Abstract
BACKGROUND: Oral mucositis (OM) is a debilitating sequela for patients treated for squamous cell carcinoma of the head and neck (HNSCC). This study investigated whether oral microbial features before treatment or during treatment are associated with the time to onset of severe OM in patients with HNSCC. METHODS: This was a cohort study of newly diagnosed patients with locoregional HNSCC who received chemotherapy with or without radiotherapy from April 2016 to September 2017. OM was based on the National Cancer Institute's Common Terminology Criteria for Adverse Events, version 4.0. The oral microbiome was characterized on the basis of the 16S ribosomal RNA V4 region with the Illumina platform. A mixture cure model was used to generate hazard ratios for the onset of severe OM. RESULTS: Eighty-six percent of the patients developed OM (n = 57 [33 nonsevere cases and 24 severe cases]) with a median time to onset of OM of 21 days. With adjustments for age, sex, and smoking status, genera abundance was associated with the hazard for the onset of severe OM as follows: 1) at the baseline (n = 66), Cardiobacterium (P = .03) and Granulicatella (P = .04); 2) immediately before the development of OM (n = 57), Prevotella (P = .03), Fusobacterium (P = .03), and Streptococcus (P = .01); and 3) immediately before the development of severe OM (n = 24), Megasphaera (P = .0001) and Cardiobacterium (P = .03). There were no differences in α-diversity between the baseline samples and Human Microbiome Project data. CONCLUSIONS: Changes in the abundance of genera over the course of treatment were associated with the onset of severe OM. The mechanism and therapeutic implications of these findings need to be investigated in future studies.