It Takes Two to Tango: A Review of Oncogenic Virus and Host Microbiome Associated Inflammation in Head and Neck Cancer

Simple Summary Certain viruses, specifically, human papillomavirus (HPV) and Epstein-Barr virus (EBV), have been linked with the development of head and neck cancer. In this study, we review the mechanisms by which (these) viruses lead to cellular transformation and a chronic inflammatory state. Given that the head and neck host a rich microbiome (which itself is intrinsically linked to inflammation), we scrutinize the literature to highlight the interplay between viruses, cellular transformation, inflammation, and the local host microbiome in head and neck cancer. While the two primary risk factors for head and neck squamous cell carcinoma (HNSCC) are alcohol and tobacco, viruses account for an important and significant upward trend in HNSCC incidence. Human papillomavirus (HPV) is the causative agent for a subset of oropharyngeal squamous cell carcinoma (OPSCC)-a cancer that is impacting a rapidly growing group of typically middle-aged non-smoking white males. While HPV is a ubiquitously present (with about 1% of the population having high-risk oral HPV infection at any one time), less than 1% of those infected with high-risk strains develop OPSCC-suggesting that additional cofactors or coinfections may be required. Epstein-Barr virus (EBV) is a similarly ubiquitous virus that is strongly linked to nasopharyngeal carcinoma (NPC). Both of these viruses cause cellular transformation and chronic inflammation. While dysbiosis of the human microbiome has been associated with similar chronic inflammation and the pathogenesis of mucosal diseases (including OPSCC and NPC), a significant knowledge gap remains in understanding the role of bacterial-viral interactions in the initiation, development, and progression of head and neck cancers. In this review, we utilize the known associations of HPV with OPSCC and EBV with NPC to investigate these interactions. We thoroughly review the literature and highlight how perturbations of the pharyngeal microbiome may impact host-microbiome-tumor-viral interactions-leading to tumor growth.

Automated summary

Certain viruses, such as human papillomavirus (HPV) and Epstein-Barr virus (EBV), are associated with the development of head and neck cancer. This study reviews the mechanisms by which these viruses cause cellular transformation and chronic inflammation, and examines the interplay between viruses, cellular transformation, inflammation, and the local host microbiome in head and neck cancer.