Data Sheet 1_Streptococcus spp. in oral cancer: host-microbe interactions, mechanistic insights, and diagnostic implications.docx

Cancers of the oral cavity, particularly the widely prevalent oral squamous cell carcinoma, are associated with microbial dynamics within the oral niche. Among them, oral Streptococcus sp. – once neglected as a commensal habitat of the oral cavity – is currently highlighted for its pivotal dual interplay in the progression and suppression of oral cancers. In this comprehensive review, we describe the association of these oral streptococcal species with oral cancer in detail – right from their abundance and depletion during the progression of the disease, mechanistic synergy involving factors such as the surface receptors playing an intricate role in biofilm and co-adhesion strategies, to the inflammatory interplay in cancerous cells, and metabolic reprogramming associated with oral cancer. We also highlight oncogenic and onco-mitigating oral streptococci as biomarkers, observing a complex microbial interaction regulating tumor initiation and development. This review serves as a novel direction to address streptococcal mediators in oral cancer by bridging research gaps in mechanistic evidence and proposing effective prospects that can address deeper exploration of streptococcal dualistic role in the tumor microenvironment to decipher effective theragnostic strategies to manage oral cancer.