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Vermeidung und Therapie HPV-assoziierter Erkrankungen durch Vakzinationsprogramme

Vaccination programs for the prevention and therapy of HPV-related anogenital diseases

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Der Gynäkologe Aims and scope

Zusammenfassung

Eine persistierende Infektion mit high-risk humanen Papillomaviren (HPV) ist eine notwendige Voraussetzung für die Entstehung der schweren Präneoplasien und Neoplasien der Zervix und Vulva. Die Durchseuchung ist sehr hoch, ca. 60–70% der Frauen machen in ihrem Leben die Infektion durch, oft symptomlos. Nur ein geringer Anteil wird eine persistierende Infektion entwickeln mit dem Risiko der Entstehung eines Genitalkrebses. Die HPV-Infektion kann durch eine prophylaktische Impfung verhindert werden. Da das Virus fast ausschließlich durch Geschlechtsverkehr übertragen wird, sollte die Impfung der jungen Mädchen (und Jungen) vor Aufnahme des ersten Sexualkontaktes erfolgen.

Derzeit in Phase-III-Studien untersuchte Impfstoffe gegen HPV 16 und 18 (6, 11), die 70% der Genitalkrebse verhindern könnten, werden voraussichtlich 2007 angeboten werden. Neben der Entwicklung eines optimalen Impfstoffes ist die Erarbeitung eines wirksamen Konzeptes für die Einführung und Anwendung der Impfung in der Zielpopulation eine entscheidende Voraussetzung für deren Erfolg.

Die Entwicklung therapeutischer Impfstoffe dient der Behandlung bereits bestehender HPV-induzierter Tumoren. High-risk-HPV-infizierte Tumorzellen überexprimieren an ihrer Oberfläche die beiden Onkoproteine E6 und E7. Eine T-Zell-Immunantwort gegen diese tumorspezifischen Antigene scheint die Hauptrolle bei einer Tumorreduktion/Auslöschung zu spielen, sodass derzeit in der Entwicklung befindliche therapeutische Impfstoffe gegen E6 und E7 gerichtet sind.

Abstract

Persistent infection with high risk human papillomaviruses (HPV) is a necessary condition for the development of precursor lesions as well as cancer of the cervix or vulva. The lifetime risk of infection for women is approximately 70%, but in most cases infection is transient and asymptomatic. Only a few cases develop persistent infection with the risk of development of cervical cancer. HPV infection can be prevented by prophylactive vaccine. Since HPV infection is a sexually transmitted disease, vaccination should be given to young girls (and boys) before they become sexually active.

Prophylactive HPV vaccines, consisting of virus like particles of HPV 16, 18 (6 and 11), are designed to prevent about 70% of cervical carcinoma cases (and 90% of condyloma). They are currently being tested in phase III trials and their introduction is planned for 2007. Development of an efficient educational program for young people and the recruitment of the target population is a challenging task required for the realization of this promising vaccination strategy.

Therapeutic vaccines are under development for the clearance of established HPV related disease. HPV induced tumors are known to express two major oncoproteins, E6 and E7. A strong T-cell response against these tumor antigens seems to be an effective target. Therefore, most of the HPV therapeutic vaccines under investigation are directed against E6 and E7.

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  1. Frauenklinik, Heinrich-Heine-Universität Düsseldorf,

    M. Hampl

  2. Frauenklinik, Heinrich-Heine-Universität, Moorenstraße 5, 40225, Düsseldorf,

    M. Hampl

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Hampl, M. Vermeidung und Therapie HPV-assoziierter Erkrankungen durch Vakzinationsprogramme. Gynäkologe 39, 122–133 (2006). https://doi.org/10.1007/s00129-005-1794-x

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