European Journal of Pediatrics

, Volume 170, Issue 3, pp 309–321

Position paper—HPV and the primary prevention of cancer; improving vaccine uptake by paediatricians

  • José Ramet
  • Diego van Esso
  • Zsofia Meszner
  • on behalf of the European Academy of Paediatrics Scientific Working Group on Vaccination
Review
  • 344 Downloads

Abstract

A large proportion of sexually active adults are infected with the human papillomaviruses (HPVs). Although largely asymptomatic, some types of HPVs (HPV-16, HPV-18) which infect the genitalia are known to cause cancers, including cervical cancer. Cervical cancer is an important public health concern and is the second most clinically important cancer to breast cancer in women aged 15–44 years. Until recently, cervical cancer strategies focussed on screening. However, as adolescents become sexually active at a much younger age, the focus is on the use of vaccination as an effective measure to prevent progression of HPV infection to cancer. HPV is also involved in the aetiology of cancers of the anus, vagina, vulva and penis as well as genital warts and laryngeal papillomatosis in young children. Primary prevention through vaccination is now possible in Europe using either the quadrivalent HPV vaccine, Gardasil® (Sanofi Pasteur MSD), or the bivalent HPV vaccine, Cervarix® (GSK), which are both highly immunogenic, with their effects persisting for at least 5 years. HPV vaccines are well tolerated, with serious vaccine-related events occurring in less than 0.1% of patients for both vaccines. Here, we review the possibilities for utilising vaccination programmes alongside current cervical cancer screening in comprehensive cervical cancer prevention programmes. The European Academy of Paediatrics Scientific Working Group on Vaccination concluded that the use of HPV vaccines will have a significant impact in primary prevention of cancers and other HPV-related disease.

Keywords

Cervical cancer Human papillomavirus Vaccination Quadrivalent HPV vaccine Bivalent HPV vaccine Paediatrics 

Abbreviations

HPV

Human papillomavirus

IARC

International Agency for Research on Cancer

HSIL

High-grade squamous intraepithelial lesion

VIN

Vulvar intraepithelial neoplasia

VaIN

Vaginal intraepithelial neoplasia

AAHS

Amorphous aluminium hydroxyphosphate sulphate adjuvant

GMT

Geometric mean titre

AIS

Adenocarcinoma in situ

References

  1. 1.
    Agence française de sécurité sanitaire des produits de santé (2008) Gardasil®: first assessment of risk surveillance in France. Press release, 15 JulyGoogle Scholar
  2. 2.
    Anttila A, von Karsa L, Aasmaa A, Fender M, Patnick J, Rebolj M, Nicula F, Vass L, Valerianova Z, Voti L, Sauvaget C, Ronco G (2009) Cervical cancer screening policies and coverage in Europe. Eur J Cancer 45(15):2649–2658PubMedCrossRefGoogle Scholar
  3. 3.
    Armstrong LR, Derkay CS, Reeves WC, the RRP Task Force (1999) Initial results from the national registry for juvenile-onset recurrent respiratory papillomatosis. Arch Otol Head Neck Surg 125:743–748Google Scholar
  4. 4.
    Ault KA, FUTURE II Study Group (2007) Effect of prophylactic human papillomavirus L1 virus-like particle vaccine on risk of cervical intraepithelial neoplasia grade 2, grade 3, and adenocarcinoma in situ: a combined analysis of four clinical trials. Lancet 369:1861–1968CrossRefGoogle Scholar
  5. 5.
    Australian Government, Department of Health and Aging Therapeutic Goods Administration (2008) Human papillomavirus vaccine (GARDASIL). http://www.tga.gov.au/alerts/medicines/gardasil.htm. Accessed 27 July 2010
  6. 6.
    Barr E, Tamms G (2007) Quadrivalent human papillomavirus vaccine. Clin Infect Dis 45:609–617PubMedCrossRefGoogle Scholar
  7. 7.
    Block SL, Nolan T, Sattler C et al (2006) Comparison of the immunogenicity and reactogenicity of a prophylactic quadrivalent human papillomavirus (types 6, 11, 16, and 18) L1 virus-like particle vaccine in male and female adolescents and young adult women. Pediatrics 118:2135–2145PubMedCrossRefGoogle Scholar
  8. 8.
    BMGF (2006) Recommendations of the Superior Austrian Medical Council. Vaccination Committee, 21 November, http://www.bmgf.gv.at. Accessed 27 July 2010
  9. 9.
    Bosch FX, de Sanjosé S (2003) Chapter 1: human papillomavirus and cervical cancer—burden and assessment of causality. J Natl Cancer Inst Monogr 31:3–13PubMedGoogle Scholar
  10. 10.
    Bosch FX, Lorincz A, Muñoz N, Meijer CJLM, Shah KV (2002) The causal relation between human papillomavirus and cervical cancer. J Clin Pathol 55:244–265PubMedGoogle Scholar
  11. 11.
    Böttiger M, Forsgren M (1997) Twenty years’ experience of rubella vaccination in Sweden: 10 years of selective vaccination (of 12-year-old girls and of women postpartum) and 13 years of a general two-dose vaccination. Vaccine 15:1538–1544PubMedCrossRefGoogle Scholar
  12. 12.
    Bozon M (2003) At what age do women and men have their first sexual intercourse? World comparisons and recent trends. Popul Soc 391:1–4Google Scholar
  13. 13.
    Bray F, Carstensen B, Moller H, Zappa M, Zakelj MP, Lawrence G, Hakama M, Weiderpass E (2005) Incidence trends of adenocarcinoma of the cervix in 13 European countries. Cancer Epidemiol Biomark Prev 14:2191–2199CrossRefGoogle Scholar
  14. 14.
    Brown DR, Schroeder JM, Bryan JT, Stoler MH, Fife KH (1999) Detection of multiple human papillomavirus types in condylomata acuminata lesions from otherwise healthy and immunosuppressed patients. J Clin Microbiol 37:3316–3322PubMedGoogle Scholar
  15. 15.
    Brown DR, Shew ML, Qadadri B et al (2005) A longitudinal study of genital human papillomavirus infection in a cohort of closely followed adolescent women. J Infect Dis 191:182–192PubMedCrossRefGoogle Scholar
  16. 16.
    Castellsagué X, Munoz N (2003) Chapter 3: cofactors in human papillomavirus carcinogenesis: role of parity, oral contraceptives, and tobacco smoking. J Natl Cancer Inst Monogr 20–28Google Scholar
  17. 17.
    Castellsagué X, Díaz M, de Sanjosé S et al (2006) Worldwide human papillomavirus etiology of cervical adenocarcinoma and its cofactors: implications for screening and prevention. J Natl Cancer Inst 98:303–315PubMedCrossRefGoogle Scholar
  18. 18.
    Centers for Disease Control (2008) Reports of health concerns following HPV vaccination. HPV vaccine safety. http://www.cdc.gov/vaccinesafety/Vaccines/HPV/gardasil.html. Accessed 27 July 2010
  19. 19.
    Cheng S, Schmidt-Grimminger DC, Murant T, Broker TR, Chow LT (1995) Differentiation-dependent up-regulation of the human papillomavirus E7 gene reactivates cellular DNA replication in suprabasal differentiated keratinocytes. Genes Dev 9:2335–2349PubMedCrossRefGoogle Scholar
  20. 20.
    Clifford GM, Gallus S, Herrero R et al (2005) Worldwide distribution of human papillomavirus types in cytologically normal women in the International Agency for Research on Cancer HPV prevalence surveys: a pooled analysis. Lancet 366:991–998PubMedCrossRefGoogle Scholar
  21. 21.
    Clifford G, Franceschi S, Diaz M, Muñoz N, Villa LL (2006) Chapter 3: HPV type-distribution in women with and without cervical neoplastic diseases. Vaccine 24(Suppl 3):S26–S34CrossRefGoogle Scholar
  22. 22.
    Collins S, Mazloomzadeh S, Winter H et al (2002) High incidence of cervical human papillomavirus infection in women during their first sexual relationship. BJOG 109:96–98PubMedCrossRefGoogle Scholar
  23. 23.
    Daling JR, Madeleine MM, Johnson LG et al (2004) Human papillomavirus, smoking and sexual practices in the etiology of anal cancer. Cancer 101:270–280PubMedCrossRefGoogle Scholar
  24. 24.
    de Sanjosé S, Diaz M, Castellsagué X et al (2007) Worldwide prevalence and genotype distribution of cervical human papillomavirus DNA in women with normal cytology: a meta-analysis. Lancet Infect Dis 7:453–459PubMedCrossRefGoogle Scholar
  25. 25.
    De Villiers EM (2001) Taxonomic classification of papillomaviruses. Papillomavirus Rep 12:57–67Google Scholar
  26. 26.
    Derkay CS (1995) Task force on recurrent respiratory papillomas. A preliminary report. Arch Otol Head Neck Surg 121:1386–1391Google Scholar
  27. 27.
    Doorbar J (2006) Molecular biology of human papillomavirus infection and cervical cancer. Clin Sci (Lond) 110:525–541CrossRefGoogle Scholar
  28. 28.
    European Medicines Agency (2008) EMEA statement on the safety of Gardasil. 24 JanuaryGoogle Scholar
  29. 29.
    FDA (2009) Approval letter—Gardasil October 16, 2009. http://www.fda.gov/BiologicsBloodVaccines/Vaccines/ApprovedProducts/ucm186991.htm. Accessed 27 July 2010
  30. 30.
    Ferlay J, Bray F, Pisani P et al (eds) (2004) GLOBOCAN 2002: cancer incidence, mortality and prevalence worldwide. IARC Cancer Base No.5. version 2.0. IARC, LyonGoogle Scholar
  31. 31.
    FitzSimons D, Vorsters A, Hoppenbrouwers K, Van Damme P (2007) Prevention and control of viral hepatitis through adolescent health programmes in Europe. Vaccine 25:8651–8659PubMedCrossRefGoogle Scholar
  32. 32.
    Garland SM, Hernandez-Avila M, Wheeler CM et al (2007) Quadrivalent vaccine against human papillomavirus to prevent anogenital diseases. N Engl J Med 356:1928–1943PubMedCrossRefGoogle Scholar
  33. 33.
    Giuliano AR, Harris R, Sedjo RL et al (2002) Incidence, prevalence, and clearance of type-specific human papillomavirus infections: the Young Women’s Health Study. J Infect Dis 186:462–469PubMedCrossRefGoogle Scholar
  34. 34.
    GlaxoSmithKline Biologicals s.a. (2008) Cervarix summary of product characteristics. AugustGoogle Scholar
  35. 35.
    Hampl M, Sarajuuri H, Wentzensen N et al (2006) Effect of human papillomavirus vaccines on vulvar, vaginal, and anal intraepithelial lesions and vulvar cancer. Obstet Gynecol 108:1361–1368PubMedCrossRefGoogle Scholar
  36. 36.
    Harper DM, Franco EL, Wheeler C et al (2004) 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 364:1757–1765PubMedCrossRefGoogle Scholar
  37. 37.
    Harper DM, Franco EL, Wheeler C et al (2006) sustained efficacy up to 4.5 years of a bivalent L1 virus-like particle vaccine against human papillomavirus types 16 and 18: follow-up from a randomised control trial. Lancet 367:1247–1255PubMedCrossRefGoogle Scholar
  38. 38.
    Ho GY, Bierman R, Beardsley L et al (1998) Natural history of cervicovaginal papillomavirus infection in young women. N Engl J Med 338:423–428PubMedCrossRefGoogle Scholar
  39. 39.
    Joura EA, Leodolter S, Hernandez-Avila M et al (2007) Efficacy of a quadrivalent prophylactic human papillomavirus (types 6, 11, 16, and 18) L1 virus-like-particle vaccine against high-grade vulval and vaginal lesions: a combined analysis of three randomised clinical trials. Lancet 369:1693–1702PubMedCrossRefGoogle Scholar
  40. 40.
    Joura E, FUTURE I and II Study Group (2008) Sustained protection by quadrivalent HPV (type 6, 11, 16, 18) vaccine through 4 years against HPV 6/11/16/18-related cervical intraepithelial neoplasia grade 2/3 (CIN2/3) and adenocarcinoma (AIS) of the cervix. Clinical Symposium on Cervical Cancer, presented at the 19th International Conference on Anti-cancer Treatment, Paris, France, 5–8 February (Abstract)Google Scholar
  41. 41.
    Judson PL, Habermann EB, Baxter NN et al (2006) Trends in the incidence of invasive and in situ vulvar carcinoma. Obstet Gynecol 107:1018–1022PubMedCrossRefGoogle Scholar
  42. 42.
    Kjaer SK, Munk C, Winther JF et al (2005) Acquisition and persistence of human papillomavirus infection in younger men: a prospective follow-up study among Danish soldiers. Cancer Epidemiol Biomark Prev 14:1528–1533CrossRefGoogle Scholar
  43. 43.
    Kjaer SK, Sigurdsson K, Iversen O-E, Hernandez-Avila M, Wheeler CM, Perez G, Brown DR, Koutsky LA, Tay EH, Garcia P, Ault KA, Garland SM, Leodolter S, Olsson S-E, Tang GWK, Ferris DG, Paavonen J, Lehtinen M, Steben M, Bosch FX, Dillner J, Joura EA, Majewski S, Munoz N, Myers ER, Villa LL, Taddeo FJ, Roberts C, Tadesse A, Bryan J, Maansson R, Lu S, Vuocolo S, Hesley TM, Saah A, Barr E, Haupt RM (2009) A pooled analysis of continued prophylactic efficacy of quadrivalent human papillomavirus (types 6/11/16/18) vaccine against high-grade cervical and external genital lesions. Cancer Prev Res 2:868–878CrossRefGoogle Scholar
  44. 44.
    Lacey CJN, GARDASIL Phase III Investigators (2008) Continued efficacy of quadrivalent HPV (types 6/11/16/18) L1 VLP vaccine in preventing cervical or external genital disease: 4 years of follow-up. 20th European College of Obstetrics and Gynecology, Lisbon, Portugal, 4–8 March (Abstract)Google Scholar
  45. 45.
    Longworth MS, Laimins LA (2004) Pathogenesis of human papillomaviruses in differentiating epithelia. Microbiol Mol Biol Rev 68:362–372PubMedCrossRefGoogle Scholar
  46. 46.
  47. 47.
    Middleton K, Peh W, Southern S et al (2003) Organization of human papillomavirus productive cycle during neoplastic progression provides a basis for selection of diagnostic markers. J Virol 77:10186–10201PubMedCrossRefGoogle Scholar
  48. 48.
    Moscicki AB, Shiboski S, Broering J et al (1998) The natural history of human papillomavirus infection as measured by repeated DNA testing in adolescent and young women. J Pediatr 132:277–284PubMedCrossRefGoogle Scholar
  49. 49.
    Münger K, Howley PM (2002) Human papillomavirus immortalization and transformation functions. Virus Res 89:213–228PubMedCrossRefGoogle Scholar
  50. 50.
    Münger K, Baldwin A, Edwards KM et al (2004) Mechanisms of human papillomavirus-induced oncogenesis. J Virol 78:11451–11460PubMedCrossRefGoogle Scholar
  51. 51.
    Muñoz N, Bosch FX, de Sanjosé S et al (2003) Epidemiologic classification of human papillomavirus types associated with cervical cancer. N Engl J Med 348:518–527PubMedCrossRefGoogle Scholar
  52. 52.
    Muñoz N, Bosch FX, Castellsagué X et al (2004) Against which human papillomavirus types shall we vaccinate and screen? The international perspective. Int J Cancer 111:278–285PubMedCrossRefGoogle Scholar
  53. 53.
    Muñoz N, Méndez F, Posso H et al (2004) Incidence, duration, and determinants of cervical human papillomavirus infection in a cohort of Columbian women with normal cytological results. J Infect Dis 190:2077–2087PubMedCrossRefGoogle Scholar
  54. 54.
    Muñoz N, Castellsagué X, Berrington de González A, Gissmann L (2006) Chapter 1: HPV in the etiology of human cancer. Vaccine 24(Suppl 3):S1–S10CrossRefGoogle Scholar
  55. 55.
    Olsson SE, Villa LL, Costa RL, Petta CA et al (2007) Induction of immune memory following administration of a prophylactic quadrivalent human papillomavirus (HPV) types 6/11/16/18 L1 virus-like particle (VLP) vaccine. Vaccine 25:4931–4939PubMedCrossRefGoogle Scholar
  56. 56.
    Oster NV, McPhillips-Tangum CA, Averhoff F, Howell K (2005) Barriers to adolescent immunization: a survey of family physicians and pediatricians. J Am Board Fam Pract 18:13–19PubMedCrossRefGoogle Scholar
  57. 57.
    Paavonen J, Jenkins D, Bosch FX et al (2007) Efficacy of a prophylactic adjuvanted bivalent L1 virus-like-particle vaccine against infection with human papillomavirus types 16 and 18 in young women: an interim analysis of a phase III double-blind, randomised controlled trial. Lancet 369:2161–2170PubMedCrossRefGoogle Scholar
  58. 58.
    Paavonen J, Naud P, Salmeron J et al (2009) Efficacy of human papillomavirus (HPV)-16/18 AS04-adjuvanted vaccine against cervical infection and precancer caused by oncogenic HPV types (PATRICIA): final analysis of a double-blind, randomised study in young women. Lancet 374:301–314PubMedCrossRefGoogle Scholar
  59. 59.
    Parkin DM, Whelan SL, Ferlay J, Teppo L, Thomas DB (2002) Cancer incidence in five continents, vol. VIII. IARC Scientific Publications no. 155. IARC, LyonGoogle Scholar
  60. 60.
    Pedersen C, Petaja T, Strauss G et al (2007) Immunization of early adolescent females with human papillomavirus type 16 and 18 L1 virus-like particle vaccine containing AS04 adjuvant. J Adolesc Health 40:564–571PubMedCrossRefGoogle Scholar
  61. 61.
    Peh WL, Middleton K, Christensen N et al (2002) Life cycle heterogeneity in animal models of human papillomavirus-associated disease. J Virol 76:10401–10416PubMedCrossRefGoogle Scholar
  62. 62.
    Peto J, Gilham C, Fletcher O, Matthews FE (2004) The cervical cancer epidemic that screening has prevented in the UK. Lancet 364:249–256PubMedCrossRefGoogle Scholar
  63. 63.
    Quinn M, Babb P, Jones J, Allen E, on behalf of the United Kingdom Association of Cancer Registries (1999) Effect of screening on incidence of and mortality from cancer or cervix in England: evaluation based on routinely collected statistics. BMJ 318:904–908PubMedGoogle Scholar
  64. 64.
    Reeves WC, Ruparelia SS, Swanson KI et al (2003) National registry for juvenile-onset recurrent respiratory papillomatosis. Arch Otolaryngol Head Neck Surg 129:976–982PubMedCrossRefGoogle Scholar
  65. 65.
    Reimers LL, Anderson WF, Rosenberg PS, Henson DE, Castle PE (2009) Etiologic heterogeneity for cervical carcinoma by histopathologic type, using comparative age-period-cohort models. Cancer Epidemiol Biomark Prev 18:792–800CrossRefGoogle Scholar
  66. 66.
    Reisinger KS, Block SL, Lazcano-Ponce E et al (2007) Safety and persistent immunogenicity of a quadrivalent human papillomavirus types 6, 11, 16, 18 L1 virus-like particle vaccine in preadolescents and adolescents: a randomized controlled trial. Pediatr Infect Dis J 26:201–209PubMedCrossRefGoogle Scholar
  67. 67.
    Richardson H, Kelsall G, Tellier P et al (2003) The natural history of type-specific human papillomavirus infections in female university students. Cancer Epidemiol Biomark Prev 12:485–490Google Scholar
  68. 68.
    Ross J, Godeau E, Dias S (2004) Sexual health. In: Currie C, Roberts C, Morgan A, et al. (eds) Young people’s health in context. Health behaviour in School-aged Children (HSBC) study: international report from the 2001/2002 survey. Health policy for children and adolescents, no. 4. World Health Organization, pp 153–160Google Scholar
  69. 69.
    Rubin MA, Kleter B, Zhou M et al (2001) Detection and typing of human papillomavirus DNA in penile carcinoma: evidence for multiple independent pathways of penile carcinogenesis. Am J Pathol 159:1211–1218PubMedCrossRefGoogle Scholar
  70. 70.
    Sanofi Pasteur MSD (2008) Gardasil summary of product characteristics. SeptemberGoogle Scholar
  71. 71.
    Schiffman M, Herrero R, DeSalle R et al (2005) The carcinogenicity of human papillomavirus types reflects viral evolution. Virology 337:76–84PubMedCrossRefGoogle Scholar
  72. 72.
    Silverberg MJ, Thorsen P, Lindeberg H, Grant LA, Shah KV (2003) Condyloma in pregnancy is strongly predictive of juvenile-onset recurrent respiratory papillomatosis. Obstet Gynecol 101:645–652PubMedCrossRefGoogle Scholar
  73. 73.
    Silverberg MJ, Thorsen P, Lindeberg H et al (2004) Clinical course of recurrent respiratory papillomatosis in Danish children. Arch Otolaryngol Head Neck Surg 130:711–716PubMedCrossRefGoogle Scholar
  74. 74.
    Smith HO, Tiffany MF, Qualls CR, Key CR (2000) The rising incidence of adenocarcinoma relative to squamous cell carcinoma of the uterine cervix in the United States—a 24-year population-based study. Gynecol Oncol 78:97–105PubMedCrossRefGoogle Scholar
  75. 75.
    Smith JS, Lindsay L, Hoots B et al (2007) Human papillomavirus type distribution in invasive cervical cancer and high-grade cervical lesions: a meta-analysis update. Int J Cancer 121:621–632PubMedCrossRefGoogle Scholar
  76. 76.
    Stanley M (2006) Immune responses to human papillomavirus. Vaccine 24(Suppl 1):S106–S113CrossRefGoogle Scholar
  77. 77.
    The FUTURE II Study Group (2007) Quadrivalent vaccine against human papillomavirus to prevent high-grade cervical lesions. N Engl J Med 356:1915–1927CrossRefGoogle Scholar
  78. 78.
    The Protocol 024 Investigators (2008) An open-label, randomized, multicenter study of the safety, tolerability, and immunogenicity of a quadrivalent HPV 6/11/16/18 vaccine (GARDASIL™) given concomitantly with REPEVAX™ in healthy adolescents 11–17 years of age. In: 6th European Conference of Infectious Diseases in Obstetrics and Gynecology, 28–31 August, Leuven, Belgium (Abstract)Google Scholar
  79. 79.
    The UK Collaborative Group for HIV and STI Surveillance (2006) A complex picture HIV and other sexually transmitted infections in the United Kingdom: 2006. Health Protection Agency, Centre for Infections, London, NovemberGoogle Scholar
  80. 80.
    VAERS (2010) Gardasil, US. http://www.medalerts.org/vaersdb/index.html. Accessed 27 July 2010
  81. 81.
    Villa LL, Ault KA, Giuliano AR et al (2006) Immunologic responses following administration of a vaccine targeting human papillomavirus Types 6, 11, 16, and 18. Vaccine 24:5571–5583PubMedCrossRefGoogle Scholar
  82. 82.
    Vizcaino AP, Moreno V, Bosch FX et al (1998) International trends in the incidence of cervical cancer: I. Adenocarcinoma and adenosquamous cell carcinomas. Int J Cancer 75:536–545PubMedCrossRefGoogle Scholar
  83. 83.
    von Krogh G (2001) Management of anogenital warts (condylomata acuminata). Eur J Dermatol 11:598–603Google Scholar
  84. 84.
    Walboomers JM, Jacobs MV, Manos MM et al (1999) Human papillomavirus is a necessary cause of invasive cervical cancer worldwide. J Pathol 189:12–19PubMedCrossRefGoogle Scholar
  85. 85.
    Watson M, Saraiya M, Benard V, Coughlin SS, Flowers L, Cokkinides V, Schwenn M, Huang Y, Giuliano A (2008) Burden of cervical cancer in the United States, 1998–2003. Cancer 113(10 suppl):2855–2864PubMedCrossRefGoogle Scholar
  86. 86.
    Wellings K, Collumbien M, Slaymaker E, Singh S, Patel D, Bajos N (2006) Sexual behaviour in context: a global perspective. Lancet. doi:10.1016/S0140-6736(06)69479-8 Google Scholar
  87. 87.
    Wheeler CM, Bautista OM, Tomassini JE et al (2008) Safety and immunogenicity of co-administered quadrivalent human papillomavirus (HPV)-6/11/16/18 L1 virus-like particle (VLP) and hepatitis B (HBV) vaccines. Vaccine 26:686–696PubMedCrossRefGoogle Scholar
  88. 88.
    Winer RL, Lee SK, Hughes JP et al (2003) Genital human papillomavirus infection: incidence and risk factors in a cohort of female university students. Am J Epidemiol 157:218–226PubMedCrossRefGoogle Scholar
  89. 89.
    Wu X, Xiao W, Brandsma JL (1994) Papilloma formation by cottontail rabbit papillomavirus requires E1 and E2 regulatory genes in addition to E6 and E7 transforming genes. J Virol 68:6097–6102PubMedGoogle Scholar
  90. 90.
    Xi LF, Demers GW, Koutsky LA et al (1995) Analysis of human papillomavirus type 16 variants indicates establishment of persistent infections. J Infect Dis 172:747–755PubMedGoogle Scholar

Copyright information

© Springer-Verlag 2010

Authors and Affiliations

  • José Ramet
    • 1
    • 4
  • Diego van Esso
    • 2
  • Zsofia Meszner
    • 3
  • on behalf of the European Academy of Paediatrics Scientific Working Group on Vaccination
  1. 1.Universitair Ziekenhuis Antwerpen, University of AntwerpEdegemBelgium
  2. 2.CAP SerrapareraBarcelonaSpain
  3. 3.National Institute of Child HealthBudapestHungary
  4. 4.Universitair Ziekenhuis AntwerpenEdegemBelgium

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