title: Low etiologic fraction for high-risk human papillomavirus in oral cavity squamous cell carcinomas.
abstract: BACKGROUND
  Human papillomavirus (HPV) is a cause of oropharyngeal cancer, but a role for HPV in the etiology of oral cavity squamous cell carcinomas (OCSCC) remains uncertain.
  
  
  METHODS
  We sought to estimate the etiologic fraction for HPV among consecutive, incident OCSCC diagnosed from 2005 to 2011 at four North American hospitals. DNA and RNA purified from paraffin-embedded tumors were considered evaluable if positive for DNA and mRNA control genes by quantitative PCR. Fifteen high-risk (HR) HPV types were detected in tumors by consensus PCR followed by type-specific HR-HPV E6/7 oncogene expression by quantitative reverse-transcriptase PCR. P16 expression was evaluated by immunohistochemistry (IHC). A study of 400 cases allowed for precision to estimate an etiologic fraction of as low as 0% (97.5% confidence interval, 0-0.92%).
  
  
  RESULTS
  Of 409 evaluable OCSCC, 24 (5.9%, 95%CI 3.6-8.2) were HR-HPV E6/7 expression positive; 3.7% (95%CI 1.8-5.5) for HPV16 and 2.2% (95%CI 0.8-3.6) for other HR-HPV types. HPV-positive tumors arose from throughout the oral cavity (floor of mouth [n=9], anterior tongue [6], alveolar process [4], hard palate [3], gingiva [1] and lip [1]) and were significantly associated with male gender, small tumor stage, poor tumor differentiation, and basaloid histopathology. P16 IHC had very good-to-excellent sensitivity (79.2%, 95%CI 57.9-92.9), specificity (93.0%, 95%CI 90.0-95.3), and negative-predictive value (98.6%, 95%CI 96.8-99.6), but poor positive-predictive value (41.3%, 95%CI 27.0-56.8) for HR-HPV E6/7 expression in OCSCC.
  
  
  CONCLUSIONS
  The etiologic fraction for HR-HPV in OCSCC was 5.9%. p16 IHC had poor positive predictive value for detection of HPV in these cancers.
authors: Department of Pathology, University of Chicago, Chicago, IL, USA.
authors: Mark W
authors: MW
authors: Lingen
authors: Weihong
authors: W
authors: Xiao
authors: Alessandra
authors: A
authors: Schmitt
authors: Bo
authors: B
authors: Jiang
authors: Robert
authors: R
authors: Pickard
authors: Paul
authors: P
authors: Kreinbrink
authors: Bayardo
authors: B
authors: Perez-Ordonez
authors: Richard C
authors: RC
authors: Jordan
authors: Maura L
authors: ML
authors: Gillison
mesh_terms: D052685:Alphapapillomavirus / Q000235:genetics / Q000302:isolation & purification*; D002294:Carcinoma, Squamous Cell / Q000821:virology*; D005260:Female; D052162:Human papillomavirus 16 / Q000235:genetics / Q000302:isolation & purification; D006801:Humans; D008297:Male; D008875:Middle Aged; D009060:Mouth Floor / Q000821:virology; D009062:Mouth Neoplasms / Q000821:virology*; D060787:Neoplasm Grading; D009367:Neoplasm Staging; D009856:Oncogene Proteins, Viral / Q000032:analysis; D050725:Papillomavirus E7 Proteins / Q000032:analysis; D030361:Papillomavirus Infections / Q000821:virology*; D011237:Predictive Value of Tests; D011505:Protein-Tyrosine Kinases / Q000032:analysis; D012097:Repressor Proteins / Q000032:analysis; D012189:Retrospective Studies; D012307:Risk Factors; D012680:Sensitivity and Specificity; D012737:Sex Factors; D014062:Tongue Neoplasms / Q000821:virology
chemical_list: C068651:E6 protein, Human papillomavirus type 16; D009856:Oncogene Proteins, Viral; D050725:Papillomavirus E7 Proteins; D012097:Repressor Proteins; C059731:oncogene protein E7, Human papillomavirus type 16; D011505:Protein-Tyrosine Kinases