About The Study: This single-center cohort study found that an artificial intelligence (AI)-driven pipeline can successfully automate lymph node segmentation and imaging-based extranodal extension (iENE) classification from pretreatment computed tomography scans in human papillomavirus (HPV)-associated oropharyngeal carcinoma. Predicted iENE was independently associated with worse oncologic outcomes. External validation is required to assess generalizability and the potential for implementation in institutions without specialized imaging expertise.