Skip to main content
SpringerLink
Log in

Human Papillomavirus Testing in Head and Neck Squamous Cell Carcinoma: Best Practice for Diagnosis

  • Protocol
  • First Online:
Histopathology

Part of the book series: Methods in Molecular Biology ((MIMB,volume 1180))

Abstract

Human papillomavirus (HPV)-associated oropharyngeal carcinoma is now recognized as a clinically distinct subtype of head and neck cancer with important prognostic implications. HPV testing is recommended as the standard of care for all patients diagnosed with oropharyngeal squamous cell carcinoma. Here, we describe a practical approach to HPV testing within the setting of the diagnostic histopathology laboratory.

This is a preview of subscription content, log in via an institution to check access.

Access this chapter

Log in via an institution
Protocol
USD 49.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD 89.00
Price excludes VAT (USA)
  • Available as EPUB and PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD 119.99
Price excludes VAT (USA)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info
Hardcover Book
USD 169.99
Price excludes VAT (USA)
  • Durable hardcover edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Institutional subscriptions

References

  1. Chaturvedi AK, Engels EA, Anderson WF et al (2008) Incidence trends for human papillomavirus-related and -unrelated oral squamous cell carcinomas in the United States. J Clin Oncol 26(4):612–619. doi:10.1200/JCO.2007.14.1713

    Article  PubMed  Google Scholar 

  2. Price G, Roche M, Crowther R et al. (2010) Profile of head and neck cancers in England: incidence, mortality and survival, OCIU

    Google Scholar 

  3. Blomberg M, Nielsen A, Munk C et al (2011) Trends in head and neck cancer incidence in Denmark, 1978-2007: focus on human papillomavirus associated sites. Int J Cancer 129(3):733–741. doi:10.1002/ijc.25699

    Article  CAS  PubMed  Google Scholar 

  4. Reddy VM, Cundall-Curry D, Bridger MW (2010) Trends in the incidence rates of tonsil and base of tongue cancer in England, 1985-2006. Ann R Coll Surg Engl 92(8):655–659. doi:10.1308/003588410X12699663904871

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  5. Syrjanen S (2004) HPV infections and tonsillar carcinoma. J Clin Pathol 57(5): 449–455

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  6. Braakhuis BJ, Visser O, Leemans CR (2009) Oral and oropharyngeal cancer in The Netherlands between 1989 and 2006: increasing incidence, but not in young adults. Oral Oncol 45(9):e85–e89. doi:10.1016/j.oraloncology.2009.03.010

    Article  PubMed  Google Scholar 

  7. Junor EJ, Kerr GR, Brewster DH (2010) Oropharyngeal cancer. Fastest increasing cancer in Scotland, especially in men. BMJ 340:c2512

    Article  PubMed  Google Scholar 

  8. Chung CH, Gillison ML (2009) Human papillomavirus in head and neck cancer: its role in pathogenesis and clinical implications. Clin Cancer Res 15(22):6758–6762. doi:10.1158/1078-0432.CCR-09-0784

    Article  CAS  PubMed  Google Scholar 

  9. Chaturvedi AK, Engels EA, Pfeiffer RM et al (2011) Human papillomavirus and rising oropharyngeal cancer incidence in the United States. J Clin Oncol 29(32):4294–4301. doi:10.1200/JCO.2011.36.4596

    Article  PubMed Central  PubMed  Google Scholar 

  10. Marur S, D’Souza G, Westra WH et al (2010) HPV-associated head and neck cancer: a virus-related cancer epidemic. Lancet Oncol 11(8):781–789. doi:10.1016/S1470-2045(10)70017-6

    Article  PubMed  Google Scholar 

  11. Herrero R, Castellsague X, Pawlita M et al (2003) Human papillomavirus and oral cancer: the International Agency for Research on Cancer multicenter study. J Natl Cancer Inst 95(23):1772–1783

    Article  PubMed  Google Scholar 

  12. Kreimer AR, Clifford GM, Boyle P et al (2005) Human papillomavirus types in head and neck squamous cell carcinomas worldwide: a systematic review. Cancer Epidemiol Biomarkers Prev 14(2):467–475. doi:10.1158/1055-9965.EPI-04-0551

    Article  CAS  PubMed  Google Scholar 

  13. Campisi G, Giovannelli L (2009) Controversies surrounding human papilloma virus infection, head & neck vs oral cancer, implications for prophylaxis and treatment. Head Neck Oncol 1:8. doi:10.1186/1758-3284-1-8

    Article  PubMed Central  PubMed  Google Scholar 

  14. Hobbs CG, Sterne JA, Bailey M et al (2006) Human papillomavirus and head and neck cancer: a systematic review and meta-analysis. Clin Otolaryngol 31(4):259–266. doi:10.1111/j.1749-4486.2006.01246.x

    Article  CAS  PubMed  Google Scholar 

  15. Ang KK, Harris J, Wheeler R et al (2010) Human papillomavirus and survival of patients with oropharyngeal cancer. N Engl J Med 363(1):24–35. doi:10.1056/NEJMoa0912217

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  16. Gillison ML, Koch WM, Capone RB et al (2000) Evidence for a causal association between human papillomavirus and a subset of head and neck cancers. J Natl Cancer Inst 92(9):709–720

    Article  CAS  PubMed  Google Scholar 

  17. Chaturvedi AK (2012) Epidemiology and clinical aspects of HPV in head and neck cancers. Head Neck Pathol 6(Suppl 1):S16–S24. doi:10.1007/s12105-012-0377-0

    Article  PubMed  Google Scholar 

  18. Goldenberg D, Begum S, Westra WH et al (2008) Cystic lymph node metastasis in patients with head and neck cancer: an HPV-associated phenomenon. Head Neck 30(7): 898–903. doi:10.1002/hed.20796

    Article  PubMed  Google Scholar 

  19. Fakhry C, Gillison ML (2006) Clinical implications of human papillomavirus in head and neck cancers. J Clin Oncol 24(17):2606–2611. doi:10.1200/JCO.2006.06.1291

    Article  PubMed  Google Scholar 

  20. Schache AG, Liloglou T, Risk JM et al (2011) Evaluation of human papilloma virus diagnostic testing in oropharyngeal squamous cell carcinoma: sensitivity, specificity, and prognostic discrimination. Clin Cancer Res 17(19):6262–6271. doi:10.1158/1078-0432.CCR-11-0388

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  21. D’Souza G, Zhang HH, D’Souza WD et al (2010) Moderate predictive value of demographic and behavioral characteristics for a diagnosis of HPV16-positive and HPV16-negative head and neck cancer. Oral Oncol 46(2):100–104. doi:10.1016/j.oraloncology.2009.11.004

    Article  PubMed Central  PubMed  Google Scholar 

  22. Ragin CC, Taioli E (2007) Survival of squamous cell carcinoma of the head and neck in relation to human papillomavirus infection: review and meta-analysis. Int J Cancer 121(8):1813–1820. doi:10.1002/ijc.22851

    Article  CAS  PubMed  Google Scholar 

  23. Fakhry C, Westra WH, Li S et al (2008) Improved survival of patients with human papillomavirus-positive head and neck squamous cell carcinoma in a prospective clinical trial. J Natl Cancer Inst 100(4):261–269. doi:10.1093/jnci/djn011

    Article  CAS  PubMed  Google Scholar 

  24. Weinberger PM, Yu Z, Haffty BG et al (2006) Molecular classification identifies a subset of human papillomavirus-associated oropharyngeal cancers with favorable prognosis. J Clin Oncol 24(5):736–747. doi:10.1200/JCO.2004.00.3335

    Article  CAS  PubMed  Google Scholar 

  25. Licitra L, Perrone F, Bossi P et al (2006) High-risk human papillomavirus affects prognosis in patients with surgically treated oropharyngeal squamous cell carcinoma. J Clin Oncol 24(36):5630–5636. doi:10.1200/JCO.2005.04.6136

    Article  CAS  PubMed  Google Scholar 

  26. Lassen P, Eriksen JG, Hamilton-Dutoit S et al (2009) Effect of HPV-associated p16INK4A expression on response to radiotherapy and survival in squamous cell carcinoma of the head and neck. J Clin Oncol 27(12):1992–1998. doi:10.1200/JCO.2008.20.2853

    Article  CAS  PubMed  Google Scholar 

  27. Schache AG, Liloglou T, Risk JM et al (2013) Validation of a novel diagnostic standard in HPV-positive oropharyngeal squamous cell carcinoma. Br J Cancer 108(6):1332–1339. doi:10.1038/bjc.2013.63

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  28. Lewis JS Jr (2012) p16 Immunohistochemistry as a standalone test for risk stratification in oropharyngeal squamous cell carcinoma. Head Neck Pathol 6(Suppl 1):S75–S82. doi:10.1007/s12105-012-0369-0

    Article  PubMed  Google Scholar 

  29. Chernock RD (2012) Morphologic features of conventional squamous cell carcinoma of the oropharynx: ‘keratinizing’ and ‘nonkeratinizing’ histologic types as the basis for a consistent classification system. Head Neck Pathol 6(Suppl 1): S41–S47. doi:10.1007/s12105-012-0373-4

    Article  PubMed  Google Scholar 

  30. Klingenberg B, Hafkamp HC, Haesevoets A et al (2010) p16 INK4A overexpression is frequently detected in tumour-free tonsil tissue without association with HPV. Histopathology 56(7):957–967. doi:10.1111/j.1365-2559.2010.03576.x

    Article  PubMed  Google Scholar 

  31. Helliwel T, Woolgar JA (2011) Standards and datasets for reporting cancers Dataset for histopathology reporting of mucosal malignancies of the pharynx. Royal College of Pathologists. http://www.rcpath.org/Resources/RCPath/Migrated%20Resources/Documents/G/G111_PharynxMucosalDataset_Dec11.pdf

  32. NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines). Head and Neck (2013) http://www.nccn.org/professionals/physician_gls/f_guidelines.asp#site. Accessed on 26 Jun 2013

  33. College of American Pathologists. Protocol for the Examination of Specimens From Patients With Carcinomas of the Pharynx (2012) http://www.cap.org/apps/docs/committees/cancer/cancer_protocols/2012/Pharynx_12protocol.pdf. Accessed on 26 Jun 2013

  34. El-Mofty SK (2012) HPV-related squamous cell carcinoma variants in the head and neck. Head Neck Pathol 6(Suppl 1):S55–S62. doi:10.1007/s12105-012-0363-6

    Article  PubMed  Google Scholar 

  35. Lopes V, Murray P, Williams H et al (2011) Squamous cell carcinoma of the oral cavity rarely harbours oncogenic human papillomavirus. Oral Oncol 47(8):698–701. doi:10.1016/j.oraloncology.2011.04.022

    Article  CAS  PubMed  Google Scholar 

  36. Hoffmann M, Tribius S, Quabius ES et al (2012) HPV DNA, E6*I-mRNA expression and p16INK4A immunohistochemistry in head and neck cancer - how valid is p16INK4A as surrogate marker? Cancer Lett 323(1):88–96. doi:10.1016/j.canlet.2012.03.033

    Article  CAS  PubMed  Google Scholar 

  37. Krane JF (2013) Role of cytology in the diagnosis and management of HPV-associated head and neck carcinoma. Acta Cytol 57(2):117–126. doi:10.1159/000346715

    Article  PubMed  Google Scholar 

  38. Cao D, Begum S, Ali SZ et al (2010) Expression of p16 in benign and malignant cystic squamous lesions of the neck. Hum Pathol 41(4):535–539. doi:10.1016/j.humpath.2009.09.006

    Article  CAS  PubMed  Google Scholar 

  39. Bishop JA, Maleki Z, Valsamakis A et al (2012) Application of the hybrid capture 2 assay to squamous cell carcinomas of the head and neck: a convenient liquid-phase approach for the reliable determination of human papillomavirus status. Cancer Cytopathol 120(1):18–25. doi:10.1002/cncy.20175

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  40. Solomides CC, Bibbo M, Wang ZX (2012) Assessment of fine needle aspiration specimen adequacy for high-risk HPV detection and genotyping in oropharyngeal squamous cell carcinoma. Acta Cytol 56(2):196–198. doi:10.1159/000335730

    Article  PubMed  Google Scholar 

  41. Isayeva T, Li Y, Maswahu D, Brandwein-Gensler M (2012) Human papillomavirus in non-oropharyngeal head and neck cancers: a systematic literature review. Head Neck Pathol 6(Suppl 1):S104–S120. doi:10.1007/s12105-012-0368-1

    Article  PubMed  Google Scholar 

  42. Lingen MW, Xiao W, Schmitt A et al (2013) Low etiologic fraction for high-risk human papillomavirus in oral cavity squamous cell carcinomas. Oral Oncol 49(1):1–8. doi:10.1016/j.oraloncology.2012.07.002

    Article  PubMed  Google Scholar 

  43. Robinson M, Suh YE, Paleri V et al (2013) Oncogenic human papillomavirus-associated nasopharyngeal carcinoma: an observational study of correlation with ethnicity, histological subtype and outcome in a UK population. Infect Agent Cancer 8(1):30. doi:10.1186/1750-9378-8-30

    Article  PubMed Central  PubMed  Google Scholar 

  44. Jordan RC, Lingen MW, Perez-Ordonez B et al (2012) Validation of methods for oropharyngeal cancer HPV status determination in US cooperative group trials. Am J Surg Pathol 36(7):945–954. doi:10.1097/PAS.0b013e318253a2d1

    Article  PubMed  Google Scholar 

  45. Lee LA, Huang CG, Liao CT et al (2012) Human papillomavirus-16 infection in advanced oral cavity cancer patients is related to an increased risk of distant metastases and poor survival. PLoS One 7(7):e40767. doi:10.1371/journal.pone.0040767

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  46. Fakhry C, Rosenthal BT, Clark DP et al (2011) Associations between oral HPV16 infection and cytopathology: evaluation of an oropharyngeal “pap-test equivalent” in high-risk populations. Cancer Prev Res (Phila) 4(9): 1378–1384. doi:10.1158/1940-6207.CAPR-11-0284

    Article  Google Scholar 

  47. Leemans CR, Braakhuis BJ, Brakenhoff RH (2011) The molecular biology of head and neck cancer. Nat Rev Cancer 11(1):9–22. doi:10.1038/nrc2982

    Article  CAS  PubMed  Google Scholar 

  48. van Houten VM, Snijders PJ, van den Brekel MW et al (2001) Biological evidence that human papillomaviruses are etiologically involved in a subgroup of head and neck squamous cell carcinomas. Int J Cancer 93(2):232–235. doi:10.1002/ijc.1313

    Article  PubMed  Google Scholar 

  49. Wiest T, Schwarz E, Enders C et al (2002) Involvement of intact HPV16 E6/E7 gene expression in head and neck cancers with unaltered p53 status and perturbed pRb cell cycle control. Oncogene 21(10):1510–1517. doi:10.1038/sj.onc.1205214

    Article  CAS  PubMed  Google Scholar 

  50. Robinson M, Schache A, Sloan P et al (2012) HPV specific testing: a requirement for oropharyngeal squamous cell carcinoma patients. Head Neck Pathol 6(Suppl 1):S83–S90. doi:10.1007/s12105-012-0370-7

    Article  PubMed  Google Scholar 

  51. Smeets SJ, Hesselink AT, Speel EJ et al (2007) A novel algorithm for reliable detection of human papillomavirus in paraffin embedded head and neck cancer specimen. Int J Cancer 121(11):2465–2472. doi:10.1002/ijc.22980

    Article  CAS  PubMed  Google Scholar 

  52. Begum S, Cao D, Gillison M et al (2005) Tissue distribution of human papillomavirus 16 DNA integration in patients with tonsillar carcinoma. Clin Cancer Res 11(16):5694–5699. doi:10.1158/1078-0432.CCR-05-0587

    Article  CAS  PubMed  Google Scholar 

  53. Perrone F, Gloghini A, Cortelazzi B et al (2011) Isolating p16-positive/HPV-negative oropharyngeal cancer: an effort worth making. Am J Surg Pathol 35(5):774–777. doi:10.1097/PAS.0b013e3182116a45, author reply 777–778

    Article  PubMed  Google Scholar 

  54. Thavaraj S, Stokes A, Guerra E et al (2011) Evaluation of human papillomavirus testing for squamous cell carcinoma of the tonsil in clinical practice. J Clin Pathol 64(4):308–312. doi:10.1136/jcp.2010.088450

    Article  PubMed  Google Scholar 

  55. Lingen MW (2011) Brush-based cytology screening in the tonsils and cervix: there is a difference! Cancer Prev Res (Phila) 4(9):1350–1352. doi:10.1158/1940-6207.CAPR-11-0373

    Article  Google Scholar 

Download references

Acknowledgment

The authors wish to thank Dr B Conn, Royal Infirmary of Edinburgh, Scotland for kind permission to use Fig. 4d.

Author information

Authors and Affiliations

  1. Department of Molecular and Clinical Cancer Medicine, University of Liverpool, Pembroke Place, Liverpool, Merseyside, L3 5PS, UK

    Andrew Schache

  2. Department of Histopathology, Royal Brompton and Harefield NHS Foundation Trust, Sydney Street, London, SW3 6NP, UK

    James Croud

  3. Centre for Oral Health research, School of Dental Sciences, Newcastle University, Framlington Place, Newcastle upon Tyne, NE2 4BW, UK

    Max Robinson

  4. Clinical and Diagnostic Science, King’s College London, Great Maze Pond, London, SE1 9RT, UK

    Selvam Thavaraj

Authors
  1. Andrew Schache
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. James Croud
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Max Robinson
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Selvam Thavaraj
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Selvam Thavaraj .

Editor information

Editors and Affiliations

  1. Department of Pathology, USC Keck School of Medicine, Los Angeles, California, USA

    Christina E. Day

Rights and permissions

Reprints and permissions

Copyright information

© 2014 Springer Science+Business Media, New York

About this protocol

Cite this protocol

Schache, A., Croud, J., Robinson, M., Thavaraj, S. (2014). Human Papillomavirus Testing in Head and Neck Squamous Cell Carcinoma: Best Practice for Diagnosis. In: Day, C. (eds) Histopathology. Methods in Molecular Biology, vol 1180. Humana Press, New York, NY. https://doi.org/10.1007/978-1-4939-1050-2_13

Download citation

  • DOI: https://doi.org/10.1007/978-1-4939-1050-2_13

  • Published:

  • Publisher Name: Humana Press, New York, NY

  • Print ISBN: 978-1-4939-1049-6

  • Online ISBN: 978-1-4939-1050-2

  • eBook Packages: Springer Protocols

Publish with us

Policies and ethics

Search

Navigation