title: High-risk human papillomavirus DNA detected in primary squamous cell carcinoma of urinary bladder.
abstract: BACKGROUND
  We reported previously that more than one-third (37%) of primary bladder squamous cell carcinomas (SCCs) demonstrate diffuse p16 immunoreactivity independent of gender. This observation made us question whether p16 overexpression in bladder carcinoma is due to human papillomavirus (HPV)-dependent mechanisms.
  
  
  OBJECTIVE
  To determine whether the presence of high-risk HPV (HR-HPV) DNA could be detected in these tumor cells.
  
  
  METHODS
  Fourteen cases of primary bladder SCC, which were positive for p16 by immunohistochemistry, were probed for the detection of HR-HPV by in situ hybridization and the signal amplification Invader assay. Samples positive for detection of HR-HPV by Invader assay were amplified by using HR-HPV type-specific primers, and amplification products were DNA sequenced.
  
  
  RESULTS
  Detection of HR-HPV by the in situ hybridization method was negative in all cases (0 of 14). However, in 3 of 14 cases (21.4%), the presence of HR-HPV DNA was detected with the Cervista HPV HR Invader assay, which was followed by identification of genotype. All positive cases were confirmed by using HR-HPV type-specific amplification followed by DNA sequencing. Identified HR-HPV genotypes included HPV 16 (2 cases) and HPV 35 (1 case).
  
  
  CONCLUSIONS
  High-risk HPV DNA is detectable in a subset of primary bladder SCCs. Based on the well-documented carcinogenic potential of HR-HPV, there is a necessity for additional studies to investigate the role of HR-HPV in bladder carcinogenesis.
authors.affiliation: Department of Pathology & Laboratory Medicine, University of Miami, Miami, Florida 33136, USA.
authors.forename: Jennifer Rose
authors.initials: JR
authors.lastname: Chapman-Fredricks
authors.forename: Maureen
authors.initials: M
authors.lastname: Cioffi-Lavina
authors.forename: Molly A
authors.initials: MA
authors.lastname: Accola
authors.forename: William M
authors.initials: WM
authors.lastname: Rehrauer
authors.forename: Monica T
authors.initials: MT
authors.lastname: Garcia-Buitrago
authors.forename: Carmen
authors.initials: C
authors.lastname: Gomez-Fernandez
authors.forename: Parvin
authors.initials: P
authors.lastname: Ganjei-Azar
authors.forename: Mercè
authors.initials: M
authors.lastname: Jordà
mesh_terms: D001483:Base Sequence; D002294:Carcinoma, Squamous Cell / Q000209:etiology / Q000378:metabolism / Q000821:virology*; D019941:Cyclin-Dependent Kinase Inhibitor p16 / Q000378:metabolism; D015344:DNA Probes, HPV; D004279:DNA, Viral / Q000235:genetics / Q000302:isolation & purification; D005260:Female; D061809:Human Papillomavirus DNA Tests; D052162:Human papillomavirus 16 / Q000235:genetics / Q000302:isolation & purification / Q000472:pathogenicity; D006801:Humans; D008297:Male; D008969:Molecular Sequence Data; D027383:Papillomaviridae / Q000235:genetics / Q000302:isolation & purification* / Q000472:pathogenicity*; D030361:Papillomavirus Infections / Q000150:complications / Q000378:metabolism / Q000821:virology; D012189:Retrospective Studies; D012307:Risk Factors; D001749:Urinary Bladder Neoplasms / Q000209:etiology / Q000378:metabolism / Q000821:virology*
chemical_list: D019941:Cyclin-Dependent Kinase Inhibitor p16; D015344:DNA Probes, HPV; D004279:DNA, Viral