An observational study comparing HPV prevalence and type distribution between HPV-vaccinated and -unvaccinated girls after introduction of school-based HPV vaccination in Norway

Espen Enerly, Ragnhild Flingtorp, Irene Kraus Christiansen, Suzanne Campbell, Mona Hansen, Tor Åge Myklebust, Elisabete Weiderpass, Mari Nygård, Espen Enerly, Ragnhild Flingtorp, Irene Kraus Christiansen, Suzanne Campbell, Mona Hansen, Tor Åge Myklebust, Elisabete Weiderpass, Mari Nygård

Abstract

Background: Many countries have initiated school-based human papillomavirus (HPV) vaccination programs. The real-life effectiveness of HPV vaccines has become increasingly evident, especially among girls vaccinated before HPV exposure in countries with high vaccine uptake. In 2009, Norway initiated a school-based HPV vaccination program for 12-year-old girls using the quadrivalent HPV vaccine (Gardasil®), which targets HPV6, 11, 16, and 18. Here, we aim to assess type-specific vaginal and oral HPV prevalence in vaccinated compared with unvaccinated girls in the first birth cohort eligible for school-based vaccination (born in 1997).

Methods: This observational, cross-sectional study measured the HPV prevalence ratio (PR) between vaccinated and unvaccinated girls in Norway. Facebook advertisement was used to recruit participants and disseminate information about the study. Participants self-sampled vaginal and oral specimens using an Evalyn® Brush and a FLOQSwab™, respectively. Sexual behavior was ascertained through a short questionnaire.

Results: Among the 312 participants, 239 (76.6%) had received at least one dose of HPV vaccine prior to sexual debut. 39.1% of vaginal samples were positive for any HPV type, with similar prevalence among vaccinated and unvaccinated girls (38.5% vs 41.1%, PR: 0.93, 95% confidence interval [CI]: 0.62-1.41). For vaccine-targeted types there was some evidence of lower prevalence in the vaccinated (0.4%) compared to the unvaccinated (6.8%) group (PR: 0.06, 95%CI: 0.01-0.52). This difference remained after adjusting for sexual behavior (PR: 0.04, 95%CI: 0.00-0.42). Only four oral samples were positive for any HPV type, and all of these participants had received at least one dose of HPV vaccine at least 1 year before oral sexual debut.

Conclusion: There is evidence of a lower prevalence of vaccine-targeted HPV types in the vagina of vaccinated girls from the first birth cohort eligible for school-based HPV vaccination in Norway; this was not the case when considering all HPV types or types not included in the quadrivalent HPV vaccine.

Conflict of interest statement

The authors have read the journal's policy and the authors of this manuscript have the following competing interests: M.N. received research grants from MSD/Merck through the affiliating institute.

Figures

Fig 1. CONSORT flow diagram of the…
Fig 1. CONSORT flow diagram of the study population.
Fig 2. Prevalence of human papillomavirus (HPV)…
Fig 2. Prevalence of human papillomavirus (HPV) types in vaginal samples by HPV vaccination status.
Error bars show 95% confidence intervals.

References

    1. Chesson HW, Dunne EF, Hariri S, Markowitz LE. The estimated lifetime probability of acquiring human papillomavirus in the United States. Sex Transm Dis. 2014;41(11):660–4. Epub 2014/10/10. 10.1097/OLQ.0000000000000193 .
    1. IARC Monographs on the Evaluation of Carcinogenic Risks to Humans IARC Monographs, Volume 100 (B) ed. Lyon, France: International Agency for Research on Cancer; 2012.
    1. Wheeler CM. The natural history of cervical human papillomavirus infections and cervical cancer: gaps in knowledge and future horizons. Obstet Gynecol Clin North Am. 2013;40(2):165–76. 10.1016/j.ogc.2013.02.004 .
    1. Smith JS, Lindsay L, Hoots B, Keys J, Franceschi S, Winer R, et al. Human papillomavirus type distribution in invasive cervical cancer and high-grade cervical lesions: a meta-analysis update. Int J Cancer. 2007;121(3):621–32. Epub 2007/04/04. 10.1002/ijc.22527 .
    1. Parkin DM, Bray F. Chapter 2: The burden of HPV-related cancers. Vaccine. 2006;24 Suppl 3:S3/11–25. Epub 2006/09/05. 10.1016/j.vaccine.2006.05.111 .
    1. Ault KA. 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 randomised clinical trials. Lancet. 2007;369(9576):1861–8. Epub 2007/06/05. S0140-6736(07)60852-6 [pii] 10.1016/S0140-6736(07)60852-6 .
    1. Paavonen J, Naud P, Salmeron J, Wheeler CM, Chow SN, Apter D, et al. 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. 2009;374(9686):301–14. 10.1016/S0140-6736(09)61248-4 .
    1. Joura EA, Giuliano AR, Iversen OE, Bouchard C, Mao C, Mehlsen J, et al. A 9-valent HPV vaccine against infection and intraepithelial neoplasia in women. N Engl J Med. 2015;372(8):711–23. 10.1056/NEJMoa1405044 .
    1. Garland SM, Steben M, Sings HL, James M, Lu S, Railkar R, et al. Natural history of genital warts: analysis of the placebo arm of 2 randomized phase III trials of a quadrivalent human papillomavirus (types 6, 11, 16, and 18) vaccine. J Infect Dis. 2009;199(6):805–14. 10.1086/597071 .
    1. Kjaer SK, Tran TN, Sparen P, Tryggvadottir L, Munk C, Dasbach E, et al. The burden of genital warts: a study of nearly 70,000 women from the general female population in the 4 Nordic countries. J Infect Dis. 2007;196(10):1447–54. Epub 2007/11/17. JID38148 [pii] 10.1086/522863 .
    1. Bruni L, Diaz M, Barrionuevo-Rosas L, Herrero R, Bray F, Bosch FX, et al. Global estimates of human papillomavirus vaccination coverage by region and income level: a pooled analysis. The Lancet Global Health. 2016;4(7):e453–e63. 10.1016/S2214-109X(16)30099-7
    1. Garland SM, Kjaer SK, Munoz N, Block SL, Brown DR, DiNubile MJ, et al. Impact and Effectiveness of the Quadrivalent Human Papillomavirus Vaccine: A Systematic Review of 10 Years of Real-world Experience. Clin Infect Dis. 2016;63(4):519–27. Epub 2016/05/28. 10.1093/cid/ciw354 .
    1. Lee LY, Garland SM. Human papillomavirus vaccination: the population impact. F1000Research. 2017;6:866 Epub 2017/07/01. 10.12688/f1000research.10691.1 .
    1. Guo F, Hirth JM, Berenson AB. Comparison of HPV prevalence between HPV-vaccinated and non-vaccinated young adult women (20–26 years). Hum Vaccin Immunother. 2015;11(10):2337–44. Epub 2015/09/17. 10.1080/21645515.2015.1066948 .
    1. Drolet M, Benard E, Boily MC, Ali H, Baandrup L, Bauer H, et al. Population-level impact and herd effects following human papillomavirus vaccination programmes: a systematic review and meta-analysis. Lancet Infect Dis. 2015;15(5):565–80. 10.1016/S1473-3099(14)71073-4 .
    1. 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. The Lancet Infectious Diseases. 2014;14(10):958–66. 10.1016/S1473-3099(14)70841-2
    1. Hirth JM, Chang M, Resto VA. Prevalence of oral human papillomavirus by vaccination status among young adults (18-30years old). Vaccine. 2017;35(27):3446–51. Epub 2017/05/21. 10.1016/j.vaccine.2017.05.025 .
    1. Mehanna H, Bryant TS, Babrah J, Louie K, Bryant JL, Spruce RJ, et al. Human papillomavirus (HPV) vaccine effectiveness and potential herd immunity for reducing oncogenic oropharyngeal HPV16 prevalence in the UK; a cross-sectional study. Clinical Infectious Diseases. 2018:ciy1081 10.1093/cid/ciy1081
    1. Bergsaker MAR, Feiring B, Hagerup-Jenssen M, Flem E, Aase A, Arnesen T, et al. Barnevaksinasjonsprogrammet i Norge. Rapport for 2011. 2012.
    1. Aaberge I AA, Arnesen T, Bergsager G, Blystad H, Bruun T, Daae A, Dudman S, Feiring B, Greve-Isdahl M, Kongsrud S, Løvlie AL, Mengshoel AT, Steinbakk M, Stålcrantz J, Trogstad L, Vestrheim D, Watle S, Wiklund BS, Winje BA. Barnevaksinasjonsprogrammet i Norge. Rapport for 2017. 2018.
    1. Feiring B, Laake I, Christiansen IK, Hansen M, Stalcrantz J, Ambur OH, et al. Substantial Decline in Prevalence of Vaccine-Type and Nonvaccine-Type Human Papillomavirus (HPV) in Vaccinated and Unvaccinated Girls 5 Years After Implementing HPV Vaccine in Norway. J Infect Dis. 2018;218(12):1900–10. Epub 2018/07/17. 10.1093/infdis/jiy432 .
    1. The Norwegian Directorate of eHealth. Helse Norge 2019. [cited 2019 02.01.2019]. Available from: .
    1. van Baars R, Bosgraaf RP, ter Harmsel BW, Melchers WJ, Quint WG, Bekkers RL. Dry storage and transport of a cervicovaginal self-sample by use of the Evalyn Brush, providing reliable human papillomavirus detection combined with comfort for women. J Clin Microbiol. 2012;50(12):3937–43. 10.1128/JCM.01506-12 .
    1. Schmitt M, Bravo IG, Snijders PJ, Gissmann L, Pawlita M, Waterboer T. Bead-based multiplex genotyping of human papillomaviruses. J Clin Microbiol. 2006;44(2):504–12. 10.1128/JCM.44.2.504-512.2006 .
    1. Soderlund-Strand A, Carlson J, Dillner J. Modified general primer PCR system for sensitive detection of multiple types of oncogenic human papillomavirus. J Clin Microbiol. 2009;47(3):541–6. 10.1128/JCM.02007-08 .
    1. Althubaiti A. Information bias in health research: definition, pitfalls, and adjustment methods. Journal of multidisciplinary healthcare. 2016;9:211–7. Epub 2016/05/25. 10.2147/JMDH.S104807 .
    1. Dillner J, Nygard M, Munk C, Hortlund M, Hansen BT, Lagheden C, et al. Decline of HPV infections in Scandinavian cervical screening populations after introduction of HPV vaccination programs. Vaccine. 2018;36(26):3820–9. Epub 2018/05/21. 10.1016/j.vaccine.2018.05.019 .
    1. Gillison ML, Broutian T, Pickard RKL, Tong Z-y, Xiao W, Kahle L, et al. Prevalence of Oral HPV Infection in the United States, 2009–2010. JAMA. 2012;307(7):693–703. 10.1001/jama.2012.101
    1. Dillner J, Kjaer SK, Wheeler CM, Sigurdsson K, Iversen OE, Hernandez-Avila M, et al. Four year efficacy of prophylactic human papillomavirus quadrivalent vaccine against low grade cervical, vulvar, and vaginal intraepithelial neoplasia and anogenital warts: randomised controlled trial. Bmj. 2010;341:c3493 Epub 2010/07/22. 10.1136/bmj.c3493 .
    1. Tranberg M, Jensen JS, Bech BH, Blaakaer J, Svanholm H, Andersen B. Good concordance of HPV detection between cervico-vaginal self-samples and general practitioner-collected samples using the Cobas 4800 HPV DNA test. BMC Infect Dis. 2018;18(1):348 Epub 2018/07/29. 10.1186/s12879-018-3254-y .
    1. Jentschke M, Chen K, Arbyn M, Hertel B, Noskowicz M, Soergel P, et al. Direct comparison of two vaginal self-sampling devices for the detection of human papillomavirus infections. J Clin Virol. 2016;82:46–50. Epub 2016/07/20. 10.1016/j.jcv.2016.06.016 .
    1. Ketelaars PJW, Bosgraaf RP, Siebers AG, Massuger L, van der Linden JC, Wauters CAP, et al. High-risk human papillomavirus detection in self-sampling compared to physician-taken smear in a responder population of the Dutch cervical screening: Results of the VERA study. Prev Med. 2017;101:96–101. Epub 2017/06/06. 10.1016/j.ypmed.2017.05.021 .
    1. Ejegod DM, Pedersen H, Alzua GP, Pedersen C, Bonde J. Time and temperature dependent analytical stability of dry-collected Evalyn HPV self-sampling brush for cervical cancer screening. Papillomavirus research (Amsterdam, Netherlands). 2018;5:192–200. Epub 2018/04/25. 10.1016/j.pvr.2018.04.005 .
    1. Conway DI, Robertson C, Gray H, Young L, McDaid LM, Winter AJ, et al. Human Papilloma Virus (HPV) Oral Prevalence in Scotland (HOPSCOTCH): A Feasibility Study in Dental Settings. PLoS One. 2016;11(11):e0165847 Epub 2016/11/20. 10.1371/journal.pone.0165847 .
    1. Lupato V, Holzinger D, Hofler D, Menegaldo A, Giorgi Rossi P, Del Mistro A, et al. Prevalence and Determinants of Oral Human Papillomavirus Infection in 500 Young Adults from Italy. PLoS One. 2017;12(1):e0170091 Epub 2017/01/20. 10.1371/journal.pone.0170091 .
    1. Leinonen MK, Schee K, Jonassen CM, Lie AK, Nystrand CF, Rangberg A, et al. Safety and acceptability of human papillomavirus testing of self-collected specimens: A methodologic study of the impact of collection devices and HPV assays on sensitivity for cervical cancer and high-grade lesions. J Clin Virol. 2018;99–100:22–30. 10.1016/j.jcv.2017.12.008 .
    1. de Souza MMA, Hartel G, Whiteman DC, Antonsson A. Detection of oral HPV infection—Comparison of two different specimen collection methods and two HPV detection methods. Diagn Microbiol Infect Dis. 2018;90(4):267–71. Epub 2018/01/11. 10.1016/j.diagmicrobio.2017.12.004 .
    1. Kosinski M, Matz SC, Gosling SD, Popov V, Stillwell D. Facebook as a research tool for the social sciences: Opportunities, challenges, ethical considerations, and practical guidelines. The American psychologist. 2015;70(6):543–56. Epub 2015/09/09. 10.1037/a0039210 .
    1. Akers L, Gordon JS. Using Facebook for Large-Scale Online Randomized Clinical Trial Recruitment: Effective Advertising Strategies. Journal of medical Internet research. 2018;20(11):e290 Epub 2018/11/10. 10.2196/jmir.9372 .
    1. Subasinghe AK, Nguyen M, Wark JD, Tabrizi SN, Garland SM. Targeted Facebook Advertising is a Novel and Effective Method of Recruiting Participants into a Human Papillomavirus Vaccine Effectiveness Study. JMIR research protocols. 2016;5(3):e154 Epub 2016/07/28. 10.2196/resprot.5679 .
    1. Ipsos. Ipsos SoMe-tracker Q4'17 2018 [updated 17.01.2018; cited 2019 06.09.2019]. Available from: .
    1. Hansen BT, Kjaer SK, Arnheim-Dahlstrom L, Liaw KL, Jensen KE, Thomsen LT, et al. Human papillomavirus (HPV) vaccination and subsequent sexual behaviour: evidence from a large survey of Nordic women. Vaccine. 2014;32(39):4945–53. 10.1016/j.vaccine.2014.07.025 .

Source: PubMed

Sponsorit ja yhteistyökumppanit

Sairaudet

Huumeiden interventiot

3
Tilaa