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2025 theme: Vaccines

Abstract

BACKGROUND

Danish women vaccinated with the 4-valent human papillomavirus (HPV) vaccine (HPV types: 6/11/16/18) at age 14 in 2008 reached screening age in 2017, allowing assessment of long-term effects on prevalence, persistence and incidence of HPV infections.

AIM

To examine the HPV status of cervical samples over time among women vaccinated as girls.

METHODS

Between February 2017 and February 2024, residual material from cytology-analysed samples collected through the ‘Trial23’ study, part of the national screening programme, was tested for HPV16/18 and non-vaccine high-risk (HR) HPV types. Prevalence in first, second and third samples, and persistence and incidence between samples were calculated.

RESULTS

Over 7 years, 8,659 women provided at least one sample, 5,835 at least two and 2,461 at least three. In 7,800 vaccinated women, HPV16/18 prevalence was 0.4% (95% confidence interval (CI): 0.2–0.5), 0.3% (95% CI: 0.1–0.4) and 0.2% (95% CI: 0.0–0.4) in three consecutive samples. Prevalence of non-vaccine HR HPV was 32% (95% CI: 31–33), 28% (95% CI: 27–29) and 31% (95% CI: 29–33). Persistence of HPV16/18 and non-vaccine HPV among vaccinated women was 40% and 53%. In adjusted analyses comparing vaccinated vs unvaccinated women, incidence was significantly lower for HPV16/18 (adjusted relative risk (aRR) < 0.10) while incidence of non-vaccine HR HPV types was higher (aRR: 1.66; 95% CI: 1.12–2.45). No significant difference was observed for persistence.

CONCLUSION

Our study provides real-world evidence of stable protection against HPV16/18 infections in women vaccinated as girls. Less intensive screening seems reasonable until women vaccinated with the 9-valent vaccine reach screening age, when screening should be reconsidered.

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2025-07-10
2025-07-12
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References

  1. National Cancer Institute (NCI). HPV and Cancer. Washington: NCI; 2019. Available from: https://www.cancer.gov/about-cancer/causes-prevention/risk/infectious-agents/hpv-and-cancer
  2. Anttila A, Ronco G, Clifford G, Bray F, Hakama M, Arbyn M, et al. Cervical cancer screening programmes and policies in 18 European countries. Br J Cancer. 2004;91(5):935-41.  https://doi.org/10.1038/sj.bjc.6602069  PMID: 15280916 
  3. Elfström KM, Arnheim-Dahlström L, von Karsa L, Dillner J. Cervical cancer screening in Europe: Quality assurance and organisation of programmes. Eur J Cancer. 2015;51(8):950-68.  https://doi.org/10.1016/j.ejca.2015.03.008  PMID: 25817010 
  4. World Health Organization (WHO). WHO guideline for screening and treatment of cervical pre-cancer lesions for cervical cancer prevention. Second edition. Geneva: WHO; 2021. Available from: https://www.who.int/publications/i/item/9789240030824
  5. European Commission (EC). European Health Union: new approach on cancer screening. Brussels: EC; 2022. Available from: https://ec.europa.eu/commission/presscorner/detail/en/ip_22_7548
  6. Garland SM, Hernandez-Avila M, Wheeler CM, Perez G, Harper DM, Leodolter S, et al. , Females United to Unilaterally Reduce Endo/Ectocervical Disease (FUTURE) I Investigators. Quadrivalent vaccine against human papillomavirus to prevent anogenital diseases. N Engl J Med. 2007;356(19):1928-43.  https://doi.org/10.1056/NEJMoa061760  PMID: 17494926 
  7. Walboomers JM, Jacobs MV, Manos MM, Bosch FX, Kummer JA, Shah KV, et al. Human papillomavirus is a necessary cause of invasive cervical cancer worldwide. J Pathol. 1999;189(1):12-9.  https://doi.org/10.1002/(SICI)1096-9896(199909)189:1<12::AID-PATH431>3.0.CO;2-F  PMID: 10451482 
  8. Kjaer SK, Falkenthal TEH, Sundström K, Munk C, Sture T, Bautista O, et al. , Thomas Group. Long-term effectiveness of the nine-valent human papillomavirus vaccine: Interim results after 12 years of follow-up in Scandinavian women. Hum Vaccin Immunother. 2024;20(1):2377903.  https://doi.org/10.1080/21645515.2024.2377903  PMID: 39373579 
  9. Statens Serum Institut (SSI). Overvågning i tal, grafer og kort. HPV 1 piger, Vaccinationstilslutning. [Monitoring in numbers, graphs and maps: HPV 1 girls, vaccination coverage]. Copenhagen: SSI. [Accessed: 17 Sep 2021]. Danish. Available from: https://statistik.ssi.dk//sygdomsdata#!/?vaccination=5&sex=0&landsdel=100&xaxis=Cohort&show=Graph&datatype=Vaccination
  10. Statens Serum Institut (SSI). Vaccinationsintervaller og tilpasning. [Vaccination intervals and adaptation]. Copenhagen: SSI. [Accessed: 26 Feb 2025]. Danish. Available from: https://www.ssi.dk/vaccinationer/boernevaccination/vaccination-mod-livmoderhalskraeft/vaccinationsintervaller-og-tilpasning
  11. Kjær SK, Munk C, Junge J, Iftner T. 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. 2014;25(2):179-89.  https://doi.org/10.1007/s10552-013-0320-z  PMID: 24242002 
  12. Nonboe MH, Napolitano GM, Kann C, Andersen B, Bennetsen MH, Christiansen S, et al. Screening outcome of HPV-vaccinated women: Data from the Danish Trial23 cohort study. PLoS One. 2024;19(6):e0306044.  https://doi.org/10.1371/journal.pone.0306044  PMID: 38917143 
  13. Thamsborg LH, Andersen B, Larsen LG, Christensen J, Johansen T, Hariri J, et al. Danish method study on cervical screening in women offered HPV vaccination as girls (Trial23): a study protocol. BMJ Open. 2018;8(5):e020294.  https://doi.org/10.1136/bmjopen-2017-020294  PMID: 29804060 
  14. Lynge E, Thamsborg L, Larsen LG, Christensen J, Johansen T, Hariri J, et al. Prevalence of high-risk human papillomavirus after HPV-vaccination in Denmark. Int J Cancer. 2020;147(12):3446-52.  https://doi.org/10.1002/ijc.33157  PMID: 32542644 
  15. Bell M, Verberckmoes B, Devolder J, Vermandere H, Degomme O, Guimarães YM, et al. Comparison between the Roche Cobas 4800 human papillomavirus (HPV), Abbott realtime high-risk HPV, Seegene Anyplex II HPV28, and Novel Seegene Allplex HPV28 assays for High-Risk HPV detection and genotyping in mocked self-samples. Microbiol Spectr. 2023;11(4):e0008123.  https://doi.org/10.1128/spectrum.00081-23  PMID: 37284753 
  16. Wickham H, Averick M, Bryan J, Chang W, McGowan L, François R, et al. Welcome to the Tidyverse. J Open Source Softw. 2019;4(43):1686.  https://doi.org/10.21105/joss.01686 
  17. Zeileis A, Köll S, Graham N. Various versatile variances: an object-oriented implementation of clustered covariances in R. J Stat Softw. 2020;95(1). Available from: http://www.jstatsoft.org/v95/i01 https://doi.org/10.18637/jss.v095.i01 
  18. Zeileis A. Object-oriented computation of sandwich estimators. J Stat Softw. 2006;16(9). Available from: http://www.jstatsoft.org/v16/i09/ https://doi.org/10.18637/jss.v016.i09 
  19. Zeileis A, Hothorn T. Diagnostic checking in regression relationships. R News. 2002;2(3):7-10. https://journal.r-project.org/articles/RN-2002-018
  20. The Danish Clinical Quality Program. Beskrivelse af Dansk Kvalitetsdatabase for Livmoderhalskræftscreening og link til årsrapport. [Description of the Danish Quality Database for Cervical Cancer Screening and link to the annual report]. National Clinical Registries (RKKP). [Accessed: 24 Oct 2024]. Danish. Available from: https://www.sundhed.dk/sundhedsfaglig/kvalitet/kliniske-kvalitetsdatabaser/screening/livmoderhalskraeftscreening
  21. Nonboe MH, Napolitano G, Schroll JB, Vejborg I, Waldstrøm M, Lynge E. Impact of COVID-19 pandemic on breast and cervical cancer screening in Denmark: A register-based study. eLife. 2023;12:e81605.  https://doi.org/10.7554/eLife.81605  PMID: 36943035 
  22. Preisler S, Rebolj M, Untermann A, Ejegod DM, Lynge E, Rygaard C, et al. Prevalence of human papillomavirus in 5,072 consecutive cervical SurePath samples evaluated with the Roche cobas HPV real-time PCR assay. PLoS One. 2013;8(3):e59765.  https://doi.org/10.1371/journal.pone.0059765  PMID: 23533648 
  23. Statens Institut for Folkesundhed (SIF). Skolebørnsundersøgelsen 2010. [School survey 2010]. Copenhagen: Syddansk Universitet; 2011. Danish. Available from: https://www.sdu.dk/da/sif/rapporter/2011/skoleboernsundersoegelsen_2010
  24. Hampson IN, Oliver AW. Update on Effects of the Prophylactic HPV Vaccines on HPV Type Prevalence and Cervical Pathology. Viruses. 2024;16(8):1245.  https://doi.org/10.3390/v16081245  PMID: 39205218 
  25. Lynge E, Thamsborg L, Larsen LG, Christensen J, Johansen T, Hariri J, et al. Prevalence of high-risk human papillomavirus after HPV-vaccination in Denmark. Int J Cancer. 2020;147(12):3446-52.  https://doi.org/10.1002/ijc.33157  PMID: 32542644 
  26. Smith MA, Sherrah M, Sultana F, Castle PE, Arbyn M, Gertig D, et al. National experience in the first two years of primary human papillomavirus (HPV) cervical screening in an HPV vaccinated population in Australia: observational study. BMJ. 2022;376:e068582.  https://doi.org/10.1136/bmj-2021-068582  PMID: 35354610 
  27. Cancer Australia. HPV vaccination uptake. National Cancer Control Indicators. Strawberry Hills: Cancer Australia. [Accessed: 15 Nov 2022]. Available from: https://ncci.canceraustralia.gov.au/prevention/hpv-vaccination-uptake/hpv-vaccination-uptake
  28. Tabrizi SN, Brotherton JML, Kaldor JM, Skinner SR, Liu B, Bateson D, et al. Assessment of herd immunity and cross-protection after a human papillomavirus vaccination programme in Australia: a repeat cross-sectional study. Lancet Infect Dis. 2014;14(10):958-66.  https://doi.org/10.1016/S1473-3099(14)70841-2  PMID: 25107680 
  29. Rebolj M, Pesola F, Mathews C, Mesher D, Soldan K, Kitchener H. The impact of catch-up bivalent human papillomavirus vaccination on cervical screening outcomes: an observational study from the English HPV primary screening pilot. Br J Cancer. 2022;127(2):278-87.  https://doi.org/10.1038/s41416-022-01791-w  PMID: 35347326 
  30. Checchi M, Mesher D, Panwar K, Anderson A, Beddows S, Soldan K. The impact of over ten years of HPV vaccination in England: Surveillance of type-specific HPV in young sexually active females. Vaccine. 2023;41(45):6734-44.  https://doi.org/10.1016/j.vaccine.2023.10.002  PMID: 37821315 
  31. Kavanagh K, Pollock KG, Cuschieri K, Palmer T, Cameron RL, Watt C, et al. Changes in the prevalence of human papillomavirus following a national bivalent human papillomavirus vaccination programme in Scotland: a 7-year cross-sectional study. Lancet Infect Dis. 2017;17(12):1293-302.  https://doi.org/10.1016/S1473-3099(17)30468-1  PMID: 28965955 
  32. Bonde J, Hammer A. Discontinuation of cervical cancer screening for HPV-vaccinated women? Acta Obstet Gynecol Scand. 2024;103(11):2122-3.  https://doi.org/10.1111/aogs.14978  PMID: 39315708 
  33. Lynge E, Bennekou Schroll J, Andersen B, Balasubramaniam K, Poulsgaard Frandsen A, Ibfelt EH, et al. Cervical cancer incidence in Denmark: Disentangling determinants of time trend. Int J Cancer. 2024;155(10):1769-79.  https://doi.org/10.1002/ijc.35081  PMID: 39003657 
  34. Kim JJ, Burger EA, Sy S, Campos NG. Optimal cervical cancer screening in women vaccinated against human papillomavirus. J Natl Cancer Inst. 2016;109(2):djw216.  https://doi.org/10.1093/jnci/djw216  PMID: 27754955 
  35. Schmidt M, Schmidt SAJ, Adelborg K, Sundbøll J, Laugesen K, Ehrenstein V, et al. The Danish health care system and epidemiological research: from health care contacts to database records. Clin Epidemiol. 2019;11:563-91.  https://doi.org/10.2147/CLEP.S179083  PMID: 31372058 
  36. Sander BB, Vázquez-Prada M, Rebolj M, Valentiner-Branth P, Lynge E. Mothers’ and their daughters’ use of preventive measures against cervical cancer. Scand J Public Health. 2015;43(4):415-22.  https://doi.org/10.1177/1403494815574155  PMID: 25743877 
  37. Fernández de Casadevante V, Cantarero-Arévalo L, Gil Cuesta J, Valentiner-Branth P. Ethnic background and human papillomavirus vaccine uptake in Denmark: A countrywide retrospective cohort study including 274,154 women aged 19-28 years. Papillomavirus Res. 2016;2:78-84.  https://doi.org/10.1016/j.pvr.2016.03.003  PMID: 29074189 
  38. Voss SS, Nørgaard SK, Valentiner-Branth P. Identification of subgroups in the Danish population for targeted human papillomavirus vaccination efforts. Vaccine. 2023;41(23):3525-33.  https://doi.org/10.1016/j.vaccine.2023.04.060  PMID: 37142460 
  39. Bigaard J, Franceschi S. Vaccination against HPV: boosting coverage and tackling misinformation. Mol Oncol. 2021;15(3):770-8.  https://doi.org/10.1002/1878-0261.12808  PMID: 33058497 
  40. Baumann A, Andersen B, Østergaard L, Larsen MB. Sense & sensibility: Decision-making and sources of information in mothers who decline HPV vaccination of their adolescent daughters. Vaccine X. 2019;2:100020.  https://doi.org/10.1016/j.jvacx.2019.100020  PMID: 31384740 
  41. Danish Health Authority (SST). Screening for livmoderhalskræft. [Cervical cancer screening]. Copenhagen: SST. [Accessed: 12 Mar 2025]. Danish. Available from: http://www.sst.dk/da/Borger/Sygdomme-og-lidelser/Kræftsygdom/Screening-for-kraeft/Livmoderhalskraeft
  42. Dansk Selskab for Gynækologi og Obstetrik (DSOG). Gynækologiske guidelines – Cervix – Forebyggelse, udredning og behandling af dysplasi på Cervix. [Gynecological guidelines – Cervix – Prevention, investigation and treatment of dysplasia on the Cervix]. DSOG; 2022. Danish. Available from: https://www.dsog.dk/gynkologi
Human papillomavirus prevalence in first, second and third cervical cell samples from women HPV-vaccinated as girls, Denmark, 2017 to 2024: data from the Trial23 cohort study
<p class="citation"> <span>Citation style for this article:</span> <span class="meta-value authors"> <a href="/search?value1=Mette+Hartmann+Nonboe&option1=author&noRedirect=true" class="nonDisambigAuthorLink">Nonboe Mette Hartmann</a>, <a href="/search?value1=George+Maria+Napolitano&option1=author&noRedirect=true" class="nonDisambigAuthorLink">Napolitano George Maria</a>, <a href="/search?value1=Jeppe+Bennekou+Schroll&option1=author&noRedirect=true" class="nonDisambigAuthorLink">Schroll Jeppe Bennekou</a>, <a href="/search?value1=Berit+Andersen&option1=author&noRedirect=true" class="nonDisambigAuthorLink">Andersen Berit</a>, <a href="/search?value1=Mary+Holten+Bennetsen&option1=author&noRedirect=true" class="nonDisambigAuthorLink">Bennetsen Mary Holten</a>, <a href="/search?value1=Sanne+Christiansen&option1=author&noRedirect=true" class="nonDisambigAuthorLink">Christiansen Sanne</a>, <a href="/search?value1=Anna+Poulsgaard+Frandsen&option1=author&noRedirect=true" class="nonDisambigAuthorLink">Frandsen Anna Poulsgaard</a>, <a href="/search?value1=Carsten+Rygaard&option1=author&noRedirect=true" class="nonDisambigAuthorLink">Rygaard Carsten</a>, <a href="/search?value1=Rouzbeh+Salmani&option1=author&noRedirect=true" class="nonDisambigAuthorLink">Salmani Rouzbeh</a>, <a href="/search?value1=Estrid+Vilma+Solyom+H%C3%B8gdall&option1=author&noRedirect=true" class="nonDisambigAuthorLink">Høgdall Estrid Vilma Solyom</a>, <a href="/search?value1=Elsebeth+Lynge&option1=author&noRedirect=true" class="nonDisambigAuthorLink">Lynge Elsebeth</a></span>. Human papillomavirus prevalence in first, second and third cervical cell samples from women HPV-vaccinated as girls, Denmark, 2017 to 2024: data from the Trial23 cohort study. <a href="/content/ecdc">Euro Surveill.</a> 2025;30(27):pii=2400820. <a href="https://doi.org/10.2807/1560-7917.ES.2025.30.27.2400820" title="doi link" target="_blank">https://doi.org/10.2807/1560-7917.ES.2025.30.27.2400820</a> <span class="ES_Article_citation"> <span class="generated">Received</span>: 13 Dec 2024;&nbsp;&nbsp; <span class="generated">Accepted</span>: 25 Mar 2025 </span> </p>
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