Impact of a school-based and primary care-based multicomponent intervention on HPV vaccination coverage among French adolescents: a cluster randomised controlled trial protocol (the PrevHPV study)

Aurélie Bocquier, Morgane Michel, Bruno Giraudeau, Stéphanie Bonnay, Amandine Gagneux-Brunon, Aurélie Gauchet, Serge Gilberg, Anne-Sophie Le Duc-Banaszuk, Judith E Mueller, Karine Chevreul, Nathalie Thilly, PrevHPV Study group, Nelly Agrinier, Estelle Fall, Céline Pulcini, Sébastien Bruel, Marie Ecollan, Dragos-Paul Hagiu, Josselin Le Bel, Henri Partouche, Juliette Pinot, Louise Rossignol, Arthur Tron, Minghui Zuo, Gaëlle Vareilles, Julie Bros, Catherine Juneau, Marion Branchereau, Elisabeth Botelho-Nevers, Géraldine Jambon, Florian Jeanleboeuf, Julie Kalecinski, Christine Lasset, Laetitia Marie DitAsse, Jonathan Sicsic, Jocelyn Raude, Sandra Chyderiotis, Damien Oudin-Doglioni, Anne-Sophie Barret, Isabelle Bonmarin, Daniel Levy-Bruhl, Clémence Castagnet, Mélanie Simony, Aurélie Bocquier, Morgane Michel, Bruno Giraudeau, Stéphanie Bonnay, Amandine Gagneux-Brunon, Aurélie Gauchet, Serge Gilberg, Anne-Sophie Le Duc-Banaszuk, Judith E Mueller, Karine Chevreul, Nathalie Thilly, PrevHPV Study group, Nelly Agrinier, Estelle Fall, Céline Pulcini, Sébastien Bruel, Marie Ecollan, Dragos-Paul Hagiu, Josselin Le Bel, Henri Partouche, Juliette Pinot, Louise Rossignol, Arthur Tron, Minghui Zuo, Gaëlle Vareilles, Julie Bros, Catherine Juneau, Marion Branchereau, Elisabeth Botelho-Nevers, Géraldine Jambon, Florian Jeanleboeuf, Julie Kalecinski, Christine Lasset, Laetitia Marie DitAsse, Jonathan Sicsic, Jocelyn Raude, Sandra Chyderiotis, Damien Oudin-Doglioni, Anne-Sophie Barret, Isabelle Bonmarin, Daniel Levy-Bruhl, Clémence Castagnet, Mélanie Simony

Abstract

Introduction: Vaccination is an effective and safe strategy to prevent Human papillomavirus (HPV) infection and related harms. Despite various efforts by French authorities to improve HPV vaccine coverage (VC) these past few years, VC has remained far lower than in most other high-income countries. To improve it, we have coconstructed with stakeholders a school-based and primary care-based multicomponent intervention, and plan to evaluate its effectiveness, efficiency and implementation through a cluster randomised controlled trial (cRCT).

Methods and analysis: This pragmatic cRCT uses an incomplete factorial design to evaluate three components applied alone or in combination: (1) adolescents and parents' education and motivation at school, using eHealth tools and participatory learning; (2) general practitioners' training on HPV using motivational interviewing techniques and provision of a decision aid tool; (3) free-of-charge access to vaccination at school. Eligible municipalities (clusters) are located in one of 14 preselected French school districts and must have only one secondary school which enrols at least 2/3 of inhabitants aged 11-14 years. A randomisation stratified by school district and deprivation index allocated 90 municipalities into 6 groups of 15. The expected overall sample size estimate is 41 940 adolescents aged 11-14 years. The primary endpoint is the HPV VC (≥1 dose) among adolescents aged 11-14 years, at 2 months, at the municipality level (data from routine databases). Secondary endpoints include: HPV VC (≥1 dose at 6 and 12 months; and 2 doses at 2, 6 and 12 months); differences in knowledge, attitudes, behaviours, and intention among adolescents, parents and general practitioners between baseline and 2 months after intervention (self-administered questionnaires); incremental cost-effectiveness ratio. Implementation measures include dose, fidelity, adaptations, reached population and satisfaction (activity reports and self-administered questionnaires).

Ethics and dissemination: This protocol was approved by the French Ethics Committee 'CPP Sud-Est VI' on 22 December 2020 (ID-RCB: 2020-A02031-38). No individual consent was required for this type of research; all participants were informed of their rights, in particular not to participate or to oppose the collection of data concerning them. Findings will be widely disseminated (conference presentations, reports, factsheets and academic publications).

Trial registration number: NCT04945655.

Keywords: medical education & training; public health.

Conflict of interest statement

Competing interests: None declared.

© Author(s) (or their employer(s)) 2022. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.

Figures

Figure 1
Figure 1
PrevHPV study flow chart of expected number of participating municipalities. GPs, general practitioners; HPV, human papillomavirus.

References

    1. World Health Organisation . Human papillomavirus (HPV) and cervical cancer, 2022. Available:
    1. World Health Organisation . Human papillomavirus vaccines: who position paper, may 2017. Weekly epidemiological record 2017;2017:241–68.
    1. Chesson HW, Dunne EF, Hariri S, et al. . The estimated lifetime probability of acquiring human papillomavirus in the United States. Sex Transm Dis 2014;41:660–4. 10.1097/OLQ.0000000000000193
    1. de Martel C, Georges D, Bray F, et al. . Global burden of cancer attributable to infections in 2018: a worldwide incidence analysis. Lancet Glob Health 2020;8:e180–90. 10.1016/S2214-109X(19)30488-7
    1. de Sanjose S, Quint WG, Alemany L, et al. . Human papillomavirus genotype attribution in invasive cervical cancer: a retrospective cross-sectional worldwide study. Lancet Oncol 2010;11:1048–56. 10.1016/S1470-2045(10)70230-8
    1. International Agency for Research on Cancer, World Health Organization . The Global Cancer Observatory - World. Source: Globocan 2020, 2021. Available:
    1. International Agency for Research on Cancer, World Health Organization . The Global Cancer Observatory - France. Source: Globocan 2020, 2021. Available:
    1. Arbyn M, Xu L, Simoens C, et al. . Prophylactic vaccination against human papillomaviruses to prevent cervical cancer and its precursors. Cochrane Database Syst Rev 2018;5:CD009069. 10.1002/14651858.CD009069.pub3
    1. Bergman H, Buckley BS, Villanueva G, et al. . Comparison of different human papillomavirus (HPV) vaccine types and dose schedules for prevention of HPV-related disease in females and males. Cochrane Database Syst Rev 2019;2019:CD013479. 10.1002/14651858.CD013479
    1. Drolet M, Bénard Élodie, Pérez N, et al. . Population-level impact and herd effects following the introduction of human papillomavirus vaccination programmes: updated systematic review and meta-analysis. Lancet 2019;394:497–509. 10.1016/S0140-6736(19)30298-3
    1. Garland SM, Kjaer SK, Muñoz N, 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;63:519–27. 10.1093/cid/ciw354
    1. Lei J, Ploner A, Elfström KM, et al. . HPV vaccination and the risk of invasive cervical cancer. N Engl J Med 2020;383:1340–8. 10.1056/NEJMoa1917338
    1. Bruni L, Saura-Lázaro A, Montoliu A, et al. . HPV vaccination introduction worldwide and who and UNICEF estimates of national HPV immunization coverage 2010-2019. Prev Med 2021;144:106399. 10.1016/j.ypmed.2020.106399
    1. Nguyen-Huu N-H, Thilly N, Derrough T, et al. . Human papillomavirus vaccination coverage, policies, and practical implementation across Europe. Vaccine 2020;38:1315–31. 10.1016/j.vaccine.2019.11.081
    1. Ministère des solidarités et de la santé . Calendrier des vaccinations et recommandations vaccinales, 2021, 2021. Available:
    1. Institut National Du Cancer . Le plan cancer 2009-2013. available:. Available:
    1. Haute Autorité de Santé (HAS) . Cancer du col de l’utérus : une meilleure couverture vaccinale et un dépistage renforcé restent la priorité, 2017. Available:
    1. Fonteneau L, Barret AS, Lévy-Bruhl D. Evolution de la couverture vaccinale du vaccin contre le papillomavirus en France - 2008-2018. Bull Epidémiol Hebd 2019;22:424–30
    1. Bruel S, Rakoto Z, Agrinier N. French health students’ knowledge about human papilloma virus infections and vaccine: it is time to fill the gaps. In: Abstract book 2020 European Congress of clinical microbiology and infectious diseases, 2020.
    1. Chyderiotis S, Sicsic J, Raude J, et al. . Optimising HPV vaccination communication to adolescents: a discrete choice experiment. Vaccine 2021;39:3916–25. 10.1016/j.vaccine.2021.05.061
    1. Chan A-W, Tetzlaff JM, Gøtzsche PC, et al. . Spirit 2013 explanation and elaboration: guidance for protocols of clinical trials. BMJ 2013;346:e7586. 10.1136/bmj.e7586
    1. Ganry O, Bernin-Mereau A-S, Gignon M, et al. . Human papillomavirus vaccines in Picardy, France: coverage and correlation with socioeconomic factors. Rev Epidemiol Sante Publique 2013;61:447–54. 10.1016/j.respe.2013.04.005
    1. Rodriguez SA, Mullen PD, Lopez DM, et al. . Factors associated with adolescent HPV vaccination in the U.S.: a systematic review of reviews and multilevel framework to inform intervention development. Prev Med 2020;131:105968. 10.1016/j.ypmed.2019.105968
    1. Karafillakis E, Simas C, Jarrett C, et al. . HPV vaccination in a context of public mistrust and uncertainty: a systematic literature review of determinants of HPV vaccine hesitancy in Europe. Hum Vaccin Immunother 2019;15:1615–27. 10.1080/21645515.2018.1564436
    1. Bouchez M, Ward JK, Bocquier A, et al. . Physicians' decision processes about the HPV vaccine: a qualitative study. Vaccine 2021;39:521–8. 10.1016/j.vaccine.2020.12.019
    1. Loudon K, Treweek S, Sullivan F, et al. . The PRECIS-2 tool: designing trials that are fit for purpose. BMJ 2015;350:h2147. 10.1136/bmj.h2147
    1. Tuppin P, Rudant J, Constantinou P, et al. . Value of a national administrative database to guide public decisions: from the système national d'information interrégimes de l'Assurance Maladie (SNIIRAM) to the système national des données de santé (SNDS) in France. Rev Epidemiol Sante Publique 2017;65 Suppl 4:S149–67. 10.1016/j.respe.2017.05.004
    1. MacDonald NE, SAGE Working Group on Vaccine Hesitancy . Vaccine hesitancy: definition, scope and determinants. Vaccine 2015;33:4161–4. 10.1016/j.vaccine.2015.04.036
    1. Betsch C, Schmid P, Heinemeier D, et al. . Beyond confidence: development of a measure assessing the 5C psychological antecedents of vaccination. PLoS One 2018;13:e0208601. 10.1371/journal.pone.0208601
    1. Seanehia J, Treibich C, Holmberg C, et al. . Quantifying population preferences around vaccination against severe but rare diseases: a conjoint analysis among French university students, 2016. Vaccine 2017;35:2676–84. 10.1016/j.vaccine.2017.03.086
    1. Briançon S, Bonsergent E, Agrinier N, et al. . PRALIMAP: study protocol for a high school-based, factorial cluster randomised interventional trial of three overweight and obesity prevention strategies. Trials 2010;11:119. 10.1186/1745-6215-11-119
    1. Haute Autorité de Santé (HAS) . Guide méthodologique - choix méthodologiques pour l’évaluation économique la HAS, 2011. Available:
    1. Suarez L, Simpson DM, Smith DR. Errors and correlates in parental recall of child immunizations: effects on vaccination coverage estimates. Pediatrics 1997;99:e3. 10.1542/peds.99.5.e3
    1. Leite S. The basics about community based research. Advances in Social Sciences Research Journal 2019;6:178–83.
    1. Bleijenberg N, de Man-van Ginkel JM, Trappenburg JCA, et al. . Increasing value and reducing waste by optimizing the development of complex interventions: enriching the development phase of the medical Research Council (MRC) framework. Int J Nurs Stud 2018;79:86–93. 10.1016/j.ijnurstu.2017.12.001
    1. Blondel C, Barret A, Pelat C. Influence des facteurs socioéconomiques sur la vaccination contre les infections HPV chez les adolescentes en France. Bull Epidémiol Hebd 2019:441–50.
    1. Walling EB, Benzoni N, Dornfeld J, et al. . Interventions to improve HPV vaccine uptake: a systematic review. Pediatrics 2016;138. 10.1542/peds.2015-3863. [Epub ahead of print: 13 06 2016].
    1. Smulian EA, Mitchell KR, Stokley S. Interventions to increase HPV vaccination coverage: a systematic review. Hum Vaccin Immunother 2016;12:1566–88. 10.1080/21645515.2015.1125055
    1. Moore GF, Audrey S, Barker M, et al. . Process evaluation of complex interventions: medical Research Council guidance. BMJ 2015;350:h1258. 10.1136/bmj.h1258
    1. Brownson RC, Kumanyika SK, Kreuter MW, et al. . Implementation science should give higher priority to health equity. Implementation Sci 2021;16:28. 10.1186/s13012-021-01097-0

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