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HPV-associated oropharyngeal squamous cell carcinoma

Monday 12 September 2011

HPV-related OPSCC

Human papillomavirus (HPV) is established as causative in oropharyngeal squamous cell carcinomas (OSCCs), being detected in 50% to 80% of tumors by DNA in situ hybridization (ISH) and/or polymerase chain reaction.

- mRNA

  • However, these tests do not assess viral transcription. Many consider E6/E7 messenger ribonucleic acid (mRNA) the best indicator of HPV status.
  • RNA ISH is more sensitive than DNA ISH in detecting HPV in OSCC, and it correlates strongly with p16. Although both tests were comparable, p16 more strongly stratified patient outcomes. (21836494)

- Partial p16 staining in oropharyngeal squamous cell carcinoma: extent and pattern correlate with human papillomavirus RNA status. (22596101)

  • Human papillomavirus (HPV)-related oropharyngeal squamous cell carcinoma has unique biology and better outcomes.
  • p16 immunostaining is used as a surrogate marker for transcriptionally active HPV.
  • Although diffuse staining is generally accepted as positive, the significance of partial staining has not been established, nor has the cutoff for extent of p16 staining that should be used to identify a tumor as HPV-related.
  • Greater than 75% p16 staining or, alternatively, >50% staining combined with >25% confluent areas, are suitable cutoffs for defining positivity. (22596101)


- p16

  • Retinoblastoma (Rb) downregulation by HPV E7 results in p16 upregulation. We hypothesized that p16 overexpression in OSCC defines HPV-induced tumors with favorable prognosis.
  • Using this system for classification, it has been defined the molecular profile of HPV+ OSCC with favorable prognosis, namely HPV+/p16 high (class III). (16401683)

Open references

- Virology and molecular pathogenesis of HPV (human papillomavirus)-associated oropharyngeal squamous cell carcinoma. Miller DL, Puricelli MD, Stack MS. Biochem J. 2012 Apr 15;443(2):339-53. doi : 10.1042/BJ20112017 PMID: 22452816 [Free]

- Molecular classification identifies a subset of human papillomavirus—associated oropharyngeal cancers with favorable prognosis. Weinberger PM, Yu Z, Haffty BG, Kowalski D, Harigopal M, Brandsma J, Sasaki C, Joe J, Camp RL, Rimm DL, Psyrri A. J Clin Oncol. 2006 Feb 10;24(5):736-47. PMID: 16401683 [Free]


- Tumor cell anaplasia and multinucleation are predictors of disease recurrence in oropharyngeal squamous cell carcinoma, including among just the human papillomavirus-related cancers. Lewis JS Jr, Scantlebury JB, Luo J, Thorstad WL. Am J Surg Pathol. 2012 Jul;36(7):1036-46. PMID: 22743286

- Validation of Methods for Oropharyngeal Cancer HPV Status Determination in US Cooperative Group Trials. Jordan RC, Lingen MW, Perez-Ordonez B, He X, Pickard R, Koluder M, Jiang B, Wakely P, Xiao W, Gillison ML. Am J Surg Pathol. 2012 Jul;36(7):945-954. PMID: 22743284

- Partial p16 staining in oropharyngeal squamous cell carcinoma: extent and pattern correlate with human papillomavirus RNA status. Lewis JS Jr, Chernock RD, Ma XJ, Flanagan JJ, Luo Y, Gao G, Wang X, El-Mofty SK. Mod Pathol. 2012 May 18. PMID: 22596101

- High-Risk Human Papillomavirus E6/E7 mRNA Detection by a Novel In Situ Hybridization Assay Strongly Correlates With p16 Expression and Patient Outcomes in Oropharyngeal Squamous Cell Carcinoma. Ukpo OC, Flanagan JJ, Ma XJ, Luo Y, Thorstad WL, Lewis JS. Am J Surg Pathol. 2011 Sep;35(9):1343-50. PMID: 21836494