Relative tumour budding (TB rel) predicts occult nodal metastasis, aggressiveness and survival in oral squamous cell carcinoma.

Tumour budding (TB) is known as a histopathological parameter defined as single tumour cells or clusters of up to 4 cells at the tumour invasion front (TIF) (TB score 1: 0-4 buds, TB score 2: 5-9 buds, TB score 3: ≥10 buds). However, conventional assessment based on a single section may not capture heterogeneity within the TIF. Therefore, this study applied a novel quantitative approach (TB rel), in which all available sections were evaluated and summarized as an average score. 256 patients with oral squamous cell carcinomas (OSCC) were included and 1289 haematoxylin and eosin-stained sections were analysed. Based on TB rel, patients were stratified into prognostic clusters: Cluster C1 (TB rel = 1.0) and cluster C2 (TB rel >1.0). Increased TB rel was associated with adverse histopathological features reflecting tumour aggression. In clinically node-negative patients (cN0), TB rel identified occult lymph node metastasis (pN+) with an odds ratio of 6.32. Furthermore, patients with higher TB rel showed a higher risk of poorer overall disease progression and survival compared to patients having consistently low TB scores along the TIF. Given its prognostic relevance, TB rel should be integrated into routine diagnostics. This may support more individualized indication for neck dissections.