title: Clinical features of human papilloma virus-related head and neck squamous cell carcinoma of an unknown primary site.
abstract: OBJECTIVE
  Head and neck squamous cell carcinoma of an unknown primary site (HNSCCUP) is a heterogeneous group of tumors that includes the human papillomavirus (HPV)-associated oropharyngeal squamous cell carcinoma. To investigate the relationship between HNSCCUP and HPV, we reviewed p16 overexpression and HPV DNA in lymph node metastases and examined their correlation with the primary site and clinical features.
  
  
  METHODS
  Thirty-three patients with HNSCCUP were retrospectively studied. Dissected neck metastases were analyzed for p16 overexpression by immunohistochemistry, and the presence of HPV DNA was investigated by in situ hybridization.
  
  
  RESULTS
  Of the 33 patients, 8 (24%) exhibited p16 overexpression. p16-positive lymph node metastases contained significantly more HPV DNA and were most frequently associated with occult primary lesions in the oropharynx and a favorable prognosis. Patients with a lower alcohol consumption, only level II/III metastasis, and cystic lymph node metastasis tended to have p16 overexpression.
  
  
  CONCLUSIONS
  This is the first report on the relationship of HNSCCUP with p16 and HPV DNA status in Asian patients. In total, 24% of the HNSCCUP patients were p16 positive. p16 overexpression in neck metastasis was predictive of both an occult primary lesion in the oropharynx and an association with HPV infection. Alcohol consumption, location, and features of neck metastasis were correlated with p16 expression.
authors.affiliation: Department of Otolaryngology, Head and Neck Surgery, The University of Tokyo Hospital, Tokyo, Japan.
authors.forename: Kenya
authors.initials: K
authors.lastname: Kobayashi
authors.forename: Yuki
authors.initials: Y
authors.lastname: Saito
authors.forename: Go
authors.initials: G
authors.lastname: Omura
authors.forename: Mizuo
authors.initials: M
authors.lastname: Ando
authors.forename: Takashi
authors.initials: T
authors.lastname: Sakamoto
authors.forename: Tatsuya
authors.initials: T
authors.lastname: Yamasoba
authors.forename: Takahiro
authors.initials: T
authors.lastname: Asakage
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D014408:Biomarkers, Tumor; D002294:Carcinoma, Squamous Cell / Q000378:metabolism / Q000473:pathology* / Q000821:virology*; D019941:Cyclin-Dependent Kinase Inhibitor p16; D004279:DNA, Viral / Q000378:metabolism; D005260:Female; D006258:Head and Neck Neoplasms / Q000378:metabolism / Q000473:pathology* / Q000821:virology*; D006801:Humans; D007150:Immunohistochemistry; D017403:In Situ Hybridization; D008198:Lymph Nodes / Q000378:metabolism / Q000473:pathology; D008207:Lymphatic Metastasis; D008297:Male; D008875:Middle Aged; D009363:Neoplasm Proteins / Q000378:metabolism; D009382:Neoplasms, Unknown Primary / Q000378:metabolism / Q000473:pathology* / Q000821:virology*; D027383:Papillomaviridae / Q000235:genetics; D030361:Papillomavirus Infections / Q000473:pathology*; D012189:Retrospective Studies; D000077195:Squamous Cell Carcinoma of Head and Neck
chemical_list: D014408:Biomarkers, Tumor; C000614131:CDKN2A protein, human; D019941:Cyclin-Dependent Kinase Inhibitor p16; D004279:DNA, Viral; D009363:Neoplasm Proteins