Ganly I, et al. - Since the lack of recognized risk factors of smoking, alcohol consumption, and human papilloma virus (HPV) has been reported in many new cases of oral cavity squamous cell cancer (OC-SCC), researchers investigated whether there exists a link between oral microbiome and OC-SCC in non-smoking, HPV-negative patients. Comparisons were made with respect to oral microbiome of HPV-negative non-smoker OC-SCC (n=18), premalignant lesions (PML; n=8), and normal control patients (n=12). In OC-SCC, periodontal pathogens Fusobacterium, Prevotella, and Alloprevotella were enriched, while commensal Streptococcus was depleted. Two types of oral microbiome were defined on the basis of four genera plus a marker genus Veillonella for PML. Along the controls→PML→OC-SCC progression sequence, the investigators found a progressive increase of genes encoding HSP90 and ligands for TLRs 1, 2, and 4 in gene/pathway analysis. Overall, periodontal pathogens were found to be related to OC-SCC in non-smoking, HPV-negative patients.