Skip to main content
SpringerLink
Log in

Rolle von humanen Papillomviren (HPV) in der Entwicklung von Hautkarzinomen

Role of human papillomavirus (HPV) in the development of skin cancer

  • Leitthema
  • Published:
Der Hautarzt Aims and scope Submit manuscript

Zusammenfassung

Nichtmelanozytärer Hautkrebs stellt die am häufigsten beim Menschen auftretende Krebserkrankung dar, deren Inzidenz sogar immer weiter ansteigt. Die Entwicklung von präkanzerösen aktinischen Keratosen und des Plattenepithelkarzinoms der Haut (cSCC) wird mit Infektionen von humanen Papillomviren (HPV) des Genus beta (betaHPV) in Verbindung gebracht. Persistierende betaHPV-Infektionen sind bei immunkompetenten Individuen sehr gut kontrolliert und verlaufen weitestgehend asymptomatisch, eine geschwächte Immunkontrolle hingegen führt zu hohen betaHPV-Mengen in der Haut. Die Folge ist eine erhöhte Aktivität der viralen Onkoproteine, was mit einem signifikant erhöhten Hautkrebsrisiko einhergeht. Doch auch bei immunkompetenten Personen steigt das Risiko für cSCC mit zunehmendem Alter stark an, bedingt durch die Akkumulation von UV-Schäden in der Haut. Interessanterweise scheint der Mechanismus der betaHPV-abhängigen Karzinogenese bei immunkompetenten Menschen anders zu verlaufen als bei immunsupprimierten Patienten. Der zugrunde liegende Mechanismus der Onkogenese ist bei immunkompetenten Patienten jedoch weit weniger gut verstanden. Dieser Übersichtsbeitrag fasst jüngste Forschungsdaten zusammen. Diese deuten darauf hin, dass kutane Papillomviren, insbesondere im Zusammenspiel mit UV-Licht, über einen „Hit-and-Run“-Mechanismus die Hautkarzinogenese fördern. Dies geschieht, indem sie die genotoxischen Wirkungen von UV-Licht in der ersten Phase dieses mehrstufigen Prozesses verstärken. Des Weiteren wird ein Überblick über sich derzeit in Entwicklung befindende Impfansätze gegen Papillomviren gegeben, die in Zukunft die Behandlungsmöglichkeiten von Hochrisikopatienten erheblich verbessern könnten.

Abstract

The incidence of nonmelanoma skin cancer, the most common cancer in humans, continues to rise. The development of precancerous actinic keratoses and cutaneous squamous cell carcinoma (cSCC) is associated with infection with human papillomavirus (HPV) of genus beta (betaHPV). Persistent betaHPV infections in immunocompetent individuals are generally very well controlled by the immune system and largely asymptomatic. However, immunosuppression results in high levels of betaHPV in the skin and consequently increased viral oncoprotein activity, which in turn leads to a significantly increased risk for skin cancer. However, even in immunocompetent individuals, the risk of cSCC increases with age as a result of accumulated UV-induced DNA damage in the skin. In these patients, the mechanism of betaHPV-dependent carcinogenesis seems to be different from that observed in immunocompromised patients. The underlying mechanism of oncogenesis in immunocompetent patients is currently less well understood. This review summarizes the current research data, which provide compelling evidence that cutaneous papillomaviruses, particularly in interaction with UV light, promote skin carcinogenesis via a “hit-and-run” mechanism by enhancing the genotoxic effects of UV light in the initial phases of this multistep process. Furthermore, an overview of novel vaccination strategies against papillomaviruses that are currently tested in clinical trials is provided, which could significantly improve the treatment options for high-risk patients in the future.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Abb. 1
Abb. 2

Literatur

  1. Akgül B, Garcia-Escudero R, Ghali L et al (2005) The E7 protein of cutaneous human papillomavirus type 8 causes invasion of human keratinocytes into the dermis in organotypic cultures of skin. Cancer Res 65:2216–2223

    Article  Google Scholar 

  2. Augustin J, Kis A, Sorbe C et al (2018) Epidemiology of skin cancer in the German population: impact of socioeconomic and geographic factors. J Eur Acad Dermatol Venereol 32:1906–1913

    Article  CAS  Google Scholar 

  3. Bouvard V, Baan R, Straif K et al (2009) A review of human carcinogens—Part B: biological agents. Lancet Oncol 10:321–322

    Article  Google Scholar 

  4. Bouwes Bavinck JN, Feltkamp MCW, Green AC et al (2018) Human papillomavirus and posttransplantation cutaneous squamous cell carcinoma: A multicenter, prospective cohort study. Am J Transplant 18:1220–1230

    Article  Google Scholar 

  5. Dorfer S, Strasser K, Schrockenfuchs G et al (2021) Mus musculus papillomavirus 1 is a key driver of skin cancer development upon immunosuppression. Am J Transplant 21:525–539

    Article  CAS  Google Scholar 

  6. Fu Y, Cao R, Schafer M et al (2020) Expression of different L1 isoforms of Mastomys natalensis papillomavirus as mechanism to circumvent adaptive immunity. Elife 9:e57626. https://doi.org/10.7554/eLife.57626

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  7. Hasche D, Stephan S, Braspenning-Wesch I et al (2017) The interplay of UV and cutaneous papillomavirus infection in skin cancer development. PLoS Pathog 13:e1006723

    Article  Google Scholar 

  8. Hasche D, Vinzon SE, Rosl F (2018) Cutaneous papillomaviruses and non-melanoma skin cancer: causal agents or innocent bystanders? Front Microbiol 9:874

    Article  Google Scholar 

  9. Hasche D et al (2022) Isoforms of the Papillomavirus Major Capsid Protein Differ in Their Ability to Block Viral Spread and Tumor Formation. Front Immunol. https://doi.org/10.3389/fimmu.2022.811094

    Article  PubMed  PubMed Central  Google Scholar 

  10. Heuser S, Hufbauer M, Steiger J et al (2016) The fibronectin/alpha3beta1 integrin axis serves as molecular basis for keratinocyte invasion induced by betaHPV. Oncogene 35:4529–4539

    Article  CAS  Google Scholar 

  11. Huber B, Wang JW, Roden RBS et al (2021) RG1-VLP and other L2-based, broad-spectrum HPV vaccine candidates. J Clin Med 10(5):1044. https://doi.org/10.3390/jcm10051044

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  12. Hufbauer M, Akgül B (2017) Molecular mechanisms of human papillomavirus induced skin carcinogenesis. Viruses 9(7):187. https://doi.org/10.3390/v9070187

    Article  CAS  PubMed Central  Google Scholar 

  13. Hufbauer M, Biddle A, Borgogna C et al (2013) Expression of betapapillomavirus oncogenes increases the number of keratinocytes with stem cell-like properties. J Virol 87:12158–12165

    Article  CAS  Google Scholar 

  14. Hufbauer M, Cooke J, Van Der HGT et al (2015) Human papillomavirus mediated inhibition of DNA damage sensing and repair drives skin carcinogenesis. Mol Cancer 14:183

    Article  Google Scholar 

  15. Loenenbach A, Pawlita M, Waterboer T et al (2022) Seroprevalence of mucosal and cutaneous human papillomavirus (HPV) types among children and adolescents in the general population in Germany. BMC Infect Dis 22:44

    Article  CAS  Google Scholar 

  16. Marcuzzi GP, Awerkiew S, Hufbauer M et al (2014) Tumor prevention in HPV8 transgenic mice by HPV8-E6 DNA vaccination. Med Microbiol Immunol 203:155–163

    Article  CAS  Google Scholar 

  17. Marcuzzi GP, Hufbauer M, Kasper HU et al (2009) Spontaneous tumour development in human papillomavirus type 8 E6 transgenic mice and rapid induction by UV-light exposure and wounding. J Gen Virol 90:2855–2864

    Article  CAS  Google Scholar 

  18. Mcbride AA (2022) Human papillomaviruses: diversity, infection and host interactions. Nat Rev Microbiol 20:95–108

    Article  CAS  Google Scholar 

  19. Neale RE, Weissenborn S, Abeni D et al (2013) Human papillomavirus load in eyebrow hair follicles and risk of cutaneous squamous cell carcinoma. Cancer Epidemiol Biomarkers Prev 22:719–727

    Article  CAS  Google Scholar 

  20. Pickering CR, Zhou JH, Lee JJ et al (2014) Mutational landscape of aggressive cutaneous squamous cell carcinoma. Clin Cancer Res 20:6582–6592

    Article  CAS  Google Scholar 

  21. Pogoda CS, Roden RB, Garcea RL (2016) Immunizing against anogenital cancer: HPV vaccines. PLoS Pathog 12:e1005587

    Article  Google Scholar 

  22. Pouyanfard S, Muller M (2017) Human papillomavirus first and second generation vaccines-current status and future directions. Biol Chem 398:871–889

    Article  CAS  Google Scholar 

  23. Pouyanfard S, Spagnoli G, Bulli L et al (2018) Minor capsid protein L2 Polytope induces broad protection against oncogenic and mucosal human papillomaviruses. J Virol 92(4):e01930–e01917. https://doi.org/10.1128/JVI.01930-17

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  24. Proby CM, Purdie KJ, Sexton CJ et al (2000) Spontaneous keratinocyte cell lines representing early and advanced stages of malignant transformation of the epidermis. Exp Dermatol 9:104–117

    Article  CAS  Google Scholar 

  25. Purdie KJ, Sexton CJ, Proby CM et al (1993) Malignant transformation of cutaneous lesions in renal allograft patients: a role for human papillomavirus. Cancer Res 53:5328–5333

    CAS  PubMed  Google Scholar 

  26. Schaper ID, Marcuzzi GP, Weissenborn SJ et al (2005) Development of skin tumors in mice transgenic for early genes of human papillomavirus type 8. Cancer Res 65:1394–1400

    Article  CAS  Google Scholar 

  27. Smola S (2020) Human papillomaviruses and skin cancer. Adv Exp Med Biol 1268:195–209

    Article  CAS  Google Scholar 

  28. Uberoi A, Yoshida S, Frazer IH et al (2016) Role of ultraviolet radiation in Papillomavirus-induced disease. PLoS Pathog 12:e1005664

    Article  Google Scholar 

  29. Viarisio D, Muller-Decker K, Accardi R et al (2018) Beta HPV38 oncoproteins act with a hit-and-run mechanism in ultraviolet radiation-induced skin carcinogenesis in mice. PLoS Pathog 14:e1006783

    Article  Google Scholar 

  30. Vinzon SE, Braspenning-Wesch I, Muller M et al (2014) Protective vaccination against papillomavirus-induced skin tumors under immunocompetent and immunosuppressive conditions: a preclinical study using a natural outbred animal model. PLoS Pathog 10:e1003924

    Article  Google Scholar 

  31. Weissenborn SJ, Nindl I, Purdie K et al (2005) Human papillomavirus-DNA loads in actinic keratoses exceed those in non-melanoma skin cancers. J Invest Dermatol 125:93–97

    Article  CAS  Google Scholar 

Download references

Danksagung

Die Autoren danken Prof. Frank Rösl (DKFZ) für die kritische Durchsicht des Manuskriptes.

Author information

Authors and Affiliations

  1. Abteilung Virale Transformationsmechanismen; Forschungsschwerpunkt „Infektion, Entzündung und Krebs“, Deutsches Krebsforschungszentrum (DKFZ), Heidelberg, Deutschland

    Daniel Hasche

  2. Institut für Virologie der Universität zu Köln, Medizinische Fakultät und Uniklinik Köln, Fürst-Pückler-Str. 56, 50935, Köln, Deutschland

    Baki Akgül

Authors
  1. Daniel Hasche
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Baki Akgül
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Baki Akgül.

Ethics declarations

Interessenkonflikt

D. Hasche und B. Akgül geben an, dass kein Interessenkonflikt besteht.

Für diesen Beitrag wurden von den Autoren keine Studien an Menschen oder Tieren durchgeführt. Für die aufgeführten Studien gelten die jeweils dort angegebenen ethischen Richtlinien.

Additional information

figure qr

QR-Code scannen & Beitrag online lesen

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Hasche, D., Akgül, B. Rolle von humanen Papillomviren (HPV) in der Entwicklung von Hautkarzinomen. Hautarzt 73, 417–425 (2022). https://doi.org/10.1007/s00105-022-04990-x

Download citation

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00105-022-04990-x

Schlüsselwörter

Keywords

Search

Navigation