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

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

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.

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Danksagung

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

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Correspondence to Baki Akgül.

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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.

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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

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

Schlüsselwörter

  • Beta-Papillomviren
  • UV-Licht
  • Immunsuppression
  • Plattenepithelkarzinome
  • Tiermodelle

Keywords

  • Betapapillomaviruses
  • UV light
  • Immunosuppression
  • Squamous cell carcinoma
  • Animal models