Co‐development of a school‐based and primary care‐based multicomponent intervention to improve HPV vaccine coverage amongst French adolescents (the PrevHPV Study)

Abstract Introduction Despite various efforts to improve human papillomavirus (HPV) vaccine coverage in France, it has always been lower than in most other high‐income countries. The health authorities launched in 2018 the national PrevHPV research programme to (1) co‐develop with stakeholders and (2) evaluate the impact of a multicomponent complex intervention aimed at improving HPV vaccine coverage amongst French adolescents. Objective To describe the development process of the PrevHPV intervention using the GUIDance for rEporting of intervention Development framework as a guide. Methods To develop the intervention, we used findings from (1) published evidence on effective strategies to improve vaccination uptake and on theoretical frameworks of health behaviour change; (2) primary data on target populations' knowledge, beliefs, attitudes, preferences, behaviours and practices as well as the facilitators and barriers to HPV vaccination collected as part of the PrevHPV Programme and (3) the advice of working groups involving stakeholders in a participatory approach. We paid attention to developing an intervention that would maximise reach, adoption, implementation and maintenance in real‐world contexts. Results We co‐developed three components: (1) adolescents' and parents' education and motivation using eHealth tools (web conferences, videos, and a serious video game) and participatory learning at school; (2) general practitioners' e‐learning training on HPV using motivational interviewing techniques and provision of a decision aid tool and (3) easier access to vaccination through vaccination days organised on participating middle schools' premises to propose free of charge initiation of the HPV vaccination. Conclusion We co‐developed a multicomponent intervention that addresses a range of barriers and enablers of HPV vaccination. The next step is to build on the results of its evaluation to refine it before scaling it up if proven efficient. If so, it will add to the small number of multicomponent interventions aimed at improving HPV vaccination worldwide. Patient or Public Contribution The public (adolescents, their parents, school staff and health professionals) participated in the needs assessment using a mixed methods approach. The public was also involved in the components' development process to generate ideas about potential activities/tools, critically revise the successive versions of the tools and provide advice about the intervention practicalities, feasibility and maintenance.

Funding information ITMO Cancer AVIESAN serious video game) and participatory learning at school; (2) general practitioners' elearning training on HPV using motivational interviewing techniques and provision of a decision aid tool and (3) easier access to vaccination through vaccination days organised on participating middle schools' premises to propose free of charge initiation of the HPV vaccination.
Conclusion: We co-developed a multicomponent intervention that addresses a range of barriers and enablers of HPV vaccination. The next step is to build on the results of its evaluation to refine it before scaling it up if proven efficient. If so, it will add to the small number of multicomponent interventions aimed at improving HPV vaccination worldwide.
Patient or Public Contribution: The public (adolescents, their parents, school staff and health professionals) participated in the needs assessment using a mixed methods approach. The public was also involved in the components' development process to generate ideas about potential activities/tools, critically revise the successive versions of the tools and provide advice about the intervention practicalities, feasibility and maintenance. Depending on HPV genotypes, persistent HPV infections can cause anogenital warts (HPV 6/11), precancerous lesions of the cervix, vagina, vulva, anus, penis and head and neck, which may sometimes progress to cancers. 3 The two most common 'high-risk' genotypes (HPV 16/18) cause about 70% of all cervical cancers, the most common HPV-related cancers. 2 It is the fourth most frequent cancer in women worldwide, accounting for 604,127 new cases and 341,831 deaths in 2020 (respectively, 3379 and 1452 in France). 4,5 Vaccination is the most effective primary prevention strategy against HPV infection. 2,5 Bivalent, quadrivalent, and nonavalent vaccines have been marketed. All vaccines target HPV 16/18, while the quadrivalent vaccine also targets HPV 6/11 and the nonavalent one adds five oncogenic types. 2

HPV vaccination programmes have
shown substantial impacts on HPV infections, anogenital warts and high-grade precancerous cervical lesions. [6][7][8][9] They have also recently been associated with a reduced risk of invasive cervical cancer. 10,11 HPV vaccines have an 'excellent safety profile' according to the World Health Organisation. 2 Since 2006, most high-income countries have introduced HPV vaccination in their vaccination schedules for adolescents, either for girls only or for girls and boys, depending on the country. 12 The objective of the present article is to describe the development of the PrevHPV intervention. The protocol for the evaluation of its effectiveness, efficiency and implementation (NCT 04945655) has been described in detail elsewhere. 18

| METHODS
We describe the development of the PrevHPV intervention using the GUIDance for rEporting of intervention Development (GUIDED) framework as a guide 19 (see completed GUIDED checklist in Supporting Information Materials: Appendix B). In accordance with this framework, we first describe the context in which the intervention was developed.

| Context of the PrevHPV intervention
In France, HPV vaccination was initially recommended for girls aged 14 years, 20 then for girls aged 11-14 years 21 ; in 2021, it was included in the vaccine schedule for all adolescents, girls and boys, aged 11-14 years. 22 The currently recommended vaccine is the latest nonavalent one with two injections 6 months apart. A catch-up with three injections is possible up to age 19 and for men having sex with men up to age 26.
HPV vaccination in France depends on persons' initiative, requires parental authorization for those under 18 years, and is prescribed and administered by physicians or midwives; in practice, general practitioners (GPs) are the main prescribers and providers of HPV vaccination, for both doses. 23 Since April 2022, under specific medical prescriptions, it can also be administered to individuals aged 16 or older by nurses or pharmacists trained in vaccination. There is currently no nationwide school-based vaccination programme in France. Care pathways to access vaccination often include several steps: for the majority of cases, adolescents and their parents must first get the vaccine prescription during an appointment with a physician, then go to a community pharmacy to obtain the vaccine, and finally, make another appointment with their physician for its administration. Occasionally, individuals will also get vaccinated at vaccination centres, but their geographical accessibility can be difficult. The HPV vaccine is costly (116 euros for 1 dose in 2022).
It is only partially (65%) covered by the National Social Health Insurance but the financial barrier to access remains low as 95% of the population with complementary health insurance are fully reimbursed.
France has been one of the European countries with the highest percentage of the general population with low confidence in vaccine safety for a long time, and the recent 2020 data confirmed this fact. 24 Regarding the HPV vaccine, 32% of French mothers of adolescent girls agree that the HPV vaccine may lead to long-term health problems and 20% that it is unsafe. 25

| Target populations
Target populations of the PrevHPV intervention included: 1. adolescents attending middle schools, typically aged 11-14 years, who are the main target population for HPV vaccination in

| Contribution of published intervention development approach
The UK Medical Research Council (MRC) framework for developing and evaluating complex interventions guided our overall approach to the development of the PrevHPV intervention. It recommends incorporating evidence and theories into the intervention development process. 17

| How evidence from different sources informed the intervention development process
To develop the PrevHPV intervention, we based our decisions on findings from published evidence, primary data collected as part of the PrevHPV Programme, and the advice of working groups involving stakeholders (see details in Section 2.9).

| Published evidence
Facilitators and barriers to the uptake of HPV vaccination: The following facilitators of HPV vaccination have been identified in systematic literature reviews: recent or regular visits with a physician, physician recommendation, parental acceptance, peer encouragement and health insurance coverage. The identified barriers included the cost of the vaccine, parental concerns (child not sexually active, safety of the vaccine, belief that the vaccine will encourage sexual activity, preference to wait till their child is older) and lack of information/knowledge. [33][34][35] A meta-analysis showed that physician recommendation had the greatest influence on parents' uptake of HPV vaccine for their child, followed by HPV vaccine safety concerns. 36 Interventions to improve general vaccination rates amongst adolescents: We used the catalogue published by the European Centre for Disease Prevention and Control, which offers a collection of interventions that address vaccine hesitancy in general 37 and other published evidence (e.g., a review of the literature on adolescent vaccination 38 ).
The evidence suggests that the use of a combination of different interventions (i.e., multicomponent/multilevel interventions, each component/level addressing an identified barrier) appears to be more effective than single-component interventions. 39 Of note, educational strategies based on motivational interviews implemented in maternity wards have been found effective in reducing vaccine hesitancy amongst parents of newborns; it may be a promising way to motivate hesitant individuals to accept vaccination. 40 Interventions to improve HPV vaccination coverage: Less evidence is available for interventions aiming to increase HPV vaccine uptake.
Interventions targeted (separately or in combination) adolescents, parents, health professionals and the environment.
Interventions targeting both parent's and adolescents' psychosocial factors (knowledge, beliefs, outcome expectations, intention to vaccinate) have shown promising results. Amongst interventions targeting health professionals, those which combined reminder and education were found to be more effective. Overall, substantial impacts were observed with multicomponent/multilevel interventions combining interventions at the parental/adolescent and provider levels. [41][42][43][44][45][46] Strategies at the environmental level may take place in hospitals, postpartum units, schools and universities/community colleges. 43 In particular, evidence shows that most European countries with high HPV vaccine coverage such as Belgium Flanders, the United Kingdom and Scandinavian countries have implemented school-based vaccination programmes with no mandatory medical prescription. 13 Potential of eHealth technologies to increase vaccination rates: An overview of systematic reviews led to a recommendation of using and evaluating eHealth technologies (i.e., information and communication technologies in support of health and health-related areas) to encourage immunizations and increase vaccination adherence. 47 eHealth tools (e.g., videos, websites, serious video games) are promising to improve HPV vaccine uptake. 48,49 2.5.2 | Primary data collected as part of the PrevHPV Programme Before and during the development of the PrevHPV intervention, we carried out the PrevHPV diagnostic phase aimed at identifying knowledge, beliefs, attitudes, behaviours and practices, preferences, as well as the facilitators and barriers to HPV vaccination amongst four different population groups in France: adolescents, their parents, school staff (e.g., teachers, school nurses) and health professionals (GPs and health students). We also aimed at assessing the acceptability of school involvement in promoting the HPV vaccine and carrying out HPV vaccinations in schools.
We used a mixed methods approach and carried out quantitative cross-sectional online surveys, qualitative studies using focus groups and semistructured individual interviews, and discrete choice experiment (DCE). 50  Drawing from several previous theories (e.g., the Theory of Planned Behavior, 53 the Self-Determination Theory 54 ), the IBC Model posits autonomous motivation (i.e., a person acts because he/she is convinced that a particular behaviour is good for his/her health) as a distal determinant of behaviour. The effects of autonomous motivation on behaviour are mediated by attitudes, subjective norms and perceived behavioural control which themselves determine intention. It thus ascribes much importance to people's need for autonomy, which, in the case of vaccination, can be supported by a healthy environment (e.g., during interactions with physicians). In addition, the IBC model stresses the role of action planning as a way to reduce the gap between intention and behaviour.

| PrevHPV intervention theory
We developed a general logic model for the PrevHPV intervention  56 In particular, we aimed at developing playful activities/tools to motivate the active and interactive participation of the adolescents to involve them in their learning.
Regarding component 2 (GPs' training), we took care to minimize the time required for GPs and maximize the accessibility of the training (online format) and ease of use of the decision aid tool.
For component 3 (easier access to vaccination), we aimed to develop documents (e.g., information sheets and consent forms for parents, templates of posters to inform pupils on school premises) that can be used in routine practice easily. We also facilitated the first contact between schools and vaccination centres and then let them discuss to organise the vaccination days.

| Working groups involving stakeholders
For each component of the intervention, we set up a working group comprising members of the consortium and several professional stakeholders (e.g., school nurses, staff from vaccination centres, GPssee details in Table 1). Each group aimed at defining the organisation of the component (e.g., activities, duration, content, the role of each actor) and developing the tools for a participatory approach in a co-construction process. 57 They met virtually approximatively every month throughout the development process (January 2020 to June 2021). Stakeholders generated ideas about potential activities/tools together with members of the consortium, critically revised the successive versions of the tools and provided advice about the intervention practicalities, feasibility and maintenance.
During the development process of specific tools, other stakeholders (e.g., adolescents, parents of adolescents, health T A B L E 1 Stakeholders' involvement in the PrevHPV intervention development process.

Professional stakeholders participating in the working group
Other stakeholders involved in the intervention development process

Component 1: Adolescents' and parents' education and motivation
Expert in education and health promotion (n = 1) Expert in public health, responsible for medical students' training (n = 1) Expert in education sciences (n = 2) School nurse technical advisor at the school district level (n = 1) Expert in serious video games' development (n = 2) Serious video game: adolescents and parents of adolescents (n = 17) provided feedback on the serious video game's visual aspects, suitability and readability of the quizzes (questions, answers) through online questionnaires (March-April 2020). Videos: one medical student created the videos as part of a contest organised by the research teams (April-October 2020). School staff handbook: one teacher in life sciences and one school nurse technical advisor critically revised the handbook which describes activities to implement during sessions with adolescents (June 2021).

GP (n = 9)
Decision aid tool-phase 1 (design): adolescents' knowledge, beliefs towards HPV and its vaccination, needs and expectations towards such a tool (e.g., content, visual aspects) were explored through online focus groups (n = 14 adolescents) (October-December 2020). Decision aid tool-phase 2 (test of the alpha version) Adolescents (n = 6) and parents of adolescents (n = 8) provided feedback on the decision aid tool through online focus groups and one individual interview (January-April 2021). GPs (n = 11) pilot tested the decision aid tool in real-life settings during 2-6 weeks and provided feedback to the research team through individual semistructured interviews (May-September 2021).

Component 3: Easier access to vaccination
Medical staff from vaccination centres (n = 2) School nurse technical advisor at the school district level (n = 1) School psychologist (n = 1) Vaccination day poster: adolescents (n = 5), one school nurse technical advisor at the school district level and one GP provided feedback on the poster (e.g., visual aspects, suitability) aimed at informing adolescents on the vaccination day in the school premises (June 2021).
Abbreviation: HPV, human papillomavirus. students) were involved to coproduce the tools and/or providing feedback on some features (e.g., length, suitability, readability, visual aspects) (see details in Table 1).

| How the intervention changed in content and format from the start of the development process
Due to the iterative nature of the intervention development process, there were some changes in the intervention content and format throughout the development process.
Regarding the content, based on results from the PrevHPV diagnostic phase and discussions amongst working groups, we made special efforts to define the best way to communicate HPV and its vaccination amongst adolescents and their parents. For example, we presented HPV infection as a sexually transmitted infection, and have been careful to talk about cancer risks without inducing fear. Also, during the development of an eHealth tool targeting adolescents (a serious video game, see details below in Section 3.1) feedback from parents and adolescents also led to several changes to improve readability and suitability; minor changes included changing a word to an easier one or rewording some questions/answers that were hard to understand.
Regarding the format, a noticeable change was in the mode of delivery of the information action targeting parents of adolescents. We initially planned to organise face-to-face meetings on school premises.
Due to the COVID-19 pandemic, we switched to online meetings.

| RESULTS
The three components of the PrevHPV intervention are described below using the Template for Intervention Description and Replication checklist as a guide. 58 For more details, see the completed checklist in Supporting Information Materials: Appendix D.

| Adolescents and parents' education and motivation (component 1)
This component is carried out in middle schools because schools occupy a great part of adolescents' life and offer a unique opportunity to reach most adolescents.

| DISCUSSION
In this paper, we described the development process of the PrevHPV school-based and primary care-based multicomponent intervention whose primary aim was to improve HPV vaccine coverage amongst French adolescents.
We described its development in a transparent and structured manner using the GUIDED checklist as recommended by the latest UK MRC framework for the development and evaluation of complex interventions. 61 This approach helps intervention developers/funders understand the context and methods that were used and make judgements about the quality and relevance of the intervention and whether to implement an intervention within their specific context. It also enables methodological lessons to be learned and incorporated into future intervention development studies. 19 The PrevHPV intervention development process has several  57 We also involved regional and national stakeholders (e.g., policymakers, funders) throughout the development process. We have also systematically paid attention to the future implementation of the intervention in a real-world context. This approach is recommended to develop new interventions that have a better chance of being effective when evaluated and then of being adopted widely in the real world. 64 One limitation of the intervention development process is that it was conducted during the COVID-19 pandemic. As schools were closed from March to May 2020 in France, the collection of primary data (the PrevHPV diagnostic phase) had to be delayed. The pandemic context has also limited the availability of stakeholders and the opportunities to involve them in face-to-face interviews/meetings. This has finally required great adaptability from all professionals involved in the development process to maintain collaborative work through online meetings. In addition, the stakeholders involved in the development process were volunteered and thus probably particularly interested in the topic and supportive of the HPV vaccination. It would have been helpful to test the intervention tools amongst vaccine-hesitant people as well.
At the end of the intervention development process, we have a good understanding of the rationale of the PrevHPV intervention and the underpinning evidence and theory. We provided professionals (e.g., school staff, experts, GPs) with guidelines and tools that they can apply with some flexibility to take into account the constraints and the schools/GPs' practises environment. 65