Functional profiling of the oral microbiome reveals microbial and oncogenic signatures in never-smoking female patients with oral squamous cell carcinoma.

Background: The pathogenesis of oral squamous cell carcinoma (OSCC) in never-smoking females remains poorly understood, as these patients lack traditional risk factors. This subgroup accounts for an increasing proportion of OSCC cases and may exhibit distinct tumor biology. Here, we investigated the association between the alterations in the salivary microbiome and OSCC in never-smoking female patients. Materials and methods: Saliva samples from 72 never-smoking female patients with OSCC and 494 never-smoking healthy female controls were analyzed using 16S rRNA gene sequencing. Microbial community structure and function were compared using statistical analyses, machine learning algorithms, and pathway prediction with PICRUSt2. Results: Patients with OSCC exhibited significantly different microbial diversity and composition compared to controls. The genera Conclusions: Salivary microbiome alterations, both taxonomic and functional, are associated with OSCC in never-smoking females. These findings suggest a potential microbial contribution to carcinogenesis in this unique patient population and offer novel insights into disease mechanisms.