The Genomic Landscape of Head and Neck Cancer-associated Streptococci

Disruption of the oral microbiome is increasingly implicated in head and neck cancer (HNC), yet the genomic adaptations that commensal bacteria acquire in tumour-associated environments remain unclear. We performed genome-resolved analyses of 101 complete Streptococcus genomes from the tumours and oral cavities of 31 HNC patients. Phylogenomic analysis identified 35 species, including ten novel species belonging to the Mitis group. The Streptococcus genus shared 29 core genes, with analysis of accessory genomes (1.7-2.5 Mbp) showing extensive horizontal gene transfer (HGT), supported by 245 ICE clusters, 82 prophages and 4 plasmid groups. Comparison with 391 published genomes from the oral cavities of healthy individuals showed that tumour-associated isolates exhibited niche-specific expansions of carbohydrate-active enzymes and enrichment of genes involved in sugar transport, thiamine biosynthesis and antimicrobial resistance. Together, these findings reveal distinct HGT-driven genomic remodelling in tumour-associated Streptococcus and provide the first comprehensive genomic resource for examining microbiome adaptation in HNC. Graphical Abstract