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

Abstract

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.

Microbiota and Oral Cancer as A Complex and Dynamic Microenvironment: A Narrative Review from Etiology to Prognosis

“…Interestingly, from several studies it has emerged that oncogenic viruses require inflammation to promote tumorigenesis [ 37 , 41 ]. Both HPV and EBV have been reported as oncovirus interplaying with local microbiome to promote host inflammatory carcinogenesis in head and neck cancers [ 42 ].…”

The Risks and Repercussions of Poor Oral Health Among Immigrants

“…Oral health and hygiene are particularly important given the recent research showing the associations between the oral microbiome and oral cavity cancer . Early studies examined bacterial cultures and metabolite levels, showing, for example, that people with more dental disease had nearly twice as much carcinogenic metabolite production and more complex bacterial composition .…”

“…3 Therefore, we, as health care practitioners and researchers, must consider and address the ubiquitous structures that marginalize certain peoples.Oral health and hygiene are particularly important given the recent research showing the associations between the oral microbiome and oral cavity cancer. 6 Early studies examined bacterial cultures and metabolite levels, showing, for example, that people with more dental disease had nearly twice as much carcinogenic metabolite production and more complex bacterial composition. 6,7 More recent studies use nextgeneration sequencing; comparing healthy controls with patients with precancerous and cancerous lesions, they show that as cancer progresses to advanced stages, the oral microbiome also has increasingly higher complexity and expression of genes involved in carbohydrate metabolism.…”

“…6 Early studies examined bacterial cultures and metabolite levels, showing, for example, that people with more dental disease had nearly twice as much carcinogenic metabolite production and more complex bacterial composition. 6,7 More recent studies use nextgeneration sequencing; comparing healthy controls with patients with precancerous and cancerous lesions, they show that as cancer progresses to advanced stages, the oral microbiome also has increasingly higher complexity and expression of genes involved in carbohydrate metabolism. [6][7][8] Opinion EDITORIAL jamaotolaryngology.com (Reprinted) JAMA Otolaryngology-Head & Neck Surgery…”

“…6,7 More recent studies use nextgeneration sequencing; comparing healthy controls with patients with precancerous and cancerous lesions, they show that as cancer progresses to advanced stages, the oral microbiome also has increasingly higher complexity and expression of genes involved in carbohydrate metabolism. [6][7][8] Opinion EDITORIAL jamaotolaryngology.com (Reprinted) JAMA Otolaryngology-Head & Neck Surgery…”