Skip to main content
Top
Published in: Head and Neck Pathology 2/2007

01-12-2007 | Meeting Report

Human Papillomavirus (HPV) Related Carcinomas of the Upper Aerodigestive Tract

Author: Samir K. El-Mofty

Published in: Head and Neck Pathology | Issue 2/2007

Login to get access

Abstract

Epidemiologic, clinical, morphologic and molecular evidence show that high risk HPV, particularly type 16, is a prerequisite for some carcinomas of the upper aerodigestive tract (UADT), particularly tonsil and base of tongue. Sexual transmission is an important mode of infection while tobacco use and excessive drinking are not considered risk factors. HPV + tumors are distinct clinically and pathologically. They are more common in young patients (<40 years) with a male to female ratio of 4:1. They usually present as a small or occult primary tumor with advanced neck disease. Microscopically they are non-keratinizing squamous cell carcinomas with basaloid features, excessive mitosis and comedo type necrosis. The tumors have a distinct immunohistochemical profile characterized by strong and diffuse p16 reactivity, low or negative p53 staining and high Ki67 labeling scores. HPV + carcinomas are more radio-sensitive and have a better prognosis than the classical keratinizing SCC of the UADT. An anti-HPV vaccine has recently been made available for prevention of cervical cancer. The impact of the vaccine on the prevalence of HPV related carcinomas of the UADT is currently not known but likely beneficial.
Literature
1.
go back to reference Parkin DM, Bray F, Ferlay J, et al. Global cancer statistics. Cancer J Clin 2005;55:74–108.CrossRef Parkin DM, Bray F, Ferlay J, et al. Global cancer statistics. Cancer J Clin 2005;55:74–108.CrossRef
2.
go back to reference Walboomers JM, Jacobs MV, Manos MM, et al. Human papillomavirus is a necessary cause of invasive cervical cancer worldwide. J Pathol 1999;189:12–9.PubMedCrossRef Walboomers JM, Jacobs MV, Manos MM, et al. Human papillomavirus is a necessary cause of invasive cervical cancer worldwide. J Pathol 1999;189:12–9.PubMedCrossRef
3.
go back to reference zur Hausen H. Molecular pathogenesis of cancer of the cervix and its causation by specific human papillomavirus types. Curr Top Microbiol Immunol 1994;186:131–56.PubMed zur Hausen H. Molecular pathogenesis of cancer of the cervix and its causation by specific human papillomavirus types. Curr Top Microbiol Immunol 1994;186:131–56.PubMed
4.
go back to reference Snijders PJ, Steenbergen RD, Heideman DA, Meijer CJ. HPV-mediated cervical carcinogenesis: concepts and clinical implications. J Pathol 2006;208:152–64.PubMedCrossRef Snijders PJ, Steenbergen RD, Heideman DA, Meijer CJ. HPV-mediated cervical carcinogenesis: concepts and clinical implications. J Pathol 2006;208:152–64.PubMedCrossRef
5.
go back to reference El-Mofty SK, Lu DW. Prevalence of high-risk human papillomavirus DNA in nonkeratinizing (cylindrical cell) carcinoma of the sinonasal tract: a distinct clinicopathologic and molecular disease entity. Am J Surg Pathol 2005;29:1367–72.PubMedCrossRef El-Mofty SK, Lu DW. Prevalence of high-risk human papillomavirus DNA in nonkeratinizing (cylindrical cell) carcinoma of the sinonasal tract: a distinct clinicopathologic and molecular disease entity. Am J Surg Pathol 2005;29:1367–72.PubMedCrossRef
6.
go back to reference El-Mofty SK, Lu DW. Prevalence of human papillomavirus type 16 DNA in squamous cell carcinoma of the palatine tonsil, and not the oral cavity, in young patients: a distinct clinicopathologic and molecular disease entity. Am J Surg Pathol 2003;27:1463–70.PubMedCrossRef El-Mofty SK, Lu DW. Prevalence of human papillomavirus type 16 DNA in squamous cell carcinoma of the palatine tonsil, and not the oral cavity, in young patients: a distinct clinicopathologic and molecular disease entity. Am J Surg Pathol 2003;27:1463–70.PubMedCrossRef
7.
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;101:339–45.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;101:339–45.PubMedCrossRef
8.
go back to reference Franceschi S, Munoz N, Bosch XF, Snijders PJ, Walboomers JM. Human papillomavirus and cancers of the upper aerodigestive tract: a review of epidemiological and experimental evidence. Cancer Epidemiol Biomarkers Prev 1996;5:567–75.PubMed Franceschi S, Munoz N, Bosch XF, Snijders PJ, Walboomers JM. Human papillomavirus and cancers of the upper aerodigestive tract: a review of epidemiological and experimental evidence. Cancer Epidemiol Biomarkers Prev 1996;5:567–75.PubMed
9.
go back to reference Gillison ML, Koch WM, Capone RB, et al. Evidence for a causal association between human papillomavirus and a subset of head and neck cancers. J Natl Cancer Inst 2000;92:709–20.PubMedCrossRef Gillison ML, Koch WM, Capone RB, et al. Evidence for a causal association between human papillomavirus and a subset of head and neck cancers. J Natl Cancer Inst 2000;92:709–20.PubMedCrossRef
10.
go back to reference Herrero R, Castellsague X, Pawlita M, et al. Human papillomavirus and oral cancer: the International Agency for Research on Cancer multicenter study. J Natl Cancer Inst 2003;95:1772–83.PubMed Herrero R, Castellsague X, Pawlita M, et al. Human papillomavirus and oral cancer: the International Agency for Research on Cancer multicenter study. J Natl Cancer Inst 2003;95:1772–83.PubMed
11.
go back to reference Loning T, Ikenberg H, Becker J, Gissmann L, Hoepfer I, zur Hausen H. Analysis of oral papillomas, leukoplakias, and invasive carcinomas for human papillomavirus type related DNA. J Invest Dermatol 1985;84:417–20.PubMedCrossRef Loning T, Ikenberg H, Becker J, Gissmann L, Hoepfer I, zur Hausen H. Analysis of oral papillomas, leukoplakias, and invasive carcinomas for human papillomavirus type related DNA. J Invest Dermatol 1985;84:417–20.PubMedCrossRef
12.
go back to reference Mineta H, Ogino T, Amano HM, et al. Human papillomavirus(HPV) type 16and 18 detected in head and neck squamous cell carcinoma. Anticancer Res 1998;18:4765–8.PubMed Mineta H, Ogino T, Amano HM, et al. Human papillomavirus(HPV) type 16and 18 detected in head and neck squamous cell carcinoma. Anticancer Res 1998;18:4765–8.PubMed
13.
go back to reference Mork J, Lie AK, Glatter E, et al. Human papillomavirus infection as a risk factor for squamous cell carcinoma of the head and neck. N Eng J Med 2001;344:1125–31.CrossRef Mork J, Lie AK, Glatter E, et al. Human papillomavirus infection as a risk factor for squamous cell carcinoma of the head and neck. N Eng J Med 2001;344:1125–31.CrossRef
14.
go back to reference van Houten VM, Snijders PJ, van den Brekel MW, et al. Biological evidence that human papillomaviruses are etiologically involved in a subgroup of head and neck squamous cell carcinomas. Int J Cancer 2001;93:232–5.PubMedCrossRef van Houten VM, Snijders PJ, van den Brekel MW, et al. Biological evidence that human papillomaviruses are etiologically involved in a subgroup of head and neck squamous cell carcinomas. Int J Cancer 2001;93:232–5.PubMedCrossRef
15.
go back to reference Chen XS, Garcea RL, Goldberg I, et al. Structure of small virus-like particles assembled from L1 protein of human papillomavirus 16. Mol Cell 2000;5:557–67.PubMedCrossRef Chen XS, Garcea RL, Goldberg I, et al. Structure of small virus-like particles assembled from L1 protein of human papillomavirus 16. Mol Cell 2000;5:557–67.PubMedCrossRef
16.
go back to reference Syrjanen SM, Syrjanen KJ. New concepts on the role of human papillomavirus in cell cycle regulation. Ann Med 1999;31:175–87.PubMed Syrjanen SM, Syrjanen KJ. New concepts on the role of human papillomavirus in cell cycle regulation. Ann Med 1999;31:175–87.PubMed
17.
go back to reference Frisch M, Hjalgrim H, Jaeger AB, et al. Changing pattern of tonsillar squamous cell carcinoma in the United States. Cancer Causes Control:CCC 2000;11:489–495.PubMedCrossRef Frisch M, Hjalgrim H, Jaeger AB, et al. Changing pattern of tonsillar squamous cell carcinoma in the United States. Cancer Causes Control:CCC 2000;11:489–495.PubMedCrossRef
18.
go back to reference Shiboski CH, Schmidt BL, Jordan RCK. Tongue and tonsil carcinoma: increasing trends in the US population ages 20–44 years. Cancer 2005;103:1843–9.PubMedCrossRef Shiboski CH, Schmidt BL, Jordan RCK. Tongue and tonsil carcinoma: increasing trends in the US population ages 20–44 years. Cancer 2005;103:1843–9.PubMedCrossRef
19.
go back to reference Schwartz SM, Daling JR, Doody DR, et al. Oral cancer risk in relation to sexual history and evidence of human papillomavirus infection. J Natl Cancer Inst 1998;90:1626–36.PubMedCrossRef Schwartz SM, Daling JR, Doody DR, et al. Oral cancer risk in relation to sexual history and evidence of human papillomavirus infection. J Natl Cancer Inst 1998;90:1626–36.PubMedCrossRef
20.
go back to reference Hemminki K, Dong C, Frisch M. Tonsillar and other upper aerodigestive tract carcers among cervical cancer patients and their husbands. Eur J Cancer Prev 2000;9:433–7.PubMedCrossRef Hemminki K, Dong C, Frisch M. Tonsillar and other upper aerodigestive tract carcers among cervical cancer patients and their husbands. Eur J Cancer Prev 2000;9:433–7.PubMedCrossRef
21.
go back to reference El-Mofty SK, Zhang MQ, Davila RM. Detection of HPV in metastatic squamous cell carcinoma in cervical lymph nodes: a tool for identification of the site of occult head and neck primary. Mod Pathol 2007;20:1016A. El-Mofty SK, Zhang MQ, Davila RM. Detection of HPV in metastatic squamous cell carcinoma in cervical lymph nodes: a tool for identification of the site of occult head and neck primary. Mod Pathol 2007;20:1016A.
22.
go back to reference El-Naggar AK, Lai S, Clayman GL, et al. Expression of p16, Rb, and cyclin D1 gene products in oral and laryngeal squamous carcinoma: biological and clinical implications. Hum Pathol 1999;30:1013–8.PubMedCrossRef El-Naggar AK, Lai S, Clayman GL, et al. Expression of p16, Rb, and cyclin D1 gene products in oral and laryngeal squamous carcinoma: biological and clinical implications. Hum Pathol 1999;30:1013–8.PubMedCrossRef
23.
go back to reference Dray M, Russell P, Dalrymple C, et al. p16INK4a as complimentary marker of high-grade intraepithelial lesions of the uterine cervix: experience with squamous lesions in 189 consecutive cervical biopsies. Pathology 2005;37:112–4.PubMedCrossRef Dray M, Russell P, Dalrymple C, et al. p16INK4a as complimentary marker of high-grade intraepithelial lesions of the uterine cervix: experience with squamous lesions in 189 consecutive cervical biopsies. Pathology 2005;37:112–4.PubMedCrossRef
24.
go back to reference Lu DW, El-Mofty SK, Wang HL. Expression of p16, Rb, and p53 proteins in squamous cell carcinomas of the anorectal region harboring human papillomavirus DNA. Mod Pathol 2003;16:692–9.PubMedCrossRef Lu DW, El-Mofty SK, Wang HL. Expression of p16, Rb, and p53 proteins in squamous cell carcinomas of the anorectal region harboring human papillomavirus DNA. Mod Pathol 2003;16:692–9.PubMedCrossRef
25.
go back to reference Samama B, Lipsker D, Boehm N. p16 expression in relation to human papillomavirus in anogenital lesions. Human Pthol 2006;37:513–9.CrossRef Samama B, Lipsker D, Boehm N. p16 expression in relation to human papillomavirus in anogenital lesions. Human Pthol 2006;37:513–9.CrossRef
26.
go back to reference Zhang MQ, Davila R, El-Mofty SK. Fine needle aspirarion cytology of cervical lymph nodes as an aid for localization of occult primary tumor. IAP abstract, Montreal Canada: 2006. Zhang MQ, Davila R, El-Mofty SK. Fine needle aspirarion cytology of cervical lymph nodes as an aid for localization of occult primary tumor. IAP abstract, Montreal Canada: 2006.
27.
go back to reference Zhang MQ, El-Mofty SK, Davila RM. Detection of HPV by ISH in FNA biopsies of cervical metastasis of head and neck squamous cell carcinoma: a tool for identifying the site of occult primary. Mod Pathol 2007;20:385A. Zhang MQ, El-Mofty SK, Davila RM. Detection of HPV by ISH in FNA biopsies of cervical metastasis of head and neck squamous cell carcinoma: a tool for identifying the site of occult primary. Mod Pathol 2007;20:385A.
28.
go back to reference Dahlgren L, Dahlstrand HM, Lindquist D, et al. Human papillomavirus is more common in base of tongue than in mobile tongue cancer and is a favorable prognostic factor in base of tongue cancer patients. Int J Cancer 2004;112:1015–9.PubMedCrossRef Dahlgren L, Dahlstrand HM, Lindquist D, et al. Human papillomavirus is more common in base of tongue than in mobile tongue cancer and is a favorable prognostic factor in base of tongue cancer patients. Int J Cancer 2004;112:1015–9.PubMedCrossRef
29.
go back to reference Li W, Thompson CH, O’Brien CJ, et al. Human papillomavirus positivity predicts favourable outcome for squamous carcinoma of the tonsil. Int J Cancer 2003;106:553–8.PubMedCrossRef Li W, Thompson CH, O’Brien CJ, et al. Human papillomavirus positivity predicts favourable outcome for squamous carcinoma of the tonsil. Int J Cancer 2003;106:553–8.PubMedCrossRef
30.
go back to reference Lindel K, Beer KT, Laissue J, Greiner RH, Aebersold DM. Human papillomavirus positive squamous cell carcinoma of the oropharynx: a radiosensitive subgroup of head and neck carcinoma. Cancer 2001;92:805–13.PubMedCrossRef Lindel K, Beer KT, Laissue J, Greiner RH, Aebersold DM. Human papillomavirus positive squamous cell carcinoma of the oropharynx: a radiosensitive subgroup of head and neck carcinoma. Cancer 2001;92:805–13.PubMedCrossRef
31.
go back to reference Mellin H, Friesland S, Lewensohn R, Dalianis T, Munck-Wikland E. Human papillomavirus (HPV) DNA in tonsillar cancer: clinical correlates, risk of relapse, and survival. Int J Cancer 2000;89:300–4.PubMedCrossRef Mellin H, Friesland S, Lewensohn R, Dalianis T, Munck-Wikland E. Human papillomavirus (HPV) DNA in tonsillar cancer: clinical correlates, risk of relapse, and survival. Int J Cancer 2000;89:300–4.PubMedCrossRef
32.
go back to reference Ritchie JM, Smith EM, Summersgill KF, et al. Human papillomavirus infection as a prognostic factor in carcinomas of the oral cavity and oropharynx. Int J Cancer 2003;104:336–44.PubMedCrossRef Ritchie JM, Smith EM, Summersgill KF, et al. Human papillomavirus infection as a prognostic factor in carcinomas of the oral cavity and oropharynx. Int J Cancer 2003;104:336–44.PubMedCrossRef
33.
go back to reference Weinberger PM, Yu Z, Haffty BG, et al. Molecular classification identifies a subset of human papillomavirus–associated oropharyngeal cancers with favorable prognosis. J Clin Oncol 2006;24:736–47.PubMedCrossRef Weinberger PM, Yu Z, Haffty BG, et al. Molecular classification identifies a subset of human papillomavirus–associated oropharyngeal cancers with favorable prognosis. J Clin Oncol 2006;24:736–47.PubMedCrossRef
34.
go back to reference Cohen J. Public health. High hopes and dilemmas for a cervical cancer vaccine. Science 2005;308(5722):618–21.PubMedCrossRef Cohen J. Public health. High hopes and dilemmas for a cervical cancer vaccine. Science 2005;308(5722):618–21.PubMedCrossRef
35.
go back to reference Harper DM, Franco EL, Wheeler C, et al. Efficacy of a bivalent L1 virus-like particle vaccine in prevention of infection with human papillomavirus types 16 and 18 in young women: a randomised controlled trial. Lancet 2004;364(9447):1757–65.PubMedCrossRef Harper DM, Franco EL, Wheeler C, et al. Efficacy of a bivalent L1 virus-like particle vaccine in prevention of infection with human papillomavirus types 16 and 18 in young women: a randomised controlled trial. Lancet 2004;364(9447):1757–65.PubMedCrossRef
36.
37.
go back to reference Schiffman M, Castle PE. The promise of global cervical-cancer prevention. N Engl J Med 2005;353:2101–4.PubMedCrossRef Schiffman M, Castle PE. The promise of global cervical-cancer prevention. N Engl J Med 2005;353:2101–4.PubMedCrossRef
Metadata
Title
Human Papillomavirus (HPV) Related Carcinomas of the Upper Aerodigestive Tract
Author
Samir K. El-Mofty
Publication date
01-12-2007
Publisher
Humana Press Inc
Published in
Head and Neck Pathology / Issue 2/2007
Electronic ISSN: 1936-0568
DOI
https://doi.org/10.1007/s12105-007-0021-6

Other articles of this Issue 2/2007

Head and Neck Pathology 2/2007 Go to the issue

Sine qua none Radiology-Pathology

Head Neck Pathol Radiology Pathology Classics