title: No evidence for active human papillomavirus (HPV) in fields surrounding HPV-positive oropharyngeal tumors.
abstract: BACKGROUND
  Patients with human papillomavirus (HPV)-positive oropharyngeal squamous cell carcinomas (OPSCCs) have a better prognosis than patients with HPV-negative OPSCCs. Important factors contributing to this better prognosis are relatively low numbers of local/regional recurrences (LRRs) and second primary tumors (SPTs) in patients with HPV-positive OPSCC. These low numbers may be explained in addition by the absence of a 'field cancerization' effect, which is a cause of LRRs and SPTs in patients with HPV-negative OPSCC. We aimed to detect a possible 'field effect' in patients with HPV-positive OPSCC. As HPV is involved in the early stage of carcinogenesis in OPSCCs, its presence is considered a reliable marker for the detection of such a field effect. Therefore, the presence of transcriptionally active HPV was analyzed in the mucosa surrounding HPV-positive OPSCCs.
  
  
  METHODS
  We included 20 patients who were surgically treated for an HPV-positive OPSCC in the period 2000-2006. Of each patient, the formalin-fixed paraffin-embedded tumor sample and all available resection margins were collected. In total, 97 resection margins were investigated with an average of five resection margins per tumor. All samples were analyzed for the presence of tumor and the presence of transcriptionally active HPV by HPV16-E6-mRNA detection.
  
  
  RESULTS
  All tumors were HPV16-E6-mRNA positive. HPV16-E6-mRNA could be detected in the resection margins that contained tumor (n = 6). All tumor-negative resection margins (n = 91) scored negative for HPV16-E6-mRNA.
  
  
  CONCLUSIONS
  In conclusion, transcriptional active HPV could not be detected in the mucosa surrounding an HPV-positive OPSCC, which suggests the absence of field effect. This observation may explain the lower number of LRRs and SPTs in HPV-positive patients.
authors.affiliation: Department of Otolaryngology/Head and Neck Surgery, VU University Medical Center, Amsterdam, The Netherlands.
authors.forename: Michelle M
authors.initials: MM
authors.lastname: Rietbergen
authors.forename: Boudewijn J M
authors.initials: BJ
authors.lastname: Braakhuis
authors.forename: Nadia
authors.initials: N
authors.lastname: Moukhtari
authors.forename: Elisabeth
authors.initials: E
authors.lastname: Bloemena
authors.forename: Arjen
authors.initials: A
authors.lastname: Brink
authors.forename: Daoud
authors.initials: D
authors.lastname: Sie
authors.forename: Bauke
authors.initials: B
authors.lastname: Ylstra
authors.forename: Robert J
authors.initials: RJ
authors.lastname: Baatenburg de Jong
authors.forename: Peter J F
authors.initials: PJ
authors.lastname: Snijders
authors.forename: Ruud H
authors.initials: RH
authors.lastname: Brakenhoff
authors.forename: C René
authors.initials: CR
authors.lastname: Leemans
mesh_terms: D000328:Adult; D000368:Aged; D063646:Carcinogenesis / Q000473:pathology; D002294:Carcinoma, Squamous Cell / Q000473:pathology / Q000821:virology*; D002471:Cell Transformation, Neoplastic / Q000473:pathology; D015331:Cohort Studies; D004279:DNA, Viral / Q000032:analysis; D005260:Female; D052162:Human papillomavirus 16 / Q000302:isolation & purification* / Q000502:physiology; D006801:Humans; D008297:Male; D008875:Middle Aged; D020360:Neoadjuvant Therapy; D009364:Neoplasm Recurrence, Local / Q000821:virology; D016609:Neoplasms, Second Primary / Q000821:virology; D009856:Oncogene Proteins, Viral / Q000032:analysis; D009959:Oropharyngeal Neoplasms / Q000473:pathology / Q000821:virology*; D011505:Protein-Tyrosine Kinases / Q000032:analysis; D012333:RNA, Messenger / Q000032:analysis; D012097:Repressor Proteins / Q000032:analysis; D014067:Tonsillar Neoplasms / Q000473:pathology / Q000821:virology; D014779:Virus Replication / Q000502:physiology
chemical_list: D004279:DNA, Viral; C068651:E6 protein, Human papillomavirus type 16; D009856:Oncogene Proteins, Viral; D012333:RNA, Messenger; D012097:Repressor Proteins; D011505:Protein-Tyrosine Kinases
keywords: field cancerization; human papillomavirus; oropharyngeal squamous cell carcinoma; second primary tumors