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. 2025 Jul 29;91(6):101689.
doi: 10.1016/j.bjorl.2025.101689. Online ahead of print.

Cancer stem cell biomarkers in locally advanced head and neck squamous cell carcinoma

Miguel Caballero-Borrego  1 , Juan J Grau  2 , Neus Basté  3 , Paola C Castillo  4 , Cristina Teixido  4 , Izaskun Valduvieco  5 , Isabel Vilaseca  6
Affiliations

Cancer stem cell biomarkers in locally advanced head and neck squamous cell carcinoma

Miguel Caballero-Borrego et al. Braz J Otorhinolaryngol. .

Abstract

Objectives: To analyze the presence of cancer stem cells markers in consecutive patients with locally advanced Head and Neck Squamous Cell Carcinoma (HNSCC) and establish their suitability as a prognostic biomarker in samples from routine practice.

Methods: Retrospective study of 104 consecutive patients with locally advanced HNSCC treated with definitive surgery and adjuvant chemoradiotherapy. Immunohistochemical expression of CD44, HLA-I, pan-cytokeratin, and phosphorylated Epidermal Growth Factor Receptor (p-EGFR) were evaluated in surgical specimens. Overall Survival (OS) and Disease-Free Survival (DFS) rates were calculated based on clinical characteristics and the total positive score (for tumor marker expression). Hazard ratios were calculated by Cox multivariate analysis.

Results: After a median follow-up of 50-months, higher OS rates were observed for patients without cervical node pathological involvement (p < 0.001), patients with HLA-I overexpression and a total positive score ≥ 15% (p = 0.017), and patients with low CD44 expression and a total positive score ≤ 60% (p = 0.022). Grouping by p-EGFR (p = 0.648) or pan-cytokeratin (p = 0.477) expression did not show statistical differences in OS. None of the biomarkers were associated with different DFS rates. Cox multivariate analysis revealed that positive cervical nodes (HR = 1.294; 95% CI 1.025-1.634; p = 0.030) and the expressions of HLA (HR = 0.373; 95% CI 0.168‒0.829; p = 0.015) and CD44 (HR = 2.170; 95% CI 1.031-4.569; p = 0.041) were independently associated with OS.

Conclusion: Nodal involvement, HLA-I overexpression, and decreased CD44 expression are independent prognostic factors of survival in patients with locally advanced HNSCC.

Level of evidence: III.

Keywords: Biomarkers; CD44; Cancer stem cells; HLA-I; Head and neck cancer.

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Conflict of interest statement

Declaration of competing interest The authors declare no conflicts of interest.

Figures

Fig. 1
Fig. 1
Immunohistochemical characteristics of patient tissues with different prognoses.
Fig. 2
Fig. 2
Overall survival by HLA-I expression HLA+, tumor expression of HLA-I ≥15%; HLA-, tumor expression of HLA-I < 15%.
Fig. 3
Fig. 3
Overall survival by CD44 expression CD44+, tumor expression of CD44 ≥ 60%; CD44-, tumor expression of CD44 < 60%.
See this image and copyright information in PMC

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