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DOI: 10.1055/s-0043-100427
HPV-Infektionen: Diagnostik und Impfung
Publikationsverlauf
Publikationsdatum:
06. März 2017 (online)
Humane Papillomaviren (HPV) sind doppelsträngige DNA-Viren, von denen > 200 verschiedene Subtypen bekannt sind. Die HPV-Subtypen lassen sich je nach malignem Potenzial einer Infektion entweder in Niedrigrisikosubtypen (6, 11, 40, 42, 43, 44, etc.) oder Hochrisikosubtypen (6, 18, 31, 33, 35, 39 etc.) einteilen. Die häufigsten Hochrisikosubtypen sind HPV 16 und 18 (verantwortlich für 70 % der Zervixkarzinome) [1]. Die Infektion mit HPV Niedrigrisikosubtypen kann zu gutartigen Feigwarzen oder Larynxpapillomatose führen, während eine Infektion mit Hochrisikosubtypen zu invasiven Karzinomen insbesondere dem Zervixkarzinom aber auch Karzinomen des Mund-Rachenraums, Vagina-, Vulva-, Penis- und Analkarzinomen führen kann [2].
Bei Zervixkarzinomen lässt sich in 99,7 % DNA von Hochrisiko-HPV nachweisen. Bereits 1976 postulierte Harald zur Hausen, dass die Infektion mit HPV einen essenziellen Faktor bei der Pathogenese des Zervixkarzinoms darstellt, wofür er 2008 mit dem Medizin-Nobelpreis ausgezeichnet wurde.
International variiert die Prävalenz von HPV-Infektionen in Abhängigkeit von Kulturkreis, sozialer Schicht und Alter und liegt zwischen 3 % –50 % [3] [4]. In Westeuropa wird die Prävalenz von humanen Papillomaviren bei Frauen auf ca. 9 % geschätzt, wobei es einen Altersgipfel bei 20 – 24 Jahren mit einer Prävalenz von 29 – 45 % gibt [5] [6] [7].
Infektionen mit HPV finden häufig schon bei den ersten Sexualkontakten statt [8]. Kondome stellen keinen absoluten Schutz vor der Übertragung dar, können aber vermutlich die Wahrscheinlichkeit einer Übertragung verringern [9]. Bislang wurde eine Reihe von Risikofaktoren für eine HPV-Infektion identifiziert ([Tab. 1]) [10] [11] [12] [13].
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Literatur
- 1 Bzhalava D. Guan P. Franceschi S. et al. A systematic review of the prevalence of mucosaland cutaneous human papillomavirus types. Virology 2013; 445: 224-231
- 2 Cavalar M. Beyer D. Humane Papillomaviren Karzinogenese, Nachweismethoden, Impfstrategien. Gynäkologe 2016; 49: 311-318
- 3 Schneider A. Hoyer H. Lotz B. et al. Screening for high-grade cervical intra-epithelial neoplasia and cancer by testing for high-risk HPV, routine cytology or colposcopy. Int J Cancer 2000; 89: 529-534
- 4 Van Den Brule AJC. Walboomers JMM. Maine MD. et al. Difference in prevalence of human papillomavirus genotypes in cytomorphologically normal cervical smears is associated with a history of cervical intraepithelial neoplasia. Int J Cancer 1991; 48: 404-408
- 5 Bruni L. Diaz M. Castellsague X. et al. Cervical human papillomavirus prevalence in 5 continents: meta-analysis of 1 million women with normal cytological findings. J Infect Dis 2010; 202: 1789-1799
- 6 de Sanjose S. Diaz M. Castellsague X. et al. Worldwide prevalence and genotype distribution of cervical human papillomavirus DNA in women with normal cytology: a meta-analysis. Lancet Infect Dis 2007; 7: 453-459
- 7 De Vuyst H. Clifford G. Li N. et al. HPV infection in Europe. Europ J Cancer 2009; 45: 2632-2639
- 8 Braly P. Preventing cervical cancer. Nat Med 1996; 2: 749-751
- 9 Manhart LE. Koutsky LA. Do condoms prevent genital HPV infection, external genital warts, or cervical neoplasia? A meta-analysis. Sex Transm Dis 2002; 29: 725-735
- 10 Gadducci A. Barsotti C. Cosio S. et al. Smoking habit, immune suppression, oral contraceptive use, and hormone replacement therapy use and cervical carcinogenesis: a review of the literature. Gynecol Endocrinol 2011; 27: 597-604
- 11 Plummer M. Herrero R. Franceschi S. et al. Smoking and cervical cancer: pooled analysis of the IARC multi-centric case-control study. Cancer Causes Contr 2003; 14: 805-814
- 12 Castellsague X. Munoz N. Chapter 3: Cofactors in human papillomavirus carcinogenesis – role of parity, oral contraceptives, and tobacco smoking. J Natl Cancer Inst Monogr 2003; 31: 20-28
- 13 Appleby P. Beral V. Berrington de González A. et al. Cervical cancer and hormonal contraceptives: collaborative reanalysis of individual data for 16573 women with cervical cancer and 35509 women without cervical cancer from 24 epidemiological studies. Lancet 2007; 370: 1609-1621
- 14 Doorbar J. Quint W. Banks L. et al. The biology and life-cycle of human papillomaviruses. Vaccine 2012; 30: 55-70
- 15 Schiffman M. Castle PE. Jeronimo J. et al. Human papillomavirus and cervical cancer. Lancet 2007; 370: 890-907
- 16 Cullen AP. Reid R. Campion M. et al. Analysis of the physical state of different human papillomavirus DNAs in intraepithelial and invasive cervical neoplasm. J Virol 1991; 65: 606-612
- 17 Hopman AH. Smedts F. Dignef W. et al. Transition of high-grade cervical intraepithelial neoplasia to micro-invasive carcinoma is characterized by integration of HPV 16/18 and numerical chromosome abnormalities. J Pathol 2004; 202: 23-33
- 18 Matsukura T. Sugase M. Pitfalls in the epidemiologic classification of human papillomavirus types associated with cervical cancer using polymerase chain reaction: driver and passenger. Int J Gynecol Cancer 2008; 18: 1042-1050 . Erratum in: Int J Gynecol Cancer 2008; 18: 1388
- 19 Ganguly N. Parihar SP. Human papillomavirus E6 and E7 oncoproteins as risk factors for tumorigenesis. J Biosci 2009; 34: 113-123
- 20 Dickson EL. Vogel RI. Geller MA. et al. Cervical cytology and multiple type HPV infection: a study of 8182 women ages 31–65. Gynecol Oncol 2014; 133: 405-408
- 21 Östor AG. Natural history of cervical intraepithelial neoplasia: a critical review. Int J Gynecol Pathol 1993; 12: 186-192
- 22 Cuzick J. Clavel C. Petry KU. 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
- 23 Coste J. Cochand-Priollet B. Le GC. et al. Cross sectional study of conventional cervical smear, monolayer cytology, and human papillomavirus DNA testing for cervical cancer screening. Brit Med J 2003; 326: 733
- 24 Mayrand MH. Duarte-Franco E. Rodrigues I. et al. Human papillomavirus DNA versus Papanicolaou screening tests for cervical cancer. N Engl J Med 2007; 357: 1579-1588
- 25 Bauer HM. Ting Y. Greer CE. et al. Genital human papillomavirus infection in female university students as determined by a PCR-based method. JAMA 1991; 265: 472-477
- 26 Castle PE. Stoler MH. Wright TC. et al. Performance of carcinogenic human papillomavirus (HPV) testing and HPV16 or HPV18 genotyping for cervical cancer screening of women aged 25 years and older: a subanalysis of the ATHENA study. Lancet Oncol 2011; 12: 880-890
- 27 Poljak M. Kocjan BJ. Ostrbenk A. et al. Commercially available molecular tests for human papillomaviruses (HPV): 2015 update. J Clin Virol 2016; 76: S3-S13
- 28 Meijer CJ. Berkhof J. Castle PE. et al. Guidelines for human papillomavirus DNA test requirements for primary cervical cancer screening in women 30 years and older. Int J Cancer 2009; 124: 516-520
- 29 Elfgren K. Elfstrom KM. Naucler P. et al. Management of women with human papillomavirus persistence: long-term follow-up of a randomized clinical trial. Am J Obstet Gynecol 2016; DOI: 10.1016/j.ajog.2016.10.042.
- 30 Schmitt M. Depuydt C. Benoy I. et al. Multiple human papillomavirus infections with high viral loads are associated with cervical lesions but do not differentiate grades of cervical abnormalities. J Clin Microbiol 2013; 51: 1458-1464
- 31 Delere Y. Remschmidt C. Leuschner J. et al. Human Papillomavirus prevalence and probable first effects of vaccination in 20 to 25 year-old women in Germany: a population-based cross-sectional study via home-based self-sampling. BMC Infect Dis 2014; 14: 87
- 32 Ganguly N. Parihar SP. Human papillomavirus E6 and E7 oncoproteins as risk factors for tumorigenesis. J Biosci 2009; 34: 113-123
- 33 Jeon S. Lambert PF. Integration of human papillomavirus type 16 DNA into the human genome leads to increased stability of E6 and E7 mRNAs: implications for cervical carcinogenesis. Proc Natl Acad Sci USA 1995; 92: 1654-1658
- 34 Jeon S. len-Hoffmann BL. Lambert PF. Integration of human papillomavirus type 16 into the human genome correlates with a selective growth advantage of cells. J Virol 1995; 69: 2989-2997
- 35 Karlsen F. Kalantari M. Jenkins A. et al. Use of multiple PCR primer sets for optimal detection of human papillomavirus. J Clin Microbiol 1996; 34: 2095-2100
- 36 Romanczuk H. Howley PM. Disruption of either the E1 or the E2 regulatory gene of human papillomavirus type 16 increases viral immortalization capacity. Proc Natl Acad Sci USA 1992; 89: 3159-3163
- 37 Morris BJ. Cervical human papillomavirus screening by PCR: advantages of targeting the E6 / E7 region. Clin Chem Lab Med 2005; 43: 1171-1177
- 38 Tjalma WA. Depuydt CE. Cervical cancer screening: which HPV test should be used – L1 or E6 / E7?. Eur J Obstet Gynecol Reprod Biol 2013; 170: 45-46
- 39 Speich N. Schmitt C. Bollmann R. et al. Human papillomavirus (HPV) study of 2916 cytological samples by PCR and DNA sequencing: genotype spectrum of patients from the west German area. J Med Microbiol 2004; 53: 125-128
- 40 Castle PE. Dockter J. Giachetti C. et al. A cross-sectional study of a prototype carcinogenic human papillomavirus E6 / E7 messenger RNA assay for detection of cervical precancer and cancer. Clin Cancer Res 2007; 13: 2599-2605
- 41 Villa LL. Costa RL. Petta CA. 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 efficacy trial. Lancet Oncol 2005; 6: 271-278
- 42 Harper DM. Franco EL. Wheeler C. 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
- 43 Giannini SL. Hanon E. Moris P. et al. Enhanced humoral and memory B cellular immunity using HPV16/18 L1 VLP vaccine formulated with the MPL/aluminium salt combination (AS04) compared to aluminium salt only. Vaccine 2006; 24: 5937-5949
- 44 Fachinformation GARDASIL® 9. sanofi-pasteur MSD 10.07.2016. Abgerufen von www.impfservice.de/fileadmin/user_upload/pdfs/Fachinformationen/FI_Gardasil9_05-2016_RLFS.pdf
- 45 Robert Koch-Institut. Impfung gegen humane Papillomaviren (HPV) für Mädchen von 12 bis 17 Jahren – Empfehlung und Begründung. Epidemiologisches Bulletin 2007; 12: 99
- 46 Joura EA. Garland SM. Paavonen J. et al. Effect of the human papillomavirus (HPV) quadrivalent vaccine in a subgroup of women with cervical and vulvar disease: retrospective pooled analysis of trial data. Brit Med J 2012; 344: e1401
- 47 Poethko-Müller C. Buttmann-Schweiger N. KiGGS Study Group HPV vaccination coverage in German girls: results of the KiGGS study: first follow-up (KiGGS Wave 1). Bundesgesundheitsblatt Gesundheitsforschung Gesundheitsschutz 2014; 57: 869-877
- 48 Ali H. Guy RJ. Wand H. et al. Decline in in-patient treatments of genital warts among young Australians following the national HPV vaccination program. BMC Infect Dis 2013; 13: 140
- 49 Donovan B. Franklin N. Guy R. et al. Quadrivalent human papillomavirus vaccination and trends in genital warts in Australia: analysis of national sentinel surveillance data. Lancet Infect Dis 2011; 11: 39-44
- 50 Fairley CK. Hocking JS. Gurrin LC. et al. Rapid decline in presentations of genital warts after the implementation of a national quadrivalent human papillomavirus vaccination programme for young women. Sex Transm Infect 2009; 85: 499-502
- 51 Read TR. Hocking JS. Chen MY. et al. The near disappearance of genital warts in young women 4 years after commencing a national human papillomavirus (HPV) vaccination programme. Sex Transm Infect 2011; 87: 544-547
- 52 Gross G. et al. Impfprävention HPV-assoziierter Neoplasien. 2013 Abgerufen von: www.awmf.org/leitlinien/detail/ll/082-002.html
- 53 Brotherton JM. Fridman M. May CL. et al. Early effect of the HPV vaccination programme on cervical abnormalities in Victoria, Australia: an ecological study. Lancet 2011; 377: 2085-2092