Retrospective study of association of intratumoral microbiota with prognosis in head and neck squamous cell carcinoma

A retrospective cohort study at Montefiore Einstein Cancer Center (New York, NY) investigated whether intratumoral bacterial load and diversity are associated with survival outcomes in head and neck squamous cell carcinoma (HNSCC) as well as the survival impact of HPV status. The study included 312 adults with surgically treated, primary HNSCC between 2000 and 2023. Intratumoral bacterial load was quantified via PCR, and microbial diversity was assessed via 16S rRNA in 312 tumor and 34 paired normal tissues. HNSCC tumors showed higher bacterial load and lower bacterial diversity compared with adjacent normal tissues, High bacterial load (HR 1.85; p<0.001) and low bacterial diversity (HR 1.65; p=0.003) were independently associated with reduced overall survival, with the greatest risk in patients carrying both features (HR 3.0; p<0.001). The high-risk bacterial features were less frequent in HPV-positive than in HPV-negative tumors (high load: OR 0.46; p=0.001; low diversity: OR 0.51; p=0.004) and their prognostic significance was more pronounced in HPV-negative cases. Taxonomic profiling revealed marked depletion of predominant bacterial taxa in HNSCC, especially in HPV-negative tumors. Loss of the class TM7-3 and the orders Actinomycetales and Burhholderiales was associated with poor HNSCC survival. The authors conclude that high intratumoral bacterial load and low diversity are prognostic factors in HNSCC.