# Role of Human Microbiome in Development and Management of Head and Neck Squamous Cell Carcinoma

## TL;DR

This review explores how the human microbiome, especially oral bacteria, influences head and neck cancer development and treatment outcomes.

## Contribution

The paper highlights specific microbial associations with HNSCC and their impact on treatment efficacy and toxicity reduction through microbiome modulation.

## Key findings

- Specific oral bacteria like Fusobacterium nucleatum and Porphyromonas gingivalis are linked to HNSCC development.
- Microbiome modulation, such as probiotics, can reduce treatment toxicities like mucositis in HNSCC patients.
- Fecal microbiota transplantation from responders can improve immunotherapy outcomes in HNSCC.

## Abstract

The human microbiome plays a crucial role in the development and treatment of head and neck squamous cell carcinoma (HNSCC). Recently, a strong association between specific microbial alterations, such as increased levels of Fusobacterium nucleatum and Porphyromonas gingivalis, and the incidence of HNSCC was described. Our narrative review aims to explain how the oral microbiome influences the efficacy of various treatments, including chemotherapy and radiotherapy, noting that specific bacterial profiles may predict treatment responses. Additionally, the potential of microbiome modulation, through probiotics, to improve patient outcomes and reduce treatment-related toxicities like oral mucositis was described. Despite the promising links between microbiome composition and cancer treatment, further research to establish definitive causal relationships and therapeutic applications in HNSCC management is needed.

The oral microbiome is the largest and most diverse microbiome in the human body, second only to the gut microbiome. Mounting evidence supports its role in the genesis, promotion, and aggressiveness of oral cancer as well as certain cancers of distant sites. In this review, we focus on describing specific microbial alterations, which were proven to be associated either with head and neck squamous cell carcinoma (HNSCC) development or with its treatment efficacy, especially with radiotherapy, chemotherapy, targeted treatment, and immunotherapy. Purpose: To discuss associations of oral and gut microbiome with the development of HNSCC and with its anti-cancer treatment efficacy. Methods: A literature search was conducted in PubMed/Medline. Due to the nature of this narrative review, we prioritized the most recent studies. Regarding the type of studies, umbrella reviews, meta-analyses, and systematic reviews were prioritized, in that order, over individual studies. Results: The microbiome plays an important role in cancer development, progression, and treatment response across solid tumors, including HNSCC. Better treatment response and/or reduction in treatment toxicities can be achieved through microbiome alteration; e.g., the use of specific probiotics can result in a reduction in acute radiotherapy-induced mucositis in HNSCC radiotherapy, and fecal microbiota transplantation from immune-checkpoint inhibitor (ICI) responders to non-responders can overcome primary resistance to ICI. Conclusions: We highlighted specific research areas on how to utilize microbiome modification to enhance anti-cancer treatment response and/or decrease the incidence and severity of anti-cancer treatment toxicities.