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Humane Papillomaviren und das Oropharynxkarzinom

Frequently asked questions
  • Nora WuerdemannEmail author
  • Johannes Doescher
  • Simon Laban
  • Thomas K. Hoffmann
  • Jens Peter Klussmann
Leitthema
  • 18 Downloads

Zusammenfassung

Hintergrund

Das humane Papillomavirus (HPV) gehört zur Familie der Papillomaviren. Basierend auf dem karzinogenen Potenzial der Viren erfolgt die Einteilung in Niedrig- und Hochrisikotypen. Niedrigrisikotypen sind verantwortlich für genitale Papillome und die rekurrierende respiratorische Papillomatose, während HPV-Hochrisikotypen weltweit 5 % der Karzinome induzieren. HPV gilt als sexuell übertragbare Erkrankung und ist, neben der Entstehung anogenitaler Karzinome, im Kopf-Hals-Bereich für die Pathogenese des HPV-assoziierten Oropharynxkarzinoms (OPSCC) verantwortlich.

Methoden

Diese Arbeit basiert auf einer selektiven Literaturrecherche in der Datenbank PubMed zum Thema HPV-assoziierte OPSCC.

Ergebnisse

Die Inzidenz dieser vorrangig in der Tonsille sowie im Zugengrund lokalisierten HPV-assoziierten Kopf-Hals-Karzinome steigt. Aufgrund der virusgetriebenen Karzinogenese unterscheiden sich HPV-assoziierte OPSCC hinsichtlich genetischer und molekularbiologischer Aspekte von den noxenassoziierten OPSCC und weisen im Vergleich eine signifikant verbesserte Prognose auf. Der Nachweis einer HPV-Assoziation erfolgt u. a. über den immunhistochemischen Nachweis einer Überexpression des Surrogatmarkers p16, welcher seit 2017 in der 8. Auflage der TNM-Klassifikation maligner Tumoren berücksichtigt wird. Bisher wird bei der Wahl der Therapie nicht aufgrund des HPV-Status unterschieden, welches in beiden Entitäten zu einer hohen Nebenwirkungsrate führt.

Schlussfolgerung

Um zukünftig eine Therapiedeeskalation bestimmter Patientengruppen zu ermöglichen, wurden prognostische Modelle zur Risikostratifizierung entwickelt. Zur Überwachung des Krankheitsverlaufs sowie der frühzeitigen Detektion eines Therapieversagens werden aktuell Screeningmethoden wie die Flüssigbiopsie auf ihre Validität geprüft. Die HPV-Impfung, welche der primären Prophylaxe einer Tumorentstehung dient, wird für Mädchen sowie seit kurzem auch für Jungen im Alter von 9 bis 14 Jahren von der Ständigen Impfkommission (STIKO) empfohlen.

Schlüsselwörter

Kopf-Hals-Karzinome Oropharynxkarzinom Inzidenzen Risikofaktoren Impfung 

Human papillomavirus and oropharyngeal squamous cell carcinoma

Frequently asked questions

Abstract

Introduction

The human papillomavirus (HPV) belongs to the papillomavirus family. Based on the carcinogenic potential of the virus, it is classified into low-risk and high-risk types. Low-risk types are responsible for the development of genital papillomas and recurrent respiratory papillomatosis, whereas 5% of all carcinomas worldwide are caused by HPV high-risk types. HPV is considered a sexually transmitted disease and is not only responsible for the development of anogenital carcinomas but also for a subgroup of HPV-associated oropharyngeal squamous cell carcinoma (OPSCC) in the head and neck area.

Methods

This work is based on a selective literature search in the PubMed database on the subject of HPV-associated OPSCC.

Results

The OPSCCs are located primarily in the tonsils or base of the tongue and represent a tumor entity with a significantly increasing incidence. Due to virus-driven carcinogenesis, these tumors differ from smoking and alcohol-associated OPSCC in both genetic and molecular biological aspects and are distinguished by a significantly improved prognosis. HPV-association is confirmed by the expression of the surrogate marker p16, which has been included in the 8th edition of the TNM classification of malignant tumors since 2017. Nevertheless, the choice of treatment is currently not based on HPV status, which leads to a high rate of side effects in both entities.

Conclusion

Prognostic models for risk stratification have been developed in order to enable treatment deintensification for certain patient groups in the future. In order to monitor the course of disease and early detection of treatment failure, current screening and surveillance methods, such as liquid biopsy are being tested. The HPV vaccination, which serves as a primary prophylaxis with respect to tumor development, is recommended by the Standing Vaccination Committee for girls and recently also for boys aged 9–14 years.

Keywords

Head and neck cancer Oropharyngeal squamous cell carcinoma Incidences Risk factors Vaccination 

Notes

Einhaltung ethischer Richtlinien

Interessenkonflikt

S. Laban: Advisory Boards: AstraZeneca (AZ), Merck Sharp & Dohme (MSD). Vortragshonorare: Bristol-Myers Squibb (BMS), Merck Serono, MSD. T.K. Hoffmann: Advisory Board für MSD. Vortragshonorare: Merck Serono, BMS. N. Wuerdemann, J. Doescher und J.P. Klussmann geben an, dass kein Interessenkonflikt besteht.

Dieser Beitrag beinhaltet keine von den Autoren durchgeführten Studien an Menschen oder Tieren.

Literatur

  1. 1.
    de Villiers EM et al (2004) Classification of papillomaviruses. Virology 324(1):17–27CrossRefGoogle Scholar
  2. 2.
    Lacey CJ, Lowndes CM, Shah KV (2006) Chapter 4: Burden and management of non-cancerous HPV-related conditions: HPV-6/11 disease. Vaccine 24(Suppl 3):S35–S41CrossRefGoogle Scholar
  3. 3.
    Dickens P et al (1991) Human papillomavirus 6, 11, and 16 in laryngeal papillomas. J Pathol 165(3):243–246CrossRefGoogle Scholar
  4. 4.
    Alberico S et al (1996) Maternal-fetal transmission of human papillomavirus. Minerva Ginecol 48(5):199–204PubMedGoogle Scholar
  5. 5.
    D’Souza G et al (2007) Case-control study of human papillomavirus and oropharyngeal cancer. N Engl J Med 356(19):1944–1956CrossRefGoogle Scholar
  6. 6.
    Hernandez BY et al (2008) Transmission of human papillomavirus in heterosexual couples. Emerg Infect Dis 14(6):888–894CrossRefGoogle Scholar
  7. 7.
    Gillison ML 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(6):407–420CrossRefGoogle Scholar
  8. 8.
    Dahlstrom KR et al (2015) Socioeconomic characteristics of patients with oropharyngeal carcinoma according to tumor HPV status, patient smoking status, and sexual behavior. Oral Oncol 51(9):832–838CrossRefGoogle Scholar
  9. 9.
    Vahl JM, Hoffmann TK (2018) HPV-positive oropharyngeal cancer-risk for the partner? HNO.  https://doi.org/10.1007/s00106-018-0584-4 CrossRefPubMedGoogle Scholar
  10. 10.
    Mirghani H et al (2017) Is there an increased risk of cancer among spouses of patients with an HPV-related cancer: A systematic review. Oral Oncol 67:138–145CrossRefGoogle Scholar
  11. 11.
    D’Souza G et al (2014) Oral human papillomavirus (HPV) infection in HPV-positive patients with oropharyngeal cancer and their partners. J Clin Oncol 32(23):2408–2415CrossRefGoogle Scholar
  12. 12.
    Wieland U, Kreuter A, Pfister H (2014) Human papillomavirus and immunosuppression. Curr Probl Dermatol 45:154–165CrossRefGoogle Scholar
  13. 13.
    Gillison ML et al (2012) Prevalence of oral HPV infection in the United States, 2009–2010. JAMA 307(7):693–703CrossRefGoogle Scholar
  14. 14.
    Kreimer AR et al (2010) Oral human papillomavirus in healthy individuals: A systematic review of the literature. Sex Transm Dis 37(6):386–391PubMedGoogle Scholar
  15. 15.
    Kreimer AR et al (2013) Incidence and clearance of oral human papillomavirus infection in men: The HIM cohort study. Lancet 382(9895):877–887CrossRefGoogle Scholar
  16. 16.
    D’Souza G et al (2007) Six-month natural history of oral versus cervical human papillomavirus infection. Int J Cancer 121(1):143–150CrossRefGoogle Scholar
  17. 17.
    Kreuter A, Wieland U (2009) Human papillomavirus-associated diseases in HIV-infected men who have sex with men. Curr Opin Infect Dis 22(2):109–114CrossRefGoogle Scholar
  18. 18.
    Chaturvedi AK et al (2018) Effect of prophylactic human papillomavirus (HPV) vaccination on oral HPV infections among young adults in the United States. J Clin Oncol 36(3):262–267CrossRefGoogle Scholar
  19. 19.
    de Martel C et al (2017) Worldwide burden of cancer attributable to HPV by site, country and HPV type. Int J Cancer 141(4):664–670CrossRefGoogle Scholar
  20. 20.
    Wagner S et al (2017) Human papillomavirus association is the most important predictor for surgically treated patients with oropharyngeal cancer. Br J Cancer 116(12):1604–1611CrossRefGoogle Scholar
  21. 21.
    Varier I et al (2016) Clinical characteristics and outcomes of oropharyngeal carcinoma related to high-risk non-human papillomavirus16 viral subtypes. Head Neck 38(9):1330–1337CrossRefGoogle Scholar
  22. 22.
    Chaturvedi AK et al (2011) Human papillomavirus and rising oropharyngeal cancer incidence in the United States. J Clin Oncol 29(32):4294–4301CrossRefGoogle Scholar
  23. 23.
    Mifsud M et al (2017) Evolving trends in head and neck cancer epidemiology: Ontario, Canada 1993–2010. Head Neck 39(9):1770–1778CrossRefGoogle Scholar
  24. 24.
    Nasman A et al (2009) Incidence of human papillomavirus (HPV) positive tonsillar carcinoma in Stockholm, Sweden: An epidemic of viral-induced carcinoma? Int J Cancer 125(2):362–366CrossRefGoogle Scholar
  25. 25.
    Baboci L et al (2016) Low prevalence of HPV-driven head and neck squamous cell carcinoma in North-East Italy. Papillomavirus Res 2:133–140CrossRefGoogle Scholar
  26. 26.
    Würdemann N et al (2017) Prognostic impact of AJCC/UICC 8th edition new staging rules in oropharyngeal squamous cell carcinoma. Front Oncol 7:129.  https://doi.org/10.3389/fonc.2017.00129 CrossRefPubMedPubMedCentralGoogle Scholar
  27. 27.
    Stenmark MH et al (2017) Influence of human papillomavirus on the clinical presentation of oropharyngeal carcinoma in the United States. Laryngoscope 127(10):2270–2278CrossRefGoogle Scholar
  28. 28.
    D’Souza G 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):100–104CrossRefGoogle Scholar
  29. 29.
    Arenz A et al (2014) Increased radiosensitivity of HPV-positive head and neck cancer cell lines due to cell cycle dysregulation and induction of apoptosis. Strahlenther Onkol 190(9):839–846CrossRefGoogle Scholar
  30. 30.
    Saber CN et al (2016) Immune cells and prognosis in HPV-associated oropharyngeal squamous cell carcinomas: Review of the literature. Oral Oncol 58:8–13CrossRefGoogle Scholar
  31. 31.
    Welters MJP et al (2018) Intratumoral HPV16-specific T cells constitute a type I‑oriented tumor microenvironment to improve survival in HPV16-driven oropharyngeal cancer. Clin Cancer Res 24(3):634–647CrossRefGoogle Scholar
  32. 32.
    Reuschenbach M et al (2016) Human papillomavirus and squamous cell cancer of the head and neck region: Prognostic, therapeutic and prophylactic implications. HNO 64(7):450–459CrossRefGoogle Scholar
  33. 33.
    Prigge ES et al (2017) Diagnostic accuracy of p16(INK4a) immunohistochemistry in oropharyngeal squamous cell carcinomas: A systematic review and meta-analysis. Int J Cancer 140(5):1186–1198CrossRefGoogle Scholar
  34. 34.
    Klussmann JP et al (2003) Expression of p16 protein identifies a distinct entity of tonsillar carcinomas associated with human papillomavirus. Am J Pathol 162(3):747–753CrossRefGoogle Scholar
  35. 35.
    El-Naggar AK, Westra WH (2012) p16 expression as a surrogate marker for HPV-related oropharyngeal carcinoma: A guide for interpretative relevance and consistency. Head Neck 34(4):459–461CrossRefGoogle Scholar
  36. 36.
    Lechner M et al (2018) Frequent HPV-independent p16/INK4A overexpression in head and neck cancer. Oral Oncol 83:32–37CrossRefGoogle Scholar
  37. 37.
    Nauta IH et al (2018) Evaluation of the eighth TNM classification on p16-positive oropharyngeal squamous cell carcinomas in the Netherlands and the importance of additional HPV DNA testing. Ann Oncol 29(5):1273–1279CrossRefGoogle Scholar
  38. 38.
    Huang SH, O’Sullivan B (2017) Overview of the 8th edition TNM classification for head and neck cancer. Curr Treat Options Oncol 18(7):40CrossRefGoogle Scholar
  39. 39.
    Amin MB et al (2017) The eighth edition AJCC cancer staging manual: Continuing to build a bridge from a population-based to a more „personalized“ approach to cancer staging. CA Cancer J Clin 67(2):93–99CrossRefGoogle Scholar
  40. 40.
    Doescher J, Veit JA, Hoffmann TK (2017) The 8th edition of the AJCC cancer staging manual: Updates in otorhinolaryngology, head and neck surgery. HNO 65(12):956–961CrossRefGoogle Scholar
  41. 41.
    Sharma SJ et al (2018) The 8th edition AJCC/UICC TNM staging for p16-positive oropharyngeal carcinoma: Is there space for improvement? Eur Arch Otorhinolaryngol 275(12):3087–3091CrossRefGoogle Scholar
  42. 42.
    Cramer JD, Ferris RL, Duvvuri U (2018) Treatment deintensification to surgery only for stage I human papillomavirus-associated oropharyngeal cancer. J Clin Oncol 36(15_suppl):6003–6003CrossRefGoogle Scholar
  43. 43.
    Sinha P et al (2015) High metastatic node number, not extracapsular spread or N‑classification is a node-related prognosticator in transorally-resected, neck-dissected p16-positive oropharynx cancer. Oral Oncol 51(5):514–520CrossRefGoogle Scholar
  44. 44.
    Gillison ML et al (2018) Radiotherapy plus cetuximab or cisplatin in human papillomavirus-positive oropharyngeal cancer (NRG Oncology RTOG 1016): A randomised, multicentre, non-inferiority trial. Lancet 393(10166):40–50CrossRefGoogle Scholar
  45. 45.
    Mehanna H et al (2018) Radiotherapy plus cisplatin or cetuximab in low-risk human papillomavirus-positive oropharyngeal cancer (De-ESCALaTE HPV): An open-label randomised controlled phase 3 trial. Lancet 393(10166):51–60CrossRefGoogle Scholar
  46. 46.
    Ferris RL et al (2016) Nivolumab for recurrent squamous-cell carcinoma of the head and neck. N Engl J Med 375(19):1856–1867CrossRefGoogle Scholar
  47. 47.
    Mehra R et al (2018) Efficacy and safety of pembrolizumab in recurrent/metastatic head and neck squamous cell carcinoma: Pooled analyses after long-term follow-up in KEYNOTE-012. Br J Cancer 119(2):153–159CrossRefGoogle Scholar
  48. 48.
    Ang KK et al (2010) Human papillomavirus and survival of patients with oropharyngeal cancer. N Engl J Med 363(1):24–35CrossRefGoogle Scholar
  49. 49.
    Gronhoj C et al (2018) Development and external validation of nomograms in oropharyngeal cancer patients with known HPV-DNA status: A European Multicentre Study (OroGrams). Br J Cancer 118(12):1672–1681CrossRefGoogle Scholar
  50. 50.
    Cao H et al (2012) Quantitation of human papillomavirus DNA in plasma of oropharyngeal carcinoma patients. Int J Radiat Oncol Biol Phys 82(3):e351–e358CrossRefGoogle Scholar
  51. 51.
    Wittekindt C et al (2018) HPV – A different view on head and neck cancer. Laryngorhinootologie 97(S 01):S48–S113CrossRefGoogle Scholar
  52. 52.
    Kreimer AR et al (2017) Kinetics of the human papillomavirus type 16 E6 antibody response prior to oropharyngeal cancer. J Natl Cancer Inst 109(8).  https://doi.org/10.1093/jnci/djx005 CrossRefPubMedPubMedCentralGoogle Scholar
  53. 53.
    Drolet M et al (2015) Population-level impact and herd effects following human papillomavirus vaccination programmes: A systematic review and meta-analysis. Lancet Infect Dis 15(5):565–580CrossRefGoogle Scholar
  54. 54.
    Novakovic D et al (2016) Juvenile recurrent respiratory papillomatosis: 10-year audit and Australian prevalence estimates. Laryngoscope 126(12):2827–2832CrossRefGoogle Scholar

Copyright information

© Springer Medizin Verlag GmbH, ein Teil von Springer Nature 2019

Authors and Affiliations

  • Nora Wuerdemann
    • 1
    Email author
  • Johannes Doescher
    • 2
  • Simon Laban
    • 2
  • Thomas K. Hoffmann
    • 2
  • Jens Peter Klussmann
    • 1
  1. 1.Klinik und Poliklinik für HNO-Heilkunde, Kopf- und Halschirurgie, Medizinische FakultätUniversität zu KölnKölnDeutschland
  2. 2.Kopf-Hals-Tumorzentrum des Comprehensive Cancer Center Ulm, Klinik für Hals‑, Nasen‑, Ohrenheilkunde und Kopf-Hals-ChirurgieUniversitätsklinik UlmUlmDeutschland

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