PURPOSE: This study aimed to evaluate the diagnostic performance of surveillance FDG PET/CT for detection of clinically unexpected recurrent disease or second primary malignancy in head and neck squamous cell carcinoma (HNSCC) patients who underwent curative treatment. PATIENTS AND METHODS: We conducted a retrospective analysis of 739 consecutive patients with HNSCC who underwent 2396 surveillance FDG PET/CT scans. Surveillance FDG PET/CT scans were defined as routine follow-up scans after curative therapy without suspicion of recurrence. The diagnostic performance of FDG PET/CT was evaluated based on sensitivity, specificity, positive predictive value, negative predictive value, and accuracy. RESULTS: Of the 2396 surveillance FDG PET/CT scans, 119 (5.0%) showed positive findings, with 93 (78.1%) confirmed as true-positives. True-positive detections included locoregional metastases, distant metastases, or second primary malignancies. The sensitivity, specificity, positive predictive value, negative predictive value, and accuracy were 97.9%, 98.9%, 78.2%, 99.9%, and 98.8%, respectively. The incidence of recurrence was significantly greater in patients initially diagnosed with stage IVA disease (P = 0.03) and for which 5 or more years had elapsed since treatment (P <
0.001) than in other subgroups. However, no significant differences in diagnostic performance were observed across subgroups divided by tumor location, disease stage, treatment modality, or time since treatment. CONCLUSIONS: Surveillance FDG PET/CT showed excellent diagnostic performance for detection of clinically unexpected recurrent disease or second primary malignancies in patients with HNSCC after curative therapy. The frequency and duration of surveillance could be adjusted based on the initial disease stage to optimize early detection and intervention.