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Evaluation of human papillomavirus testing for squamous cell carcinoma of the tonsil in clinical practice
  1. Selvam Thavaraj1,
  2. Angela Stokes1,
  3. Eliete Guerra2,
  4. Jon Bible3,
  5. Eugene Halligan3,
  6. Anna Long4,
  7. Atuora Okpokam4,
  8. Philip Sloan4,5,
  9. Edward Odell1,
  10. Max Robinson5
  1. 1Oral Pathology, Department of Clinical and Diagnostic Sciences, King's College London Dental Institute, London, UK
  2. 2Oral Pathology, Department of Dentistry, Faculty of Health Science, University of Brasilia, Brasilia, Brazil
  3. 3GSTS Pathology, Department of Infection, Virology Section, St Thomas' Hospital, London, UK
  4. 4Department of Cellular Pathology, Newcastle upon Tyne Hospitals NHS Foundation Trust, Newcastle Upon Tyne, UK
  5. 5Centre for Oral Health Research, School of Dental Sciences, Newcastle University, Newcastle Upon Tyne, UK
  1. Correspondence to Dr Max Robinson, Centre for Oral Health Research, School of Dental Sciences, Newcastle University, Framlington Place, Newcastle Upon Tyne NE2 4BW, UK; max.robinson{at}


Background Oncogenic human papillomavirus (HPV)-associated oropharyngeal squamous cell carcinoma (SCC) is a subtype of head-and-neck cancer with a distinct clinical and prognostic profile. While there are calls to undertake HPV testing for oropharyngeal SCCs within the diagnostic setting and for clinical trials, there are currently no internationally accepted standards.

Methods 142 tonsil SCCs were tested using p16 immunohistochemistry (IHC), high-risk HPV DNA in situ hybridisation (ISH) and HPV DNA polymerase chain reaction (PCR; GP5+/6+ primers).

Results There were high levels of agreement between pathologists for p16 IHC and HPV ISH scoring; however, around 10% of HPV ISH cases showed some interobserver discrepancy that was resolved by slide review. The combination of p16 IHC and HPV ISH classified 53% of the samples as HPV-positive, whereas the combination of p16 IHC and HPV PCR classified 61% of the samples as HPV-positive. By employing a three-tiered, staged algorithm (p16 IHC/HPV ISH/HPV PCR), the authors were able to classify 98% of the cases as either HPV-positive (p16 IHC+/HPV DNA+; 62%) or HPV-negative (p16 IHC−/HPV DNA−; 35%).

Conclusions The current study suggests that using a combination of p16 IHC/HPV ISH/HPV PCR, in a three-tiered, staged algorithm, in conjunction with consensus reporting of HPV ISH, leads to less equivocal molecular classification. In order to ensure consistent reporting of this emerging disease, it is increasingly important for the head-and-neck oncology community to define the minimum requirements for assigning a diagnosis of ‘HPV-related’ oropharyngeal SCC in order to inform prognosis and for stratification in clinical trials.

  • Tonsil
  • oropharyngeal
  • squamous cell carcinoma
  • human papillomavirus
  • head and neck cancer
  • histopathology

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  • Competing interests None.

  • Provenance and peer review Not commissioned; externally peer reviewed.