Zusammenfassung
Hochrisiko-Typen von humanen Papillomaviren (HR HPV) spielen eine wichtige Rolle in der Ätiologie einer Gruppe von Kopf- und Hals-Plattenepithelkarzinomen. Diese Übersicht konzentriert sich auf die epidemiologischen, molekularen und klinischen Aspekte der HPV-Infektion im Kopf- und Hals-Karzinom. Die DNA von HR HPV wurde in unterschiedlich hohen Anteilen von Kopf- und Halstumoren identifiziert, mit der höchsten Prävalenz im Oropharynx. Patienten mit HPV-assoziierten Tumoren zeichnen sich durch moderaten Tabak- und Alkoholkonsum aus. Manche Aspekte des Sexuallebens können einen Risikofaktor darstellen. Es wurde kürzlich festgestellt, dass sich die HPV-Infektion ausbreitet, und die steigende Prävalenz von HPV-positiven Tumoren ist wahrscheinlich in dieser Epidemie begründet. Auf der molekularen Ebene hat man bewiesen, dass die Onkoproteine E6 und E7 an der Onkogenese beteiligt sind. HPV-positive Karzinome haben eine bessere Prognose, und der HPV-Status sollte bei der klinischen Entscheidung eine Rolle spielen. Der steigende Anteil der HPV-positiven Tumoren unterstreicht die Bedeutung der HPV-Vakzination auch in der Prophylaxe der Kopf- und Halstumoren.
Summary
High-risk types of human papillomaviruses (HR HPV) play an important role in the etiology of a group of head and neck squamous cell cancers (HNSCC). This review is focused on epidemiological, molecular, and clinical aspects of HPV infection in head and neck cancer. High risk HPV DNA is being detected in a very different proportion of HNSCC with the highest prevalence in oropharynx. Patients with HPV-associated tumors are characterized by moderate tobacco and alcohol consumption. Some aspects of sexual behavior may represent a risk factor. Recently, it has been shown that HPV infection is spreading and the rising prevalence of HPV-positive tumors can probably be attributed to this epidemic. On molecular level the viral oncoproteins E6 and E7 were shown to be involved in oncogenesis. HPV-positive cancers have better prognosis and HPV status should be considered in clinical decision-making. The rising proportion of HPV-positive tumors underlines the importance of HPV vaccination also for the prevention of HNSCC.
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References
Carbone M, Klein G, Gruber J, et al. Modern criteria to establish human cancer etiology. Cancer Res, 64: 5518–5524, 2004
Kreimer AR, Clifford GM, Boyle P, et al. Human papillomavirus types in head and neck squamous cell carcinomas worldwide: a systematic review. Cancer Epidemiol Biomarkers Prev, 14: 467–475, 2005
Hafkamp HC, Manni JJ, Haesevoets A, et al. Marked differences in survival rate between smokers and nonsmokers with HPV 16-associated tonsillar carcinomas. Int J Cancer, 122: 2656–2664, 2008
Lindel K, Beer KT, Laissue J, et al. Human papillomavirus positive squamous cell carcinoma of the oropharynx: a radiosensitive subgroup of head and neck carcinoma. Cancer, 92: 805–813, 2001
D'Souza G, Kreimer AR, Viscidi R, et al. Case-control study of human papillomavirus and oropharyngeal cancer. N Engl J Med, 356: 1944–1956, 2007
Tachezy R, Klozar J, Salakova M, et al. HPV and other risk factors of oral cavity/oropharyngeal cancer in the Czech Republic. Oral Dis, 11: 181–185, 2005
Klussmann JP, Weissenborn SJ, Wieland U, et al. Human papillomavirus-positive tonsillar carcinomas: a different tumor entity? Med Microbiol Immunol (Berl), 192: 129–132, 2003
Gillison ML, D'Souza G, Westra W, et al. Distinct risk factor profiles for human papillomavirus type 16-positive and human papillomavirus type 16-negative head and neck cancers. J Natl Cancer Inst, 100: 407–420, 2008
Smith EM, Ritchie JM, Summersgill KF, et al. Age, sexual behavior and human papillomavirus infection in oral cavity and oropharyngeal cancers. Int J Cancer, 108: 766–772, 2004
Fakhry C, Westra WH, Li S, et al. Improved survival of patients with human papillomavirus-positive head and neck squamous cell carcinoma in a prospective clinical trial. J Natl Cancer Inst, 100: 261–269, 2008
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, 95: 1772–1783, 2003
Tachezy R, Klozar J, Rubenstein L, et al. Demographic and risk factors in patients with head and neck tumors. J Med Virol, 81: 878–887, 2009
Haddad R, Crum C, Chen Z, et al. HPV16 transmission between a couple with HPV-related head and neck cancer. Oral Oncol, 44: 812–815, 2008
Hemminki K, Dong C, Frisch M. Tonsillar and other upper aerodigestive tract cancers among cervical cancer patients and their husbands. Eur J Cancer Prev, 9: 433–437, 2000
D'Souza G, Agrawal Y, Halpern J, et al. Oral Sexual Behaviors Associated with Prevalent Oral Human Papillomavirus Infection. J Infect Dis, 199: 1263–1269, 2009
Sturgis EM, Cinciripini PM. Trends in head and neck cancer incidence in relation to smoking prevalence: an emerging epidemic of human papillomavirus-associated cancers? Cancer, 110: 1429–1435, 2007
Chaturvedi AK, Engels EA, Anderson WF, et al. Incidence trends for human papillomavirus-related and -unrelated oral squamous cell carcinomas in the United States. J Clin Oncol, 26: 612–619, 2008
Shiboski CH, Schmidt BL, Jordan RC. Tongue and tonsil carcinoma: increasing trends in the U.S. population ages 20–44 years. Cancer, 103: 1843–1849, 2005
Hammarstedt L, Lindquist D, Dahlstrand H, et al. Human papillomavirus as a risk factor for the increase in incidence of tonsillar cancer. Int J Cancer, 119: 2620–2623, 2006
Syrjanen S. HPV infections and tonsillar carcinoma. J Clin Pathol, 57: 449–455, 2004
Rotnaglova E, Tachezy R, Klozar J. Epidemiology of tonsilar cancer in the Czech Republic and its relationship with HPV infection. Eur J Med Res, 13: 111 (abstr 628), 2008
Narisawa-Saito M, Kiyono T. Basic mechanisms of high-risk human papillomavirus-induced carcinogenesis: roles of E6 and E7 proteins. Cancer Sci, 98: 1505–1511, 2007
Gillison ML. Human papillomavirus-associated head and neck cancer is a distinct epidemiologic, clinical, and molecular entity. Semin Oncol, 31: 744–754, 2004
Westra WH, Taube JM, Poeta ML, et al. Inverse relationship between human papillomavirus-16 infection and disruptive p53 gene mutations in squamous cell carcinoma of the head and neck. Clin Cancer Res, 14: 366–369, 2008
Taylor D, Koch WM, Zahurak M, et al. Immunohistochemical detection of p53 protein accumulation in head and neck cancer: correlation with p53 gene alterations. Hum Pathol, 30: 1221–1225, 1999
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, 24: 736–747, 2006
Smeets SJ, Hesselink AT, Speel EJ, et al. A novel algorithm for reliable detection of human papillomavirus in paraffin embedded head and neck cancer specimen. Int J Cancer, 121: 2465–2472, 2007
Mellin H, Dahlgren L, Munck-Wikland E, et al. Human papillomavirus type 16 is episomal and a high viral load may be correlated to better prognosis in tonsillar cancer. Int J Cancer, 102: 152–158, 2002
Strati K, Pitot HC, Lambert PF. Identification of biomarkers that distinguish human papillomavirus (HPV)-positive versus HPV-negative head and neck cancers in a mouse model. Proc Natl Acad Sci USA, 103: 14152–14157, 2006
Li SL, Kim MS, Cherrick HM, Doniger J, Park NH. Sequential combined tumorigenic effect of HPV-16 and chemical carcinogens. Carcinogenesis, 13: 1981–1987, 1992
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, 90: 1626–1636, 1998
Simen-Kapeu A, Kataja V, Yliskoski M, et al. Smoking impairs human papillomavirus (HPV) type 16 and 18 capsids antibody response following natural HPV infection. Scand J Infect Dis, 40: 745–751, 2008
Lindquist D, Romanitan M, Hammarstedt L, et al. Human papillomavirus is a favourable prognostic factor in tonsillar cancer and its oncogenic role is supported by the expression of E6 and E7. Mol Oncol, 1: 350–355, 2007
Li W, Thompson CH, O'Brien CJ, et al. Human papillomavirus positivity predicts favourable outcome for squamous carcinoma of the tonsil. Int J Cancer, 106: 553–558, 2003
Klozar J, Kratochvil V, Salakova M, et al. HPV status and regional metastasis in the prognosis of oral and oropharyngeal cancer. Eur Arch Otorhinolaryngol 265(Suppl. 1): S75–S82, 2008
Klussmann JP, Mooren JJ, Lehnen M, et al. Genetic signatures of HPV-related and unrelated oropharyngeal carcinoma and their prognostic implications. Clin Cancer Res, 15: 1779–1786, 2009
Mellin H, Friesland S, Lewensohn R, et al. Human papillomavirus (HPV) DNA in tonsillar cancer: clinical correlates, risk of relapse, and survival. Int J Cancer, 89: 300–304, 2000
Strome SE, Savva A, Brissett AE, et al. Squamous cell carcinoma of the tonsils: a molecular analysis of HPV associations. Clin Cancer Res, 8: 1093–1100, 2002
Hoffmann M, Gorogh T, Gottschlich S, et al. Human papillomaviruses in head and neck cancer: 8 year-survival-analysis of 73 patients. Cancer Lett, 218: 199–206, 2005
Smith EM, Wang D, Rubenstein LM, et al. Association between p53 and human papillomavirus in head and neck cancer survival. Cancer Epidemiol Biomarkers Prev, 17: 421–427, 2008
Smith EM, Wang D, Kim Y, et al. P16INK4a expression, human papillomavirus, and survival in head and neck cancer. Oral Oncol, 44: 133–142, 2008
Shonka D Jr, Shoustari A, Read P, et al. Predicting residual neck disease in patients with oropharyngeal squamouc cell carcinoma treated with radiation therapy: utility of p16 status American Head and Neck Society 2009 Annual Meeting. Phoenix, AZ: American Head and Neck Society, 33 (abstr S003), 2009
Lehtinen M, Dillner J, Knekt P, et al. Serologically diagnosed infection with human papillomavirus type 16 and risk for subsequent development of cervical carcinoma: nested case-control study. BMJ, 312: 537–539, 1996
Dahlstrom KR, Adler-Storthz K, Etzel CJ, et al. Human papillomavirus type 16 infection and squamous cell carcinoma of the head and neck in never-smokers: a matched pair analysis. Clin Cancer Res, 9: 2620–2626, 2003
Smith EM, Ritchie JM, Pawlita M, et al. Human papillomavirus seropositivity and risks of head and neck cancer. Int J Cancer, 120: 825–832, 2007
Carter JJ, Koutsky LA, Hughes JP, et al. Comparison of human papillomavirus types 16, 18, and 6 capsid antibody responses following incident infection. J Infect Dis, 181: 1911–1919, 2000
Hamsikova E, Ludvikova V, Smahel M, et al. Prevalence of antibodies to human papillomaviruses in the general population of the Czech Republic. Int J Cancer, 77: 689–694, 1998
Ravaggi A, Romani C, Pasinetti B, et al. Correlation between serological immune response analyzed by a new ELISA for HPV-16/18 E7 oncoprotein and clinical characteristics of cervical cancer patients. Arch Virol, 151: 1899–1916, 2006
Baay MF, Duk JM, Burger MP, et al. Humoral immune response against proteins E6 and E7 in cervical carcinoma patients positive for human papilloma virus type 16 during treatment and follow-up. Eur J Clin Microbiol Infect Dis, 18: 126–132, 1999
Begum S, Gillison ML, Ansari-Lari MA, et al. Detection of human papillomavirus in cervical lymph nodes: a highly effective strategy for localizing site of tumor origin. Clin Cancer Res, 9: 6469–6475, 2003
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Klozar, J., Tachezy, R., Rotnáglová, E. et al. Human papillomavirus in head and neck tumors: epidemiological, molecular and clinical aspects. Wien Med Wochenschr 160, 305–309 (2010). https://doi.org/10.1007/s10354-010-0782-5
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DOI: https://doi.org/10.1007/s10354-010-0782-5