Oral Microbial Profile Analysis in Patients with Oral and Pharyngeal Cancer Reveals That Tumoral Fusobacterium nucleatum Promotes Oral Cancer Progression by Activating YAP

Abstract

The incidence of oral cancer has recently been increasing worldwide, particularly among young individuals and women. The primary risk factors for head and neck cancers, including oral and pharyngeal cancers, are smoking, alcohol consumption, poor oral hygiene, and repeated exposure to mechanical stimuli. However, approximately one-third of the patients with oral and pharyngeal cancers are neither smokers nor drinkers, which points to the existence of other mechanisms. Recently, human microbes have been linked to various diseases, including cancer. Oral pathogens, especially periodontal pathobionts, are reported to play a role in the development of colon and other types of cancer. In this study, we employed a series of bioinformatics analyses to pinpoint Fusobacterium nucleatum as the predominant oral bacterial species in oral and pharyngeal cancer tissue samples. We successfully isolated Fn. polymorphum from the saliva of patients with oral cancer and demonstrated that Fn. polymorphum indeed promoted oral squamous cell carcinoma development by activating YAP in a mouse tongue cancer model. Our research offers scientific evidence for the role of the oral microbiome in oral cancer progression and provides insights that would help in devising preventative strategies against oral cancer, potentially by altering oral bacterial profiles.