The Emerging Impact of Tumor Budding in Oral Squamous Cell Carcinoma: Main Issues and Clinical Relevance of a New Prognostic Marker

SIMPLE SUMMARY: The results of tumor budding are an independent prognostic factor of locoregional recurrences in many solid cancers, including colorectal, nasopharyngeal, esophageal, and lung cancer. Regarding oral squamous cell carcinoma, tumor budding predicts poor survival outcomes regardless of the tumor subsite and the pathological stage. Several detection methods for tumor budding have been proposed in the literature in order to reach an agreement on a standardized scoring system. However, the lack of a standardized assessment method prevents its evaluation in a multidisciplinary setting. In this context, this study aims to critically review the literature data regarding the prognostic role of tumor budding in oral squamous cell carcinoma. The validation of a tumor budding detection method based on tumor stage and site could be relevant to improving risk stratification and planning the clinical management of patients. Moreover, tumor budding could be included in daily pathological practice to better predict the patient’s outcomes. ABSTRACT: Tumor Budding (TB) represents a single cancer cell or a small cluster of less than five cancer cells on the infiltrative tumor front. Accumulating evidence suggests TB is an independent prognostic factor in oral squamous cell carcinoma (OSCC). However, its exact role is not yet elucidated, and a standardized scoring system is still necessary. The study aims to extensively review the literature data regarding the prognostic role of TB in OSCC. The results of TB are an independent prognostic factor of poor survival outcomes in OSCC. To date, the manual detection of hematoxylin and eosin-staining or pancytokeratin-immunostaining sections are the most commonly used methods. Between the several cut-offs, the two-tier system with five buds/field cut-offs provides better risk stratification. The prognostic role of the BD model in predicting survival outcomes was extensively validated; however, the inclusion of DOI, which is already a staging parameter, encouraged other authors to propose other models, integrating TB count with other adverse risk factors, such as the tumor–stroma ratio and tumor-infiltrated lymphocytes. The prognostic relevance of TB in OSCC highlights its evaluation in daily pathological practice. Therefore, the TB detection method and the TB scoring system should be validated based on tumor stage and site.