title: Human papillomavirus and cystic node metastasis in oropharyngeal cancer and cancer of unknown primary origin.
abstract: The clinical significance of human papillomavirus (HPV) in neck node metastasis from cancer of unknown primary (CUP) is not well established. We aimed to address the relationship of HPV status between node metastasis and the primary tumor, and also the relevance of HPV status regarding radiographically detected cystic node metastasis in head and neck squamous cell carcinoma (HNSCC) and CUP. HPV DNA was examined in 68 matched pairs of node metastasis and primary tumor, and in node metastasis from 27 CUPs. In surgically treated CUPs, p16 was examined immunohistochemically. When tonsillectomy proved occult tonsillar cancer in CUP, HPV DNA and p16 were also examined in the occult primary. Cystic node metastasis on contrast-enhanced computed tomography scans was correlated with the primary site and HPV status in another series of 255 HNSCCs and CUPs with known HPV status. Node metastasis was HPV-positive in 19/37 (51%) oropharyngeal SCCs (OPSCCs) and 10/27 (37%) CUPs, but not in non-OPSCCs. Fluid was collected from cystic node metastasis using fine needle aspiration in two OPSCCs and one CUP, and all fluid collections were HPV-positive. HPV status, including the presence of HPV DNA, genotype, and physical status, as well as the expression pattern of p16 were consistent between node metastasis and primary or occult primary tumor. Occult tonsillar cancer was found more frequently in p16-positive CUP than in p16-negative CUP (odds ratio (OR), 39.0; 95% confidence interval (CI), 1.4-377.8; P = 0.02). Radiographically, cystic node metastasis was specific to OPSCC and CUP, and was associated with HPV positivity relative to necrotic or solid node metastasis (OR, 6.2; 95% CI, 1.2-45.7; P = 0.03). In conclusion, HPV status remains unchanged after metastasis. The occult primary of HPV-positive CUP is most probably localized in the oropharynx. HPV status determined from fine needle aspirates facilitates the diagnosis of cystic node metastasis.
authors.affiliation: Department of Otorhinolaryngology-Head and Neck Surgery, Osaka University Faculty of Medicine, Suita, Osaka, Japan.
authors.forename: Toshimichi
authors.initials: T
authors.lastname: Yasui
authors.affiliation: Department of Pathology, Osaka University Faculty of Medicine, Suita, Osaka, Japan.
authors.forename: Eiichi
authors.initials: E
authors.lastname: Morii
authors.affiliation: Department of Otorhinolaryngology-Head and Neck Surgery, Osaka University Faculty of Medicine, Suita, Osaka, Japan.
authors.forename: Yoshifumi
authors.initials: Y
authors.lastname: Yamamoto
authors.affiliation: Department of Otorhinolaryngology-Head and Neck Surgery, Osaka University Faculty of Medicine, Suita, Osaka, Japan.
authors.forename: Tadashi
authors.initials: T
authors.lastname: Yoshii
authors.affiliation: Department of Otorhinolaryngology-Head and Neck Surgery, Osaka University Faculty of Medicine, Suita, Osaka, Japan.
authors.forename: Yukinori
authors.initials: Y
authors.lastname: Takenaka
authors.affiliation: Department of Otorhinolaryngology-Head and Neck Surgery, Osaka University Faculty of Medicine, Suita, Osaka, Japan.
authors.forename: Susumu
authors.initials: S
authors.lastname: Nakahara
authors.affiliation: Department of Radiation Biology and Medical Genetics, Osaka University Faculty of Medicine, Suita, Osaka, Japan.
authors.forename: Takeshi
authors.initials: T
authors.lastname: Todo
authors.affiliation: Department of Otorhinolaryngology-Head and Neck Surgery, Osaka University Faculty of Medicine, Suita, Osaka, Japan.
authors.forename: Hidenori
authors.initials: H
authors.lastname: Inohara
mesh_terms: D002294:Carcinoma, Squamous Cell / Q000453:epidemiology; D019941:Cyclin-Dependent Kinase Inhibitor p16 / Q000378:metabolism; D006258:Head and Neck Neoplasms / Q000453:epidemiology; D006801:Humans; D007150:Immunohistochemistry; D008198:Lymph Nodes / Q000000981:diagnostic imaging / Q000473:pathology*; D008207:Lymphatic Metastasis / Q000000981:diagnostic imaging / Q000473:pathology*; D009382:Neoplasms, Unknown Primary / Q000000981:diagnostic imaging / Q000453:epidemiology / Q000473:pathology* / Q000821:virology*; D009959:Oropharyngeal Neoplasms / Q000000981:diagnostic imaging / Q000453:epidemiology / Q000473:pathology* / Q000821:virology*; D027383:Papillomaviridae / Q000502:physiology*; D015995:Prevalence; D000077195:Squamous Cell Carcinoma of Head and Neck; D014057:Tomography, X-Ray Computed
chemical_list: D019941:Cyclin-Dependent Kinase Inhibitor p16
references.citation: Laryngoscope. 2009 Dec;119(12):2348-54
references.pmid: 19718744
references.citation: Cancer Sci. 2014 Apr;105(4):409-17
references.pmid: 24521534
references.citation: N Engl J Med. 2001 Apr 12;344(15):1125-31
references.pmid: 11297703
references.citation: Laryngoscope. 2000 Oct;110(10 Pt 1):1637-41
references.pmid: 11037817
references.citation: Head Neck. 2013 Jan;35(1):123-32
references.pmid: 22034046
references.citation: Diagn Cytopathol. 1997 Jul;17(1):70-3
references.pmid: 9218909
references.citation: Head Neck. 2011 Jun;33(6):856-62
references.pmid: 20737490
references.citation: Clin Cancer Res. 2007 Feb 15;13(4):1186-91
references.pmid: 17317828
references.citation: J Virol Methods. 2004 Dec 1;122(1):87-93
references.pmid: 15488625
references.citation: Pathol Res Pract. 2010 Apr 15;206(4):229-34
references.pmid: 20138710
references.citation: Cancer. 1998 Mar 1;82(5):944-56
references.pmid: 9486586
references.citation: Clin Cancer Res. 2003 Dec 15;9(17):6469-75
references.pmid: 14695150
references.citation: Cancer Epidemiol Biomarkers Prev. 2005 Feb;14(2):467-75
references.pmid: 15734974
references.citation: Diagn Cytopathol. 2012 Oct;40(10):893-7
references.pmid: 21472871
references.citation: J Virol. 2003 Jun;77(11):6227-34
references.pmid: 12743279
references.citation: Am J Clin Pathol. 2004 Aug;122(2):266-74
references.pmid: 15323144
references.citation: Head Neck Pathol. 2008 Sep;2(3):163-8
references.pmid: 20614311
references.citation: Head Neck. 2008 Jul;30(7):898-903
references.pmid: 18383529
references.citation: Oral Oncol. 2012 Dec;48(12):1250-6
references.pmid: 22728322
references.citation: Laryngoscope. 2010 Sep;120(9):1756-72
references.pmid: 20669304
references.citation: Br J Cancer. 1999 Mar;79(9-10):1437-42
references.pmid: 10188887