Experimental Modeling of Host-Bacterial Interactions in Head and Neck Squamous Cell Carcinoma

Simple Summary The microbiome has been implicated in both homeostasis and disease states, including cancer. Mechanistic investigations into the role of the microbiome in head and neck squamous cell carcinoma (HNSCC) are in their relative infancy. To date, the literature suggests an altered microbiome in subjects with HNSCC, but the mechanisms behind these changes remain to be elucidated. The use of in vitro models utilizing co-culture of cancer cells with microbes, including traditional monolayer culture, 3D organotypic culture, and 3D organoids, may help characterize the underpinnings of the complex relationship between the microbiome and HNSCC, with the goal of improving risk stratification and ultimately guiding treatment.Abstract The microscopic species colonizing the human body, collectively referred to as the microbiome, play a crucial role in the maintenance of tissue homeostasis, immunity, and the development of disease. There is evidence to suggest associations between alterations in the microbiome and the development of head and neck squamous cell carcinomas (HNSCC). The use of two-dimensional (2D) modeling systems has made significant strides in uncovering the role of microbes in carcinogenesis; however, direct mechanistic links remain in their infancy. Patient-derived three-dimensional (3D) HNSCC organoid and organotypic models have recently been described. Compared to 2D models, 3D organoid culture systems effectively capture the genetic and epigenetic features of parent tissue in a patient-specific manner and may offer a more nuanced understanding of the role of host-microbe responses in carcinogenesis. This review provides a topical literature review assessing the current state of the field investigating the role of the microbiome in HNSCC; including in vivo and in vitro modeling methods that may be used to characterize microbiome-epithelial interactions.