Oral squamous cell carcinoma is associated with altered salivary microbiome structure and reduced community evenness.

Oral squamous cell carcinoma (OSCC) remains a major global health burden, highlighting the need for improved non-invasive tools for early detection and disease monitoring. Because saliva is easily accessible and reflects the oral microenvironment, the salivary microbiome has emerged as a promising source of candidate biomarkers. In this study, we characterized the salivary microbiota of 113 individuals, including 52 patients with OSCC and 61 healthy controls, using 16S rRNA gene sequencing targeting the V3-V4 region. Microbial diversity and composition were analyzed using complementary bioinformatic and statistical approaches, including four differential abundance methods (MaAsLin2, ANCOM-BC2, LinDA, and ALDEx2). OSCC was associated with significant differences in overall microbial community structure, as shown by beta diversity analyses, together with reduced community evenness but no major loss of richness. Differential abundance analyses identified several taxa overrepresented in OSCC, including the genera Tannerella, Solobacterium, Dialister, and Bergeyella, as well as species such as Solobacterium moorei, Tannerella forsythia, and Prevotella nigrescens. In contrast, Leptotrichia was underrepresented in OSCC. These findings support the existence of an OSCC-associated salivary dysbiosis characterized by ecological restructuring rather than global diversity loss. The identified taxa represent exploratory candidate microbial signatures associated with OSCC that require validation in larger, independent, and longitudinal cohorts before any potential clinical application can be considered.