The correlation between immature neutrophils in the tumor microenvironment and the prognosis of HPV-negative head and neck squamous cell carcinoma

doi:10.19438/j.cjoms.2026.03.005

Abstract

Abstract: PURPOSE: To characterize neutrophil features in the tumor microenvironment(TME) of head and neck squamous cell carcinoma(HNSCC) under different human papillomavirus (HPV) infection status, and to investigate the association between immature neutrophils and disease progression in HPV-negative HNSCC. METHODS: Single-cell RNA sequencing data from the GSE164690 dataset were analyzed to compare neutrophil heterogeneity in the TME of HNSCC with different HPV status. Survival analysis based on the TCGA database was performed to evaluate the relationship between immature neutrophils and tumor progression in HPV-negative HNSCC patients. Immunohistochemical staining and flow cytometry analysis of clinical samples were used to validate the prognostic significance of immature neutrophils in predicting poor outcomes. RESULTS: This study systematically delineated the functional characteristics of neutrophils in the TME of both HPV-negative and HPV-positive HNSCC. Results demonstrated that immature neutrophils were significantly enriched in HPV-negative HNSCC and correlated with unfavorable patient prognosis. This neutrophil subset also exhibited elevated expression of multiple genes associated with tumor progression and inflammatory responses, including CCL20, INHBA, IL6, CXCL2 and CXCL8. Clinical sample validation confirmed the presence of neutrophils within HPV-negative HNSCC tumor tissues, with significantly higher infiltration levels of immature neutrophils in tumor tissues compared to adjacent normal tissues. CONCLUSIONS: Neutrophils in the TME of HNSCC display distinct characteristics depending on HPV status. Immature neutrophils are closely associated with poor prognosis and tumor progression in HPV-negative HNSCC.

Key words: Neutrophils, Human papillomavirus, Head and neck squamous cell carcinoma, Tumor microenvironment, Prognostic biomarker

CLC Number:

R739.8

Liang Weipeng, Dai Zhenlin, Yan Ming, Ruan Min, Zhang Chenping. The correlation between immature neutrophils in the tumor microenvironment and the prognosis of HPV-negative head and neck squamous cell carcinoma[J]. China Journal of Oral and Maxillofacial Surgery, 2026, 24(3): 234-240.

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