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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author 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
author_facet 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
author_sort Moritz Knebel
collection DOAJ
description 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.
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spelling doaj-art-25ce6ff4e2db44b6b77ce957f7842e432025-08-20T02:27:39ZengWileyCancer Medicine2045-76342025-02-01144n/an/a10.1002/cam4.70685Optimizing Prognostic Assessment in High‐Risk Head and Neck Squamous Cell Carcinomas: The Impact of Tumor Budding and a Novel Histomorphological Scoring SystemMoritz Knebel0Jan Philipp Kühn1Sandrina Körner2Felix Braun3Lukas Brust4Silke Wemmert5Sigrun Smola6Martin Ertz7Mathias Wagner8Bernhard Schick9Luc G. T. Morris10Maximilian Linxweiler11Gilbert Georg Klamminger12Institute of Otorhinolaryngology Saarland University Homburg GermanyInstitute of Otorhinolaryngology Saarland University Homburg GermanyInstitute of Otorhinolaryngology Saarland University Homburg GermanyInstitute of Otorhinolaryngology Saarland University Homburg GermanyInstitute of Otorhinolaryngology Saarland University Homburg GermanyInstitute of Otorhinolaryngology Saarland University Homburg GermanyInstitute of Virology Saarland University Medical Center Homburg/Saar GermanyDepartment of General and Special Pathology Saarland University Medical Center (UKS) Homburg GermanyDepartment of General and Special Pathology Saarland University Medical Center (UKS) Homburg GermanyInstitute of Otorhinolaryngology Saarland University Homburg GermanyDepartment of Surgery Memorial Sloan Kettering Cancer Center New York City New York USAInstitute of Otorhinolaryngology Saarland University Homburg GermanyDepartment of General and Special Pathology Saarland University Medical Center (UKS) Homburg GermanyABSTRACT 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.https://doi.org/10.1002/cam4.70685HNSCCprognosticationtumor budding
spellingShingle 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
Optimizing Prognostic Assessment in High‐Risk Head and Neck Squamous Cell Carcinomas: The Impact of Tumor Budding and a Novel Histomorphological Scoring System
Cancer Medicine
HNSCC
prognostication
tumor budding
title Optimizing Prognostic Assessment in High‐Risk Head and Neck Squamous Cell Carcinomas: The Impact of Tumor Budding and a Novel Histomorphological Scoring System
title_full Optimizing Prognostic Assessment in High‐Risk Head and Neck Squamous Cell Carcinomas: The Impact of Tumor Budding and a Novel Histomorphological Scoring System
title_fullStr Optimizing Prognostic Assessment in High‐Risk Head and Neck Squamous Cell Carcinomas: The Impact of Tumor Budding and a Novel Histomorphological Scoring System
title_full_unstemmed Optimizing Prognostic Assessment in High‐Risk Head and Neck Squamous Cell Carcinomas: The Impact of Tumor Budding and a Novel Histomorphological Scoring System
title_short Optimizing Prognostic Assessment in High‐Risk Head and Neck Squamous Cell Carcinomas: The Impact of Tumor Budding and a Novel Histomorphological Scoring System
title_sort optimizing prognostic assessment in high risk head and neck squamous cell carcinomas the impact of tumor budding and a novel histomorphological scoring system
topic HNSCC
prognostication
tumor budding
url https://doi.org/10.1002/cam4.70685
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