Oral microbial signatures of head and neck cancer patients with diverse longitudinal oral mucositis severity patterns.

Background: Oral mucositis is a painful complication commonly observed in head and neck cancer patients receiving cancer treatment. Emerging evidence suggests that changes in the oral microbiome can contribute to oral mucositis development, making microbial signatures potential targets for therapeutic interventions. This study aimed to: (1) characterize longitudinal microbial patterns of oral mucositis severity among head and neck cancer patients; (2) determine clinically relevant patient clusters based on oral mucositis severity trajectories; and (3) identify microbial signatures specific to these clusters. Results: We derived a calibrated oral mucositis score by applying non-negative sparse principal component analysis to seven oral mucositis related symptom ratings, using longitudinal microbiome data from 140 head and neck cancer patients. Functional data analysis and hierarchical clustering identified three distinct patient clusters with differing microbial trajectories of oral mucositis progression. One cluster exhibited patients with a rapid increase in oral mucositis severity following treatment initiation, while the other clusters displayed more gradual increase. Demographic comparisons revealed significant differences in age and weight distributions between clusters, with older, lighter patients more common in clusters experiencing more gradual oral mucositis progression. Partial least squares knockoff analysis identified cluster-specific microbial signatures: notably, Conclusions: Distinct trajectories of oral mucositis scores in head and neck cancer patients are linked to specific oral microbial profiles and demographic factors. The identification of cluster-specific microbial profiles highlights the potential for microbiome-targeted interventions to manage oral mucositis severity. While most taxa were cluster-specific,