Background Despite immune microenvironment of head and neck squamous cell carcinoma (HNSCC) has been studied, there are no sufficient data on the role of tumor stroma factors. The aim of the study was to explore the prognostic and predictive role of these factors in a large series of HNSCC. Methods This is a retrospective study of 266 patients with laryngeal and pharyngeal SCC. Clinical data were correlated with the following histological parameters: tumor‐stroma ratio (TSR), tumor budding activity (BA), cell nests size (CNS), and stroma type. Results Stroma‐rich tumors, tumor budding, smaller CNS at core and front area, and fibroblastic stroma type, were all adverse prognostic factors (P < 0.0001, 0.001, 0.003, 0.001, 0.007, respectively). Stroma‐poor tumors and with larger CNS showed good response to induction chemotherapy (P = 0.009 and 0.02, respectively). Conclusions TSR, tumor budding, CNS, and stroma type are important prognostic and predictive factors in laryngeal and pharyngeal SCC.

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