title: Human papillomavirus infection and biomarkers in sinonasal inverted papillomas: clinical significance and molecular mechanisms.
abstract: BACKGROUND
  The role of human papillomavirus (HPV) in sinonasal inverted papillomas (IPs) is controversial. Determining the prevalence of HPV infection and its impact on the molecular biology of these tumors is critical to characterizing its role in the pathogenesis of IPs.
  
  
  METHODS
  A total of 112 paraffin-embedded IPs from 90 patients were studied. A tissue microarray was constructed and stained for p16, p53, epidermal growth factor receptor (EGFR), and cyclin D1. HPV presence and types were determined using PGMY 09/11 primers and integration using HPV 11 detection of integrated papillomavirus sequences by ligation-mediated polymerase chain reaction (DIPS-PCR).
  
  
  RESULTS
  HPV was detected in 11 of 90 (12%) patients. HPV 11 was found in 9 samples. HPV 6 and HPV 27 were found in 1 sample each. EGFR staining proportion was higher in HPV-positive IPs vs HPV-negative specimens (56.2% vs 23.6%; p = 0.009). Differences in p16, p53, and cyclin D1 staining were not significant. HPV-positive lesions tend to progress to malignancy (p = 0.064). Three samples were analyzed for integration. Viral integration was found in both malignant tumors but not in the precursor IP.
  
  
  CONCLUSIONS
  Degradation of p53 and p16/cyclin D1 dysregulation are not important mechanisms in low-risk HPV-related IP. The low prevalence of HPV in this series indicates it is not a main etiological factor for IPs; however, when present, low-risk HPV may contribute to the biology of IPs through an increase of EGFR expression and a predisposition for malignant progression by integration into the cellular genome.
authors.affiliation: Department of Otolaryngology, University of Michigan Health Systems, Ann Arbor, MI.
authors.forename: Adam
authors.initials: A
authors.lastname: Scheel
authors.affiliation: Department of Otolaryngology, University of Michigan Health Systems, Ann Arbor, MI.
authors.forename: Giant C
authors.initials: GC
authors.lastname: Lin
authors.affiliation: Department of Pathology, University of Michigan Health Systems, Ann Arbor, MI.
authors.forename: Jonathan B
authors.initials: JB
authors.lastname: McHugh
authors.affiliation: Department of Otolaryngology, University of Michigan Health Systems, Ann Arbor, MI.
authors.forename: Christine M
authors.initials: CM
authors.lastname: Komarck
authors.affiliation: Department of Otolaryngology, University of Michigan Health Systems, Ann Arbor, MI.
authors.forename: Heather M
authors.initials: HM
authors.lastname: Walline
authors.affiliation: Department of Otolaryngology, University of Michigan Health Systems, Ann Arbor, MI.
authors.forename: Mark E
authors.initials: ME
authors.lastname: Prince
authors.affiliation: Department of Otolaryngology, University of Michigan Health Systems, Ann Arbor, MI.
authors.forename: Mark A
authors.initials: MA
authors.lastname: Zacharek
authors.affiliation: Department of Otolaryngology, University of Michigan Health Systems, Ann Arbor, MI.
authors.forename: Thomas E
authors.initials: TE
authors.lastname: Carey
mesh_terms: D014408:Biomarkers, Tumor / Q000378:metabolism*; D002294:Carcinoma, Squamous Cell / Q000821:virology*; D019938:Cyclin D1 / Q000378:metabolism; D019941:Cyclin-Dependent Kinase Inhibitor p16; D004279:DNA, Viral / Q000378:metabolism; D018450:Disease Progression; D066246:ErbB Receptors / Q000378:metabolism; D005260:Female; D052140:Human papillomavirus 11 / Q000235:genetics / Q000302:isolation & purification*; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D009363:Neoplasm Proteins / Q000378:metabolism; D009364:Neoplasm Recurrence, Local / Q000821:virology; D018308:Papilloma, Inverted / Q000821:virology*; D030361:Papillomavirus Infections / Q000150:complications*; D010255:Paranasal Sinus Neoplasms / Q000821:virology*; D016133:Polymerase Chain Reaction; D016159:Tumor Suppressor Protein p53 / Q000378:metabolism
chemical_list: D014408:Biomarkers, Tumor; C530104:CCND1 protein, human; C000614131:CDKN2A protein, human; D019941:Cyclin-Dependent Kinase Inhibitor p16; D004279:DNA, Viral; D009363:Neoplasm Proteins; D016159:Tumor Suppressor Protein p53; D019938:Cyclin D1; C512478:EGFR protein, human; D066246:ErbB Receptors
keywords: Cyclin D1; DIPS-PCR; EGFR; HPV; integration; inverted papilloma; p16; p53