Purpose: Squamous cell carcinoma of unknown primary of the head and neck (SCCUP) is a heterogenous disease entity and scrutinization to find hidden primary is essential prior to definitive treatments. Therefore, we examined the diagnostic value of 18F-FDG PET/CT versus biomarkers such as human papilloma virus (HPV), p16, and Epstein-Barr virus (EBV) expression in metastatic lymph nodes.
Patients and methods: We prospectively enrolled 54 patients with SCCUP who received 18F-FDG PET/CT and HPV, p16, and EBV examinations from lymph node fine-needle aspirates and subsequently underwent palatine tonsillectomy and guided biopsy to detect primary tumors. The diagnostic performance of 18F-FDG PET/CT and biomarkers were calculated and compared using receiver operating characteristics (ROC) curve analyses with histopathological results as the reference for primary tumors.
Results: Primary tumors were identified at 28 of 54 patients (52%): 24 patients in the palatine tonsil, 1 patient in the base of the tongue, 2 patients in the nasopharynx, and 1 patient in the hypopharynx. The sensitivity of p16, HPV, and 18F-FDG PET/CT was 85.7%, 71.4%, and 42.9%, respectively, and these specificity was 80.8%, 100%, and 96.2%, respectively. The sensitivity of p16 and the accuracy of HPV were higher than those of 18F-FDG PET/CT (p <0.05). Area under the ROC curve analysis of HPV was higher than that of 18F-FDG PET/CT (0.857 vs 0.695, p=0.013). The patients with primary tumor detection or p16 nodal immunopositivity showed higher disease-free survival rates than the counter parts (p <0.05).
Conclusion: This prospective study shows that detection of HPV and p16 from metastatic lymph nodes can help identify hidden primary tumors as to guide definitive treatments and predict patient survival.