18 F-FDG PET/CT vs. human papillomavirus, p16 and Epstein-Barr virus detection in cervical metastatic lymph nodes for identifying primary tumors.

Squamous cell carcinoma of unknown primary of the head and neck (SCCUP) is a heterogeneous disease entity that requires careful examination to locate the occult primary. We examined the diagnostic value of expression of biomarkers, such as human papillomavirus (HPV), p16 and Epstein-Barr virus (EBV), in metastatic lymph nodes vs. 18 F-fluorodeoxyglucose (18 F-FDG) positron emission tomography/computed tomography (PET/CT). We prospectively enrolled 54 consecutive SCCUP patients who received HPV, p16 and EBV analyses of lymph node fine-needle aspirates and 18 F-FDG PET/CT scans and subsequently underwent examinations and biopsies under general anesthesia to detect primary tumors. The diagnostic performance of the biomarkers and 18 F-FDG PET/CT were compared by using receiver operating characteristics (ROC) curve analyses with histopathological results for identification of primary tumors. Primary tumors were identified in 28 (51.9%) of 54 patients: the palatine tonsil in 24, base of the tongue in 1, nasopharynx in 2, and hypopharynx in 1. The sensitivity of p16 (85.7%) and accuracy of HPV (85.2%) were higher than those (42.9% and 68.5%) of 18 F-FDG PET/CT (p < 0.05). The area under the ROC curve of HPV was higher than that of 18 F-FDG PET/CT (0.857 vs. 0.666, p = 0.007). The disease-free survival rates were higher in the patients with primary tumor detection or p16 nodal immunopositivity than in the other patients (p < 0.05). The results showed that HPV and p16 detection in metastatic lymph nodes can help locate hidden primary tumors, guide definitive treatment and predict patient survival.