title: Human papillomavirus (HPV) transcripts in malignant inverted papilloma are from integrated HPV DNA.
abstract: OBJECTIVE
  The objectives of the study were to detect human papillomavirus (HPV) sequences in nasal inverted papilloma (IP) lesions and to determine whether HPV is involved in the progression of IP to sinonasal squamous cell carcinoma (SCC).
  
  
  METHODS
  A retrospective study was performed on 14 patients diagnosed with IP within the last 12 years. Three of these 14 patients developed SCC.
  
  
  METHODS
  Eighteen formalin-fixed, paraffin-embedded tissue blocks were obtained for these 14 patients. After DNA extraction, polymerase chain reaction (PCR) was performed, followed by hybridization using HPV 6, 11, 16, 18, 31, 33, 35, 45, and 52 specific DNA probes, in an attempt to identify HPV type in each specimen. After RNA extraction, the integration status of the HPV genome was evaluated based on the relative abundance of E7 and E5 viral transcripts, assessed by quantitative real-time PCR.
  
  
  RESULTS
  HPV sequences were detected in samples from 3 of the 14 patients with IP. Of the three patients with SCC, HPV sequences were detected in two patients, whereas one patient was negative for the oligoprobes tested. Of the 11 patients diagnosed only with IP, 1 patient was positive for HPV DNA (HPV type 11). This difference in HPV positivity between IP and SCC was not statistically significant (P = .09, Fisher's Exact test, two tailed). Viral transcripts were detected in both patients with SSC who were HPV positive. Because HPV early transcripts are polycistronic, loss of 3' transcript sequences (E5) and retention of 5' sequences (E7) indicates integration. One of the SSC containing HPV 18 sequences showed a E7/E5 ratio of 776:1. The other SSC showed E7 transcripts and an absence of E5 transcripts
  
  
  CONCLUSIONS
  HPV transcripts were present in SCC positive for HPV, and the relative level of E7 to E5 transcripts indicates integration of the viral genome. These findings are suggestive of HPV having an active role in the lesion. More extensive studies are needed to determine the exact role of HPV in IP and progression to SCC.
authors.affiliation: Department of Otolaryngology, Wayne State University, 4301 St. Antoine, Detroit, MI 48202, U.S.A. smckay@med.wayne.edu
authors.forename: Shawn P
authors.initials: SP
authors.lastname: McKay
authors.forename: Lucie
authors.initials: L
authors.lastname: Grégoire
authors.forename: Fulvio
authors.initials: F
authors.lastname: Lonardo
authors.forename: Patrick
authors.initials: P
authors.lastname: Reidy
authors.forename: Robert H
authors.initials: RH
authors.lastname: Mathog
authors.forename: Wayne D
authors.initials: WD
authors.lastname: Lancaster
mesh_terms: D002294:Carcinoma, Squamous Cell / Q000473:pathology*; D002471:Cell Transformation, Neoplastic; D004279:DNA, Viral / Q000032:analysis; D005260:Female; D006801:Humans; D008297:Male; D009669:Nose Neoplasms / Q000473:pathology / Q000821:virology*; D018308:Papilloma, Inverted / Q000473:pathology / Q000821:virology*; D027383:Papillomaviridae / Q000302:isolation & purification*; D030361:Papillomavirus Infections / Q000175:diagnosis*; D011230:Precancerous Conditions / Q000473:pathology*; D011379:Prognosis; D012189:Retrospective Studies; D018570:Risk Assessment; D012494:Sampling Studies; D012680:Sensitivity and Specificity; D046509:Tissue Culture Techniques
chemical_list: D004279:DNA, Viral