Oral Microbiota in Early- and Late-Onset Tongue Cancers: A Pilot Case-Control Study

Evidence for the role of oral microbiota in tongue cancers is limited despite early-onset and unexplained etiology. We assessed oral microbiota profiles in saliva among participants with tongue cancers in the oral cavity compared with cancer-free controls. We conducted a case-control study in a tertiary care cancer hospital in Chennai, South India. Cases (N = 31) were those with newly diagnosed, pretreatment, biopsy-confirmed, early-stage (<4 cm size) tongue cancers, further classified as early-onset [diagnosed at 20-49 years (N = 12)] or late-onset cancers [diagnosed ≥50 years (N = 19)] for secondary exploratory analyses. Cancer-free controls (N = 31) were unrelated and frequency-matched to the cases on age and sex. Bacterial characterization of saliva was performed using 16S rRNA sequencing. Analyses (n = 175 genera) included linear regression for α-diversity, constrained analysis of principal coordinates, permutational multivariable analysis of variance for β-diversity, and analysis of compositions of microbiomes with bias correction for taxa abundance. We also examined differences in established bacterial pathogens selected a priori. The median age of participants was 52 years, and a third were women. Although there was no difference in α-diversity, β-diversity showed distinct clustering of bacterial genera in controls, early-onset, and late-onset cases. In overall and early-onset cases (vs. controls), genera Eikenella and Campylobacter showae were enriched. Furthermore, in early-onset cases (vs. controls), genera Alloprevotella, Comamonas, and Aggregatibacter were enriched, Oribacterium was depleted, and W5053 had differentially absent patterns. Beyond the established pathogens, this study offers important leads for future etiologic investigations, particularly in exploratory analyses of early-onset tongue cancers in the oral cavity.

This pilot study identified differences in overall microbiota and specific bacteria between cancer-free controls and tongue cancer cases in the oral cavity, specifically for early-onset cancers. The identified bacteria, including novel ones, can further be studied as salivary biomarkers for early-onset tongue cancers and to determine causality for prevention.