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HPV-assoziierte Plattenepithelkarzinogenese

HPV-associated squamous cell carcinogenesis

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Zusammenfassung

Infektionen mit High-risk- (HR-) Typen humaner Papillomaviren (HPV) werden für die Entstehung von 7–8% aller Malignome verantwortlich gemacht. Neben dem Zervixkarzinom ist v. a. das Plattenepithelkarzinom der Anogenitalregion und des Oropharynx HR-HPV assoziiert. Die HPV-Infektion erfolgt in aller Regel durch sexuellen Kontakt. Für die Entdeckung der ätiologischen Bedeutung von HR-HPV-Infektionen in der Entstehung des Zervixkarzinoms wurde Harald zur Hausen 2008 mit dem Nobelpreis für Medizin ausgezeichnet. Mittlerweile sind prophylaktische Impfstoffe gegen HPV-16 und HPV-18, die beiden häufigsten HR-Typen, verfügbar. Auf molekularer Ebene stellt die persistierende HR-HPV-Infektion den zentralen Risikofaktor für die Entstehung HPV-assoziierter Neoplasien dar. Im Rahmen dieser Infektionen sorgt die kontinuierliche Expression der viralen Onkogene E6 und E7 für eine Inaktivierung der Zellzykluskontrolle. In den betroffenen Zellen induziert dies eine unbeschränkte Proliferationsfähigkeit und Apoptoseresistenz, führt aber auch zur Akquisition von Mutationen und genomischer Instabilität, die schließlich in der malignen Transformation und Ausbildung eines Plattenepithelkarzinoms münden können.

Abstract

About 7–8% of all human cancers are thought to be related to infections with high-risk (HR) human papilloma virus (HPV). Besides cervical cancer, especially squamous cell carcinomas of the anogenital and oropharyngeal regions are associated with HR-HPV. Transmission of HPV is due to sexual activity. Harald zur Hausen was awarded in 2008 with the Nobel price in medicine for the establishment of a causal link between certain HPV infections and cervical cancer. Meanwhile potent prophylactic vaccines are available to prevent infections with HPV-16 and HPV-18, the two most frequently observed HR HPV types worldwide. On molecular grounds a persistent HPV infection is the central risk factor for the development of HPV-associated neoplasias. Continued expression of the viral E6 and E7 oncogenes disrupts cell cycle control mechanisms in infected cells, thereby gaining limitless proliferative capacity and resistance against apoptotic signals. However acquisition of mutations and genomic instability might cause malignant transformation in these cells.

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  1. Pathologisches Institut, Ludwig-Maximilians-Universität München, Thalkirchner Straße 36, 80337, München, Deutschland

    G. Assmann &  K. Sotlar

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Assmann, G., Sotlar, K. HPV-assoziierte Plattenepithelkarzinogenese. Pathologe 32, 391–398 (2011). https://doi.org/10.1007/s00292-011-1442-2

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