title: Highly aggressive human papillomavirus-related oropharyngeal cancer: clinical, radiologic, and pathologic characteristics.
abstract: OBJECTIVE
  Although the majority of human papillomavirus (HPV)-positive oropharyngeal squamous cell carcinomas have a favorable prognosis, we search for markers of poor prognosis by carefully examining a subset of highly aggressive cases.
  
  
  METHODS
  Seven patients with HPV-positive oropharyngeal cancer who presented with non-pulmonary distant metastasis or developed distant metastasis posttreatment were identified. Eight control cases were chosen which responded well to treatment. Pathologic and radiologic studies were reviewed and compared.
  
  
  RESULTS
  Two cases displayed a small cell carcinoma (SmCC) component upon pathologic review. Biomarker analysis revealed lower expression of NOTCH1 in the aggressive cohort in comparison to controls (P = .04). Cases showed a predominance of clustering of lymph nodes, extracapsular spread, and central tumor necrosis.
  
  
  CONCLUSIONS
  Although most HPV-related oropharyngeal cancers display a positive prognosis, it is evident that there is a subset, which behaves more aggressively. This early investigation identifies pathologic and radiologic features that may help to predict this behavior.
authors.affiliation: Department of Otolaryngology, The Ohio State University Wexner Medical Center, Columbus, OH 43212, USA. Azeem.kaka@osumc.edu
authors.forename: Azeem S
authors.initials: AS
authors.lastname: Kaka
authors.forename: Bhavna
authors.initials: B
authors.lastname: Kumar
authors.forename: Pawan
authors.initials: P
authors.lastname: Kumar
authors.forename: Paul E
authors.initials: PE
authors.lastname: Wakely
authors.forename: Claudia M
authors.initials: CM
authors.lastname: Kirsch
authors.forename: Matthew O
authors.initials: MO
authors.lastname: Old
authors.forename: Enver
authors.initials: E
authors.lastname: Ozer
authors.forename: Amit
authors.initials: A
authors.lastname: Agrawal
authors.forename: Ricardo E
authors.initials: RE
authors.lastname: Carrau
authors.forename: David E
authors.initials: DE
authors.lastname: Schuller
authors.forename: Farzan
authors.initials: F
authors.lastname: Siddiqui
authors.forename: Theodoros N
authors.initials: TN
authors.lastname: Teknos
mesh_terms: D000328:Adult; D000368:Aged; D014408:Biomarkers, Tumor / Q000032:analysis*; D002294:Carcinoma, Squamous Cell / Q000378:metabolism / Q000556:secondary / Q000821:virology*; D016022:Case-Control Studies; D015331:Cohort Studies; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D017403:In Situ Hybridization; D008207:Lymphatic Metastasis / Q000000981:diagnostic imaging / Q000473:pathology; D008297:Male; D008875:Middle Aged; D009959:Oropharyngeal Neoplasms / Q000378:metabolism / Q000556:secondary / Q000821:virology*; D030361:Papillomavirus Infections / Q000150:complications*; D011379:Prognosis; D011859:Radiography; D051881:Receptor, Notch1 / Q000032:analysis*; D016159:Tumor Suppressor Protein p53 / Q000032:analysis*
chemical_list: D014408:Biomarkers, Tumor; D051881:Receptor, Notch1; D016159:Tumor Suppressor Protein p53