Molecular Subtypes of Head and Neck Cancer in Patients of African Ancestry

Purpose: The purpose of this study was to better understand the complex molecular biomarkers and signatures of head and neck cancer (HNC) among Black patients and identify possible molecular changes associated with HNC disparities.Experimental Design: Molecular subtypes and genomic changes in HNC samples from patients of African and European ancestry in The Cancer Genome Atlas, Memorial Sloan Kettering Cancer Center, Broad Institute, MD Anderson Cancer Center, and John Hopkins University were identified. Molecular features (genomic, proteomic, transcriptomic) associated with race and genomic alterations associated with clinical outcomes were determined. An independent cohort of HNC tumor specimens was used to validate the primary findings using IHC.Results: Black patients were found to have a younger age at diagnosis, more aggressive tumor types, higher rates of metastasis, and worse survival compared with White patients. Black patients had fewer human papillomavirus-positive tumor types and higher frequencies of laryngeal subtype tumors. Higher frequencies of TP53, MYO18B, KMT2D, and UNC13C mutations and a lower frequency of PIK3CA mutations were observed in Black patients. Tumors of Black patients showed significant enrichment of c-MYC and RET-tyrosine signaling and amplifications. A signif-icant increase in tumor expression of c-MYC in Black patients was observed and was associated with poor survival outcomes in the independent cohort.Conclusions: Novel genomic modifications and molecular signatures may be related to environmental, social, and be-havioral factors associated with racial disparities in HNC. Unique tumor mutations and biological pathways have poten-tial clinical utility in providing more targeted and individualized screening, diagnostic, and treatment modalities to improve health outcomes.

Automated summary

The purpose of this study was to understand the molecular biomarkers and signatures of head and neck cancer (HNC) among Black patients and identify molecular changes associated with HNC disparities. The study identified molecular subtypes and genomic changes in HNC samples from Black and White patients, as well as their clinical outcomes. The findings showed that Black patients had more aggressive tumor types, higher frequencies of certain gene mutations, and poorer survival outcomes. The study suggests that these molecular features could be used for more targeted screening, diagnosis, and treatment to improve health outcomes.