title: Changes in Unknown Primary Squamous Cell Carcinoma of the Head and Neck at Initial Presentation in the Era of Human Papillomavirus.
abstract: OBJECTIVE
  The presence of human papillomavirus (HPV) in unknown primary squamous cell carcinoma (UPSCC) of the head and neck at initial presentation focuses the investigation for the primary tumor on the oropharynx. The trends, frequency, and detection rate of UPSCCs have not been evaluated in the context of HPV tumor status.
  
  
  OBJECTIVE
  To determine the frequency of UPSCC over time and to evaluate the proportion of HPV-positive UPSCCs.
  
  
  METHODS
  Retrospective, single-institutional case series of patients diagnosed with UPSCC and evaluated at the Johns Hopkins Hospital from January 1, 2005, to June 1, 2014. Human papillomavirus tumor status was determined by p16 immunohistochemical analysis and/or high-risk HPV DNA by in situ hybridization as clinically available.
  
  
  METHODS
  Number and clinical characteristics of UPSCC cases over time.
  
  
  RESULTS
  Eighty-four UPSCC cases were eligible for analysis. The mean age of the patients was 57.3 years (range 29-80 years), and 88.1% (n = 74) were male. The frequency of UPSCC increased significantly over time (P for trend = .01) and was significantly higher during later calendar periods (14 cases during 2005-2008 vs 39 cases during 2012-2014, P = .03). A total of 69 cases (90.7%) with available HPV tumor status were HPV-positive. The patients with HPV-positive UPSCC were significantly more likely to be male (91% vs 42.9%, P = .005) and younger (56.1 vs 67.7 years, P = .002) than the HPV-negative patients with UPSCC. The overall primary tumor site detection rate was 59.3% (n = 48). There was a nonsignificant increase in the detection rate from calendar periods 2005-2008 to 2012-2014 (50.0% vs 64.9%, P = .38). Since transoral robotic surgery was adopted in the diagnostic evaluation of UPSCC in 2011, a nonsignificant increase in the detection of primary tumors was observed (53.8% vs 64.3%, P = .34).
  
  
  CONCLUSIONS
  The frequency of UPSCC has increased significantly in recent calendar periods, and most cases are HPV-positive. As expected, patients with HPV-positive UPSCC tend to be male and younger.
authors.affiliation: Department of Otolaryngology-Head and Neck Surgery, Johns Hopkins School of Medicine, Baltimore, Maryland.
authors.forename: Kevin
authors.initials: K
authors.lastname: Motz
authors.affiliation: Department of Otolaryngology-Head and Neck Surgery, Johns Hopkins School of Medicine, Baltimore, Maryland.
authors.forename: Jesse R
authors.initials: JR
authors.lastname: Qualliotine
authors.affiliation: Department of Otolaryngology-Head and Neck Surgery, Johns Hopkins School of Medicine, Baltimore, Maryland.
authors.forename: Eleni
authors.initials: E
authors.lastname: Rettig
authors.affiliation: Department of Otolaryngology-Head and Neck Surgery, Johns Hopkins School of Medicine, Baltimore, Maryland.
authors.forename: Jeremy D
authors.initials: JD
authors.lastname: Richmon
authors.affiliation: Department of Otolaryngology-Head and Neck Surgery, Johns Hopkins School of Medicine, Baltimore, Maryland.
authors.forename: David W
authors.initials: DW
authors.lastname: Eisele
authors.affiliation: Department of Otolaryngology-Head and Neck Surgery, Johns Hopkins School of Medicine, Baltimore, Maryland.
authors.forename: Carole
authors.initials: C
authors.lastname: Fakhry
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D002294:Carcinoma, Squamous Cell / Q000453:epidemiology / Q000556:secondary* / Q000821:virology; D004279:DNA, Viral / Q000032:analysis*; D005260:Female; D006258:Head and Neck Neoplasms / Q000453:epidemiology / Q000556:secondary* / Q000821:virology; D052162:Human papillomavirus 16 / Q000235:genetics*; D006801:Humans; D007150:Immunohistochemistry; D017403:In Situ Hybridization; D015994:Incidence; D008297:Male; D008396:Maryland / Q000453:epidemiology; D008875:Middle Aged; D009382:Neoplasms, Unknown Primary; D030361:Papillomavirus Infections / Q000175:diagnosis* / Q000453:epidemiology / Q000821:virology; D012189:Retrospective Studies; D018570:Risk Assessment; D012307:Risk Factors; D000077195:Squamous Cell Carcinoma of Head and Neck
chemical_list: D004279:DNA, Viral