HPV-associated Oropharyngeal Squamous Cell Carcinoma: An Imaging Framework for AJCC Version 9 TNM Staging

Human papillomavirus (HPV)-associated oropharyngeal squamous cell carcinoma (OPSCC) is biologically and prognostically distinct from HPV-negative disease, and staging directly impacts treatment. The American Joint Committee on Cancer (AJCC) and Union for International Cancer Control version 9 TNM staging system incorporates unequivocal imaging-detected and/or clinically detected extranodal extension (iENE) into clinical nodal staging and definitive pathologic extranodal extension into pathologic nodal staging. Additionally, it provides more explicit anatomic definitions for advanced local disease (clinical T4) while maintaining T and M category definitions from the eighth edition. Radiologists play a central role in the multidisciplinary team by evaluating endophytic tumor extent, regional nodal disease and iENE, and distant metastasis using CT, MRI, and PET. This article reviews clinically relevant oropharyngeal anatomy and proposes a practical radiologic approach to assigning T, N, and M categories in HPV-associated OPSCC. It emphasizes cautious interpretation of iENE because of interreader variability and imperfect diagnostic performance, with further high-grade evidence needed to establish its consistently reproducible, incremental prognostic value as a clinical N category modifier. It also highlights multidisciplinary factors that guide selection of surgical resection versus nonsurgical therapy. Posttreatment evaluation is discussed in the context of blood-based biomarkers such as tumor tissue-modified viral HPV DNA. The goal of this article is to provide a practical, staging-focused imaging framework for evaluation of HPV-associated OPSCC. Keywords: CT, MR Imaging, Head/Neck, Neck, Pharynx, Surgery, Human Papillomavirus, Squamous Cell Carcinoma, Oropharynx, Transoral Robotic Surgery, Oropharyngeal Carcinoma, TTMV HPV DNA © RSNA, 2026.