Optimizing Prognostic Assessment in High‐Risk Head and Neck Squamous Cell Carcinomas: The Impact of Tumor Budding and a Novel Histomorphological Scoring System

ABSTRACT Background Head and neck squamous cell carcinomas (HNSCC) pose significant clinical challenges, particularly in high‐risk cases with positive lymph node status. Current prognostic biomarkers are often costly and methodologically demanding. In this regard, histomorphological biomarkers such...

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Main Authors: Moritz Knebel, Jan Philipp Kühn, Sandrina Körner, Felix Braun, Lukas Brust, Silke Wemmert, Sigrun Smola, Martin Ertz, Mathias Wagner, Bernhard Schick, Luc G. T. Morris, Maximilian Linxweiler, Gilbert Georg Klamminger
Format: Article
Language:English
Published: Wiley 2025-02-01
Series:Cancer Medicine
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Online Access:https://doi.org/10.1002/cam4.70685
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Summary:ABSTRACT Background Head and neck squamous cell carcinomas (HNSCC) pose significant clinical challenges, particularly in high‐risk cases with positive lymph node status. Current prognostic biomarkers are often costly and methodologically demanding. In this regard, histomorphological biomarkers such as tumor buds (TB) and poorly differentiated clusters (PDC) represent promising, cost‐effective prognostic indicators that are relatively straightforward to implement. Methods The prognostic significance of TB and PDC, in conjunction with stromal tumor‐infiltrating lymphocytes (sTILs) and the tumor‐stroma ratio (TSR), was evaluated in a cohort of 50 high‐risk, nodal‐positive HNSCC patients. Histomorphological features were assessed using standard hematoxylin and eosin (H&E) staining, while HPV association and PD‐L1 expression were determined by means of immunohistochemistry (IHC) and/or PCR. All variables collected were subsequently correlated with traditional histopathological and clinical parameters. Finally, a novel scoring system incorporating TB and PDC was developed, and its association with overall survival (OS) was analyzed. Results TB and PDC both demonstrated a significant impact on patients' OS (TB Log‐rank test, p = 0.0499, PDC Log‐rank test, p = 0.0235). A novel scoring system based on these features had strong association with patients' OS (Log‐rank test, p = 0.0200) in contrast to the conventional and routinely performed grading system, which evaluates the degree of differentiation within neoplastic cells (Log‐rank test, p = 0.3325). PD‐L1 expression was not associated with TB and PDC formation. HPV‐negative status was associated with a higher number of tumor buds. Conclusion This study reveals the potential prognostic value of TB and PDC in high‐risk HNSCC, which may offer a practical and cost‐effective alternative to traditional markers. Our proposed practicable and straightforward employable scoring system significantly correlates with OS, suggesting its potential benefit in clinical practice. These findings advocate for further validation to enhance prognostic accuracy and guide treatment strategies in HNSCC.
ISSN:2045-7634