title: 18F-FDG PET/CT vs. human papillomavirus, p16 and Epstein-Barr virus detection in cervical metastatic lymph nodes for identifying primary tumors.
abstract: 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.18F-fluorodeoxyglucose (18F-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 and18F-FDG PET/CT scans and subsequently underwent examinations and biopsies under general anesthesia to detect primary tumors. The diagnostic performance of the biomarkers and18F-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%) of18F-FDG PET/CT (p < 0.05). The area under the ROC curve of HPV was higher than that of18F-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.
authors.affiliation: Department of Otolaryngology, Samsung Changwon Hospital, Sungkyunkwan University School of Medicine, Changwon, Republic of Korea.
authors.forename: Gi
authors.initials: G
authors.lastname: Cheol Park
authors.affiliation: Department of Otolaryngology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Republic of Korea.
authors.forename: Jong-Lyel
authors.initials: JL
authors.lastname: Roh
authors.affiliation: Department of Pathology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Republic of Korea.
authors.forename: Kyung-Ja
authors.initials: KJ
authors.lastname: Cho
authors.affiliation: Department of Nuclear Medicine, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Republic of Korea.
authors.forename: Jae
authors.initials: J
authors.lastname: Seung Kim
authors.affiliation: Department of Biostatistics, Samsung Changwon Hospital, Sungkyunkwan University School of Medicine, Changwon, Republic of Korea.
authors.forename: Mi
authors.initials: M
authors.lastname: Hyeon Jin
authors.affiliation: Department of Otolaryngology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Republic of Korea.
authors.forename: Seung-Ho
authors.initials: SH
authors.lastname: Choi
authors.affiliation: Department of Otolaryngology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Republic of Korea.
authors.forename: Soon
authors.initials: S
authors.lastname: Yuhl Nam
authors.affiliation: Department of Otolaryngology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Republic of Korea.
authors.forename: Sang
authors.initials: S
authors.lastname: Yoon Kim
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D014408:Biomarkers, Tumor; D044963:Biopsy, Fine-Needle; D002294:Carcinoma, Squamous Cell / Q000000981:diagnostic imaging* / Q000235:genetics / Q000556:secondary / Q000821:virology; D018572:Disease-Free Survival; D005260:Female; D005462:Fluorine Radioisotopes; D019788:Fluorodeoxyglucose F18; D019942:Genes, p16; D006258:Head and Neck Neoplasms / Q000000981:diagnostic imaging* / Q000401:mortality / Q000473:pathology; D004854:Herpesvirus 4, Human / Q000302:isolation & purification*; D006801:Humans; D053208:Kaplan-Meier Estimate; D008207:Lymphatic Metastasis / Q000000981:diagnostic imaging* / Q000235:genetics; D008297:Male; D008875:Middle Aged; D009382:Neoplasms, Unknown Primary / Q000000981:diagnostic imaging* / Q000401:mortality / Q000473:pathology; D009928:Organ Specificity; D027383:Papillomaviridae / Q000302:isolation & purification*; D000072078:Positron Emission Tomography Computed Tomography; D011446:Prospective Studies; D012680:Sensitivity and Specificity; D014412:Tumor Virus Infections / Q000000981:diagnostic imaging / Q000821:virology
chemical_list: D014408:Biomarkers, Tumor; D005462:Fluorine Radioisotopes; D019788:Fluorodeoxyglucose F18
keywords: 18F-FDG PET/CT; HPV; cervical metastasis of unknown primary; occult primary; p16