title: Patients with HPV-related tonsil squamous cell carcinoma rarely harbour oncogenic HPV infection at other pharyngeal sites.
abstract: OBJECTIVE
  Patients with human papillomavirus (HPV)-related oropharyngeal squamous cell carcinoma (OPSCC) have a reduced risk of developing second primary upper aerodigestive tract (UADT) tumours compared to patients with HPV-negative primary tumours at the same site. To determine whether this finding might be explained by a lack of viral-induced field cancerisation or multifocal infection, we investigated whether there was epithelial dysplasia and/or evidence of HPV infection at other pharyngeal mucosal sites in patients presenting with the disease.
  
  
  METHODS
  Sixty-three patients with primary tonsil SCC and 108 pharyngeal endoscopic biopsies, representing at least one pharyngeal subsite from each patient, were included in this study. Tissue samples were tested using HPV PCR (GP5+/6+), p16 immunohistochemistry (IHC) and high risk HPV DNA in situ hybridisation (ISH).
  
  
  RESULTS
  There were 46 patients with HPV-related SCC and 17 patients with HPV-negative disease. PCR detected HPV DNA in a fifth of pharyngeal endoscopic biopsies and was equally likely to be from a patient with HPV-related SCC as from a patient with HPV negative disease. All PCR positive cases were tested using p16 IHC and high risk HPV ISH and only three biopsies were positive. Significantly, these three biopsies all showed evidence of epithelial dysplasia and were from patients with an HPV positive index tumour.
  
  
  CONCLUSIONS
  Our data suggest that virus-induced field cancerisation and/or multifocal oncogenic HPV infection of the pharynx is uncommon in OPSCC and supports the concept that these patients have a lower risk of developing second primary tumours of the UADT.
authors.affiliation: Oral Pathology, King's College London Dental Institute, London, United Kingdom. Electronic address: selvam.thavaraj@kcl.ac.uk.
authors.forename: Selvam
authors.initials: S
authors.lastname: Thavaraj
authors.affiliation: Oral Pathology, King's College London Dental Institute, London, United Kingdom.
authors.forename: Angela
authors.initials: A
authors.lastname: Stokes
authors.affiliation: Department of Oral Pathology, Osaka Dental University, Osaka, Japan.
authors.forename: Kazuya
authors.initials: K
authors.lastname: Mazuno
authors.affiliation: Oral Pathology, Guy's and St. Thomas' NHS Foundation Trust, London, United Kingdom.
authors.forename: Rhonda
authors.initials: R
authors.lastname: Henley-Smith
authors.affiliation: Oral Pathology, Guy's and St. Thomas' NHS Foundation Trust, London, United Kingdom.
authors.forename: Yae-Eun
authors.initials: YE
authors.lastname: Suh
authors.affiliation: Otolaryngology-Head and Neck Surgery, Newcastle upon Tyne Hospitals NHS Trust, United Kingdom.
authors.forename: Vinidh
authors.initials: V
authors.lastname: Paleri
authors.affiliation: Molecular Oncology, King's College London Dental Institute, London, United Kingdom.
authors.forename: Mahvash
authors.initials: M
authors.lastname: Tavassoli
authors.affiliation: Oral Pathology, King's College London Dental Institute, London, United Kingdom.
authors.forename: Edward
authors.initials: E
authors.lastname: Odell
authors.affiliation: Centre for Oral Health Research, School of Dental Sciences, Newcastle University, Newcastle Upon Tyne, United Kingdom.
authors.forename: Max
authors.initials: M
authors.lastname: Robinson
mesh_terms: D002294:Carcinoma, Squamous Cell / Q000150:complications* / Q000821:virology; D005260:Female; D006801:Humans; D017403:In Situ Hybridization; D008297:Male; D027383:Papillomaviridae / Q000235:genetics / Q000302:isolation & purification; D030361:Papillomavirus Infections / Q000150:complications* / Q000821:virology; D016133:Polymerase Chain Reaction; D014067:Tonsillar Neoplasms / Q000150:complications* / Q000821:virology
keywords: Field cancerisation; Human papillomavirus; Oropharynx; Squamous cell carcinoma; Tonsil