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Carcinogenic HPV prevalence and age-specific type distribution in 40,382 women with normal cervical cytology, ASCUS/LSIL, HSIL, or cervical cancer: what is the potential for prevention?

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Abstract

Background

Assessment of the prevaccination type-specific prevalence of human papillomavirus (HPV) in the general population is important for the prediction of the impact of HPV vaccination.

Methods

We collected consecutively residual specimens from liquid-based cytology samples from 40,382 women from the general population in Copenhagen, Denmark, during 2002–2005. All samples were tested for high-risk HPV using the Hybrid Capture 2 technique, and genotyping was done using LiPa (Innogenetics). Through linkage with the Pathology Data Bank, we obtained information on the cytology result, and histology if any, on all women.

Results

The participants were 14–95 years of age (median age 37 years) at enrollment. The overall prevalence of HR HPV was 20.6 % ranging from 46.0 % in 20–23-year-old women to 5.7 % in women 65 years or older. Independently of cytology/histology, HPV16 was the most prevalent type. For virtually all HPV types, the occurrence of CIN3+ was higher when the specific HPV type was present together with HPV16 than it was together with other high-risk HPV types than HPV16 or if the HPV type occurred as a single infection. The prevalence of HPV16 and/or HPV18 was 74 % in cervical cancer and the corresponding prevalence of HPV16/18/31/33/45/52/58 was 89 %.

Conclusion

This study forms a valuable starting point for monitoring the effect of HPV vaccination in Denmark. In addition, the particular carcinogenic role of HPV16 and 18 is confirmed and may support a role of genotyping for HPV16 and 18 in cervical cancer screening.

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References

  1. Ferlay J, Shin HR, Bray F, Forman D, Mathers C, Parkin DM (2010) Estimates of worldwide burden of cancer in 2008: GLOBOCAN 2008. Int J Cancer 127(12):2893–2917. doi:10.1002/ijc.25516

    Article  CAS  PubMed  Google Scholar 

  2. Muñoz N, Castellsagué X, de Gonzáles AB, Gissman L (2006) Chapter 1. HPV in the etiology of human cancer. Vaccine 24(Suppl 3):1–10

    Article  Google Scholar 

  3. NORDCAN (http://www.ancr.nu/default_old.asp) updated Oct. 2009

  4. Noehr B, Jensen A, Frederiksen K, Tabor A, Kjaer SK (2009) Loop electrosurgical excision of the cervix and subsequent risk for spontaneous preterm delivery: a population-based study of singleton deliveries during a 9-year period. Am J Obstet Gynecol 201(1):33.e1–6. doi:10.1016/j.ajog.2009.02.004

    Article  PubMed  Google Scholar 

  5. Harper DM, Franco EL, Wheeler CM, Moscicki AB, Romonowski B, Roteli-Martins CM 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 367:1247–1255

    Article  CAS  PubMed  Google Scholar 

  6. Kjaer SK, Sigurdsson K, Iversen OE, Hernandez-Avila M, Wheeler CM, Perez G et al (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 (Phila) 2(10):868–878. doi:10.1158/1940-6207.CAPR-09-0031

    Article  Google Scholar 

  7. Lehtinen M, Dillner J (2013) Clinical trials of human papillomavirus vaccines and beyond. Nat Rev Clin Oncol 10(7):400–410. doi:10.1038/nrclinonc.2013.84

    Article  CAS  PubMed  Google Scholar 

  8. Garland SM, Hernandez-Avila M, Wheeler CM, Perez G, Harper DM, Leodolter S et al (2007) Quadrivalent vaccine against human papillomavirus to prevent anogenital diseases. N Engl J Med 356(19):1928–1943

    Article  CAS  PubMed  Google Scholar 

  9. Joura EA, Leodolter S, Hernandez-Avila M, Wheeler CM, Perez G, Koutsky LA et al (2007) Efficacy of a quadrivalent prophylactic human papillomavirus (types 6, 11, 16, and 18) virus-like particle vaccine against high-grade vulvar and vaginal lesions: a combined analysis of three randomised clinical trials. Lancet 369(9574):1693–1702

    Article  CAS  PubMed  Google Scholar 

  10. Nielsen A, Kjaer SK, Munk C, Iftner T (2008) Type-specific HPV infection and multiple HPV types: prevalence and risk factor profile in nearly 12,000 younger and older Danish women. Sex Transm Dis 35(3):276–282

    Article  PubMed  Google Scholar 

  11. Kjær SK, Breugelmans G, Munk C, Junge J, Watson M, Iftner T (2008) Population-based prevalence, type- and age-specific distribution of HPV in women before introduction of an HPV-vaccination program in Denmark. Int J Cancer 123(8):1864–1870

    Article  PubMed  Google Scholar 

  12. Nielsen A, Iftner T, Nørgaard M, Munk C, Junge J, Kjaer SK (2012) The importance of low-risk HPV infection for the risk of abnormal cervical cytology/histology in more than 40 000 Danish women. Sex Transm Infect 88(8):627–632. doi:10.1136/sextrans-2011-050307

    Article  PubMed  Google Scholar 

  13. Brown DR, Kjaer SK, Sigurdsson K, Iversen OE, Hernandez-Avila M, Wheeler CM et al (2009) The impact of quadrivalent hpv (type 6/11/16/18) L1 VLP vaccine on infection and disease due to Oncogenic non-vaccine HPV types in generally HPV naive women aged 16–26. J Infect Dis 199(7):926–935

    Article  PubMed  Google Scholar 

  14. Wheeler CM, Kjaer SK, Sigurdsson K, Iversen OE, Hernandez-Avila M, Perez G (2009) The impact of quadrivalent HPV (types 6/11/16/18) L1 vlp vaccine on infection and disease due to oncogenic non-vaccine hpv types in sexually active women aged 16–26. J Infect Dis 199(7):936–944

    Article  PubMed  Google Scholar 

  15. Malagon T, Drolet M, Boily MC, Franco EL, Jit M, Brisson J, Brisson M (2012) Crossprotective efficacy of two human papillomavirus vaccines: a systematic review and meta-analysis. Lancet Infect Dis 12(10):781–789

    Article  CAS  PubMed  Google Scholar 

  16. Munk C, Kjaer SK, Poll P, Bock JE (1998) Cervical cancer screening: knowledge of own screening status among women aged 20–29 years. Acta Obstet Gynecol Scand 77(9):917–922

    Article  CAS  PubMed  Google Scholar 

  17. Pedersen CB (2011) The Danish civil registration system. Scand J Public Health 39(Suppl 7):22–25

    Article  PubMed  Google Scholar 

  18. Bjerregaard B, Larsen OB (2011) The Danish pathology register. Scand J Public Health 39(Suppl 7):72–74

    Article  PubMed  Google Scholar 

  19. Bruni L, Diaz M, Castellsagué X, Ferrer E, Bosch FX, de Sanjosé S (2010) Cervical human papillomavirus prevalence in 5 continents: meta-analysis of 1 million women with normal cytological findings. J Infect Dis 202(12):1789–1799. doi:10.1086/657321

    Article  PubMed  Google Scholar 

  20. Jensen KE, Munk C, Sparen P, Tryggvadottir L, Liaw KL, Dasbach E, Nygård M, Kjaer SK (2011) Women’s sexual behavior. Population-based study among 65,000 women from four Nordic countries before introduction of human papillomavirus vaccination. Acta Obstet Gynecol Scand 90(5):459–467. doi:10.1111/j.1600-0412.2010.01066.x

    Article  PubMed  Google Scholar 

  21. Nielsen A, Kjaer SK, Munk C, Osler M, Iftner T (2010) Persistence of high-risk human papillomavirus infection in a population-based cohort of Danish women. J Med Virol 82(4):616–623. doi:10.1002/jmv.21750

    Article  PubMed  Google Scholar 

  22. Winer RL, Hughes JP, Feng Q, Xi LF, Cherne S, O’Reilly S, Kiviat NB, Koutsky LA (2011) Early natural history of incident, type-specific human papillomavirus infections in newly sexually active young women. Cancer Epidemiol Biomarkers Prev 20(4):699–707

    Article  PubMed Central  PubMed  Google Scholar 

  23. Passmore JA, Morroni C, Shapiro S, Williamson AL, Hoffman M (2007) Papanicolaou smears and cervical inflammatory cytokine responses. J Inflamm (Lond) 4:8

    Article  Google Scholar 

  24. Arbyn M, Martin-Hirsch P, Buntinx F, Van Ranst M, Paraskevaidis E, Dillner J (2009) Triage of women with equivocal or low-grade cervical cytology results: a meta-analysis of the HPV test positivity rate. J Cell Mol Med 13(4):648–659. doi:10.1111/j.1582-4934.2008.00631.x

    Article  PubMed  Google Scholar 

  25. Arbyn M, Benoy I, Simoens C, Bogers J, Beutels P, Depuydt C (2009) Prevaccination distribution of human papillomavirus types in women attending at cervical cancer screening in Belgium. Cancer Epidemiol Biomarkers Prev 18(1):321–330. doi:10.1158/1055-9965.EPI-08-0510

    Article  CAS  PubMed  Google Scholar 

  26. Sargent A, Bailey A, Almonte M, Turner A, Thomson C, Peto J, Desai M, Mather J, Moss S, Roberts C, Kitchener HC, ARTISTIC Study Group (2008) Prevalence of type-specific HPV infection by age and grade of cervical cytology: data from the ARTISTIC trial. Br J Cancer 98(10):1704–1709. doi:10.1038/sj.bjc.6604324

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  27. Kjær SK, Frederiksen K, Munk C, Iftner T (2010) Long-term absolute risk of cervical intraepithelial neoplasia grade 3 or worse following human papillomavirus infection: role of persistence. J Natl Cancer Inst 102(19):1478–1488. doi:10.1093/jnci/djq356

    Article  PubMed  Google Scholar 

  28. Dillner J, Rebolj M, Birembaut P, Petry KU, Szarewski A, Munk C, de Sanjose S, Naucler P, Lloveras B, Kjaer S, Cuzick J, van Ballegooijen M, Clavel C, Iftner T (2008) Long term predictive values of cytology and human papillomavirus testing in cervical cancer screening: joint European cohort study. BMJ 337:a1754

    Article  PubMed Central  PubMed  Google Scholar 

  29. Kjaer S, Høgdall E, Frederiksen K, Munk C, van den Brule A, Svare E, Meijer C, Lorincz A, Iftner T (2006) The absolute risk of cervical abnormalities in high-risk human papillomavirus-positive, cytologically normal women over a 10-year period. Cancer Res 66(21):10630–10636

    Article  CAS  PubMed  Google Scholar 

  30. Castellsagué X, Díaz M, de Sanjosé S, Muñoz N, Herrero R, Franceschi S, Peeling RW, Ashley R, Smith JS, Snijders PJ, Meijer CJ, Bosch FX, International Agency for Research on Cancer Multicenter Cervical Cancer Study Group (2006) Worldwide human papillomavirus etiology of cervical adenocarcinoma and its cofactors: implications for screening and prevention. J Natl Cancer Inst 98(5):303–315

    Article  PubMed  Google Scholar 

  31. Herrero R, Castle PE, Schiffman M, Bratti MC, Hildesheim A, Morales J et al (2005) Epidemiologic profile of type-specific human papillomavirus infection and cervical neoplasia in Guanacaste, Costa Rica. J Infect Dis 191:1796–1807

    Article  PubMed  Google Scholar 

  32. Castle PE, Schiffman M, Wheeler CM, Wentzensen N, Gravitt PE (2010) Human papillomavirus genotypes in cervical intraepithelial neoplasia grade 3. Cancer Epidemiol Biomarkers Prev 19:1675–1681

    Article  PubMed Central  PubMed  Google Scholar 

  33. Castle PE, Shaber R, Lamere B, Kinney W, Fetterman B, Poitras N et al (2011) Human papillomavirus (HPV) genotypes in women with cervical precancer and cancer at Kaiser Permanente Northern California. Cancer Epidemiol Biomarkers Prev 20:946–953

    Article  PubMed Central  PubMed  Google Scholar 

  34. Baandrup L, Munk C, Andersen KK, Junge J, Iftner T, Kjær SK (2012) HPV16 is associated with younger age in women with cervical intraepithelial neoplasia grade 2 and 3. Gynecol Oncol 124(2):281–285. doi:10.1016/j.ygyno.2011.10.020

    Article  CAS  PubMed  Google Scholar 

  35. Blomberg M, Dehlendorff C, Munk C, Kjaer SK (2013) Strongly decreased risk of genital warts after vaccination against human papillomavirus: nationwide follow-up of vaccinated and unvaccinated girls in Denmark. Clin Infect Dis 57(7):929–934. doi:10.1093/cid/cit436

    Article  PubMed  Google Scholar 

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Acknowledgments

We thank Angelika Iftner and Barbara Holz at the University Hospital of Tübingen, and the study staff at Hvidovre Hospital and the Danish Cancer Society for their technical support. Funding for this study was provided by the Danish Cancer Society, Copenhagen, Denmark, Sanofi Pasteur MSD, Lyon, France, and the Mermaid 2 project. The study was funded through an institutional Grant from Sanofi Pasteur MSD (Lyon, France) and from the Danish Cancer Society. Furthermore, the study was supported by the Mermaid 2 project. The funders had no role in the conduct or interpretation of the study and had no role in the preparation, review, or approval of the manuscript, or the decision to submit the manuscript for publication. The authors take full responsibility for the content of this paper.

Conflict of interest

S.K.K. received scientific advisory board and speaker’s fees and research grants through her institution from Sanofi Pasteur MSD and Merck. C.M. received travel and speaker’s fees from Sanofi Pasteur MSD. T.I. received speaker honoraria from Gen-Probe GmbH, Hologic GmbH, and Roche Diagnostics GmbH. J.J. has received advisory board fees from Sanofi Pasteur MSD and consultant fees from Merck.

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Authors and Affiliations

  1. Unit of Virus, Lifestyle and Genes, Danish Cancer Society Research Center, Strandboulevarden 49, 2100, Copenhagen, Denmark

    Susanne K. Kjær & Christian Munk

  2. Department of Gynaecology and Obstetrics, Rigshospitalet, University of Copenhagen, Blegdamsvej 9, 2100, Copenhagen, Denmark

    Susanne K. Kjær

  3. Department of Pathology, Hvidovre Hospital, Kettegaard Alle, 2850, Copenhagen, Denmark

    Jette Junge

  4. Medical Virology, Section Experimental Virology, University Hospital of Tübingen, Elfriede-Aulhorn Str. 6, 72076, Tübingen, Germany

    Thomas Iftner

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  1. Susanne K. Kjær
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Correspondence to Susanne K. Kjær.

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Kjær, S.K., Munk, C., Junge, J. et al. Carcinogenic HPV prevalence and age-specific type distribution in 40,382 women with normal cervical cytology, ASCUS/LSIL, HSIL, or cervical cancer: what is the potential for prevention?. Cancer Causes Control 25, 179–189 (2014). https://doi.org/10.1007/s10552-013-0320-z

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