Subscribe to RSS
DOI: 10.1055/s-2007-965054
Georg Thieme Verlag KG Stuttgart · New York
HPV-Infektion und Zervixkarzinom - eine Übersicht
Aktuelles zur Diagnostik und ProphylaxeHPV-Infection and Cervical Cancer - Review State of the Art in Diagnosis and ProphylaxisPublication History
Publication Date:
13 June 2007 (online)
Zusammenfassung
Die Infektion mit humanen Papillomaviren ist mit einer Inzidenz von 50 - 80 % bei 20 - 25-Jährigen sehr häufig. Die HPV-Infektion gilt als der notwendige Risikofaktor für die Entstehung des Zervixkarzinoms, der zweithäufigsten Tumorerkrankung der Frau weltweit. Dieser Übersichtsartikel gibt einen kurzen Überblick über Grundlagen der HPV-Infektion und über Aktuelles bei Diagnostik und Prophylaxe. Für die HPV-Untersuchung gibt es bisher eine eindeutige Empfehlung bei unklaren zytologischen Abstrichergebnissen, Pap III, erstmalig Pap IIID und im Rahmen der weiteren Kontrollen nach CIN-Läsionen. Der Einsatz eines primären HPV-Screenings wird aktuell diskutiert. Derzeit läuft die Suche nach neuen spezifischen Biomarkern, die im Gegensatz zu den gängigen Testmethoden auf DNA-Basis eine prognostisch ungünstige persistierende von einer harmlosen vorübergehenden Infektion unterscheiden können. Für die Impfung gegen die häufigsten HPV-Typen 16 und 18 wurden in weltweit groß angelegten Studien positive Ergebnisse erzielt. Mit der Zulassung eines Impfstoffes wurde ein wichtiger Schritt in Richtung der Primärprävention des Zervixkarzinoms getan.
Abstract
The cumulative incidence of human papillomavirus (HPV) infection is with 50 - 80% in 20 - 25-year-old women high. The HPV-infection is causally related to cervical cancer, the second most common cancer in women worldwide. This review provides a quick overview about the principles of HPV infection and state of the art in both diagnosis and prophylaxis. There is a clear standard for HPV testing as adjunct to cytology as a triage test on cases of Pap III, first time Pap IIID and following controls after CIN lesions. At present there is a discussion on primary HPV screening. There is a lot of ongoing research to detect novel specific biomarkers, which may in contrast to the existing DNA based approach distinguish persisting infections with unfavourable prognosis from harmless transient infections. Positive results have been reported from large worldwide anti HPV-16 and 18 vaccination trials. The approval of a vaccination is an important step towards primary prevention of cervical carcinoma.
Schlüsselwörter
Zervixkarzinom - HPV‐Infektion - HPV‐Screening - HPV‐Impfung
Key words
cervical cancer - HPV‐infection - HPV‐screening - HPV‐vaccination
Literatur
- 1 Bosch F X, Manos M M, Munoz N, Sherman M, Jansen A, Petro J, Schiffman M, Moreno V, Kurman R, Shak K, Group I S. Prevalence of human papillomavirus in cervical cancer: a worldwide perspective. J Natl Cancer Inst. 1995; 87 796-802
- 2 Parkin D M, Bray F, Ferlay J, Pisani P. Global cancer statistics, 2002. LA Cancer J Clin. 2005; 55 74-108
- 3 Iftner T. Zervixkarzinom. Chancen und Risiken des Früherkennungsprogramms. Geburtsh Frauenheilk. 2006; 66 196
- 4 Schiffmann M. et al . The carcinogenicity of human papillomavirus types reflects viral evolution. Virology. 2005; 337 76-84
- 5 zur Hausen H. Human papillomaviruses and their possible role in squamous cell carcinomas. Curr Top Microbiol Immunol. 1977; 186 131-156
- 6 Stoler M H, Mills S E, Gersell D J, Walker A N. Smallcell neuroendocrine carcinoma of the cervix. A human papillomavirus type18 associated cancer. Am JJ Surg Pathol. 1991; 15 28
- 7 Carr J, Gyorfi T. Human papillomavirus. Epidemiology, transmission and pathogenesis. Clin Lab Med. 2000; 20 235
-
8 Bonnez W, Reichmann R C.
Papillomaviruses. Mandell GL, Bennet JE, Dolin R Principles and Practice of Infectious Diseases. 5th ed. Philadelphia; Churchill Livingston 2000: 1630 - 9 Franco E L, Duarte-Franco E, Ferenczy A. Cervical cancer: epidemiology, prevention and the role of human papillomavirus infection. CMAJ. 2001; 164 1017
- 10 Werness B A, Levine A J, Howley P M. Association of human papillomavirus types 16 and 18 E6 proteins with p 53. Science. 1990; 248 76-79
- 11 Dyson N, Howley P M, Munger K, Harlow E. The human papilloma virus-16, E7 oncoprotein is able to bind to the retinoblastoma gene product. Science. 1989; 243 934-937
- 12 Kiyono T, Foster S A, Koop Jl, Mcdougall J K, Galloway D A, Klingelhutz A J. Both Rb/p 16ink4a inactivation and telomerase activity are required to immortalize human epithelial cells. Nature. 1998; 396 84-88
- 13 Brehm A, Miskka E A, Mccance D J, Reid J L, Bannister A J, Kouzarides T. Retinoblastome protein recruits histone deacetylase to repress transcription. Nature. 1998; 391 597-601
- 14 Conrad M, Goldstein D, Andresson T, Schlegel R. The E5 Protein of HPV16 but not HPV 6 associates efficiently with cellular growth factor receptors. Virology. 1994; 200 796-800
- 16 Schiffman M, Wheeler Cosette M. et al . A comparison of a prototype PCR assay and hybrid capture 2 for detection of carcinogenic human papillomavirus DNA in women with equivocal or mildly abnormal papanicolao smears. Am J Pathol. 2005; 124 722-732
- 17 Lorincz A T. Molecular methods for the detection of human papilloma virus infection. Obstet Gynecol Clin North [Am]. 1996; 23 707
- 18 Pirog E C, Baergen R N, Sosolow R A, Tam D, DeMattia A E, Chen Y T, Isacson C. Diagnostic Accuracy of cervical low-grade squamous intraepithelial lesions is improved with MIB‐1 immunostaining. Am J Surg Pathol. 2002; 26 70-75
- 19 Klaes R, Benner A, Friedrich T. et al . P16(ink4a) immunohistochemistry improves interobserver agreement in the diagnosis of cervical intraepithelial neoplasia. Am J Surg Pathol. 2002; 26 1389-1399
- 20 Klaes R, Friedrich T, Spikovsky D. et al . Overexpression of p 16(ink4a) as a specific marker for dysplastic and neoplastic epithelial cells of the cervix uteri. Int J Cancer. 2001; 92 276-284
- 21 Sotlar K, Stubner A, Diemer D, Menton S, Menton M, Dietz K, Wallwiener D, Kandolf R, Bultmann B. Detection of high-risk human papillomavirus E6 and E7 oncogene transcripts in cervical scrapes by nested RT-polymerase chain reaction. J Med Virol. 2004; 74 107-116
- 22 Weissenbacher E R, Schneider A, Girardi F, Gissmann L, Gross G, Heinrich J, Hillemanns P, Ikengerg H, Leodolter S, Link M, Petry K U, Schneede P, Spitzbart H. Empfehlungen zur Diagnostik und Therapie der HPV-Infektion des weiblichen Genitale; Leitlinien der Deutschen Gesellschaft für Gynäkologie und Geurtshilfe (DGGG) aus der Arbeitsgemeinschaft für Infektionen und Infektionsimmunologie in der Gynäkologie und Geburtshilfe (AGII der DGGG), European Society for Infectious Diseases in Obstetrics and Gynaecology (ESIDOG). 08/2001;. Überarbeitung in Planung
- 23 Cuzick J. et al . Overview of the European and North American studies on HPV testing in primary cervical cancer screening. Int J Cancer. 2006; 119 1095-1101
- 24 Solomon D, Schiffmann M, Tarone R. Comparison of 3 management strategies for patients with atypical squamous cells of undetermined significance: baseline results from a randomized trial. J Natl Cancer Inst. 2001; 93 293-295
- 25 Nobbenhuis M A, Meijer C J, Van Brule A J. HPV-testing improves the current guidelines on follow-up after treatment for cervical intraepithelial neoplasia. Br J Cancer. 2001; 84 796-801
- 26 Petry K U, Böhmer G, Iftner T, Davies P, Brummer O, Kühnle H. Factors associated with an increased risk of prevalent and incident grade III cervical intraepithelial neoplasia and invasive cancer among women with Papanicolao tests classified as grades I or II cervical intraepithelial neoplasia. Am J Obst and Gyn. 2002; 186 28-34
- 27 Schneider A, Hoyer H, Lotz B. et al . Screening for high grade cervical intraepithelial neoplasia and invasive cervical cancer by testing for high risk HPV, routine cytology or colposcopy. Int J Cancer. 2000; 89 529
- 28 Koutsky L A, Ault K A, Wheeler C M. et al . A controlled trial of a human papillomavirus type 16 vaccine. N Engl J Med. 2002; 347 1645
- 29 Harper D M, Franco E L, Wheeler C M. et al . Efficacy of a bivalent L1 virus-like particle vaccine in prevention of infection with human papillomavirus types 16 and 18 in young women : a randomised controlled trial. Lancet. 2004; 364 1757-1765
- 30 Villa L L. et al . Prophylactic quadrivalent human papillomavirus types 6, 11, 16 and 18 L1 virus like particle vaccine in young women: a randomised double-blind placebo-controlled multicentre phase II trial. Lancet Oncol. 2005; 6 271-278
Dr. Annette Bachmann
Universitäts-Frauenklinik
Johann Wolfgang Goethe-Universität Frankfurt
Theodor-Stern-Kai 7
60590 Frankfurt
Email: astubner@web.de