Background: The purpose of this study was to comprehensively characterize head and neck squamous cell carcinoma (HNSCC) arising in young patients (<45 years old). Methods: We performed immunohistochemistry, silver, and fluorescence in situ hybridization using samples obtained from 396 radically resected cases among 1787 HNSCCs. Results: Young age HNSCCs occurred in 10.9% (194/1787) and were most common in the oral tongue (50.5%). They revealed distinctively lower frequency of p16 positivity, high c-MET expression, MET copy number gain, and lower pan-Trk expression. PD-L1 positivity in tumor cells and ICOS+ tumor infiltrating lymphocytes (TILs) were higher in the young age. Perineural invasion, PD-L1 positivity, and higher ratio of CD163+ tumor infiltrating macrophages to CD8 + TILs were determined to be independent factors for poor progression-free survival. Conclusion: Characterizing these features of young age HNSCC may help to identify the underlying pathogenesis and to improve patient outcome through different treatment strategies.
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