The Intersection of the Oral Microbiome and Salivary Metabolites in Head and Neck Cancer: From Diagnosis to Treatment

Head and neck cancers (HNCs) represent 4–5% of all malignancies globally. Salivary metabolites, as metabolic intermediates and signalling molecules, are gaining attention as diagnostic biomarkers for several diseases, including HNC; however, the metabolites’ role in cancer treatment outcomes and oral side effects remains underexplored. Current studies focus on the oral microbiome’s significance in promoting a pro-inflammatory environment that facilitates tumour development and invasion. Specific microorganisms and their metabolites influence chemotherapy efficacy through several mechanisms. Radiotherapy (RT), a standard HNC treatment, can modify the oral microbiota and salivary metabolite profiles, leading to a wide range of side effects. To reduce oral complications, intensity-modulated radiotherapy (IMRT) was developed; however, cancer survivors often experience a reduced quality of life. This review highlights the microbial and host interactions affecting salivary metabolites and their implications for cancer treatment and patient outcomes.