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 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 ne oplastic 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 valida tion to enhance prognostic accuracy and guide treatment strategies in HNSCC.