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DOI: 10.1055/s-2005-861232
30 Jahre dermatoonkologische Virologie - Papillomviren als Krebserreger
30 Years of Dermatooncological Virology - Papillomavirus as Cause of CancerPublikationsverlauf
Publikationsdatum:
31. Mai 2005 (online)
Zusammenfassung
In den vergangenen 30 Jahren wurden bestimmte Typen der sehr heterogenen humanen Papillomvirus (HPV) Familie mit spezifischen Krebserkrankungen des Menschen in Zusammenhang gebracht und inzwischen für einige weit verbreitete Krebsformen als auslösende Ursache identifiziert. Hier handelt es sich vorrangig um den Gebärmutterhalskrebs, aber auch um weitere anogenitale Krebserkrankungen, sowie um etwa ein Viertel aller Mundhöhlenkarzinome. In zunehmendem Maße zeichnet sich auch eine Beteiligung bestimmter Papillomvirus-Typen für die Auslösung von Plattenepithelkarzinomen der Haut ab. Diese Typen sind in der Lage, die durch UV-Licht bedingte ausgelöste Apoptose (den programmierten Tod der geschädigten Zelle) zu unterdrücken und damit weiteres Zellwachstum mutierter Zellen zu ermöglichen. Die so genannten „Hochrisikotypen” dieser Virusfamilie, mit den Prototypen HPV 16 und 18, erweisen sich als wirksame Karzinogene, auch wenn nur ein geringer Prozentsatz der infizierten Frauen später an Gebärmutterhalskrebs erkrankt. In der großen Mehrzahl infizierter Personen wird die Infektion über Immunmechanismen erfolgreich kontrolliert. Diese Viren besitzen eigene Krebsgene (Onkogene), deren Wirkungsmechanismus heute zunehmend besser verstanden wird. Global gesehen lassen sich etwa 13 - 15 % aller bei Frauen auftretenden Krebserkrankungen ursächlich auf Papillomvirus-Infektionen zurückführen. Inzwischen wurden wirksame vorbeugende Impfstoffe gegen die bedeutsamsten pathogenen Vertreter dieser Virusfamilie entwickelt, die in den kommenden zwei Jahren allgemein verfügbar werden dürften. Deren breite Anwendung lässt auf eine wirksame Kontrolle des Gebärmutterhalskrebses und seiner Vorstufen hoffen. Bisherige Versuche, auch therapeutisch effiziente Impfstoffe zu entwickeln, erwiesen sich bisher als weniger erfolgreich.
Abstract
During the past 30 years specific types of human papillomaviruses (HPV) have been linked to certain human cancers and have been identified as causative agents of these malignant proliferations. Primarly cancer of the cervix, but also other anogenital cancers and approximately 25 % of oral cancers are etiologically related to these infections. Increasing evidence points to an indirect role of other HPV infections in squamous cell carcinomas of the skin. Some of the latter types suppress apoptosis, caused by DNA damage due to UV exposure of the skin, and enable continued proliferation of mutated cells. Anogenital high risk types like HPV16 and 18 are effective carcinogens, although only a small percentage of infected women eventually will develop cancer of the cervix. Immunological surveillance appears to result in clearance of most of these infections. These viruses express their own oncogenes. The mechanism of their oncogenic function is presently partially understood. Globally about 13 - 15 % of all cancers in women are caused by HPV infections. Effective preventive vaccinations against the most prevalent high risk HPV types are presently in clinical trials. It is anticipated that they will become available in 2006 or 2007. It is expected that they will lead to an effective control of cervical cancer and its precursor lesions, if vaccination is applied to juveniles before onset of sexual activity. Present approaches for therapeutic vaccinations have been less successful and require further studies.
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Prof. Dr. med. Dr. h.c. mult. Harald zur Hausen
Deutsches Krebsforschungszentrum
Im Neuenheimer Feld 280 · 69120 Heidelberg
eMail: zurhausen@dkfz-heidelberg.de