PET / CT Diagnostic Accuracy for Synchronous Primary HPV ‐Positive Oropharyngeal Tumors: A Multi‐Institutional Study

Background The incidence of human papillomavirus‐associated (HPV) oropharyngeal squamous cell carcinoma (OPSCC) is rising, making accurate detection of synchronous primary tumors essential for staging and treatment planning. Methods This multi‐institutional retrospective cohort study (2019–2026) included adult participants across three academic tertiary centers who underwent PET/CT and subsequent biopsy or surgical resection with histopathological confirmation of p16‐positive disease. Results Among 306 patients meeting inclusion criteria, PET/CT identified 15 suspicious for synchronous primary tumors; seven (mean age 58.90 ± 11.48 years) were pathologically confirmed. PET/CT demonstrated 77.78% sensitivity, 97.31% specificity, 46.67% positive predictive value (PPV), and 99.31% negative predictive value (NPV). False positives were attributed to physiologic bilateral uptake, reactive lymphoid tissue, or inflammation. Conclusions and Relevance PET/CT demonstrates excellent NPV for excluding synchronous primary tumors in HPV‐positive OPSCC and moderate PPV for identifying them. In settings of multifocal fluorodeoxyglucose uptake, pathologic confirmation is warranted prior to definitive management.