive tumor microenvironment with its associated implications for treatment resistance and a potential link to baseline poor dentition.