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Humane Papillomavirusinfektionen bei Plattenepithelkarzinomen des Kopf- und Halsbereichs

Eine Untersuchung am Krankengut des Bundeswehrkrankenhauses Ulm

Human papillomavirus in squamous cell cancer of the head and neck

A study at the Ulm Military Hospital, Germany

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Zusammenfassung

Humane Papillomaviren (HPV) gewinnen als Risikofaktor für die Entstehung von Plattenepithelkarzinomen des oberen Atmungs- und Verdauungstrakts weltweit zunehmend an Bedeutung. Für Deutschland liegen bislang nur wenige epidemiologische Untersuchungen zu dieser Fragestellung vor. Im Rahmen der vorliegenden Untersuchung wurde die Prävalenz von HPV-Infektionen bei 223 Patienten mit Plattenepithelkarzinomen im Bereich von Mundhöhle, Oropharynx, Hypopharynx und Larynx untersucht. In 17,5 % der Fälle wurde DNA des HPV-Genotyps 16 (HPV16) nachgewiesen. Bei allen HPV16-positiven Tumoren fand sich eine Überexpression von p16INK4a im Tumorgewebe. Weitere High-Risk-HPV waren im untersuchten Tumorkollektiv nicht nachweisbar. Am häufigsten wurde HPV16 bei Tonsillenkarzinomen nachgewiesen (37,5 %), während lediglich 2,4 % der Larynxkarzinome HPV16-positiv waren. Bei HPV-positiven Tonsillenkarzinomen fanden sich signifikant häufiger Halslymphknotenmetastasen im Vergleich zu HPV-negativen Tumoren (85,7 % vs. 54,3 %; p < 0,016). Der Tabak- und Alkoholkonsum war bei Patienten mit HPV-positiven Tumoren signifikant geringer (p < 0,0001).

Abstract

There is increasing evidence worldwide that human papillomavirus is a major risk factor for head and neck cancer. Only few studies on this association have been performed in Germany to date. For the purposes of the present study, tumor specimens from 223 patients with squamous cell cancer of the oral cavity, oropharynx, hypopharynx and larynx were analyzed for HPV DNA and p16INK4a expression. The prevalence of HPV genotype 16 (HPV16) DNA in the study population was 17.5 %. Further high-risk HPV types were not detected. All HPV16-positive tumors showed intense p16INK4a expression. HPV16 prevalence was highest in tonsillar carcinoma (37.5 %) and lowest in laryngeal cancer (2.8 %). We observed a significantly higher incidence of cervical lymph node metastases in patients with HPV16-positive tonsillar carcinoma in comparison to HPV-negative tumors (p < 0.016). Tobacco and/or alcohol consumption was significantly lower in patients with HPV-positive tumors (p < 0.0001).

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Literatur

  1. Ang KK, Harris J, Wheeler R et al (2010) Human papillomavirus and survival of patients with oropharyngeal cancer. N Engl J Med 363:34–35

    Article  Google Scholar 

  2. Assmann G, Sotlar K (2011) HPV-assoziierte Plattenepithelkarzinogenese. Pathologe 32:391–398

    Article  PubMed  CAS  Google Scholar 

  3. Chaturvedi AK (2012) Epidemiology and clinical aspects of HPV in head and neck cancers. Head Neck Pathol 6(Suppl 1):16–24

    Article  Google Scholar 

  4. Dahlstrom KR, Li G, Tortolero-Luna G et al (2011) Differences in history of sexual behavior between patients with oropharyngeal squamous cell carcinoma and patients with squamous cell carcinoma at other head and neck sites. Head Neck 33:847–855

    Article  PubMed  Google Scholar 

  5. Dayyani F, Etzel CJ, Liu M et al (2010) Meta-analysis of the impact of human papillomavirus (HPV) on cancer risk and overall survival in head and neck squamous cell carcinomas (HNSCC). Head Neck Oncol 2:15

    Article  PubMed  Google Scholar 

  6. D’Souza G, Kreimer AR, Viscidi R et al (2007) Case-control study of human papillomavirus and oropharyngeal cancer. N Engl J Med 356:1944–1956

    Article  Google Scholar 

  7. D’Souza G, Agrawal Y, Halpern J et al (2009) Oral sexual behaviors associated with prevalent oral human papillomavirus infection. J Infect Dis 199(9):1263–1269

    Article  Google Scholar 

  8. Furniss CS, McClean MD, Smith JF et al (2007) Human papillomavirus 16 and head and neck squamous cell carcinoma. Int J Cancer 120:2386–2392

    Article  PubMed  CAS  Google Scholar 

  9. Gillison ML, D’Souza G, Westra W et al (2008) 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

    Article  PubMed  Google Scholar 

  10. 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 30:898–903

    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 95:1772–1783

    Article  PubMed  Google Scholar 

  12. Hoffmann M, Hoffmann AS, Tribius S (2012) Humane Papillomavirusinfektionen im Kopf-Hals-Bereich im öffentlichen Bewusstsein. Mahnung zu Präzision in Diagnostik und Öffentlichkeitsarbeit. HNO 60:968–973

    Article  PubMed  CAS  Google Scholar 

  13. Hoffmann M, Ihloff AS, Görögh T et al (2010) p16(INK4a) overexpression predicts translational active human papillomavirus infection in tonsillar cancer. Int J Cancer 127:1595–1602

    Article  PubMed  CAS  Google Scholar 

  14. Hoffmann M, Görögh T, Gottschlich S et al (2005) Human papillomaviruses in head and neck cancer: 8 year-survival-analysis of 73 patients. Cancer Lett 218:199–206

    Article  PubMed  CAS  Google Scholar 

  15. Joo YH, Jung CK, Sun DI et al (2012) High-risk human papillomavirus and cervical lymph node metastasis in patients with oropharyngeal cancer. Head Neck 34:10–14

    Article  PubMed  Google Scholar 

  16. Klussmann JP, Weissenborn S, Wieland U et al (2001) Prevalence, distribution and viral load of human papillomavirus 16 DNA in tonsillar carcinomas. Cancer 92:2875–2884

    Article  PubMed  CAS  Google Scholar 

  17. Klussmann JP, Preuss SF, Speel EJ (2009) Humane Papillomaviren und Oropharynxkarzinome – molekulare Interaktion und klinische Auswirkung. HNO 57:113–122

    Article  PubMed  CAS  Google Scholar 

  18. Kreimer AR, Alberg AJ, Daniel R et al (2004) Oral human papillomavirus infection in adults is associated with sexual behavior and HIV serostatus. J Infect Dis 189:686–698

    Article  PubMed  Google Scholar 

  19. Kreimer AR, Clifford GM, Boyle P, Franceschi S (2005) Human papillomavirus types in head and neck squamous cell carcinomas worldwide: a systematic review. Cancer Epidemiol Biomarkers Prev 14:467–475

    Article  PubMed  CAS  Google Scholar 

  20. Kreimer AR, Villa A, Nyitray AG et al (2011) The epidemiology of oral HPV infection among a multinational sample of healthy men. Cancer Epidemiol Biomarkers Prev 20(1):172–182

    Article  PubMed  Google Scholar 

  21. Kumar B, Cordell KG, Lee JS et al (2007) Response to therapy and outcomes in oropharyngeal cancer are associated with biomarkers including human papillomavirus, epidermal growth factor receptor, gender, and smoking. Int J Radiat Oncol Biol Phys 69(2 Suppl):109–111

    Article  Google Scholar 

  22. Lewis JS Jr (2012) p16 Immunohistochemistry as a standalone test for risk stratification in oropharyngeal squamous cell carcinoma. Head Neck Pathol 6(Suppl 1):75–82

    Article  Google Scholar 

  23. Maier H, Dietz A, Gewelke U et al (1992) Tobacco and alcohol and the risk of head and neck cancer. Clin Investig 70:320–327

    PubMed  CAS  Google Scholar 

  24. Marur S, D’Souza G, Westra WH, Forastiere AA (2010) HPV-associated head and neck cancer: a virus-related cancer epidemic. Lancet Oncol 11:781–789

    Article  PubMed  Google Scholar 

  25. Preuss SF, Klussmann J-P, Semrau R, Huebbers C (2010) Aktuelles zu HPV-induzierten Oropharynxkarzinomen. HNO 59:1031–1038

    Article  Google Scholar 

  26. Rautava J, Syrjänen S (2012) Biology of human papillomavirus infections in head and neck carcinogenesis. Head Neck Pathol 6(Suppl 1):3–15

    Article  Google Scholar 

  27. Ritchie JM, Smith EM, Summersgill KF et al (2003) Human papillomavirus infection as a prognostic factor in carcinomas of the oral cavity and oropharynx. Int J Cancer 104:336–344

    Article  PubMed  CAS  Google Scholar 

  28. Schwartz SM, Daling JR, Doody DR et al (1998) Oral cancer risk in relation to sexual history and evidence of human papillomavirus infection. J Natl Cancer Inst 90:1626–1636

    Article  PubMed  CAS  Google Scholar 

  29. Sedaghat AR, Zhang Z, Begum S et al (2009) Prognostic significance of human papillomavirus in oropharyngeal squamous cell carcinomas. Laryngoscope 119:1542–1549

    Article  PubMed  Google Scholar 

  30. Smith EM, Rithie JM, Summersgill KF et al (2004) Age, sexual behaviour and human papillomavirus infection in oral cavity and oropharyngeal cancers. Int J Cancer 108:766–772

    Article  PubMed  CAS  Google Scholar 

  31. Stenner M, Yosef B, Huebbers CU et al (2011) Nuclear translocation of β-catenin and decreased expression of epithelial cadherin in human papillomavirus-positive tonsillar cancer: an early event in human papillomavirus-related tumour progression? Histopathology 58:1117–1126

    Article  PubMed  Google Scholar 

  32. Syrjänen S (2005) Human papillomavirus (HPV) in head and neck cancer. J Clin Virol 32:59–66

    Article  Google Scholar 

  33. Syrjänen S, Termine N, Capra G et al (2012) Oral HPV Infection: current strategies for prevention and therapy. Curr Pharm Des 18:5452–5469

    Article  PubMed  Google Scholar 

  34. Trottier H, Burchell AN (2009) Epidemiology of mucosal human papillomavirus infection and associated diseases. Public Health Genomics 12:291–307

    Article  PubMed  Google Scholar 

  35. Weichert W, Schewe C, Denkert C et al (2009) Molecular HPV typing as a diagnostic tool to discriminate primary from metastatic squamous cell carcinoma of the lung. Am J Surg Pathol 33(4):513–520

    Article  PubMed  Google Scholar 

  36. Wittekindt C, Wagner S, Mayer CS, Klussmann JP (2012) Grundlagen der Tumorentstehung und die Bedeutung Humaner Papillomaviren (HPV) bei Kopf-Hals-Karzinomen. Laryngorhinootologie 91(Suppl 1):1–26

    Google Scholar 

  37. Yang J, Mani SA, Donaher JL et al (2004) Twist, a master regulator of morphogenesis, plays an essential role in tumor metastasis. Cell 117:927–939

    Article  PubMed  CAS  Google Scholar 

  38. Hausen H zur (2009) Papillomaviruses in the causation of human cancers – a brief historical account. Virology 384:260–265

    Article  PubMed  Google Scholar 

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Maier, M., Kraft, K., Steinestel, K. et al. Humane Papillomavirusinfektionen bei Plattenepithelkarzinomen des Kopf- und Halsbereichs. HNO 61, 593–601 (2013). https://doi.org/10.1007/s00106-013-2676-5

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  • DOI: https://doi.org/10.1007/s00106-013-2676-5

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