Tumor budding and lymphovascular invasion as prognostic factors in p16-positive oropharyngeal squamous cell carcinomas.

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We aimed to validate the prognostic significance of tumor budding (TB) in p16-positive oropharyngeal squamous cell carcinomas (OPSCC). We analyzed digitized H&E-stained slides from a multicenter cohort of five large university centers consisting of n = 275 cases of p16-positive OPSCC. We evaluated TB along with other histological parameters (morphology, tumor-stroma-ratio, lymphovascular invasion (LVI), perineural invasion) and calculated survival outcomes using both univariate and multivariate analyses. TB was identified as an independent prognostic parameter, with TB-high cases showing inferior outcomes in univariate (HR: 3.08, 95%-CI: 1.71-5.54) and multivariate analyses (HR: 4.03, 95%-CI: 1.65-9.83). Similarly, LVI remained an independent prognostic factor (HR: 3.00, 95%-CI: 1.22-7.38). A combined classification including TB and LVI stratified cases into low-, intermediate- and high-risk categories. We could not detect correlations between TB and the number of lymph node metastases or between TB and an extracapsular extension of lymph node metastases. In addition to LVI, we could identify TB as an independent prognostic factor in p16-positive OPSCC in this multicenter study cohort. Thus, evaluating TB along with LVI in a combined scheme for prognostication might help to establish a more personalized treatment regimen for patients with p16-positive OPSCC.