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Published in: Head and Neck Pathology 1/2014

01-03-2014 | Proceedings of the North American Society of Head and Neck Pathology Companion Meeting, March 2, 2014, San Diego, California

Human Papillomavirus and Epstein Barr Virus in Head and Neck Carcinomas: Suggestions for the New WHO Classification

Authors: James S. Lewis Jr., Rebecca D. Chernock

Published in: Head and Neck Pathology | Issue 1/2014

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Abstract

In the 9 years since the last World Health Organization (WHO) classification for head and neck tumors, a great deal has changed. In particular, human papillomavirus (HPV) has emerged as the major etiologic agent and patient prognostic marker for squamous cell carcinoma, most profoundly in the oropharynx. It also casts a long shadow over all of the rest of head and neck cancer given its biologic and prognostic implications. By contrast, little has changed regarding our knowledge of Epstein–Barr virus in head and neck cancers, except as it relates to HPV in nonkeratinizing-type nasopharyngeal carcinomas. This article discusses some of the major advances in our understanding of virus-related squamous cell carcinoma of the head and neck and suggests several specific concepts and terminology for incorporation into the next WHO classification.
Literature
1.
go back to reference Johnson N, Francheschi S, Ferlay J, et al. Squamous cell carcinoma of the oral cavity and oropharynx. In: Barnes EL, Eveson JW, Reichart P, Sidranksy D, editors. World Health Organization classification of tumours—pathology and genetics head and neck tumours. Lyon: IARC Press; 2005. p. 168–75. Johnson N, Francheschi S, Ferlay J, et al. Squamous cell carcinoma of the oral cavity and oropharynx. In: Barnes EL, Eveson JW, Reichart P, Sidranksy D, editors. World Health Organization classification of tumours—pathology and genetics head and neck tumours. Lyon: IARC Press; 2005. p. 168–75.
2.
go back to reference Wu X, Watson M, Wilson R, et al. Human papillomavirus-associated cancers—United States, 2004–2008. Morb Mortal Wkly Rep. 2012;61(15):258–61. Wu X, Watson M, Wilson R, et al. Human papillomavirus-associated cancers—United States, 2004–2008. Morb Mortal Wkly Rep. 2012;61(15):258–61.
3.
4.
go back to reference Chaturvedi AK, Engels EA, Pfeiffer RM, et al. Human papillomavirus and rising oropharyngeal cancer incidence in the United States. J Clin Oncol. 2011;29(32):4294–301.PubMedCentralPubMedCrossRef Chaturvedi AK, Engels EA, Pfeiffer RM, et al. Human papillomavirus and rising oropharyngeal cancer incidence in the United States. J Clin Oncol. 2011;29(32):4294–301.PubMedCentralPubMedCrossRef
5.
go back to reference Ang KK, Sturgis EM. Human papillomavirus as a marker of the natural history and response to therapy of head and neck squamous cell carcinoma. Semin Radiat Oncol. 2012;22(2):128–42.PubMedCrossRef Ang KK, Sturgis EM. Human papillomavirus as a marker of the natural history and response to therapy of head and neck squamous cell carcinoma. Semin Radiat Oncol. 2012;22(2):128–42.PubMedCrossRef
6.
go back to reference Jordan RC, Lingen MW, Perez-Ordonez B, et al. Validation of methods for oropharyngeal cancer HPV status determination in US cooperative group trials. Am J Surg Pathol. 2012;36(7):945–54.PubMedCrossRef Jordan RC, Lingen MW, Perez-Ordonez B, et al. Validation of methods for oropharyngeal cancer HPV status determination in US cooperative group trials. Am J Surg Pathol. 2012;36(7):945–54.PubMedCrossRef
7.
go back to reference Ukpo OC, Flanagan JJ, Ma XJ, et al. 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. Am J Surg Pathol. 2011;35(9):1343–50.PubMedCrossRef Ukpo OC, Flanagan JJ, Ma XJ, et al. 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. Am J Surg Pathol. 2011;35(9):1343–50.PubMedCrossRef
8.
go back to reference Robinson M, Schache A, Sloan P, et al. HPV specific testing: a requirement for oropharyngeal squamous cell carcinoma patients. Head Neck Pathol. 2012;6(Suppl 1):S83–90.PubMedCrossRef Robinson M, Schache A, Sloan P, et al. HPV specific testing: a requirement for oropharyngeal squamous cell carcinoma patients. Head Neck Pathol. 2012;6(Suppl 1):S83–90.PubMedCrossRef
9.
go back to reference Robinson M, Sloan P, Shaw R. Refining the diagnosis of oropharyngeal squamous cell carcinoma using human papillomavirus testing. Oral Oncol. 2010;46(7):492–6.PubMedCrossRef Robinson M, Sloan P, Shaw R. Refining the diagnosis of oropharyngeal squamous cell carcinoma using human papillomavirus testing. Oral Oncol. 2010;46(7):492–6.PubMedCrossRef
10.
go back to reference Lewis JS Jr. p16 immunohistochemistry as a standalone test for risk stratification in oropharyngeal squamous cell carcinoma. Head Neck Pathol. 2012;6(Suppl 1):75–82.PubMedCentralCrossRef Lewis JS Jr. p16 immunohistochemistry as a standalone test for risk stratification in oropharyngeal squamous cell carcinoma. Head Neck Pathol. 2012;6(Suppl 1):75–82.PubMedCentralCrossRef
11.
go back to reference Rietbergen MM, Brakenhoff RH, Bloemena E et al. Human papillomavirus detection and comorbidity: critical issues in selection of patients with oropharyngeal cancer for treatment de-escalation trials. Ann Oncol. 2013;24(11):2740–5. Rietbergen MM, Brakenhoff RH, Bloemena E et al. Human papillomavirus detection and comorbidity: critical issues in selection of patients with oropharyngeal cancer for treatment de-escalation trials. Ann Oncol. 2013;24(11):2740–5.
12.
go back to reference El-Mofty SK, Patil S. Human papillomavirus (HPV)-related oropharyngeal nonkeratinizing squamous cell carcinoma: characterization of a distinct phenotype. Oral Surg Oral Med Oral Pathol Oral Radiol Endod. 2006;101(3):339–45.PubMedCrossRef El-Mofty SK, Patil S. Human papillomavirus (HPV)-related oropharyngeal nonkeratinizing squamous cell carcinoma: characterization of a distinct phenotype. Oral Surg Oral Med Oral Pathol Oral Radiol Endod. 2006;101(3):339–45.PubMedCrossRef
13.
go back to reference Chernock RD, El-Mofty SK, Thorstad WL, et al. HPV-related nonkeratinizing squamous cell carcinoma of the oropharynx: utility of microscopic features in predicting patient outcome. Head Neck Pathol. 2009;3(3):186–94.PubMedCentralPubMedCrossRef Chernock RD, El-Mofty SK, Thorstad WL, et al. HPV-related nonkeratinizing squamous cell carcinoma of the oropharynx: utility of microscopic features in predicting patient outcome. Head Neck Pathol. 2009;3(3):186–94.PubMedCentralPubMedCrossRef
14.
go back to reference Chernock RD, Lewis JS Jr, Zhang Q, et al. Human papillomavirus-positive basaloid squamous cell carcinomas of the upper aerodigestive tract: a distinct clinicopathologic and molecular subtype of basaloid squamous cell carcinoma. Hum Pathol. 2010;41(7):1016–23.PubMedCrossRef Chernock RD, Lewis JS Jr, Zhang Q, et al. Human papillomavirus-positive basaloid squamous cell carcinomas of the upper aerodigestive tract: a distinct clinicopathologic and molecular subtype of basaloid squamous cell carcinoma. Hum Pathol. 2010;41(7):1016–23.PubMedCrossRef
15.
go back to reference Begum S, Westra WH. Basaloid squamous cell carcinoma of the head and neck is a mixed variant that can be further resolved by HPV status. Am J Surg Pathol. 2008;32(7):1044–50.PubMedCrossRef Begum S, Westra WH. Basaloid squamous cell carcinoma of the head and neck is a mixed variant that can be further resolved by HPV status. Am J Surg Pathol. 2008;32(7):1044–50.PubMedCrossRef
16.
go back to reference Jo VY, Mills SE, Stoler MH, et al. Papillary squamous cell carcinoma of the head and neck: frequent association with human papillomavirus infection and invasive carcinoma. Am J Surg Pathol. 2009;33(11):1720–4.PubMedCrossRef Jo VY, Mills SE, Stoler MH, et al. Papillary squamous cell carcinoma of the head and neck: frequent association with human papillomavirus infection and invasive carcinoma. Am J Surg Pathol. 2009;33(11):1720–4.PubMedCrossRef
17.
go back to reference Mehrad M, Carpenter DH, Chernock RD, et al. Papillary squamous cell carcinoma of the head and neck: clinicopathologic and molecular features with special reference to human papillomavirus. Am J Surg Pathol. 2013;37(9):1349–56.PubMedCentralPubMedCrossRef Mehrad M, Carpenter DH, Chernock RD, et al. Papillary squamous cell carcinoma of the head and neck: clinicopathologic and molecular features with special reference to human papillomavirus. Am J Surg Pathol. 2013;37(9):1349–56.PubMedCentralPubMedCrossRef
18.
go back to reference Carpenter DH, El-Mofty SK, Lewis JS Jr. Undifferentiated carcinoma of the oropharynx: a human papillomavirus-associated tumor with a favorable prognosis. Mod Pathol. 2011;24(10):1306–12.PubMedCrossRef Carpenter DH, El-Mofty SK, Lewis JS Jr. Undifferentiated carcinoma of the oropharynx: a human papillomavirus-associated tumor with a favorable prognosis. Mod Pathol. 2011;24(10):1306–12.PubMedCrossRef
19.
go back to reference Singhi AD, Stelow EB, Mills SE, et al. Lymphoepithelial-like carcinoma of the oropharynx: a morphologic variant of HPV-related head and neck carcinoma. Am J Surg Pathol. 2010;34(6):800–5.PubMedCrossRef Singhi AD, Stelow EB, Mills SE, et al. Lymphoepithelial-like carcinoma of the oropharynx: a morphologic variant of HPV-related head and neck carcinoma. Am J Surg Pathol. 2010;34(6):800–5.PubMedCrossRef
20.
go back to reference Masand RP, El-Mofty SK, Ma XJ, et al. Adenosquamous carcinoma of the head and neck: relationship to human papillomavirus and review of the literature. Head Neck Pathol. 2011;5(2):108–16.PubMedCentralPubMedCrossRef Masand RP, El-Mofty SK, Ma XJ, et al. Adenosquamous carcinoma of the head and neck: relationship to human papillomavirus and review of the literature. Head Neck Pathol. 2011;5(2):108–16.PubMedCentralPubMedCrossRef
21.
go back to reference Lewis JS Jr, Scantlebury JB, Luo J, et al. Tumor cell anaplasia and multinucleation are predictors of disease recurrence in oropharyngeal squamous cell carcinoma, including among just the human papillomavirus-related cancers. Am J Surg Pathol. 2012;36(7):1036–46.PubMedCentralPubMedCrossRef Lewis JS Jr, Scantlebury JB, Luo J, et al. Tumor cell anaplasia and multinucleation are predictors of disease recurrence in oropharyngeal squamous cell carcinoma, including among just the human papillomavirus-related cancers. Am J Surg Pathol. 2012;36(7):1036–46.PubMedCentralPubMedCrossRef
22.
go back to reference Perry ME. The specialised structure of crypt epithelium in the human palatine tonsil and its functional significance. J Anat. 1994;185(Pt 1):111–27.PubMedCentralPubMed Perry ME. The specialised structure of crypt epithelium in the human palatine tonsil and its functional significance. J Anat. 1994;185(Pt 1):111–27.PubMedCentralPubMed
23.
go back to reference Westra WH. The morphologic profile of HPV-related head and neck squamous carcinoma: implications for diagnosis, prognosis, and clinical management. Head Neck Pathol. 2012;6(Suppl 1):S48–54.PubMedCrossRef Westra WH. The morphologic profile of HPV-related head and neck squamous carcinoma: implications for diagnosis, prognosis, and clinical management. Head Neck Pathol. 2012;6(Suppl 1):S48–54.PubMedCrossRef
24.
go back to reference Park GC, Lee M, Roh JL, et al. Human papillomavirus and p16 detection in cervical lymph node metastases from an unknown primary tumor. Oral Oncol. 2012;48(12):1250–6.PubMedCrossRef Park GC, Lee M, Roh JL, et al. Human papillomavirus and p16 detection in cervical lymph node metastases from an unknown primary tumor. Oral Oncol. 2012;48(12):1250–6.PubMedCrossRef
25.
go back to reference Dogan S, Hedberg ML, Ferris RL et al. Human papillomavirus and Epstein–Barr virus in nasopharyngeal carcinoma in a low-incidence population. Head Neck. 2013. doi:10.1002/hed.23318. Dogan S, Hedberg ML, Ferris RL et al. Human papillomavirus and Epstein–Barr virus in nasopharyngeal carcinoma in a low-incidence population. Head Neck. 2013. doi:10.​1002/​hed.​23318.
26.
go back to reference Maxwell JH, Kumar B, Feng FY, et al. HPV-positive/p16-positive/EBV-negative nasopharyngeal carcinoma in white North Americans. Head Neck. 2010;32(5):562–7.PubMedCentralPubMed Maxwell JH, Kumar B, Feng FY, et al. HPV-positive/p16-positive/EBV-negative nasopharyngeal carcinoma in white North Americans. Head Neck. 2010;32(5):562–7.PubMedCentralPubMed
27.
go back to reference Robinson M, Suh YE, Paleri V, et al. Oncogenic human papillomavirus-associated nasopharyngeal carcinoma: an observational study of correlation with ethnicity, histological subtype and outcome in a UK population. Infect Agent Cancer. 2013;8(1):30.PubMedCentralPubMedCrossRef Robinson M, Suh YE, Paleri V, et al. Oncogenic human papillomavirus-associated nasopharyngeal carcinoma: an observational study of correlation with ethnicity, histological subtype and outcome in a UK population. Infect Agent Cancer. 2013;8(1):30.PubMedCentralPubMedCrossRef
28.
go back to reference Chan JKC, Bray F, McCarron P, et al. Nasopharyngeal Carcinoma. In: Barnes EL, Eveson JW, Reichart P, Sidranksy D, editors. World Health Organization classification of tumours—pathology and genetics of head and neck tumors. Lyon: IARC Press; 2005. p. 85–97. Chan JKC, Bray F, McCarron P, et al. Nasopharyngeal Carcinoma. In: Barnes EL, Eveson JW, Reichart P, Sidranksy D, editors. World Health Organization classification of tumours—pathology and genetics of head and neck tumors. Lyon: IARC Press; 2005. p. 85–97.
29.
go back to reference Lo EJ, Bell D, Woo J, et al. Human papillomavirus and WHO type I nasopharyngeal carcinoma. Laryngoscope. 2011;120(Suppl 4):S185. Lo EJ, Bell D, Woo J, et al. Human papillomavirus and WHO type I nasopharyngeal carcinoma. Laryngoscope. 2011;120(Suppl 4):S185.
30.
go back to reference Punwaney R, Brandwein MS, Zhang DY, et al. Human papillomavirus may be common within nasopharyngeal carcinoma of Caucasian Americans: investigation of Epstein–Barr virus and human papillomavirus in eastern and western nasopharyngeal carcinoma using ligation-dependent polymerase chain reaction. Head Neck. 1999;21(1):21–9.PubMedCrossRef Punwaney R, Brandwein MS, Zhang DY, et al. Human papillomavirus may be common within nasopharyngeal carcinoma of Caucasian Americans: investigation of Epstein–Barr virus and human papillomavirus in eastern and western nasopharyngeal carcinoma using ligation-dependent polymerase chain reaction. Head Neck. 1999;21(1):21–9.PubMedCrossRef
Metadata
Title
Human Papillomavirus and Epstein Barr Virus in Head and Neck Carcinomas: Suggestions for the New WHO Classification
Authors
James S. Lewis Jr.
Rebecca D. Chernock
Publication date
01-03-2014
Publisher
Springer US
Published in
Head and Neck Pathology / Issue 1/2014
Electronic ISSN: 1936-0568
DOI
https://doi.org/10.1007/s12105-014-0528-6

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