HPV status impacts oncobacteria abundance and prognostic relevance in head and neck squamous cell carcinoma

The intratumoral microbiome is emerging as an intrinsic microenvironment feature of some cancers, most notably those along the digestive tract. Opportunistic pathogenic bacteria, such as Fusobacterium nucleatum, can enrich within certain tumors, ultimately leading to alterations in the tumor microenvironment. However, why some tumors have a higher abundance of tumor-associated bacteria, or oncobacteria, than others remains unknown. To address this question, we quantified the presence of oncobacteria in head and neck squamous cell carcinomas (HNSCCs). We found that accumulation of oncobacteria was independent of tumor stage and size, as well as patient characteristics. In contrast, we discovered that human papillomavirus (HPV)-negative tumors exhibited significantly higher accumulation of oncobacteria than HPV+ tumors. Furthermore, the abundance of oncobacteria was associated with worse overall survival in HPV+ tumors. These findings were validated in an independent cohort. Subsequent analysis of Epstein-Barr virus (EBV)+ gastric cancer suggests this phenomenon generalizes to other virally mediated cancers. Co-culture studies of HNSCC cell lines with Fusobacterium nucleatum demonstrated that HPV-negative cells have enhanced proliferation in the presence of Fusobacterium nucleatum compared to HPV+ cells, suggestive of tumor cell intrinsic determinants of oncobacteria accumulation. Together, these results illuminate tumor features that contribute to the accumulation of oncobacteria.