# Implementation evaluation of a school- and primary care-based multicomponent intervention to improve HPV vaccine coverage: Results from the PrevHPV randomized controlled trial

Aurélie Bocquier, Maïa Simon, Morgane Michel, Stéphanie Bonnay, Isabelle Adam, Serge Gilberg, Sébastien Bruel, Aurélie Gauchet, Anne-Sophie Leduc-Banaszuk, Amandine Gagneux-Brunon, et al.

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Aurélie Bocquier, Maïa Simon, Morgane Michel, Stéphanie Bonnay, Isabelle Adam, et al. Implementation evaluation of a school- and primary care-based multicomponent intervention to improve HPV vaccine coverage: Results from the PrevHPV randomized controlled trial. Journal of Infection and Public Health, 2025, 18 (11), pp.102931. 10.1016/j.jiph.2025.102931. hal-05227329

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Original Article

# Implementation evaluation of a school- and primary care-based multicomponent intervention to improve HPV vaccine coverage: Results from the PrevHPV randomized controlled trial

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Aurélie Bocquier a,*, Maïa Simon a,b, Morgane Michel c,d, Stéphanie Bonnay a,
Isabelle Adam b, Serge Gilberg e, Sébastien Bruel f,g, Aurélie Gauchet h,
Anne-Sophie LeDuc-Banaszuk i, Amandine Gagneux-Brunon j,k, Judith E. Mueller l,m,
Bruno Giraudeau n,o, Nathalie Thilly a,b, on behalf of the PrevHPV Study Group

ARTICLE INFO

Article history:

Received 16 March 2025

Received in revised form 7 July 2025

Accepted 12 August 2025

Keywords:

Human papillomavirus

School-based immunization programs

General practitioners

Implementation

Mixed method study

Effectiveness

A B S T R A C T

**Background:** Human papillomavirus (HPV) vaccine coverage (VC) remains lower than expected in France. The PrevHPV national research program aimed to codevelop and evaluate an intervention including three components: 'education and motivation' of adolescents in schools, 'at-school vaccination', 'general practitioners (GPs)' training. This study aimed to evaluate the implementation outcomes of each component, whether they affected effectiveness, and identify factors influencing implementation in schools.

**Methods:** A mixed-method study embedded in a cluster randomized controlled trial in 91 French municipalities (July 2021-June 2022). Quantitative data were collected through activity reports and questionnaires, and qualitative data through focus groups with school staff. The implementation outcomes were fidelity, dose, reach, acceptability and sustainability, as defined in the Medical Research Council guidance for process evaluation of complex interventions and Proctor et al.'s Implementation Outcomes Framework; the effectiveness outcome was HPV VC (≥ 1 dose) two months after the end of the intervention. Qualitative data were analyzed using the Consolidated Framework for Implementation Research.

**Results:** The fidelity, acceptability, and sustainability of all three components among participants who completed the intervention were high. However, the withdrawal of one-third of schools before the trial started and difficulties in mobilizing GPs negatively impacted the dose and reach outcomes. Estimates for the on-treatment analyses of the effectiveness were greater than those for which the dose of intervention received was not considered; 'at-school vaccination' (11.25 percentage points, p < 0.001) and 'GPs'

<footnote>ª Université de Lorraine, Inserm, INSPIIRE, Nancy F-54000, France</footnote>

<footnote>ᵇUniversité de Lorraine, CHRU-Nancy, Département Méthodologie Promotion Investigation, Nancy F-54000, France</footnote>

<footnote>c Université Paris Cité, ECEVE, UMR 1123, Inserm, Paris F-75010, France</footnote>

<footnote>d Assistance Publique-Hôpitaux de Paris, Hôpital Robert Debré, Unité d'épidémiologie Clinique, Paris F-75019, France</footnote>

<footnote>e Université Paris Cité, Département de Médecine Générale, Paris F-75014, France</footnote>

<footnote>f Département de Médecine Générale, Faculté de Médecine Jacques Lisfranc, Université Saint-Etienne-Lyon, Saint-Etienne F-42000, France</footnote>

<footnote>g CIC-Inserm, 1408 CHU de, Saint-Etienne, France</footnote>

<footnote>h Université Savoie Mont Blanc, Université Grenoble Alpes, LIP/PC2S, Grenoble F-38000, France</footnote>

<footnote>i Centre Régional de Coordination des Dépistages des cancers/Pays de la Loire, Angers F-49000, France</footnote>

<footnote>j CIC-1408 Vaccinologie, CHU de Saint-Etienne, Saint-Etienne F-42000, France</footnote>

<footnote>k Centre International de Recherche en Infectiologie, Equipe GIMAP, Université Jean Monnet, Université Lyon 1, Inserm, U1111, CNRS, UMR530, Institut Presage
Chaire Prevacci, Université Jean Monnet, France</footnote>

<footnote>l Institut Pasteur, Université Paris Cité, Unité d'Epidémiologie des Maladies Emergentes, Paris F-75015, France</footnote>

<footnote>m Université de Rennes, EHESP, CNRS, Inserm, Arènes - UMR 6051, RSMS (Recherche sur les Services et Management en Santé) - U 1309, Rennes F-35000, France</footnote>

<footnote>n Université de Tours, Université de Nantes, SPHERE U1246, Inserm, Tours F-37044, France</footnote>

<footnote>o CIC 1415, Université de Tours, Inserm, CHRU de Tours, Tours F-37044, France</footnote>

<footnote>* Correspondence to: UMR INSPIIRE, 9 avenue de la forêt de Haye - BP 20199, Vandœuvre-lès-Nancy Cedex 54505, France.</footnote>

<footnote>E-mail address: aurelie.bocquier@univ-lorraine.fr (A. Bocquier).</footnote>
training' (3.56 percentage points, p = 0.049) increased VC, while 'education and motivation' remained nonsignificant.

**Conclusions:** Increasing HPV VC among adolescents could be achieved by combining interventions in both schools and primary care settings. This study provides practical implications for implementing such interventions in real life.

**Trial registration:** Clinicaltrials.gov, NCT 04945655. Registered 30 June 2021, https://clinicaltrials.gov/study/NCT04945655

© 2025 The Authors. Published by Elsevier Ltd on behalf of King Saud Bin Abdulaziz University for Health Sciences. This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/).

## Introduction

Human papillomavirus (HPV) infection is the most common viral infection of the reproductive tract and is a major public health issue [1]. Vaccination is the most effective primary prevention method and a safe strategy against infection [2,3]. Since 2006, most high-income countries have introduced HPV vaccination in their vaccination schedules for adolescents [4]. However, HPV vaccine coverage (VC) has always been lower than expected in many countries, notably in France [4,5]. In 2018, this VC was at 24% among 16-year-old girls [6] leading the French authorities to launch the national PrevHPV research program to improve HPV acceptability and VC among adolescents. The PrevHPV multidisciplinary research consortium (Appendix A) codeveloped with stakeholders a multi-component intervention [7] and evaluated its effectiveness and implementation through a cluster randomized controlled trial (cRCT) [8]. Based on the scientific literature [5,9–17] and the findings on facilitators and barriers to HPV vaccination in the French population, identified during the first stages of the PrevHPV program [18–20], the consortium designed three components (see [7] and Appendix B section ‘2. Why’ for the detailed rationale behind components’ design): (1) adolescents’ and parents’ education and motivation (‘Education and motivation’ component) aimed to increase vaccination demand by modifying adolescents’ and parents’ knowledge, attitudes and intention; (2) easier access to vaccination for target adolescents (‘At-school vaccination’ component) by strengthening geographical and financial accessibility to vaccination; and (3) general practitioners’ training (‘GPs’ training’ component) aimed to improve health offer by improving GPs’ knowledge on HPV and communication skills. The first analyses run without considering the dose of intervention actually received showed that the ‘at-school vaccination’ component significantly increased VC at two months, while effects were not statistically significant for the other components [21]. However, weaknesses in the implementation of the three components may negatively impact effectiveness [22]. The evaluation of the implementation of such an intervention is thus highly valuable [23].

This article aimed to (1) evaluate the implementation outcomes of the PrevHPV intervention components; (2) examine whether the effectiveness was affected by implementation outcomes (post hoc on-treatment analysis); and (3) document factors influencing school-based components’ implementation.

## Material and methods

### Study design

This study used a mixed-method design and was embedded in the PrevHPV cRCT [8] carried out in France using an incomplete factorial. The cluster was the municipality, that were eligible if (1) they were located in one of fourteen selected school districts; (2) there was only one middle school in the municipality; and (3) at least two-thirds of the 11- to 14-year-old inhabitants attended this school. Only municipalities whose middle school agreed to

participate were included and randomized into one of six groups (Fig. 1). The factorial design – chosen to allow the evaluation of each intervention component, alone and in combination – was incomplete because the ‘at-school vaccination’ component was never carried out without the ‘education and motivation’ component, in order to enable informed decision-making. This cRCT was conducted between July 2021 and April 2022, in the context of the COVID-19 vaccination campaign for 12–17 year-olds, launched by the French government in June 2021 [24].

### The PrevHPV intervention

The intervention comprised three components (see details about its development in [7], the Template for Intervention Description and Replication Checklist in Appendix B, the logic model in Appendix C and the timeline in Appendix D).

The ‘education and motivation’ component was carried out in the middle schools of the selected municipalities (Groups 1, 2, 3, 4 – Fig. 1). All parents were invited by the school to participate in a web conference on HPV infection and vaccination delivered by experts. Pupils from 8th–9th-grade classes (13–15 years old) –to align with the school curriculum– then attended two two-hour educational group sessions on those topics during school hours. Each session used participatory learning and e-health tools (videos, serious game) developed with stakeholders, combining educational content and entertainment (edutainment). These sessions were planned to be delivered by school internal staff, but in the case of a lack of school human resources, researchers suggested trained external staff. Speakers were provided with a handbook that described activities that should be implemented during each session; they were also encouraged to attend an e-learning training.

The ‘at-school vaccination’ component consisted of offering free vaccination on school premises (Groups 1, 3) during prescheduled days. Vaccines were administered by health professionals from local vaccination centers to adolescents who, according to their vaccination records, had not previously received the HPV vaccine, were ≥ 11 years old, had no contraindications, and whose parents provided written clearly expressed consent. Paper information sheets and consent forms were provided to parents by school staff approximately one month before the vaccination day. There was no additional intervention to increase the likelihood they sign the consent form.

The ‘GPs’ training component consisted of three- to four-hour individual e-learning training (Groups 1, 2, 5). It included up-to-date information on HPV infection and vaccination, an introduction to motivational interviewing techniques applied to vaccination, and a decision-aid tool. This tool was codeveloped with stakeholders and aimed to help parents and adolescents come to a shared decision regarding HPV vaccination.

### Data collection

#### Implementation data

**Quantitative data.** Based on the Medical Research Council guidance for process evaluation of complex interventions [25] and the Proctor
<figure><img src="image_3.png" /><figcaption>**Fig. 1.** Flowchart of the municipality selection and group allocation of the PrevHPV cluster randomized controlled trial GP: general practitioner Mean/median size: mean/median number of inhabitants aged 11–14 (census data) Groups 1, 2, 3 and 4 received the ‘Education and motivation’ component; groups 1 and 3 received the ‘At-school vaccination’ component; and groups 1, 2 and 5 received the ‘GPs’ training’ component.</figcaption></figure>

et al.'s Implementation Outcomes Framework [26], we collected quantitative data to measure the fidelity, dose, reach, acceptability, and sustainability for each component (see Table 1 for detailed definitions). The data were collected through standardized activity reports during and/or at the end of the implementation (completed by the research team or school staff) and self-administered questionnaires collected at the end of the implementation.

**Qualitative data.** Four focus groups were conducted in June 2022 with school staff who implemented both the ‘education and motivation’ and the ‘at-school vaccination’ components (Groups 1, 3). The research team invited school staff involved in the implementation, by email, to participate in an online focus group (expected duration: 1h30). The participant information sheet stated that participants would be offered a 50€ shopping voucher. After providing oral consent, all focus groups were recorded and transcribed.

Each focus group was performed by two members of the research team (A.B., A.G., J.A., and/or S.B.) and followed an interview guide (Appendix E) composed of open-ended questions exploring how each component had been implemented, the barriers/facilitators encountered, participants’ perceptions of the impact/satisfaction of pupils and parents, and the sustainability of the component. This guide was developed through an informal consensus by the

researchers based on their expertise in qualitative research and guidance for process evaluation of complex interventions [25].

### Effectiveness outcome

The outcome was HPV VC (at least one dose) among adolescents aged 11–14 years who lived in participating municipalities, two months after the end of the intervention (June 30th, 2022).

Two data sources were used. First, the French national reimbursement database (Système National des Données de Santé, SNDS), which contains pseudonymized data on all healthcare consumption reimbursed by statutory health insurance for > 99% of the French population, provided beneficiaries' age, municipality of residence, and information on vaccines delivered in community pharmacies. Second, information on the number of adolescents vaccinated at school (not recorded in the SNDS) in Groups 1 and 3 was collected by the research team during the implementation, along with their age and municipality of residence.

### Data analyses

#### Implementation evaluation (objective 1)

We used descriptive statistics to analyze the implementation outcomes. Quantitative variables are presented as the means and
<table><caption>**Table 1**
Quantitative data sources used to measure implementation outcomes for each of the PreVHPV intervention components.</caption><thead><tr><th rowspan="2">PreVHPV intervention component</th><th colspan="3">Educational and motivation</th><th colspan="6">Educational sessions for pupils</th><th colspan="6">At-school vaccination</th><th rowspan="2">GP's 'training</th></tr><tr><th>Web conference for parents</th><th>F</th><th>D</th><th>R</th><th>A</th><th>S</th><th>F</th><th>D</th><th>R</th><th>A</th><th>S</th><th>F</th><th>D</th><th>R</th><th>A</th><th>S</th></tr></thead><tbody><tr><td>Implementation outcomes</td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td></tr><tr><td>Data source</td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td></tr><tr><td>Research team standardized activity report completed during the components' implementation</td><td>X</td><td></td><td></td><td></td><td></td><td>X</td><td>X</td><td></td><td>X</td><td></td><td>X</td><td>X</td><td></td><td></td><td></td><td></td></tr><tr><td>School project leader standardized activity report completed during the components' implementation</td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td></tr><tr><td>Data extracted from the online web conference or training applications</td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td></tr><tr><td>Self-administered online questionnaire completed by parents at the end of the web conference</td><td>X</td><td>X</td><td></td><td></td><td>X</td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td></tr><tr><td>Educational session speaker standardized activity report and self-administered paper questionnaire</td><td></td><td></td><td></td><td></td><td></td><td></td><td>X</td><td>X</td><td></td><td>X</td><td></td><td></td><td></td><td></td><td></td><td></td></tr><tr><td>Self-administered paper questionnaire completed by adolescents immediately after vaccine administration</td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td>X</td><td></td><td></td><td></td></tr><tr><td>Self-administered online questionnaire completed by school staff the week after the vaccination day</td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td>X</td><td></td><td></td><td></td></tr><tr><td>Self-administered online questionnaire completed by GP's two months after the end of the implementation</td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td>X</td><td>X</td><td></td><td></td></tr></tbody></table>

A: acceptability ('perception among implementation stakeholders that a given treatment, service, practice or innovation is agreeable, palatable, or satisfactory'); D: dose ('how much intervention is delivered'); F: fidelity ('the consistency of what is implemented with the planned intervention'); GP: general practitioner; R: reach ('the extent to which a target audience comes into contact with the intervention, i.e., an individual-level measure of participation'); S: sustainability ('the likelihood the innovation will be put in place or delivered in the long term')

standard deviations, and categorical variables as numbers and percentages.

A 'dose of intervention' was calculated for each included municipality and each component it had to implement (according to its randomization group). The 'dose of intervention' was a quantitative variable that represented, from a population health perspective, an opportunity for adolescents to be vaccinated and was calculated as follows:

- 'Education and motivation' component:

$$ \frac{(\text{No. of classes without any session\*0}) + (\text{No. of classes with only1session\*0.5})}{(\text{No. of classes with2sessions\*1})} $$
$$ \text{Total no. of classes of the middle school} $$

- 'At-school vaccination' component:

$$ \frac{\text{No. of pupils invited to participate in the vaccination day}}{\text{Total no. of pupils of the middle school}} $$

- 'GP's 'training' component:

$$ \frac{\text{No. of GPs who completed the online training}}{\text{Total no. of eligible GPs practicing in the municipality}} $$

### #Educational group sessions for pupils at school

For each municipality and each component, the dose of intervention varied from 0 to 1; 0 if the component has not been implemented at all and 1 if the component has been fully implemented.

### Post hoc on-treatment analysis of the effectiveness (objective 2)

The analysis was carried out on all included municipalities. The effectiveness of each component was assessed using a cluster-level analysis in which each cluster was weighted by its size (i.e., the number of inhabitants aged 11–14).

In previous analyses, we did not consider the dose of intervention received (i.e., considering that each cluster received 100% of the component(s) planned in the group in which it was randomized) [21]. We constructed a linear model (dependent variable: HPV VC two months after the end of the intervention) with one fixed effect per component, adjusted for baseline HPV VC (June 30th, 2021) and their associated two second-order interaction terms ('Education and motivation'\*"GP's' training' and 'At-school vaccination'\*"GP's' training').

To perform the post hoc on-treatment analysis, we reran the model by replacing the fixed effects with the 'dose of intervention' variables.

Analyses were performed using SAS version 9.4 (SAS Institute, Cary, North Carolina, USA).

### Facilitators and barriers to school-based component implementation (objective 3)

We analyzed the transcripts of the focus groups using a thematic analysis approach, with the Consolidated Framework for Implementation Research (CFIR) [27] as a guide.

An analysis grid was developed by two researchers (A.B. and S.B.) and discussed until a consensus was reached. Each focus group was then analyzed by A.B. according to this grid.

## Results

Overall, 91 municipalities were included and randomized into six groups (Fig. 1); allocation resulted in 61, 31 and 45 municipalities exposed to the 'education and motivation', 'at-school vaccination' and 'GP's' training' components, respectively.

### Implementation outcomes

Detailed results of the implementation evaluation are presented in Table 2.
<table><caption>**Table 2**
Results of the implementation evaluation for each of the three components of the PreVHPV intervention.</caption><thead><tr><th></th><th>Education and motivation (61 schools)</th><th>Pupils</th><th>At-school vaccination (31 schools)</th><th>GP's training (45 municipalities)</th></tr></thead><tbody><tr><td>Discontinuation before the beginning of the component</td><td>Among the 61 schools:<br><b>34</b> % (n = 21) of schools withdrew their consent before the web conference for parents</td><td>Among the 61 schools:<br><b>38</b> % (n = 23) of schools withdrew their consent before the education sessions for pupils</td><td>Among the 31 schools:<br><b>39</b> % (n = 12) of schools withdrew their consent before the beginning of any action of the component</td><td>Among the 45 municipalities:<br>In <b>42</b> % (n = 19) municipalities, no GP agreed to participate in the training</td></tr><tr><td>Fidelity</td><td>Among the 40/61 schools that continued:<br><b>98</b> % (n = 39) of schools sent the web conference invitation to parents; 14 web conferences organized with, as planned, two experts each</td><td>Among the 38/61 schools that continued, accounting for 317 <sup>8th-9th-grade</sup> classes:<br><b>69</b> % (n = 218) of the 8th-9th grade classes received two educational sessions<br>Among the 257 <sup>1st</sup> sessions and 225 <sup>2nd</sup> sessions organized:<br><b>64</b> % (n = 165) of the 1st and <b>54</b> % (n = 121) of the 2nd sessions conducted as intended (i.e., all planned activities performed)<br>Among the 86 speakers who delivered at least one session:<br><b>70</b> % (n = 60) speakers were school staff (33 were teachers, mostly life sciences teachers; 24 school nurses; 3 principal education advisers or social workers); 28 % (n = 24) were external professionals<sup>a</sup></td><td>Among the 19/31 schools that continued:<br><b>89</b> % (n = 17) of schools provided invitation and consent forms to all pupils (others targeted only the 8th-9th grades)<br><b>100</b> % (n = 19) planned at least one vaccination day (11 one day, 7 two days and 1 three days)<br>Among the 1409 first injections planned in the 19 schools:<br><b>89</b> % (n = 1256) of first injections planned actually administered</td><td>Among the 199 GP's practicing in the 45 municipalities:<br><b>100</b> % of GP's have been invited to participate</td></tr><tr><td>Dose</td><td>Among the 12/14 web conferences with at least one participant:<br>Mean duration of connection = 63 ± 24 min, i.e. <b>79</b> % of mean total duration of the web conferences</td><td>Among the 61 schools selected to receive the component:<br><b>0.25 ± 0.22</b><br>For the 257 <sup>1st</sup> sessions and 225 <sup>2nd</sup> sessions organized:<br>Mean session duration = <b>1h34 ± 26 min</b> for the 1st and <b>1h21 ± 26 min</b> for the 2nd sessions<br>Among the 38/61 schools that did not discontinued, accounting for 317 <sup>8th-9th-grade</sup> classes:<br><b>Close to 100</b> % since educational sessions organized during school hours (pupils' absenteeism was not recorded)</td><td>Among the 31 schools selected to receive the component:<br><b>0.58 ± 0.48</b></td><td>Among the 45 municipalities selected to receive the component:<br><b>0.24 ± 0.30</b><br>Among the 43 GP's who completed the training:<br>Mean duration spent on the training website = 2h02 ± 2 h</td></tr><tr><td>Reach</td><td>Among the 16/672 invited parents:<br><b>&lt; 1 %</b> (n = 120) parents participated in a web conference</td><td>Among the 257 1st sessions and 225 2nd sessions organized, according to speakers:<br>Pupils' attentiveness satisfying in <b>91 %</b> (n = 233) of the 1st and <b>90 %</b> (n = 202) of the 2nd sessions Pupils' participation satisfying in <b>87 %</b> (n = 224) of the 1st and <b>88 %</b> (199) of the 2nd sessions</td><td>Among the 8257 pupils invited to initiate HPV vaccination at school (HPV vaccination status not known before the vaccination day):<br><b>15 %</b> (n = 1256) of pupils invited to initiate HPV at school get vaccinated<br>Among the 1212/1256 vaccinated adolescents who completed the postvaccination questionnaire:<br><b>96 %</b> (n = 1160) of vaccinated pupils satisfied with the organization<br>Among the 65 school staff (from 17 different schools) who completed the postvaccination day questionnaire:<br><b>78 %</b> (n = 51) of school staff satisfied with the organization<br>Among the 17/19 schools with available data<sup>b</sup>:<br><b>76 %</b> (n = 13) of schools considered conducting such vaccination day(s) during the following school year (69 % while adapting it)</td><td>Among the 199 GP's contacted:<br><b>23 %</b> (n = 46) of invited GP's have registered for the training; 22 % (n = 43) did attend it</td></tr><tr><td>Acceptability</td><td>Among the 106/120 participating parents who answered the question:<br><b>84</b> % (n = 89) of parents agreed that the meeting had met their expectations</td><td>Among the 257 1st sessions and 225 2nd sessions organized, according to speakers:<br>Pupils' attentiveness satisfying in <b>91 %</b> (n = 233) of the 1st and <b>90 %</b> (n = 202) of the 2nd sessions Pupils' participation satisfying in <b>87 %</b> (n = 224) of the 1st and <b>88 %</b> (199) of the 2nd sessions</td><td>Among the 32/38 schools with available data<sup>b</sup>:<br><b>91 %</b> (n = 32) of schools considered conducting such sessions for pupils during the following school year (79 % while adapting them)</td><td>Among 33/43 GP's who completed the posttraining questionnaire:<br><b>100 %</b> (n = 33) GP's satisfied with the up-to-date information on HPV infection/vaccination training section, and <b>94 %</b> (n = 31) with the motivation interview techniques section<br><b>64 %</b> (n = 21) GP's agreed that the decision aid tool was easy to use</td></tr><tr><td>Sustainability</td><td>Among the 32/40 schools with available data<sup>b</sup>:<br><b>56 %</b> (n = 18) of schools considered conducting such meeting for parents during the following school year (83 % of them while adapting it)</td><td></td><td></td><td>Among 33/43 GP's who completed the posttraining questionnaire:<br><b>100 %</b> (n = 33) of GP's agreed that this training should be made more widely available to other GP's and <b>61 %</b> (n = 20) with the idea of using the decision aid tool frequently</td></tr></tbody></table>

GP: general practitioner

<footnote>a Schools for which data could be collected in June 2022.</footnote>

<footnote>b Missing data for two speakers.</footnote>
<caption>**Table 3**</caption>

Effect of each component of the intervention on HPV vaccination coverage (in percentage points) at two months in 11- to 14-year-olds (n = 91 municipalities).

<table><thead><tr><th rowspan="2"></th><th colspan="3">Analyses without considering the dose of intervention actually received<sup>a</sup> [21]</th><th colspan="3">Post hoc on-treatment analysis</th></tr><tr><th>Estimate<sup>b</sup></th><th>95 % confidence interval</th><th>p</th><th>Estimate<sup>b</sup></th><th>95 % confidence interval</th><th>p</th></tr></thead><tbody><tr><td>Education and motivation</td><td>-0.08</td><td>[-2.54-2.39]</td><td>0.950</td><td>2.58</td><td>[-1.73-6.89]</td><td>0.241</td></tr><tr><td>At-school vaccination</td><td>5.50</td><td>[3.13-7.88]</td><td>&lt; 0.001</td><td>11.25</td><td>[9.09-13.40]</td><td>&lt; 0.001</td></tr><tr><td>GPs' training</td><td>-1.46</td><td>[-3.44-0.53]</td><td>0.150</td><td>3.56</td><td>[0.02-7.11]</td><td>0.049</td></tr></tbody></table>

GP: general practitioner

<sup>a</sup> The likelihood ratio test that globally assessed the significance of the interaction terms was not significant (p = 0.44); thus, interaction terms were not included in the post-hoc on-treatment analysis.

<sup>b</sup> Results of the regression model adjusted for baseline vaccination coverage.

### 'Education and motivation' component

Overall, 21/61 (34%) schools withdrew their consent before implementing this component (main reasons: challenges related to the COVID-19 pandemic, the project being perceived as too time-consuming, lack of time for school staff, lack of available school staff, school staff turnover).

Among the schools that continued, fidelity for web conferences was high: 98% of schools sent invitations to parents as planned. Less than 1% of the invited parents participated in a web conference, but those who participated attended on average 79% of the conference's duration, and mostly agreed that the meeting had met their expectations. A slight majority of schools indicated that they were considering conducting such meetings during the following school year, most often with adaptations (main adaptation: organize face-to-face meetings).

Two additional schools withdrew their consent before the educational sessions for pupils started. Among those that continued, two educational sessions were organized in 69% classes. Among the speakers who delivered at least one session, 70% were school staff (mostly teachers and school nurses), and 28% were external professionals (missing data: 2%). At the school level, the mean dose of intervention was 0.25 ± 0.22. On average, the sessions lasted 1h30, and reached nearly all pupils of targeted classes (pupils' absenteeism was not recorded). Session speakers rated pupils' attentiveness and participation (i.e., involvement in the activities during the session) satisfying for approximately 90% of the sessions. Most schools reported that they were considering conducting such sessions again during the following school year, most often with adaptations (main adaptation: shorter sessions or only one 2 h session).

### 'At-school vaccination' component

Overall, 12/31 (39%) schools withdrew their consent before implementing this component. Among the schools that continued, 89% provided consent forms to receive HPV vaccination to all pupils as planned, and all of them planned at least one vaccination day. Overall, 15% of the pupils invited to initiate HPV vaccination at school - regardless of their prior vaccination status, which was not known - were vaccinated on the scheduled vaccination day. At the school level, the mean dose of intervention was 0.58 ± 0.48. Among pupils for whom clearly expressed consent from both parents was obtained, 89% received the first injection as planned; the two main reasons for not receiving the vaccine despite parental consent were absence of the pupil on the vaccination day and the pupil having forgotten his/her vaccination record. Almost all pupils vaccinated at school reported being satisfied with the implementation of the vaccination day(s) at school. Most of the school staff who completed the postvaccination day questionnaire were also satisfied with the organization. Three-quarter of the schools were considering conducting such vaccination day(s) during the following school year, often with adaptations (main adaptation: externalizing parental consent management).

### 'GPs' training component

As planned, researchers contacted all 199 eligible GPs practicing in the 45 municipalities exposed to this component to invite them to participate in the training. Among the GPs contacted, 23% registered for

the training, and 22% ultimately attended it. This corresponds to a total of 43 GPs trained, and 26 municipalities with at least one GP trained. At the municipality level, the mean dose of the intervention was 0.24 ± 0.30. The latter were all very satisfied with the training, and agreed that it should be made more widely available to other GPs. Approximately 60% agreed that the decision aid tool was easy to use, and agreed with the idea of using it frequently.

### Post hoc on-treatment analysis of the effectiveness

For the three intervention components, estimates of the effect on VC at two months were greater for the on-treatment analyses than for the analysis that did not consider the intervention dose received (Table 3). For the 'at-school vaccination' component, the estimate increased from 5.50 percentage points (pp; p < 0.001) to 11.25 pp (p < 0.001). The 'GPs' training' component reached significance (3.56 pp, p = 0.049). No significant effect was observed for 'education and motivation'. No significant interactions between the components was found.

### Facilitators and barriers to the implementation of school-based components

Overall, 17 school staff members (Table 4) from 11 middle schools participated in the focus groups (mean duration: 1h37 ± 14 min).

<caption>**Table 4**</caption>

Characteristics of the participants in the focus groups.

<table><thead><tr><th>Participant ID</th><th>Sex</th><th>Profession</th><th>Middle school ID</th><th>Total number of pupils in the school</th></tr></thead><tbody><tr><td colspan="5"><strong>Focus Group 1</strong></td></tr><tr><td>P1</td><td>F</td><td>School nurse</td><td>MS3</td><td>[300-400]</td></tr><tr><td>P2</td><td>F</td><td>Chief education adviser</td><td>MS3</td><td>[300-400]</td></tr><tr><td>P3</td><td>F</td><td>School nurse</td><td>MS8</td><td>&lt; 200</td></tr><tr><td colspan="5"><strong>Focus Group 2</strong></td></tr><tr><td>P4</td><td>F</td><td>School nurse</td><td>MS9</td><td>&lt; 200</td></tr><tr><td>P5</td><td>F</td><td>School nurse</td><td>MS2</td><td>[400-500]</td></tr><tr><td>P6</td><td>F</td><td>Teacher in life sciences</td><td>MS6</td><td>[300-400]</td></tr><tr><td>P7</td><td>F</td><td>School nurse</td><td>MS1</td><td>[300-400]</td></tr><tr><td colspan="5"><strong>Focus Group 3</strong></td></tr><tr><td>P8</td><td>F</td><td>Head of school</td><td>MS7</td><td>[500-600]</td></tr><tr><td>P9</td><td>M</td><td>Head of school</td><td>MS11</td><td>[300-400]</td></tr><tr><td>P10</td><td>F</td><td>Teacher in life sciences</td><td>MS11</td><td>[300-400]</td></tr><tr><td>P11</td><td>M</td><td>Head of school</td><td>MS6</td><td>[300-400]</td></tr><tr><td>P12</td><td>F</td><td>Assistant head of school</td><td>MS6</td><td>[300-400]</td></tr><tr><td>P13</td><td>F</td><td>Head of school</td><td>MS5</td><td>[400-500]</td></tr><tr><td colspan="5"><strong>Focus Group 4</strong></td></tr><tr><td>P14</td><td>M</td><td>Head of school</td><td>MS10</td><td>[900-1000]</td></tr><tr><td>P15</td><td>F</td><td>Assistant head of school</td><td>MS2</td><td>[400-500]</td></tr><tr><td>P16</td><td>F</td><td>Head of school</td><td>MS4</td><td>[500-600]</td></tr><tr><td>P17</td><td>F</td><td>Assistant head of school</td><td>MS4</td><td>[500-600]</td></tr></tbody></table>

F: female; M: male; P: participant; MS: middle school
Facilitators and/or barriers were identified in each of the five CFIR domains (Table 5).

Regarding the 'Innovation domain', the materials and tools provided to deliver the educational group sessions, which were rated as very well designed, facilitated the implementation. However, schools faced difficulties in organizing educational group sessions and managing consent forms for vaccination (e.g., process to ensure timely return, to check for completeness).

External factors such as the COVID-19 pandemic (which provided schools with experience in organizing tests and vaccinations on school premises), and the National Education curriculum (providing a conducive regulatory framework for implementing educational sessions on HPV at school) were facilitators. Nevertheless, the COVID-19 pandemic has also resulted in an overload of work for school staff and, among parents, in some confusion between the COVID-19 and the HPV vaccines.

Several school's characteristics were rated as facilitators of implementation, e.g., structural characteristics (e.g., small size), good communication among the school staff, favorable attitudes toward HPV vaccine promotion at school, and the availability of different kinds of financial and material resources. In contrast, a limited on-site presence of school nurses, a lack of funding to pay staff for their participation, and a lack of computers and low-quality internet connections impaired implementation.

Many different parties can facilitate implementation in schools: national, regional and local levels of national education, head of school, school board and parents' associations. The availability and motivation of the school project leader, the presence of teachers trained in sex education, the availability of external staff to deliver educational sessions, and the skills of the vaccination center in organizing the vaccination day were also facilitators. In contrast, barriers included teachers' feelings of a lack of legitimacy to deliver educational sessions on HPV, and school nurses' discomfort in managing a classroom.

The presence of an external facilitator from the research team, the guidelines and training provided to school staff, and the adaptability of the intervention to local constraints facilitated implementation.

## Discussion

Approximately one-third of schools withdrew their consent before beginning the intervention, and parents and GPs were difficult to mobilize, resulting in low doses of intervention and limited reach of the target population. However, fidelity, acceptability and sustainability were high among those who participated. Estimates for the on-treatment analyses were statistically significant for 'at-school vaccination' and 'GPs' training.

### Schools: a significant role to play in HPV vaccine promotion but challenging settings for implementation

Offering free HPV vaccination at school significantly increased VC at two months. These results support the generalization of school vaccination campaigns among all 7th-grade pupils announced by the French government in 2023 which, according to preliminary findings, led to an increase in VC of a similar magnitude to that observed in our study [28]. We also found that the effectiveness of the 'education and motivation' component increased in on-treatment analysis, but still did not reach statistical significance. The time horizon used for the present evaluation may have been too short to highlight the benefits of education on VC; analyses of the effectiveness at six and 12 months are ongoing. Furthermore, 'education and motivation' did not target pupils from 6th–7th grade classes, which may have impaired the effect of this component. Finally, as discussed below, this component has failed to reach parents, who ultimately decide

whether to vaccinate their children. However, if school vaccination campaigns are generalized, it seems obvious for ethical reasons that they should include in the first-place education of adolescents and their parents.

Our study reveals several challenges to implementing HPV vaccine promotion at school. Approximately one-third of the schools withdrew their consent before the beginning of the intervention. These withdrawals are partly due to the COVID-19 pandemic context. Indeed, the intervention had to be postponed twice, and this may have discouraged some schools from participating. Moreover, when the intervention began in the autumn of 2021, the pandemic was still ongoing and led to an overload of work for school staff (e.g., due to staff absenteeism, the organization of nasopharyngeal tests and COVID-19 vaccination). Beyond this context, our results suggest that several barriers may impair school participation in real-life conditions, including a short presence time for school nurses, inability to pay staff for additional duties, lack of computer facilities or insufficient support from various parties. Enhancing the role of schools in HPV vaccine promotion should thus be associated with actions at the organizational level, even if they are challenging [29]. Our results also suggested that the involvement of an external facilitator may support the implementation of school-based interventions, aligning with the 'provide interactive assistance' strategy from the Expert Recommendations for Implementing Change (ERIC) project [30].

Regarding the 'education and motivation' component, we reached approximately 100% of the targeted pupils because of education group sessions organized during school time (in France, school attendance is compulsory until age 16). In contrast, one particular challenge was to reach parents. To address this, we recorded a conference and made it available online, but we could not measure the number of unique views. To improve parents' reach, one way could be to provide them with written information on HPV vaccination at the end of the school year before HPV vaccination in the next school year, as in Québec [31]. Moreover, the intervention dose for the 'education and motivation' component was low (0.25). While this is partly explained by the number of withdrawals (the dose of intervention equal to zero), the main reason is our method of calculation, which included all classes from grades 6th to 9th, even though schools were encouraged to implement educational group sessions for 8th–9th grades only. Our qualitative results also showed that planning two two-hour educational group sessions is very complex for schools and suggested that the session number and/or duration should be adapted when such interventions are generalized.

Regarding the 'at-school vaccination' component, the reach (calculated as the percentage of pupils vaccinated at school among all pupils invited, regardless of their prior HPV vaccination status) was moderate (15%). However, the reach among previously unvaccinated pupils is likely higher, as it would be calculated using the same numerator but a smaller denominator (number of invited pupils minus number of those already vaccinated). Although the exact number of eligible pupils (i.e., unvaccinated) was unknown, national data suggest they constituted the majority since HPV VC 1 dose in France in 2021 among 11–14-year-olds was approximatively 30% for girls and 10% for boys [32]). Our results have practical implications for improving reach in routine practice. First, these implications concern parental consent. According to French law, the free, informed, and clearly expressed consent of both parents (i.e., an opt-in approach) of both parents is required to vaccinate a minor. While shifting from an opt-in to an opt-out approach could positively impact HPV VC [33], such an approach is not legally permitted in France. In this context, our results suggest that parental consent forms should be made more accessible and easier to understand, and that logistical strategies should be developed to improve their return and facilitate their management. Processes to obtain parental
<caption>**Table 5**</caption>

Facilitators and barriers to the implementation of the PrevHPV school-based components of the intervention, categorised according to the five domains of the consolidated framework for implementation research (CFIR)ª.

<table><thead><tr><th></th><th>Facilitators</th><th>Barriers</th></tr></thead><tbody><tr><td><strong>I. Innovation domain</strong></td><td></td><td></td></tr><tr><td>Innovation source</td><td>Scientifically based<br>"It is certain that [...] the somewhat scientific field, well, I think that also played a small part" (P6)</td><td>/</td></tr><tr><td>Innovation complexity</td><td>/</td><td>Complicated to organize educational sessions<br>"On the logistical side, it was still [...] a major difficulty" (P5)<br>Complicated to manage consent forms<br>"I was the one in charge of managing the returns of all the files and checking that everything was complete [...] it took me an insane amount of time" (P10)</td></tr><tr><td>Innovation design</td><td>Materials for education sessions well designed<br>"It was well-detailed, did not demand much time from us because... we could make them our own, and it is rare [...] this was very well designed" (P1)</td><td>Information for parents – online format<br>"They [parents] could not connect, so they were... disappointed" (P1)<br>Consent forms – content<br>"I found that the consents were extremely complex; clearly, many families gave up on vaccination due to the complexity of the document" (P14)<br>Consent forms – paper format<br>"I no longer produce paper notices; it is a big waste of paper [...] I'm also trying to lead the school toward a sustainable development approach" (P8)</td></tr><tr><td><strong>II. Outer setting domain</strong></td><td></td><td></td></tr><tr><td>Critical incidents</td><td>Covid-19 – experience of schools in organizing vaccination day<br>"We're coming out of 2 years of a pandemic where we have had saliva tests, nasopharyngeal swabs, Covid vaccinations done in schools, so we were truly well-versed. It was not complicated at all, you know." (P8)</td><td>Covid-19 – school staff heavy workload<br>"We were still in a context where there was also Covid, so we were very busy with other things." (P15)<br>Covid-19 – parents' confusion between vaccines<br>"There was confusion among some families about whether to vaccinate their children against Covid." (P17)</td></tr><tr><td>Local attitudes</td><td>/</td><td>Negative attitudes toward vaccination<br>"[Have there been reactions from the parents?] An anti-vax phenomenon, that also depends on the location, geography, and the population" (P17)</td></tr><tr><td>Local conditions</td><td>High SSE associated with pupils' positive attitude<br>"I think that the population from more privileged categories [...] tends to be quite sensitive and interested in everything external" (P16)</td><td>High SSE associated with low parents' availability<br>"We have a majority of families, rather very privileged ones, who work and have quite a significant commuting time. [...] they were not available" (P17)<br>Low SSE associated with parents' low participation<br>"I think these families [of low SSE], we have not managed to get them involved [...] when I looked at the lists of pupils who got vaccinated, they were mostly from higher SSE backgrounds." (P14)</td></tr><tr><td>Policies & laws</td><td>Intervention in line with the official National Education curriculum<br>"Indeed, it fits perfectly within the National Education program, it is a program about sex education" (P2)<br>"We're truly connected to the cycle 4 [grades 7-9] programs." (P11)</td><td>Not mandatory<br>"As there's no obligation, at some point, we also need to target the important information among others." (P12)</td></tr><tr><td><strong>III. Inner setting domain</strong></td><td></td><td></td></tr><tr><td>Structural characteristics</td><td></td><td></td></tr><tr><td>Physical infrastructure</td><td>Small size<br>"In addition, it is a small school; so it was quite easy." (P9)</td><td>/</td></tr><tr><td>Information technology infrastructure</td><td>Availability and common use of the National Education digital workspace (ENT)<br>"The ENT [...] has expanded a lot, thanks to Covid, let us say... so now parents are used to going on this platform... it is a good communication tool." (P1)</td><td>/</td></tr><tr><td>Work infrastructure</td><td>/</td><td>School setting's specific constraints<br>"There are 'school' procedures that mean there are deadlines, moments when we cannot do things anymore, it is too late" (P8)</td></tr><tr><td>Relational connections</td><td>Good relationships within all school staff<br>"When there's no stress, when we do not feel pressure from colleagues, it makes things easier." (P1)</td><td>/</td></tr><tr><td>Communications</td><td>Good team communication<br>"They [your colleagues] should more or less know how things will unfold [...] Communication, that is what's important" (P3)</td><td>/</td></tr><tr><td>Culture</td><td>School staff favourable attitude toward intervention on HPV<br>"When we discussed it in the teachers' room, everyone actually found it interesting that we were doing these interventions [sessions on HPV]" (P10)</td><td></td></tr><tr><td>Compatibility</td><td>/</td><td>Other school-based actions<br>"Because we are extremely in demand in schools. Soon, we will no longer teach biology, maths, and French, you know. That is the problem." (P8)</td></tr></tbody></table>

(continued on next page)
<table><caption>Table 5 (continued)</caption><thead><tr><th></th><th>Facilitators</th><th>Barriers</th></tr></thead><tbody><tr><td>Available resources</td><td></td><td></td></tr><tr><td>Funding</td><td>Funding available to pay staff for overtime hours<br>"I compensated the teachers with overtime pay for leading the projects, for all the hours they worked outside of their regular teaching hours" (P8)</td><td>No funding available to pay staff for participation or overtime hours<br>"The nurse, if she did not want to participate in the project, it is also because there was no compensation planned" (P14)<br>"We did not necessarily have the means to pay these [overtime] hours to these teachers, so [...] difficulties arise" (P15)</td></tr><tr><td>Space</td><td>Adequate premises for organizing vaccination day<br>"We have facilities that truly adapt without disrupting anything else. We had everything to accommodate the vaccination. Therefore, it was very, very simple" (P1)</td><td>/</td></tr><tr><td>Materials & equipment</td><td>Availability of tablets in addition to computers<br>"We went into a multimedia room and [...] we were able to take the tablets from the library and the science tablets so that each pupil had a screen" (P12)</td><td>Lack of computer, low quality of the internet connection<br>"[What has hindered the sessions from taking place?] The internet connections. The number of computers. Access to computer or technology rooms where we have the computers." (P7)</td></tr><tr><td>Staff</td><td>Availability of contractual teacher<br>"We have a contractual teacher [...] she added herself to the setup through overtime hours. That was a facilitator" (P12)</td><td>Short attendance time of school nurses<br>"We have a nurse one day a week, so if she's involved in these sessions, she cannot do anything else." (P17)<br>School staff turnover<br>"A life sciences teacher told me, 'Great, I'm interested.' However, this teacher was on leave, expecting to return, but unfortunately faced a serious health issue and had to be replaced." (P12)<br>Unanticipated school staff absence<br>"The pupils scheduled from 8 a.m. to 9 a.m. [for vaccination], their teacher was absent. Therefore, they did not come [...] That was something we hadn't anticipated at all." (P8)</td></tr><tr><td>IV. Individuals domain</td><td></td><td></td></tr><tr><td>High-level leaders</td><td>Ministries of Education and of Health – support<br>"Maybe in the long run, it could become a public policy, a proactive one, with a real agreement between the Ministry of Health and the Ministry of National Education" (P9)<br>Regional/local level of the National Education – support<br>"I think that if we have the support of the inspectors, for example, if it goes through the back-to-school letter they send to teachers at the beginning of each year, emphasizing the importance of doing [the activity], it will also be easier to implement" (P13)<br>Head of school – support<br>"From my perspective, I'd say for this to happen, the head of school also needs to agree" (P10)<br>School board – support<br>"For me, starting the project without the partnership agreement being approved by the School Board was out of the question" (P8)<br>Committee for Health and Citizenship Education (CESC) – support<br>"There's a second lever that we did not use, which perhaps we should have, and that was the CESC" (P9)</td><td>/</td></tr><tr><td>Opinion leaders</td><td>Parents' association – support<br>"We still managed to disseminate information through [...] the Parents' Association, which was an important intermediary" (P14)</td><td>/</td></tr><tr><td>Implementation leads</td><td>School project leader – availability and motivation<br>"I was truly motivated because vaccine it is a real issue." (P3)</td><td>School project leader – availability and motivation<br>"The idea of who coordinates and how is quite variable based on the school nurse's availability. Does she wish to be involved, and is it feasible?" (P17)</td></tr><tr><td>Other implementation support</td><td>Education assistants – skills and experience<br>"Well, the education assistants are truly experienced in this kind of task. The kids who were not there in the morning or did not have their documents [the day of the vaccination] were replaced by those in the afternoon." (P11)</td><td>/</td></tr><tr><td>Innovation deliverers</td><td>Teachers – training in sex education and motivation<br>"We both have experience in sex education, so it seemed, you know, straightforward to us" (P1)<br>"I think there's also a context to consider, which is that both life sciences teachers are very active." (P16)<br>Vaccination centre – skills and experience<br>"Therefore, the main facilitator for us was precisely the approach of the vaccination centre and their organization [...] For them, everything was perfectly clear and organized" (P9)<br>External staff – availability<br>"We had to rely on volunteers who were suggested to us by the research team" (P14)</td><td>Teachers – feeling of a lack of legitimacy<br>"The teachers indeed did not feel legitimate to conduct these sessions, including in life and earth sciences..." (P14)<br>School nurse – feeling of discomfort in managing a class<br>"There were always two speakers with a class because colleagues did not necessarily feel capable, especially in terms of scientific information or handling students' questions, etc., to handle it alone. As for the nurse, it was more about intervening in front of an audience." (P10)<br>External staff – lack of resources<br>"[the research team member] had initially thought of working with midwives, and with student midwives, nursing students, etc. However, it turned out to be more complicated than anticipated." (P8)</td></tr></tbody></table>

(continued on next page)
<table><caption>**Table 5 (continued)**</caption><thead><tr><th></th><th>Facilitators</th><th>Barriers</th></tr></thead><tbody><tr><td>Innovation recipients</td><td>Pupils – enthusiasm and interest<br>"Once they [pupils] got into the theme, we could feel their interest [...] we truly felt like they had learned things and that it had engaged them" (P2)<br>Parents – lack of knowledge<br>"We did have families who thanked us for the project initiative, for raising awareness about this public health issue (P14)</td><td>Pupils – grade 9th-ones less interested<br>"with the 9th-graders, it was a bit less successful, let us say. They were more in the attitude of what they have always learned [...] not too interested" (P3)<br>Parents – hard to involve<br>"Oh... orientation meetings for the 9th graders, parents do not particularly attend those either." (P1)<br>Parents – uncomfortable with digital tools<br>"There are people who struggle a lot with digital technology." (P12)<br>Parents – negative attitudes toward vaccination<br>"Therefore, a certain anti-vax population expressed themselves either on the ENT return or during a parent-teacher meeting." (P17)</td></tr><tr><td colspan="3"><strong>V. Implementation process domain</strong></td></tr><tr><td>Planning</td><td>Planning relationships between schools and vaccination centre<br>"Yes, thankfully there was this exchange with the vaccination centre because initially, I hadn't prepared myself mentally in that way." (P1)</td><td>/</td></tr><tr><td>Doing</td><td>External facilitator from the research team – availability<br>"The support was there, the backup was available if we had any questions, the research team member was completely available for us, and so she was there on the day of the vaccination [...] she was truly a valuable addition." (P3)<br>Guidelines and training provided to help implement the intervention<br>"It was truly great to have things already written that I just needed to copy and send." (P3)<br>"And for the interventions as well, the various files, the option to train online whenever we wanted, etc. [...] it was truly comprehensive." (P10)</td><td>/</td></tr><tr><td>Adapting</td><td>Adaptations – educational sessions<br>"It still allowed us the freedom to either choose something we felt comfortable with or to use everything if it was easier for us" (P2)<br>Adaptations – vaccination day<br>"The pupil who forgot their health record, well, at that moment, the doctor directly handled it by calling the parents. I know the doctor asked the parents to take photos of the vaccination record to validate the vaccinations" (P5)</td><td>/</td></tr></tbody></table>

consent are also challenging in other countries with opt-in approaches [29,34] and may benefit from integrating new technologies [35]. Standardized procedures for sending reminders to parents who have not returned the consent form could also be implemented [31]. Second, to limit the number of pupils who cannot be vaccinated because having left their vaccination record at home, they could be checked/collected by authorized professionals before the vaccination day.

## GPs: facilitators for improving HPV VC but hard-to-reach professionals

We found that, when accounting for the dose of intervention, the effectiveness of the 'GPs' training' component reached statistical significance. This finding is consistent with previous studies [36–38] showing that interventions targeting health care professionals can effectively increase HPV VCs. Indeed, in many countries, including France, GPs are the most trusted source of information on vaccination, followed closely by health care professionals [39]. However, although statistically significant, the effect size was moderate (absolute difference between baseline and 2 months: +3.56 pp) and the public health impact limited. Besides, the effect size was smaller than that observed in previous studies (e.g., +10 pp in Dempsey et al. [36]). This might be due in part by differences in the intervention content and intensity (e.g., in Dempsey's study, communication training included a self-guided, 30-minute webinar, plus 2 in-person, group training sessions that lasted 1 h each) [36].

One of the main challenges in our study was to reach GPs. Only 23% of GPs invited to participate in the training registered. This percentage is slightly lower than the participation level obtained in another experimental study conducted in 2018 on antibiotic stewardship (30%) [40]. This may partly be due to the context of the study. Indeed, GPs were contacted in the summer and autumn of 2021, after almost two years of working during the COVID-19 pandemic, which was associated with an increased workload and high levels of work-related stress and burnout [41]. Beyond this particular context, French GPs have a heavy workload, and half admit to reducing their training time to address the tension between supply and demand for care in their practice area [42]. To generalize GPs' training on HPV and enhance participation, it may be worth considering incentives and actively promoting training through local GPs' professional networks.

## Strengths and limitations

This study has several strengths. First, it was embedded in a trial using a hybrid design, allowing us to evaluate the impact of implementation on effectiveness. Such studies are rare, yet they are essential for decision-makers when considering generalizing interventions [26]. Second, we used a pragmatic approach making the effectiveness results more accurate for real-life applications [23]. Third, to the best of our knowledge, no previous study with such a robust design has demonstrated the added benefit of implementing at-school vaccination compared to vaccination delivered solely

<footnote>ª The CFIR framework consists of five domains: (1) innovation domain (i.e., characteristics of the 'education and motivation' and 'at-school vaccination' components); (2) outer setting domain (i.e., characteristics of the middle school's external environment, including the French school system, political context and local environment's characteristics); (3) inner setting domain (i.e., characteristics of the middle school); (4) individual domain (i.e., roles and characteristics of individuals, including interested parties, involved in the implementation of the components, as well as recipients); and (5) implementation process domain (i.e., activities and strategies used to implement the components).</footnote>
through medical practices. However, countries with school-based programs consistently report higher HPV VC [5,33]. The effectiveness of GPs' training is also consistent with previous findings [36–38]. This supports the potential generalization of our findings to other countries.

We must also acknowledge some limitations. First, the target population included adolescents living in the municipality, even though not all of them attended the municipality's middle school and not all visited GPs from this municipality; this has probably led to an underestimation of the effectiveness. Second, we conducted focus groups with a small number of voluntary school staff who were perhaps more satisfied with the intervention than those who refused to participate; we nevertheless found a variety of influencing factors in each of the CFIR domains. Third, we did not explore facilitators/barriers in primary care; indeed, in the context of a heavy workload among French GPs in 2022, the researchers did not deem this feasible. Finally, the intervention was implemented after 18 months of COVID-19-related mobilization, and shortly after the launch of the COVID-19 vaccination campaign for 12–17 year-olds launched in June 2021. Our findings are therefore likely to have been influenced by the broader pandemic context. Future studies would benefit from examining the implementation outcomes of such interventions in a post-pandemic setting.

## Conclusions

The 'at-school vaccination' and 'GPs' training' components of the PrevHPV intervention have an independent positive effect on HPV VC since there was no statistically significant interaction between both components. Increasing HPV VC among adolescents thus requires the involvement of various parties and could be achieved by combining interventions in schools and primary care settings. This study also highlights challenges for involving interested parties (parents, pupils, school staff, GPs) and the organizational changes this implies. It has practical implications for implementing such interventions in real life, which is more valuable since HPV vaccination has been offered at school to all French 7th-grade pupils since 2023. It would be worth conducting further studies to explore and compare different approaches to implementing such interventions, in order to identify those that are the most acceptable and effective in real-world settings. Conducting implementation trials would help determine the most relevant strategies to maximize the impact of the interventions at the population level and support successful scale-up.

## Author contributions

AB, MM, SB, SG, SB, AG, ASL-B, AG-B, JEM, BG and NT conceptualized and designed the study. Data collection was performed by AB, MS, SB and AG. AB, MS, IA, and BG performed the quantitative data analyses. AB and SB performed the qualitative data analysis. Writing of the original draft was performed by AB, and review and editing were first performed by NT. All the authors have read and approved the final manuscript.

## Ethical statement

The Institut National de la Santé et de la Recherche Médicale (Inserm) is the sponsor of the PrevHPV study. It was granted approval by "Comité de Protection des Personnes – CPP Sud-Est VI" on 22.12.2020 and registered in a public trials registry (NCT04945655). All participants were informed of their rights, particularly not to participate or to oppose the collection of data concerning them.

## Funding

This work was supported by IReSP and ITMO Cancer AVIESAN (Alliance Nationale pour les Sciences de la Vie et de la Santé/National Alliance for Life Sciences & Health) within the framework of the Cancer Plan.

## Declaration of Competing Interest

The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: A.G-B. and A.G. report payment or honoraria for lectures, presentations, etc., by MSD, Moderna, and Pfizer, paid to her institution, as well as support for attending meetings and/or travel by MSD and Moderna.

The other authors have no conflicts of interest to report.

## Acknowledgments

The PrevHPV Study group includes the authors of the present manuscript and the following: For team 1: Estelle FALL; for team 2: Marie ECOLLAN, Josselin LE BEL, Henri PARTOUCHE, Juliette PINOT, Louise ROSSIGNOL, Arthur TRON, Dragos-Paul HAGIU; for team 3: Catherine JUNEAU, Julien AILLOUD; for team 4: Marion BRANCHEREAU; for team 5: Florian JEAN LBOEUF, Géraldine JAMBON, Elisabeth BOTELHO-NEVERS, Emilie DARLINGTON, Mabrouk NEKAA; for team 6: Karine CHEVREUL; for team 7: Jocelyn RAUDE, Jonathan SICSIC, Anne-Sophie BARRET, Sandra CHYDERIOTIS, Damien OUDIN-DOGLIONI, Josée DUSSAULT; Clémence CASTAGNET (Inserm/PRC) and Mélanie SIMONY (IReSP).

The authors would like to thank the representatives of the following institutions who participated in the steering committee of the research program: Inserm, IReSP, ITMO Cancer AVIESAN, ITMO Public Health AVIESAN, INCa (the French National Cancer Institute), the French Public Health Agency (Santé publique France), Ministry of Health, Ministry of National Education, especially Dr Brigitte MOLTRECHT from the Direction générale de l'enseignement scolaire, and the Ile-de-France Regional Health Agency.

The authors also want to thank all professionals who participated in the working groups and all individuals who agreed to participate in the diagnostic and/or co-construction phase of the PrevHPV program.

Finally, they want to thank the heads of the 91 middle schools who agreed to participate in the PrevHPV study and their staff members, as well as the pupils and parents who participated in the study. They also want to thank the general practitioners who agreed to participate in the training and the staff of the vaccination centers involved in the vaccination of adolescents at school.

## Appendix A. Supporting information

Supplementary data associated with this article can be found in the online version at doi:10.1016/j.jiph.2025.102931.

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