Impact of Tumor Budding in Head and Neck Cancers on Neck Lymph Node Metastasis and Prognosis.

Background/

Objectives

Tumor budding (TB)-clusters of one to five tumor cells at the invasive front-has emerged as a prognostic marker in various cancers. Its prognostic value in head and neck squamous cell carcinoma (HNSCC) is unclear.

Methods

We retrospectively analyzed 98 HNSCC patients. The tumor buds were counted on hematoxylin-eosin-stained sections as per the 2016 International Tumor Budding Consensus Conference (ITBCC) guidelines. An optimal cutoff was determined by ROC analysis using excisional lymph nodes and five-year overall survival (OS) as the endpoint, stratifying patients into low- (≤4 buds) and high-risk (>4 buds) groups. The associations with clinicopathological features, OS, and disease-free survival (DFS) were assessed using Kaplan-Meier curves and Cox regression.

Results

Among the 98 patients (median follow-up 58 months, range 18-108), 32 (32.7%) died. The optimal TB cutoff was 4.5 (AUC 0.85, 95% CI 0.76-0.93). High TB was associated with poorer five-year OS (26.4% vs. 85.3%). Multivariate Cox regression identified TB and extranodal extension as independent predictors of OS (TB HR: 3.4, 95% CI 1.3-9.2, p = 0.013). In the laryngeal cancer subgroup, TB was associated with worse survival in the univariate analysis (HR 7.5, 95% CI 1.6-35.6, p = 0.011), though this was not significant in the multivariate modeling. High TB independently predicted neck lymph node metastasis (multivariate OR 4.9, 95% CI 1.2-20.5, p = 0.029), which was present in 65.8% of the high-TB vs. 31.7% of the low-TB patients. High TB correlated with advanced AJCC stage and lymphovascular invasion. No clinicopathological factors, including TB, independently predicted DFS, in either the full cohort or the laryngeal subgroup.

Conclusions

High tumor budding denotes an aggressive HNSCC phenotype and may guide decisions on elective neck dissection. Its assessment is simple, cost-effective, and potentially valuable for routine pathology, pending external validation.