High-Grade Tumor Budding Stratifies Early-Stage Cervical Cancer with Recurrence Risk

OBJECTIVES This study investigated prognostic significance of tumor budding in early-stage cervical cancer (ESCC) following radical surgery and its contribution to improve the stratification of patients with recurrence risk. METHODS The archival medical records and H&E-stained slides of 643 patients with IA2-IIA stage cervical cancer who underwent radical surgery were retrospectively reviewed. Clinicopathological parameters were noted, and tumor buds were counted using immunohistochemistry for each case. The prognostic significance of tumor budding was analyzed. Prediction models that comprised tumor budding were established, and the performance was compared between the novel models and classic criteria via log-rank test and receiver operating characteristic analysis. RESULTS Tumors with high-grade tumor budding (HTB) exhibited a substantially increased risk of recurrence (hazard ratio = 4.287, P < 0.001). Nine predictive models for recurrence were established, in which HTB was combined with recognized risk factors. The model using of at least two risk factors of HTB, tumor size ≥ 4 cm, deep stromal invasion of outer 1/3, and lymphovascular space invasion to stratify patients with an intermediate risk was most predictive of recurrence compared with the classic criteria. CONCLUSIONS Tumor budding is an independent, unfavorable, prognostic factor for ESCC patients following radical surgery and holds promise for improved recurrence risk stratification.