Racial disparities in head and neck squamous cell carcinoma: Cancer stem cell pathways as drivers of outcome differences

Head and neck squamous cell carcinoma (HNSCC) affects ∼60,000 individuals annually in the United States and is the seventh most common cancer globally. African Americans experience higher recurrence rates and poorer survival than Caucasian American (CA) patients. Our research identifies cancer stem cell (CSC) mechanisms as key drivers of these disparities, particularly in HPV-negative tumors. Through spatial transcriptomics, single-cell RNA sequencing, and patient-derived xenograft models, we will provide evidence supporting elevated CSC markers (e.g., SOX2, ZSCAN4) and pluripotency pathways in AA tumors, contributing to worse clinical outcomes. These CSCs promote therapy resistance and recurrence. We aim to define racially distinct CSC biomarkers, map tumor microenvironments, and evaluate anti-CSC therapies. Our findings will aim to provide novel targets for prognostic precision and personalized treatment. This work has broad translational significance for improving survival and equity in HNSCC outcomes by guiding CSC-targeted therapy development tailored to racially distinct tumor biology.