Influence of pathogens on host genome and epigenome in development of head and neck cancer

Abstract

Background: Head and neck cancer (HNSCC) is a heterogeneous group of cancers, affecting multiple regions such as oral cavity, pharynx, larynx, and nasal region, each showing a distinct molecular profile. HNSCC accounts for more than 6 million cases worldwide, soaring mainly in the developing countries.

Recent findings: The aetiology of HNSCC is complex and multifactorial, involving both genetic and environmental factors. The critical role of microbiome, which includes bacteria, viruses, and fungi, is under spotlight due to the recent reports on their contribution in the development and progression of HNSCC. This review focuses on the effect of opportunistic pathogens on the host genome and epigenome, which contributes to the disease progression. Drawing parallels from the host-pathogen interactions observed in other tumour types arising from the epithelial tissue such as colorectal cancer, the review also calls attention to the potential explorations of the role of pathogens in HNSCC biology and discusses the clinical implications of microbiome research in detection and treatment of HNSCC.

Conclusion: Our understanding of the genomic effects of the microbes on the disease progression and the mechanistic insights of the host-pathogen interaction will pave way to novel treatment and preventive approaches in HNSCC.

Keywords: cancer associated pathogens; head and neck cancer; host-pathogen interaction.

FIGURE 1

Genomic and epigenomic influence of the pathogens in distinct anatomical sub‐sites of HNSCC. Illustration depicts the immune cell profile in the tumour micro‐environment consisting of predominant cell types such as T cells (CD4+, CD8+ in HPV positive subtype), tumour associated macrophages (TAM), regulatory T cells (TREG) (in EBV +ve subtype) and innate immune cell enrichment – dendritic cells (DCs), neutrophils and M2 macrophages (in Fusobacterium enriched tongue tumours). Inside the cytoplasm, pathogenic particles are mentioned which directly or indirectly interact with the host cellular machinery causing different types of genomic aberrations. The up‐ red arrows indicate increase in activity or expression and the down‐ green arrows indicate the decrease in activity. Black circular flags on the genome represent methylation.