# Can physicians and schools mitigate social inequalities in human papillomavirus vaccine awareness, uptake and vaccination intention among adolescents? A cross-sectional study, France, 2021 to 2022

Hadrien Moffroid, Damien Oudin Doglioni, Sandra Chyderiotis, Jonathan Sicsic, Anne-Sophie Barret, Jocelyn Raude, Sebastien Bruel, Aurelie Gauchet, Morgane Michel, Amandine Gagneux-Brunon, et al.

► To cite this version:

Hadrien Moffroid, Damien Oudin Doglioni, Sandra Chyderiotis, Jonathan Sicsic, Anne-Sophie Barret, et al.. Can physicians and schools mitigate social inequalities in human papillomavirus vaccine awareness, uptake and vaccination intention among adolescents? A cross-sectional study, France, 2021 to 2022. Eurosurveillance, 2023, 28 (46), pp.2300166. 10.2807/1560-7917.ES.2023.28.46.2300166. hal-04297135

HAL Id: hal-04297135

https://ehesp.hal.science/hal-04297135v1

Submitted on 21 Nov 2023

HAL is a multi-disciplinary open access
archive for the deposit and dissemination of sci-
entific research documents, whether they are pub-
lished or not. The documents may come from
teaching and research institutions in France or
abroad, or from public or private research centers.

L'archive ouverte pluridisciplinaire HAL, est
destinée au dépôt et à la diffusion de documents
scientifiques de niveau recherche, publiés ou non,
émanant des établissements d'enseignement et de
recherche français ou étrangers, des laboratoires
publics ou privés.

<figure><img src="image_1.png" /></figure>

Distributed under a Creative Commons CC BY 4.0 - Attribution - International License
# Can physicians and schools mitigate social inequalities in human papillomavirus vaccine awareness, uptake and vaccination intention among adolescents? A cross-sectional study, France, 2021 to 2022

Hadrien Moffroid¹,², Damien Oudin Doglioni¹, Sandra Chyderiotis¹, Jonathan Sicsic³, Anne-Sophie Barret⁴, Jocelyn Raude⁵, Sebastien Bruel⁶,⁷, Aurelie Gauchet⁸, Morgane Michel⁹,¹⁰, Amandine Gagneux-Brunon¹¹,¹², Nathalie Thilly¹³,¹⁴, Judith E Mueller¹,⁵, on behalf of the PrevHPV Consortium¹⁵

1. Institut Pasteur, Université Paris Cité, Emerging Disease Epidemiology Unit, 75015 Paris, France

2. University of Melbourne, Melbourne, Australia

3. Université Paris Cité, LIRAES, 75006, Paris, France

4. Santé Publique France, St Maurice, France

5. Université Rennes, EHESP, CNRS, Inserm, Arènes - UMR 6051, RSMS (Recherche sur les Services et Management en Santé) - U1309 - 35000 Rennes, France

6. Department of General Practice, Faculté de Médecine Jacques Lisfranc, Université Jean Monnet, Université de Lyon, Saint-Etienne, France

7. Health, Systemic, Process UR 4129 Research Unit, University Claude Bernard, University of Lyon, Lyon, France

8. Université Savoie Mont Blanc, Université Grenoble Alpes LIP/PC2S, Grenoble, France

9. Université Paris Cité, ECEVE, UMR1123, Inserm, Paris, France

10. Assistance Publique-Hôpitaux de Paris, Hôpital Robert Debré, Unité d'épidémiologie clinique, Paris, France

11. CHU de Saint-Etienne - Service d'infectiologie

12. Centre International de Recherche en Infectiologie, Team GIMAP, Université de Lyon, Université Jean Monnet, Université Claude Bernard Lyon 1, Inserm, U1111, CNRS, UMR530

13. Université de Lorraine, APEMAC, Nancy, France

14. Université de Lorraine, CHRU-Nancy, Département Méthodologie, Promotion, Investigation, Nancy, France

15. Members of the PrevHPV Consortium are listed under acknowledgements

Correspondence: Judith Mueller (Judith.mueller@ehesp.fr)

**Citation style for this article:**

Moffroid Hadrien, Doglioni Damien, Oudin, Chyderiotis Sandra, Sicsic Jonathan, Barret Anne-Sophie, Raude Jocelyn, Bruel Sebastien, Gauchet Aurelie, Michel Morgane, Gagneux-Brunon Amandine, Thilly Nathalie, Mueller Judith E, on behalf of the PrevHPV Consortium. Can physicians and schools mitigate social inequalities in human papillomavirus vaccine awareness, uptake and vaccination intention among adolescents? A cross-sectional study, France, 2021-2022. Euro Surveill. 2023;28(46):pii=2300166. https://doi.org/10.2807/1560-7917.ES.2023.28.46.2300166

Article submitted on 15 Mar 2023 / accepted on 27 Aug 2023 / published on 16 Nov 2023

**Background:** In France, human papillomavirus (HPV) vaccination coverage varies across socioeconomic levels. **Aim:** We aimed at assessing HPV vaccine awareness, uptake and vaccination intention among adolescents in France. **Methods:** In a cluster-randomised study, 13–15-year-old students in 61 French middle schools completed a web-based questionnaire. We used multivariable logistic regression to evaluate determinants of HPV vaccine awareness, self-reported uptake and vaccination intention among unvaccinated students and interaction terms to explore effects of visits to family physician and remembering school lessons on vaccination. The French deprivation index of school municipalities served as proxy for socioeconomic levels. **Results:** Among 6,992 participants, awareness was significantly associated with parental education (odds ratio (OR)=0.82; 95% confidence interval (CI): 0.71–0.95), language spoken at home (OR=0.59; 95% CI: 0.52–0.66) and deprivation level (OR=0.57; 95% CI: 0.44–0.71), regardless of physician visit or school lessons. Vaccine uptake was associated with parental education without a recent physician visit (OR=0.31; 95% CI: 0.16–0.59, vs OR=0.64; 95% CI: 0.52–0.78 with a visit, interaction

p=0.045). Vaccination intention among unvaccinated was associated with deprivation level (moderate-low vs low) among students not remembering school lessons on vaccination (OR=0.17; 95% CI: 0.05-0.62, vs OR=0.93; 95% CI: 0.51-1.67 remembering school lessons, interaction p=0.022). Parental education was associated with vaccination intention among students reporting a physician visit (OR=0.41; 95% CI: 0.26-0.64 vs OR=1.05; 95% CI: 0.50-2.20 without a visit, interaction p=0.034). **Conclusion:** Our results suggest that healthcare and school could promote vaccination and mitigate social inequalities in HPV vaccination coverage.

## Introduction

Human papillomavirus (HPV) vaccines are highly effective against cervical and other HPV-related cancers, while being safe and generating population immunity [1]. In France, HPV vaccination has been recommended to girls since 2007, with an extension to boys since 2021 [2]. The target age is 11–14 years with catch-up up to 19 years. Despite a recent increase in HPV coverage estimates, immunisation coverage in France remains among the lowest within Europe [3]. By the end of
## KEY PUBLIC HEALTH MESSAGE

**What did you want to address in this study?**

Human papillomavirus (HPV) can cause genital cancer. Vaccination against HPV protects against virus types causing most cases of cervical cancer, as well as some other cancers. Vaccine uptake among adolescents varies in France and other European countries. We wanted to investigate awareness, uptake and intention of HPV vaccination among French adolescents and factors affecting vaccination.

**What have we learnt from this study?**

Adolescents were less aware of vaccination and less often vaccinated or planning to vaccinate if their parents had a lower education, other languages than French were spoken at home and the family lived in a poorer area. Importantly, if the adolescents had recently visited a family physician or were taught about vaccinations at school, vaccination or planning to vaccinate were independent of parental education, language or neighbourhood.

**What are the implications of your findings for public health?**

Family physicians and school lessons on vaccination are important in promoting systematic vaccination of all adolescents against HPV, irrespective of their social context. How to use such communication ways to enhance vaccination in France needs further investigation.

2021, coverage of the first dose among 15-year-old girls was 45.8% and that of the second dose among 16-year-old girls was 37.4%, while coverage of the first dose among 15-year-old boys was 6% [4].

Previous studies suggest that the main barriers to HPV vaccination in France are lack of parental awareness and low perceived accessibility, combined with widespread doubts on the need and safety of the vaccine [5]. In particular, there is evidence that general practitioners (GP) do not systematically offer or recommend this vaccine to adolescents [6]. Vaccination against HPV is today available at the offices of physicians (mainly GPs) and midwives. Finally, although the HPV vaccine is entirely reimbursed for most families in France by the combination of national and complementary health insurance and can be accessed free-of-charge in certain health centres, the access is complicated by the exclusive distribution through pharmacies.

As in other countries [7], HPV vaccine coverage in France shows a substantial gradient across socioeconomic groups [4,8]. It is unclear whether these inequalities arise from lower offer and access or lower acceptance in specific groups. Thus, characterising inequalities not only in vaccine uptake, but also in awareness and intention to get vaccinated, as well as identifying mitigating factors, appears necessary.

A systematic review suggested that young adolescents, the target group for HPV vaccination in most countries, have relatively favourable attitudes towards HPV vaccination, but lack awareness [9]. To date, minors in France need parental consent for vaccination, however, increasing evidence emphasises the integral role

adolescents have in the decision-making process on HPV vaccination [10]. Little evidence is available on social inequalities around HPV vaccine awareness and intention to get vaccinated among young adolescents in Europe, but one study in Italy described better HPV knowledge among adolescents with higher level of parental education [11].

In this context, we aimed to delineate socio-educational inequalities of HPV vaccine awareness, self-reported uptake and vaccination intention among French adolescents aged 13–15 years, and to investigate whether visits to the family GP and school lessons on vaccination could mitigate these inequalities.

## Methods

### Participant recruitment

The national research programme to improve HPV vaccine coverage among French adolescents, PrevHPV, is a cluster-randomised study in mainland France evaluating the effect of a multicomponent intervention on HPV vaccine uptake among adolescents irrespective of their sex [12]. Between 22 November 2021 and February 2022, we collected data from students in French middle schools via an anonymous web-based questionnaire published on the REDcap tool (https://www.project-redcap.org/). Middle schools in nine regions throughout the French mainland were randomised as previously described [12]. Ninety-one schools were invited to participate in the survey. A total of 19,885 third and fourth grade students, typically aged 13–15 years, were eligible to participate. No written consent was required for an anonymous survey in France, but all participants were informed of their
right not to participate. After assenting to participate, the adolescents completed the questionnaires during in-class lessons, under the supervision of their biology teacher or school nurse. Parents received information about the study and could decline the participation.

## Questionnaires, data collection and management

The questionnaire included questions on socio-educational characteristics of the adolescents' family, awareness, knowledge, perceptions and behaviour around HPV-related disease and vaccination, their self-declared HPV vaccination status and intention to get vaccinated. We assessed intention to get vaccinated among unvaccinated adolescents aware of HPV vaccine as follows: refusal ('HPV vaccination is not relevant for me'), indecision ('I consider HPV vaccination as relevant for me, but I am not sure about getting vaccinated') or intention ('I have the intention to soon get vaccinated'). More details can be seen in Supplementary Table 2.

To assess the socio-educational characteristics, we collected individual and ecological variables. Educational level of the mother and the father was grouped as 'below or equal to high school', 'above high school' and 'do not know'. We assessed language by the question 'Do you commonly speak another language than French at home' (French or other languages). For specific analyses, we collated parental education (the highest achieved level among parents) and language. We assumed that the relevance of a multilingual family environment for vaccine uptake depends on the level of parental education.

As an ecological study, we used the 2015 French deprivation index (Fdep) [13], a proxy measure for an area-based socioeconomic level and disparity. The Fdep is based on the median household income, the percentage of high school graduates in the population of persons aged 15 years or over, the proportion of working class in the active population and the unemployment rate, with a mean of 0 used for mainland France. The municipalities of the participating schools had an index spanning from -2.2 to 2.2, which represents approximately the range of the index in French municipalities. Using this index, we created four categories of local deprivation level: low (least deprived: index≤-1), moderate-low (index>-1 to 0), moderate-high (index>0 to 1), and high (most deprived: index>1).

Knowledge on health-related subjects covered at school was assessed as remembering specific topics taught during school lessons (bacteria and viruses, vaccination in general; human reproduction, sexual education and sexually transmitted infections). In France, these topics can be addressed in biology classes in middle schools, but the content or the format is not harmonised. We assessed whether the students had seen their GP during the past 12 months and whether the GP had offered HPV vaccination. In the French context, the gatekeeper function of family physicians comprises

mostly GPs. Although other medical specialities (e.g. paediatricians) can take this role, for simplicity, we refer here to GPs. Adolescents commonly visit GPs for acute or chronic health issues and for medical certificates of fitness to participate in sports. Three GP visits dedicated to health promotion, including vaccination, are fully reimbursed for children between the ages of 8 and 16 years. For specific analyses, we collated these variables into one variable (no visit/visit with a vaccine offer/visit without a vaccine offer). Most questions included a 'do not know' modality, which was included into 'no'. More information can be seen in Supplementary Table SM1.

Additionally, we collected variables not part of the main hypothesis but known to impact health behaviour [14]. These included health-related behaviour and aptitudes evaluated as: self-efficacy (confidence in being able to respond to questions on one's health, rated on a 10-point scale), ease of finding information on HPV and ease of talking to health professionals and close persons about HPV and social influence variables, on the attitudes of family and the social environment towards vaccinations in general and to HPV, respectively and the HPV vaccination status of friends. We assessed specific knowledge and attitude items on HPV using a 5-point Likert scale, coding responses as disagree/undecided/agree.

## Data analysis

We performed descriptive analyses on socio-educational characteristics by sex and on HPV vaccine knowledge and attitude items between subgroups according to socio-educational and mitigation variables. We used chi squared tests for differences between subgroups.

For the first analysis on determinants of HPV vaccine awareness (binary), vaccine status (binary) and vaccination intention (three levels: refusal, indecision, intention), we built multivariable logistic and multinomial regression models including all socio-educational variables and variables related to contact with GP, health-related knowledge, behaviour and aptitudes and social influence. For each outcome, we included in the final multivariable model only variables associated in bivariable models at p value<0.2.

For the main objective of exploring social inequalities, we analysed, for each outcome, a model including only socio-educational variables (grade level, sex, parental education, language, deprivation level). We then explored mitigation including interaction terms between socio-educational determinants (parental education, language, deprivation level) and hypothetical mitigation variables (health-related knowledge and recent GP visit). Interaction terms with p<0.05 were interpreted as mitigation, and in this case, the effects of determinants were represented stratifying for the mitigation factor.
<caption>TABLE A</caption>

Awareness, uptake and intention of human papillomavirus vaccination among middle school students, France, 2021–22 (n = 6,992)ª

<table><thead><tr><th rowspan="2">Characteristics</th><th colspan="3">Awareness (n=6,992)</th><th colspan="3">Vaccine uptake among persons aware of HPV vaccination (n=4,385)</th><th colspan="3">Vaccination intention among unvaccinated (n=2,815)</th></tr><tr><th>n</th><th>%</th><th>OR</th><th>95% CI</th><th>p value</th><th>n</th><th>%</th><th>OR</th><th>95% CI</th><th>p value</th></tr></thead><tbody><tr><td colspan="10"><strong>School grade</strong></td></tr><tr><td>Fourth</td><td>3,742</td><td>53.5</td><td>1</td><td>NA</td><td>2,271</td><td>51.8</td><td>1</td><td>NA</td><td>1,521</td><td>54.0</td></tr><tr><td>Third</td><td>3,250</td><td>46.5</td><td>0.98</td><td>0.86-1.10</td><td>2,114</td><td>48.2</td><td>1.24</td><td>1.02-1.50</td><td>1,284</td><td>46.0</td></tr><tr><td>Sex</td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td></tr><tr><td>Female</td><td>3,564</td><td>51.0</td><td>1</td><td>NA</td><td>2,665</td><td>60.8</td><td>1</td><td>NA</td><td>1,388</td><td>49.3</td></tr><tr><td>Male</td><td>3,428</td><td>49.0</td><td>0.32</td><td>0.29-0.36</td><td>&lt;0.001</td><td>1,720</td><td>39.2</td><td>0.42</td><td>0.35-0.51</td><td>1,427</td><td>50.7</td></tr><tr><td colspan="10"><strong>Parental education level and languages spoken at home</strong></td></tr><tr><td colspan="10"><strong>French</strong></td></tr><tr><td>Below or equal to high school</td><td>1,122</td><td>16.1</td><td>0.87</td><td>0.73-1.04</td><td>0.119</td><td>760</td><td>17.3</td><td>0.74</td><td>0.57-0.96</td><td>510</td><td>18.1</td></tr><tr><td>Above high school</td><td>2,198</td><td>31.4</td><td>1</td><td>NA</td><td>1,597</td><td>36.4</td><td>1</td><td>NA</td><td></td><td>889</td><td>31.6</td></tr><tr><td>Do not know</td><td>2,192</td><td>31.4</td><td>0.56</td><td>0.48-0.65</td><td>&lt;0.001</td><td>1,235</td><td>28.2</td><td>0.97</td><td>0.77-1.22</td><td>841</td><td>29.9</td></tr><tr><td colspan="10"><strong>Other languages</strong></td></tr><tr><td>Below or equal to high school</td><td>335</td><td>4.8</td><td>0.50</td><td>0.38-0.65</td><td>&lt;0.001</td><td>185</td><td>4.2</td><td>0.56</td><td>0.33-0.92</td><td>139</td><td>4.9</td></tr><tr><td>Above high school</td><td>541</td><td>7.7</td><td>0.47</td><td>0.38-0.59</td><td>&lt;0.001</td><td>309</td><td>7.1</td><td>1.02</td><td>0.71-1.48</td><td>206</td><td>7.3</td></tr><tr><td>Do not know</td><td>604</td><td>8.6</td><td>0.37</td><td>0.30-0.46</td><td>&lt;0.001</td><td>299</td><td>6.8</td><td>0.68</td><td>0.46-1.01</td><td>230</td><td>8.2</td></tr><tr><td colspan="10"><strong>Local deprivation index</strong></td></tr><tr><td>Number of responses</td><td>6,903</td><td></td><td></td><td></td><td>4,333</td><td></td><td></td><td></td><td></td><td>2,782</td><td></td></tr><tr><td>Low</td><td>611</td><td>8.9</td><td>1</td><td>NA</td><td>438</td><td>10.1</td><td>1</td><td>NA</td><td></td><td>257</td><td>9.2</td></tr><tr><td>Moderate-low</td><td>2,462</td><td>35.7</td><td>0.62</td><td>0.56-0.77</td><td>&lt;0.001</td><td>1,474</td><td>34.0</td><td>0.84</td><td>0.61-1.12</td><td>275</td><td>949</td></tr><tr><td>Moderate-high</td><td>2,520</td><td>36.5</td><td>0.84</td><td>0.67-1.04</td><td>0.116</td><td>1,669</td><td>38.5</td><td>0.75</td><td>0.55-1.03</td><td>0.90</td><td>1,090</td></tr><tr><td>High</td><td>1,310</td><td>19.0</td><td>0.56</td><td>0.44-0.71</td><td>&lt;0.001</td><td>752</td><td>17.4</td><td>1.03</td><td>0.72-1.47</td><td>0.883</td><td>496</td></tr><tr><td colspan="10"><strong>Health-related behaviour and aptitudes</strong></td></tr><tr><td colspan="10"><strong>Self-efficacy<sup>a</sup></strong></td></tr><tr><td>0-2.5</td><td>247</td><td>3.5</td><td>1</td><td>NA</td><td>106</td><td>2.4</td><td>NA<sup>c</sup></td><td></td><td></td><td>70</td><td>2.5</td></tr><tr><td>2.6-5.0</td><td>757</td><td>10.8</td><td>1.22</td><td>0.87-1.70</td><td>0.244</td><td>391</td><td>8.9</td><td></td><td></td><td>273</td><td>9.7</td></tr><tr><td>5.1-7.5</td><td>1,363</td><td>19.5</td><td>1.49</td><td>1.08-2.04</td><td>0.014</td><td>799</td><td>18.2</td><td></td><td></td><td>554</td><td>19.7</td></tr><tr><td>7.6-10</td><td>4,625</td><td>66.2</td><td>1.84</td><td>1.36-2.50</td><td>&lt;0.001</td><td>3,089</td><td>70.4</td><td></td><td></td><td>1,918</td><td>68.1</td></tr><tr><td colspan="10"><strong>Ease to find information about HPV vaccination</strong></td></tr><tr><td>Number of responses</td><td>NA</td><td></td><td></td><td></td><td>4,241</td><td></td><td></td><td></td><td></td><td>2,713</td><td></td></tr><tr><td>Disagree</td><td>NA<sup>b</sup></td><td></td><td></td><td></td><td>302</td><td>7.1</td><td>1</td><td>NA</td><td></td><td>215</td><td>7.9</td></tr><tr><td>Unsure</td><td></td><td></td><td></td><td></td><td>1,860</td><td>43.9</td><td>0.81</td><td>0.56-1.18</td><td>0.265</td><td>1,247</td><td>46.0</td></tr><tr><td>Agree</td><td></td><td></td><td></td><td></td><td>2,079</td><td>49.0</td><td>0.76</td><td>0.52-1.10</td><td>0.146</td><td>1,251</td><td>46.1</td></tr></tbody></table>

CI: confidence interval; HPV: human papillomavirus; NA: not applicable; OR: odds ratio.

ª In case the number of responses differs from the total number of respondents, the numbers are given by the variable.

ᵇ Self-efficacy was evaluated on a 10-point scale.

ᶜ Not included in the model because p≥0.20 in bivariable analysis.

Multivariable models for the three outcomes human papillomavirus vaccine awareness, uptake and intention containing all variables that demonstrated a p-value<0.2 in bivariable analyses.
<caption>TABLE B</caption>

Awareness, uptake and intention of human papillomavirus vaccination among middle school students, France, 2021–22 (n = 6,992)ª

<table><thead><tr><th rowspan="2">Characteristics</th><th colspan="3">Awareness (n = 6,992)</th><th colspan="3">Vaccine uptake among persons aware of HPV vaccination (n = 4,385)</th><th colspan="3">Vaccination intention among unvaccinated (n = 2,815)</th><th rowspan="2">p value</th></tr><tr><th>n</th><th>%</th><th>OR</th><th>95% CI</th><th>p value</th><th>n</th><th>%</th><th>OR</th><th>95% CI</th><th>%</th></tr></thead><tbody><tr><td colspan="11"><strong>Difficult to talk to close family or friends about HPV vaccination</strong></td></tr><tr><td>Agree</td><td>NA</td><td></td><td></td><td>592</td><td>13.5</td><td>1</td><td>NA</td><td>440</td><td>15.6</td><td>1</td><td>NA</td></tr><tr><td>Ursure</td><td></td><td></td><td></td><td>1,100</td><td>25.1</td><td>1.28</td><td>0.92-1.78</td><td>0.149</td><td>802</td><td>0.89</td><td>0.51-1.54</td><td>0.680</td></tr><tr><td>Disagree</td><td></td><td></td><td></td><td>2,693</td><td>61.4</td><td>1.04</td><td>0.77-1.41</td><td>0.786</td><td>1,573</td><td>1.04</td><td>0.63-1.72</td><td>0.874</td></tr><tr><td colspan="11"><strong>Difficult to talk to health professionals about HPV vaccination</strong></td></tr><tr><td>Agree</td><td>NA</td><td></td><td></td><td>580</td><td>13.2</td><td>1</td><td>NA</td><td>412</td><td>14.6</td><td>1</td><td>NA</td></tr><tr><td>Ursure</td><td></td><td></td><td></td><td>1,250</td><td>28.5</td><td>1.38</td><td>1.00-1.92</td><td>0.050</td><td>892</td><td>31.7</td><td>0.95</td><td>0.56-1.63</td><td>0.862</td></tr><tr><td>Disagree</td><td></td><td></td><td></td><td>2,555</td><td>58.3</td><td>1.21</td><td>0.90-1.64</td><td>0.199</td><td>1,511</td><td>53.7</td><td>1.21</td><td>0.73-1.99</td><td>0.464</td></tr><tr><td colspan="11"><strong>GP visit during the past 12 months</strong></td></tr><tr><td>Number of responses</td><td>6,861</td><td></td><td></td><td>NA</td><td></td><td></td><td></td><td></td><td></td><td></td><td></td></tr><tr><td>No visit</td><td>1,233</td><td>18.0</td><td>1</td><td>NA</td><td></td><td></td><td></td><td></td><td></td><td></td><td></td></tr><tr><td>Do not remember</td><td>1,030</td><td>15.0</td><td>1.43</td><td>1.19-1.73</td><td>&lt;0.001</td><td></td><td></td><td></td><td></td><td></td><td></td></tr><tr><td>Visited</td><td>4,598</td><td>67.0</td><td>1.60</td><td>1.39-1.85</td><td>&lt;0.001</td><td></td><td></td><td></td><td></td><td></td><td></td></tr><tr><td colspan="11"><strong>GP visit during the past 12 months and a vaccine offer</strong></td></tr><tr><td>Number of responses</td><td>NA</td><td></td><td></td><td>4,382</td><td></td><td></td><td></td><td></td><td></td><td></td><td></td></tr><tr><td>No visit</td><td>NA</td><td></td><td></td><td>1,002</td><td>22.9</td><td>1</td><td>NA</td><td>922</td><td>32.8</td><td>1</td><td>NA</td></tr><tr><td>Visit, vaccine not offered</td><td></td><td></td><td></td><td>1,520</td><td>34.7</td><td>1.47</td><td>1.08-1.99</td><td>0.045</td><td>1,338</td><td>47.6</td><td>0.97</td><td>0.67-1.40</td><td>0.883</td></tr><tr><td>Visit, vaccine offered</td><td></td><td></td><td></td><td>1,960</td><td>42.5</td><td>19.09</td><td>14.38-25.34</td><td>&lt;0.001</td><td>552</td><td>19.6</td><td>3.21</td><td>1.91-5.39</td><td>&lt;0.001</td></tr><tr><td colspan="11"><strong>General attitude to vaccination within the family</strong></td></tr><tr><td>Unfavourable</td><td>705</td><td>10.1</td><td>1</td><td>NA</td><td></td><td></td><td></td><td></td><td></td><td></td><td></td></tr><tr><td>Ursure</td><td>1,547</td><td>22.1</td><td>0.98</td><td>0.80-1.20</td><td>0.848</td><td></td><td></td><td></td><td></td><td></td><td></td></tr><tr><td>Favourable</td><td>4,740</td><td>67.8</td><td>1.24</td><td>1.03-1.50</td><td>0.020</td><td></td><td></td><td></td><td></td><td></td><td></td></tr><tr><td colspan="11"><strong>Attitude to HPV vaccination in the social environment</strong></td></tr><tr><td>Number of responses</td><td>NA</td><td></td><td></td><td>4,114</td><td></td><td></td><td></td><td></td><td></td><td></td><td></td></tr><tr><td>Unfavourable</td><td>NA</td><td></td><td></td><td>427</td><td>10.4</td><td>1</td><td>NA</td><td>356</td><td>13.7</td><td>1</td><td>NA</td></tr><tr><td>Ursure</td><td></td><td></td><td></td><td>1,342</td><td>32.6</td><td>1.80</td><td>1.24-2.62</td><td>0.002</td><td>1,057</td><td>40.7</td><td>7.28</td><td>4.41-12.01</td><td>&lt;0.001</td></tr><tr><td>Favourable</td><td></td><td></td><td></td><td>2,345</td><td>57.0</td><td>3.73</td><td>2.61-5.34</td><td>&lt;0.001</td><td>1,187</td><td>45.7</td><td>31.07</td><td>18.02-53.57</td><td>&lt;0.001</td></tr><tr><td colspan="11"><strong>HPV vaccination status of friends</strong></td></tr><tr><td>Number of responses</td><td>NA</td><td></td><td></td><td>4,306</td><td></td><td></td><td></td><td></td><td></td><td></td><td></td></tr><tr><td>Not vaccinated</td><td>NA</td><td></td><td></td><td>446</td><td>10.4</td><td>1</td><td>NA</td><td>382</td><td>13.8</td><td>1</td><td>NA</td></tr><tr><td>Do not know</td><td></td><td></td><td></td><td>1,642</td><td>38.1</td><td>1.78</td><td>1.23-2.60</td><td>0.002</td><td>1,270</td><td>46.0</td><td>1.90</td><td>1.20-3.01</td><td>0.006</td></tr><tr><td>Vaccinated</td><td></td><td></td><td></td><td>2,218</td><td>51.5</td><td>2.97</td><td>2.07-4.26</td><td>&lt;0.001</td><td>1,110</td><td>40.2</td><td>3.17</td><td>1.98-5.07</td><td>&lt;0.001</td></tr></tbody></table>

CI: confidence interval; HPV: human papillomavirus; NA: not applicable; OR: odds ratio.

Multivariable models for the three outcomes human papillomavirus vaccine awareness, uptake and intention containing all variables that demonstrated a p-value<0.2 in bivariable analyses.

<footnote>ª In case the number of responses differs from the total number of respondents, the numbers are given by the variable.</footnote>

<footnote>ᵇ Self-efficacy was evaluated on a 10-point scale.</footnote>

<footnote>ᶜ Not included in the model because p≥0.20 in bivariable analysis.</footnote>
<caption>TABLE C</caption>

Awareness, uptake and intention of human papillomavirus vaccination among middle school students, France, 2021–22 (n = 6,992)¹

<table><thead><tr><th rowspan="2">Characteristics</th><th colspan="3">Awareness (n=6,992)</th><th colspan="3">Vaccine uptake among persons aware of HPV vaccination (n=4,385)</th><th colspan="3">Vaccination intention among unvaccinated (n=2,815)</th><th rowspan="2">p value</th></tr><tr><th>n</th><th>%</th><th>OR</th><th>95% CI</th><th>p value</th><th>n</th><th>%</th><th>OR</th><th>95% CI</th><th>n</th><th>%</th><th>OR</th><th>95% CI</th></tr></thead><tbody><tr><td colspan="15"><strong>Remembrance of school lessons</strong></td></tr><tr><td colspan="15"><strong>Infections by bacteria or viruses</strong></td></tr><tr><td>Number of responses</td><td>6,899</td><td></td><td></td><td>4,315</td><td></td><td></td><td></td><td></td><td></td><td>2,767</td><td></td><td></td><td></td></tr><tr><td>No/do not know</td><td>2,482</td><td>36.0</td><td>1</td><td>NA</td><td></td><td>1,426</td><td>33.1</td><td>NA<sup>c</sup></td><td></td><td>905</td><td>32.7</td><td>1</td><td>NA</td></tr><tr><td>Yes</td><td>4,417</td><td>64.0</td><td>1.09</td><td>0.97-1.23</td><td>0.16</td><td>2,889</td><td>67.0</td><td></td><td></td><td>1,862</td><td>67.3</td><td>0.87</td><td>0.61-1.25</td><td>0.454</td></tr><tr><td colspan="15"><strong>Vaccination</strong></td></tr><tr><td>Number of responses</td><td>6,903</td><td></td><td></td><td>4,328</td><td></td><td></td><td></td><td></td><td></td><td>2,773</td><td></td><td></td><td></td></tr><tr><td>No/do not know</td><td>1,989</td><td>28.8</td><td>1</td><td>NA</td><td></td><td>1,108</td><td>25.6</td><td>1</td><td>NA</td><td>685</td><td>24.7</td><td>1</td><td>NA</td></tr><tr><td>Yes</td><td>4,914</td><td>71.2</td><td>1.51</td><td>1.34-1.72</td><td>&lt;0.001</td><td>3,220</td><td>74.4</td><td>0.87</td><td>0.71-1.08</td><td>0.204</td><td>2,088</td><td>75.3</td><td>0.94</td><td>0.59-1.49</td><td>0.789</td></tr><tr><td colspan="15"><strong>Human reproduction (anatomy and physiology)</strong></td></tr><tr><td>Number of responses</td><td>6,901</td><td></td><td></td><td>4,337</td><td></td><td></td><td></td><td></td><td></td><td>2,779</td><td></td><td></td><td></td></tr><tr><td>No/do not know</td><td>1,135</td><td>16.5</td><td>1</td><td>NA</td><td></td><td>655</td><td>15.1</td><td>NA<sup>c</sup></td><td></td><td>433</td><td>15.6</td><td>NA<sup>c</sup></td><td></td></tr><tr><td>Yes</td><td>5,766</td><td>83.6</td><td>0.88</td><td>0.74-1.04</td><td>0.14</td><td>3,682</td><td>84.9</td><td></td><td></td><td>2,346</td><td>84.4</td><td></td><td></td></tr><tr><td colspan="15"><strong>Sexual education on behavioural and social aspects</strong></td></tr><tr><td>Number of responses</td><td>6,872</td><td></td><td></td><td>4,317</td><td></td><td></td><td></td><td></td><td></td><td>2,770</td><td></td><td></td><td></td></tr><tr><td>No/do not know</td><td>2,834</td><td>41.2</td><td>1</td><td>NA</td><td></td><td>1,715</td><td>39.7</td><td>1</td><td>NA</td><td>1,131</td><td>40.8</td><td>NA<sup>c</sup></td><td></td></tr><tr><td>Yes</td><td>4,038</td><td>58.8</td><td>1.01</td><td>0.89-1.15</td><td>0.91</td><td>2,602</td><td>60.3</td><td>1.00</td><td>0.80-1.25</td><td>0.991</td><td>1,639</td><td>59.2</td><td>NA<sup>c</sup></td></tr><tr><td colspan="15"><strong>Sexually transmitted infections</strong></td></tr><tr><td>Number of responses</td><td>6,846</td><td></td><td></td><td>4,300</td><td></td><td></td><td></td><td></td><td></td><td>2,760</td><td></td><td></td><td></td></tr><tr><td>No/do not know</td><td>2,231</td><td>32.6</td><td>1</td><td>NA</td><td></td><td>1,233</td><td>28.7</td><td>1</td><td>NA</td><td>821</td><td>29.8</td><td>NA<sup>c</sup></td><td></td></tr><tr><td>Yes</td><td>4,615</td><td>67.4</td><td>1.50</td><td>1.32-1.72</td><td>&lt;0.001</td><td>3,067</td><td>71.3</td><td>1.03</td><td>0.84-1.25</td><td>0.810</td><td>1,939</td><td>70.3</td><td>NA<sup>c</sup></td></tr></tbody></table>

CI: confidence interval; HPV: human papillomavirus; NA: not applicable; OR: odds ratio.

Multivariable models for the three outcomes human papillomavirus vaccine awareness, uptake and intention containing all variables that demonstrated a p-value<0.2 in bivariable analyses.

<footnote>a In case the number of responses differs from the total number of respondents, the numbers are given by the variable.</footnote>

<footnote>b Self-efficacy was evaluated on a 10-point scale.</footnote>

<footnote>c Not included in the model because p≥0.20 in bivariable analysis.</footnote>
Statistical significance was defined as p value < 0.05. Data analyses were performed on Stata Version 17 (StataCorp, the United States).

## Results

### Participant characteristics

Given constraints during the COVID-19 pandemic, only 61 middle schools with 12,833 students in third and fourth grades participated in the survey. While no information on the number of school classes was collected, we estimated that baseline questionnaires were administered in 70% of classes. More details can be seen in Supplementary Figure SM2.

In total, 7,632 persons opened the questionnaire, with 7,580 accepting participation and 6,992 leaving valid responses, or 54.5% (6,992/12,833) of the eligible students. There were 3,564 females and 3,428 males responding, approximately equally distributed over the two school grade levels and with similar socio-educational characteristics. More information can be seen in Supplementary Table SM3. Almost half of the participants were unaware of at least one parent's educational level, while 32.3% and 25.4%, respectively, reported higher education for their mothers and fathers. Other languages than French were spoken at home of 1,480 (21.2%) respondents. Of these, 335 (4.8%) had parents with lower education and 541 (7.7%) had higher education. A total of 611 (8.7%) participants attended school in a low and 1,310 (18.7%) in a high deprivation area. Overall, 1,233 (17.6%) 24.1% participants reported no recent GP visit (more frequent among males and those with lower parental education) and 35.7% reported a visit without an offer to vaccinate against HPV (more frequent among males). More information can be seen in Supplementary Table SM4. Similarly, 70.3% remembered school lessons on vaccination.

Overall, 4,051 (57.9%) participants had heard about the HPV vaccine (75.9% of females, 51.6% of males) and 421 (6.0%) were not sure. More information can be seen in Supplementary Figures SM5 and SM6. Among the participants aware of HPV vaccine or not sure but reporting their vaccination status (n = 4,385, information missing from 87 respondents), 1,568 (35.8%) knew they were vaccinated (48.0% of females, 17.0% of males), while 2,344 (53.5%) were not and 473 (10.8%) were not sure, seen in Supplementary Figures SM5 and SM7. Among the 2,815 participants aware of the HPV vaccine but not vaccinated or not sure of vaccination, 939 (33.4%) intended to get vaccinated (38.1% of females, 28.7% of males) and 311 (11.1%) did not, while 1,565 (55.6%) were not sure, seen in Supplementary Figures SM5 and SM8. In summary, among the 4,385 participants aware of the HPV vaccine, 2,507 (57.2%; 67.7% of females and 40.8% of males) were either vaccinated or intended to get vaccinated.

### Awareness of human papillomavirus vaccine

In general multivariable analyses, awareness of HPV vaccine was significantly associated with male sex (odds ratio (OR)=0.32; 95% confidence interval (CI): 0.29-0.36), language spoken at home (OR=0.37-0.50, depending on the level of parental education), high local deprivation (OR=0.56; 95% CI: 0.44-0.71), high self-efficacy (OR=1.84; 95% CI:1.36-2.50, a GP visit (OR=1.60; 95% CI: 1.39-1.85) and knowledge on vaccination (OR=1.51; 95% CI: 1.34-1.72) or on sexually transmitted infections (OR=1.50; 95% CI: 1.32-1.72) (Table). More details can be seen in Supplementary Table 6. When only variables grade level, sex, parental education, language and deprivation level were included in the model, the respondents were less aware of the HPV vaccine if they lived in an area with high local deprivation (OR=0.57; 95% CI: 0.44-0.71), spoke other languages than French at home (OR=0.59; 95% CI: 0.52-0.66) and had parents with a lower level of education (OR=0.82; 95% CI: 0.71-0.95) (Figure 1). Visits to the GP or school lessons did not increase awareness in these respondents.

### Uptake of human papillomavirus vaccine

Self-reported vaccine uptake among respondents aware of the vaccine was significantly associated with a GP visit with (OR=19.09; 95% CI: 14.38-25.34) and without (OR=1.47; 95% CI: 1.08-1.99) a vaccine offer, a social environment favourable to HPV vaccination (OR=3.73; 95% CI: 2.61-5.34), friends being vaccinated against HPV (OR=2.97; 95% CI: 2.07-4.26), male sex (OR=0.42; 95% CI: 0.35-0.51) and fourth grade at school (instead or third) (OR=1.24; 95% CI: 1.02-1.50) (Table). More information can be seen in Supplementary Table SM7. In the model focusing on socio-educational determinants, vaccine uptake was decreased when the parents had a lower level of education (OR=0.60; 95% CI: 0.51-0.72) and other languages than French were spoken at home (OR=0.60; 95% CI: 0.50-0.72) (Figure 2). Low level of parental education was significantly less strongly associated with vaccine uptake among participants who reported a recent GP visit (OR=0.64; 95% CI: 0.52-0.78) than among those who did not (OR=0.31; 95% CI: 0.16-0.59, interaction term p=0.045).

### Intention to get vaccinated among unvaccinated participants

The participants had significantly higher intention to get vaccinated if the attitudes towards HPV vaccination were more favourable in their social environment (OR=31.07; 95% CI: 18.02-53.57) or in the family (OR=3.66; 95% CI: 2.20-6.08), they had visited the GP and received a vaccine offer (OR=3.21; 95% CI: 1.91-5.39), their friends were vaccinated (OR=3.17; 95% CI: 1.98-5.07) or they considered finding of HPV-vaccine-related information easy (OR=2.63; 95% CI: 1.55-4.47) (Table). Notably, males were 0.47 times (95% CI: 0.34-0.66) less likely intending to get vaccinated than females. In the model focusing on socio-educational determinants, the intention was decreased
FIGURE 1

Awareness of human papillomavirus vaccine among
middle school students, France, 2021–22 (n = 6,992)

<table><thead><tr><th>Variable</th><th>OR</th><th>LCL</th><th>UCL</th></tr></thead><tbody><tr><td><strong>Grade level</strong></td><td></td><td></td><td></td></tr><tr><td>Third grade</td><td>1.11</td><td>1.00</td><td>1.23</td></tr><tr><td><strong>Sex</strong></td><td></td><td></td><td></td></tr><tr><td>Males</td><td>0.32</td><td>0.29</td><td>0.36</td></tr><tr><td><strong>Parental education</strong></td><td></td><td></td><td></td></tr><tr><td>Below or equal to high school level</td><td>0.82</td><td>0.71</td><td>0.95</td></tr><tr><td>Do not know</td><td>0.53</td><td>0.47</td><td>0.60</td></tr><tr><td><strong>Language</strong></td><td></td><td></td><td></td></tr><tr><td>Other languages than French spoken at home</td><td>0.59</td><td>0.52</td><td>0.66</td></tr><tr><td><strong>Local deprivation level</strong></td><td></td><td></td><td></td></tr><tr><td>Moderate-low</td><td>0.63</td><td>0.51</td><td>0.77</td></tr><tr><td>Moderate-high</td><td>0.82</td><td>0.67</td><td>1.01</td></tr><tr><td>High</td><td>0.57</td><td>0.44</td><td>0.71</td></tr></tbody></table>

LCL: lower 95% confidence limit; OR: odds ratio; UCL: upper 95% confidence limit.

Multivariable regression model including only socio-demographic characteristics. No significant interaction between a recent visit to the general practitioner or school lessons on vaccination was found.

if other languages than French were spoken at home (OR=0.41; 95% CI: 0.30-0.56), the local area was highly deprived (OR=0.50; 95% CI: 0.29-0.87) or the parents had a lower level of education (OR=0.56; 95% CI: 0.40-0.80) (Figure 3). The deprivation level of the school area was significantly associated with vaccine intention only among participants who did not remember school lessons on vaccination, but not among those remembering such lessons. This mitigation effect was significant (interaction term p=0.022) for moderate-low deprivation vs low deprivation (OR=0.17; 95% CI: 0.05-0.62 with remembering lesson vs. OR=0.93; 95% CI: 0.51-1.67 not remembering). By contrast, the association between lower level of parental education and vaccination intention was found only among participants who reported a recent GP visit (OR=0.41; 95% CI: 0.26-0.64, interaction term p=0.034).

## Knowledge and perceptions surrounding human papillomavirus vaccination

Participants who had visited a GP and been offered a vaccine had better knowledge on HPV and HPV vaccine than those with no GP visit (Figure 4). For example, 5,697 (81.5%) participants with a GP visit and a vaccine offer had knowledge about the recommended age of HPV vaccination, 3,653 (52.3%) of those with a GP visit but not a vaccine offer had knowledge about the age and 3,223 (46.1%) persons with no GP visit had knowledge (p value<0.001). Considering HPV vaccine as safe varied between these groups (46.7% with no GP visit, 54.5% with a GP visit but no vaccine offers and 76.3% with GP visit and a vaccine offer, p value<0.001). Similarly, considering that HPV vaccine was easy to access varied (40.4%, 51.3% and 81.3%), respectively, p value<0.001).

## Discussion

In this cross-sectional study among adolescents aged 13–15 years in France, we identified several socio-educational inequalities in HPV vaccine awareness, uptake and vaccination intention, relating to lower parental education, languages spoken at home and higher local deprivation levels. Recent GP visits mitigated inequalities in vaccine uptake and school lessons on vaccination mitigated inequalities in vaccination intention among unvaccinated adolescents. Surprisingly, for unvaccinated adolescents, we found disparities in vaccination intention by parental education specifically among those who reported a recent GP visit.

The use of other languages than French at home was associated with lower HPV vaccine awareness, uptake and vaccination intention, irrespective of parental education level. Following French research regulations on good ethical practice, we did not collect information on family origin, ethnicity or religious background, and consequently, we cannot fully interpret this disparity. However, given the independence from parental education level, the most relevant explanation may be language or cultural barriers leading to lower understanding of and lower feeling of being targeted by health promotion messages. This would be consistent with studies from the United States that have demonstrated the challenges faced by diverse communities regarding access to culturally and linguistically adapted HPV information [15,16]. These observations call for further exploration in the French context and possibly more targeted communication.

The fact that inequalities in HPV vaccine awareness were not mitigated by school lessons on vaccination or recent physician visit appears surprising. Further investigation is needed to explore the reasons behind such inequalities, including lower health literacy (capacity to understand the vaccine information) and selective information (to not mention HPV vaccines towards specific groups). To overcome inequalities in HPV vaccine awareness among adolescents, specific targeted interventions on HPV vaccine may be needed.

The prominent role of GPs in our study echoes previous research highlighting that limited access to GPs, GPs not offering the vaccine and challenges faced by GPs in promoting the HPV vaccine act as major barriers to HPV vaccination in France [6] and other countries [17,18]. These barriers include low adherence to routine consultations for adolescents, limited time during consultations, competing priorities for preventive interventions, extensive discussions needed with families regarding HPV vaccination, temptation to selectively offer vaccination to avoid refusal and optimise time, doubts about the vaccine usefulness, effectiveness and safety, as well as the sensitive nature of the association of the HPV vaccine with sexuality [6]. Our results suggest that these barriers contribute to social inequalities in vaccine awareness, uptake and vaccination intention. Various interventions, such as policies
FIGURE 2

Uptake of human papillomavirus vaccine among middle school students aware of HPV vaccine and mitigation by physicians and school on vaccination, France, 2021–22 (n = 4,333)

<table><thead><tr><th>Variable</th><th>OR</th><th>LCL</th><th>UCL</th></tr></thead><tbody><tr><td><strong>Grade level</strong></td><td></td><td></td><td></td></tr><tr><td>Third grade</td><td>1.22</td><td>1.06</td><td>1.39</td></tr><tr><td><strong>Sex</strong></td><td></td><td></td><td></td></tr><tr><td>Males</td><td>0.22</td><td>0.19</td><td>0.25</td></tr><tr><td><strong>Parental education</strong></td><td></td><td></td><td></td></tr><tr><td>Below or equal to high school level</td><td>0.60</td><td>0.51</td><td>0.72</td></tr><tr><td>By recent GP visit: no visit<sup>a</sup></td><td>0.31</td><td>0.16</td><td>0.59</td></tr><tr><td>By recent GP visit: do not know</td><td>1.30</td><td>0.73</td><td>2.30</td></tr><tr><td>By recent GP visit: visit<sup>a</sup></td><td>0.64</td><td>0.52</td><td>0.78</td></tr><tr><td>Do not know</td><td>0.59</td><td>0.51</td><td>0.69</td></tr><tr><td><strong>Language</strong></td><td></td><td></td><td></td></tr><tr><td>Other languages than French spoken at home</td><td>0.60</td><td>0.59</td><td>0.72</td></tr><tr><td><strong>Local deprivation level</strong></td><td></td><td></td><td></td></tr><tr><td>Moderate-low</td><td>0.80</td><td>0.63</td><td>1.01</td></tr><tr><td>Moderate-high</td><td>0.82</td><td>0.65</td><td>1.03</td></tr><tr><td>High</td><td>0.83</td><td>0.64</td><td>1.07</td></tr></tbody></table>

GP: general practitioner; LCL: lower 95% confidence limit; OR: odds ratio; UCL: upper 95% confidence limit.

Multivariable regression models including only socio-demographic characteristics. Subgroup strata are represented if interaction terms with a recent visit to a general practitioner and school lessons on vaccination showed a p value < 0.05.

on adolescent routine consultations and vaccine provision, improved medical training and decision-aid tools, could address these difficulties. The PrevHPV project, for which our data were collected, includes an evaluation of the effectiveness of such decision-aid tool and communication training for GPs to improve practice and increase HPV vaccine uptake.

Knowledge and perceptions on HPV vaccine among teenagers have been well researched across Europe and the world [19,20], however, with little attention to social disparities. In this study, we describe significant disparities in knowledge and perceptions among adolescents based on social, economic and educational factors. There were large differences in knowledge and perception among participants depending on whether the adolescents had recently visited a physician. In the absence of comparable studies, such differences should be monitored in other European settings.

Adolescents' HPV knowledge remains sub-optimal, with only 51.8% across 16 European countries [19]. Many young adolescents are not aware of the vaccine and lack support from healthcare providers, despite relatively positive attitudes [6,10]. In our study, participants showed more favourable knowledge and attitudes compared with previous studies involving adolescents in France [21] and the European Union [6,22]. Notably, only a small proportion of adolescents in our study expressed a negative perception of vaccine safety and both sexes had positive attitudes towards the utility and accessibility of vaccines.

FIGURE 3

Intention to get vaccinated against human papillomavirus among unvaccinated middle school students, by recent visit to a general practitioner and school lessons on vaccination, France, 2021–22 (n = 2,782)

<table><thead><tr><th>Variable</th><th>OR</th><th>LCL</th><th>UCL</th></tr></thead><tbody><tr><td><strong>Grade level</strong></td><td></td><td></td><td></td></tr><tr><td>Third grade</td><td>1.18</td><td>0.90</td><td>1.54</td></tr><tr><td><strong>Sex</strong></td><td></td><td></td><td></td></tr><tr><td>Males</td><td>0.45</td><td>0.34</td><td>0.59</td></tr><tr><td><strong>Parental education</strong></td><td></td><td></td><td></td></tr><tr><td>Below or equal to high school level</td><td>0.56</td><td>0.40</td><td>0.80</td></tr><tr><td>By recent GP visit: no visit<sup>a</sup></td><td>1.05</td><td>0.52</td><td>2.13</td></tr><tr><td>By recent GP visit: do not know</td><td>1.18</td><td>0.36</td><td>3.85</td></tr><tr><td>By recent GP visit: visit<sup>a</sup></td><td>0.41</td><td>0.26</td><td>0.64</td></tr><tr><td>Do not know</td><td>0.41</td><td>0.30</td><td>2.13</td></tr><tr><td>Language: Other languages than French spoken at home</td><td>0.41</td><td>0.30</td><td>0.56</td></tr><tr><td><strong>Local deprivation level</strong></td><td></td><td></td><td></td></tr><tr><td>Moderate-low</td><td>0.68</td><td>0.41</td><td>1.14</td></tr><tr><td>By school teachings: do not remember<sup>b</sup></td><td>0.17</td><td>0.05</td><td>0.62</td></tr><tr><td>By school teachings: remember<sup>b</sup></td><td>0.93</td><td>0.51</td><td>1.67</td></tr><tr><td>Moderate-high</td><td>0.88</td><td>0.53</td><td>1.46</td></tr><tr><td>By school teachings: do not remember<sup>c</sup></td><td>0.28</td><td>0.08</td><td>1.01</td></tr><tr><td>By school teachings: remember<sup>c</sup></td><td>1.14</td><td>0.63</td><td>2.05</td></tr><tr><td>High</td><td>0.50</td><td>0.29</td><td>0.87</td></tr><tr><td>By school teachings: do not remember<sup>d</sup></td><td>0.15</td><td>0.04</td><td>0.58</td></tr><tr><td>By school teachings: remember<sup>d</sup></td><td>0.64</td><td>0.34</td><td>1.21</td></tr></tbody></table>

GP: general practitioner; LCL: lower confidence limit; OR: odds ratio; UCL: upper confidence limit.

Multivariable regression model including only socio-demographic characteristics. Subgroup strata are represented if interaction terms with recent visit to the general practitioner and school lessons on vaccination showed a p value < 0.05.

In the analysis of wider determinants, the opinion of the social environment on HPV vaccination was the dominant determinant of vaccine intention among unvaccinated adolescents, concordant with the existing literature [23]. However, as many as 68% of female adolescents aware of the HPV vaccine were vaccinated or intended to get vaccinated – a coverage level that would allow significant public health benefit. Negative social influences may thus act as a major barrier to vaccination for one third of female adolescents and therefore should not be considered an insurmountable barrier to a successful vaccination programme. Appropriate interventions should address HPV vaccine attitudes in the wider population, and some studies showed a burgeoning success of social media campaigns in HPV health promotion [24,25], while peer-focused interventions may be particularly relevant for adolescents [26].

The mitigation of inequality by socioeconomic level in case of school lessons on vaccination was largely carried by an increase in intention in municipalities with

<footnote>a Interaction term p=0.045.</footnote>

<footnote>a Interaction term p value 0.034.</footnote>

<footnote>b Interaction term p value 0.022.</footnote>

<footnote>c Interaction term p value 0.053.</footnote>

<footnote>d Interaction term p value 0.063.</footnote>
FIGURE 4

Perceptions and knowledge on human papillomavirus vaccination among middle school students aware of human papillomavirus vaccination, by visit to the general practitioner and offer of a vaccine in last 12 months, France, 2021–22 (n = 4,333)

<figure><img src="image_2.png" /></figure>

higher deprivation levels, with little change in low-deprivation areas. Studies on free school-based HPV vaccine access in Belgium and in Canada have described a similar pattern, with such interventions benefiting higher-deprivation areas [27,28]. Thus, the development of vaccine access policies should be evidence-driven, as the benefits may be less tangible to the social environment of decision-makers. School-based interventions need careful design to avoid further increase of inequalities; therefore, the ongoing PrevHPV project [12] is evaluating the effect of co-constructed lesson material on HPV vaccine uptake, attitudes, and knowledge, using material that was designed based on adolescents' preferences around vaccination [29].

Our study has several limitations. Firstly, a self-administered questionnaire among adolescents is at risk of low-quality answers given haphazardly or too quickly, particularly if respondents lacked interest or did not understand the question. We tried to minimise these effects by offering a 'do not know' answer modality. We did not analyse durations of questionnaire administrations, but teachers or school nurses were present and surveyed questionnaire administration, which should guarantee a minimal level of information quality. Additionally, the use of anonymous self-administration should have limited the risk of social desirability bias.

Secondly, our participants were not a representative sample of middle school students in France, given the fact that participation depended on the school

directors' agreement and on parental non-opposition, which may have excluded students with parents with strongly negative attitudes towards vaccination. Prevalence estimates should therefore be interpreted with caution. Nevertheless, the HPV vaccine prevalence of 36% among girls and 9% among boys is close to the national estimates for 2021 (37% and 6%). Across all study participants, 21% reported a multilingual background, which corresponds to national survey data from the French Ministry of Culture [30]. Furthermore, our sample included adolescents from a wide range of socio-demographic and socio-economic backgrounds, urban and rural areas and several regions, which allowed an analysis of determinants and should allow a reasonably good generalisability of the identified determinants to the adolescent population in France. Although our study included a relatively large sample, the small sample size in specific subgroups did limit some stratified analyses.

Finally, the requirement of parental consent to vaccination in France could have impacted in a differential way the vaccine intention expressed by adolescents in different socio-educational subgroups.

## Conclusion

Coverage of HPV vaccination in France has been steadily increasing over the last decade, but larger efforts are required to meet programmatic objectives. Of particular importance will be addressing the social inequalities in vaccine awareness, intention to get vaccinated
and uptake, demonstrated throughout this study, that could lead to substantial inequalities in HPV-related cancer risk. The adolescents contribute to making decisions on vaccine uptake and our data suggest that policies facilitating and harmonising HPV vaccine promotion by healthcare professionals and adapted school lessons on HPV vaccination could mitigate inequalities in vaccine coverage. A first nation-wide vaccination campaign for 12-13-year-olds is scheduled in France during the current school year 2023-2024, and there is hope that this will not only increase coverage rates, but also reduce related social inequalities.

## Ethical statement

This protocol was approved by the French Ethics Committee 'CPP Sud-Est VI' on 22 December 2020 (ID-RCB:2020-A02031-38) and registered on ClinicalTrials.gov (NCT04945556).

## Funding statement

The study is conducted with the support of IReSP and with financial support from 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 2014-2019. The ITMO Cancer AVIESAN had no role in the design of the study and in writing the manuscript; it will have no role in the collection, analysis, and interpretation of data.

## Data availability

The data that support the findings of this study are not publicly available. They are, however, available upon restrictions from the authors upon reasonable request and with permission of the French National Institute for Health and Medical Research (Inserm). The reuse of data is subject to compliance with the General Data Protection Regulation (GDPR) and French regulations.

## Acknowledgements

The authors thank members of the National Education for the collaboration in this study, in particular the direction générale de l'enseignement scolaire (DGESCO) and participating schools.

The PrevHPV Study group includes, beyond the authors of the present manuscript, for team 1: Nelly Agrinier, Estelle Fall; for team 2: Marie Ecollan, Serge Gilberg, Josselin Le Bel, Henri Partouche, Juliette Pinot, Louise Rossignol, Arthur Tron, Minghui Zuo; for the team 3: Julien Ailloud, Julie Bros, Olivier Epaulard, Catherine Juneau, Gaëlle Vareilles; for team 5: Elisabeth Botelho-Nevers, Emily Darlington, Géraldine Jambon, Florian Jeanleboeuf, Julie Kalecinski, Christine Lasset, Laetitia Marie Dit Asse, Mabrouk Nekaa; for team 7: Anne-Sophie Barret, Isabelle Bonmarin, Daniel Levy-Bruhl, Jocelyn Raude, Jonathan Sicsic; for team 8: Bruno Giraudeau; Clémence Castagnet (Inserm/PRC) and Mélanie Simony (IReSP).

## Conflict of interest

None declared.

## Authors' contribution

JEM, ODO, SC, JS, ASB, JR, SB, AG, MM, AGB, and NT contributed to questionnaire development and data collection. JEM, HM and DOD conceived the original study concept and the analysis plan. HM performed the statistics and wrote the first draft. All authors contributed to interpretation, revised and approved the final version of the manuscript.

## References

1. Markowitz LE, Unger ER. Human papillomavirus vaccination. N Engl J Med. 2023;388(19):1790-8. https://doi.org/10.1056/NEJMcp2108502 PMID: 37163625

2. Ministère de la santé et de la prévention (MDS). Calendrier des vaccinations et recommandations vaccinales 2023. [Vaccination calendar and vaccine recommendations 2023]. Paris: MDS. [Accessed: 15 Oct 2023]. French. Available from: https://sante.gouv.fr/IMG/pdf/calendrier_vaccinal_maj-juin23.pdf

3. Nguyen-Huu N-H, Thilly N, Derrough T, Sdona E, Claudot F, Pulcini C, et al. Human papillomavirus vaccination coverage, policies, and practical implementation across Europe. Vaccine. 2020;38(6):1315-31. https://doi.org/10.1016/j.vaccine.2019.11.081 PMID: 31836255

4. Hanguerard R, Gautier A, Soullier N, Barret AS, Parent du Chatelet I, Vaux S. Couverture vaccinale contre les infections à papillomavirus humain des filles âgées de 15 à 18 ans et determinants de vaccination, France, 2021. [Vaccination coverage against human papillomavirus infections in girls aged 15 to 18 and determinants of vaccination, France, 2021]. Bull Epidemiol Hebd (Paris). 2022;(24-25):446-55. French.

5. Karafillakis E, Simas C, Jarrett C, Verger P, Peretti-Watel P, Dib F, 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(7-8):1615-27. https://doi.org/10.1080/21645515.2018.1564436 PMID: 30633623

6. Collange F, Fressard L, Pulcini C, Sebbah R, Peretti-Watel P, Verger P. General practitioners' attitudes and behaviors toward HPV vaccination: A French national survey. Vaccine. 2016;34(6):762-8. https://doi.org/10.1016/j.vaccine.2015.12.054 PMID: 26752063

7. Polonijo AN, Carpiano RM. Social inequalities in adolescent human papillomavirus (HPV) vaccination: a test of fundamental cause theory. Soc Sci Med. 2013;82:115-25. https://doi.org/10.1016/j.socscimed.2012.12.020 PMID: 23337830

8. Blondel C, Barret AS, Pelat C, Lucas E, Fonteneau L, Lévy-Bruhl D. Influence des facteurs socioéconomiques sur la vaccination contre les infections à HPV chez les adolescentes en France. [Influence of socioeconomic factors on vaccination against HPV infections among adolescent girls in France]. Bull Epidemiol Hebd (Paris). 2019;(22-23):441-50. French.

9. Herman R, McNutt L-A, Mehta M, Salmon DA, Bednarczyk RA, Shaw J. Vaccination perspectives among adolescents and their desired role in the decision-making process. Hum Vaccin Immunother. 2019;15(7-8):1752-9. https://doi.org/10.1080/21645515.2019.1571891 PMID: 30735440

10. Cadeddu C, Castagna C, Sapienza M, Lanza TE, Messina R, Chiavarini M, et al. Understanding the determinants of vaccine hesitancy and vaccine confidence among adolescents: a systematic review. Hum Vaccin Immunother. 2021;17(11):4470-86. https://doi.org/10.1080/21645515.2021.1961466 PMID: 34473589

11. Pelullo CP, Di Giuseppe G. Vaccinations among Italian adolescents: Knowledge, attitude and behavior. Hum Vaccin Immunother. 2018;14(7):1566-72. https://doi.org/10.1080/21645515.2017.1421877 PMID: 29303677

12. Bocquier A, Michel M, Giraudeau B, Bonnay S, Gagneux-Brunon A, Gauchet A, et al. 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). BMJ Open. 2022;12(3):e057943. https://doi.org/10.1136/bmjopen-2021-057943 PMID: 35332045

13. Rey G, Jougla E, Fouillet A, Hémon D. Ecological association between a deprivation index and mortality in France over the period 1997-2001: variations with spatial scale, degree of urbanicity, age, gender and cause of death. BMC Public Health. 2009;9(1):33. https://doi.org/10.1186/1471-2458-9-33 PMID: 19161613

14. Strecher VJ, Champion VL, Rosenstock IM. The health belief model and health behavior. In: Gochman DS, editor.
Handbook of health behavior research 1: Personal and social determinants. New York: Plenum Press; 1997. P. 71-91.

15. Lai D, Bodson J, Davis FA, Lee D, Tavake-Pasi F, Napia E, et al. Diverse families' experiences with HPV vaccine information sources: a community-based participatory approach. J Community Health. 2017;42(2):400-12. https://doi.org/10.1007/s10900-016-0269-4 PMID: 27734247

16. Lee HY, Luo Y, Neese J, Daniel C, Hahm HC. The role of English proficiency in HPV and HPV vaccine awareness: a cross-sectional study across race/ethnicity. Asian Pac J Cancer Prev. 2021;22(2):349-57. https://doi.org/10.31557/APJCP.2021.22.2.349 PMID: 33639647

17. Gilkey MB, McRee AL. Provider communication about HPV vaccination: A systematic review. Hum Vaccin Immunother. 2016;12(6):1454-68. https://doi.org/10.1080/21645515.2015.1129090 PMID: 26838681

18. Leung SOA, Akinwunmi B, Elias KM, Feldman S. Educating healthcare providers to increase Human Papillomavirus (HPV) vaccination rates: A Qualitative Systematic Review. Vaccine X. 2019;3:100037. https://doi.org/10.1016/j.jvacx.2019.100037 PMID: 31463471

19. López N, García-Sánchez M, Panizo MB, de la Cueva IS, Artés MT, Ramos B, et al. HPV knowledge and vaccine acceptance among European adolescents and their parents: a systematic literature review. Public Health Rev. 2020;41(1):10. https://doi.org/10.1186/s40985-020-00126-5 PMID: 32435520

20. Loke AY, Kwan ML, Wong YT, Wong AKY. The uptake of Human Papillomavirus vaccination and its associated factors among adolescents: a systematic review. J Prim Care Community Health. 2017;8(4):349-62. https://doi.org/10.1177/2150131917742299 PMID: 29161946

21. Huon JF, Grégoire A, Meireles A, Lefebvre M, Péré M, Coutherut J, et al. Evaluation of the acceptability in France of the vaccine against papillomavirus (HPV) among middle and high school students and their parents. PLoS One. 2020;15(10):e0234693. https://doi.org/10.1371/journal.pone.0234693 PMID: 33091021

22. López N, García-Sánchez M, Panizo MB, de la Cueva IS, Artés MT, Ramos B, et al. HPV knowledge and vaccine acceptance among European adolescents and their parents: a systematic literature review. Public Health Rev. 2020;41(1):10. https://doi.org/10.1186/s40985-020-00126-5 PMID: 32435520

23. Konstantinou P, Georgiou K, Kumar N, Kyprianidou M, Nicolaides C, Karekla M, et al. Transmission of vaccination attitudes and uptake based on social contagion theory: A scoping review. Vaccines (Basel). 2021;9(6):607. https://doi.org/10.3390/vaccines9060607 PMID: 34198885

24. Maisonneuve AR, Witteman HO, Brehaut J, Dubé È, Wilson K. Educating children and adolescents about vaccines: a review of current literature. Expert Rev Vaccines. 2018;17(4):311-21. https://doi.org/10.1080/14760584.2018.1456921 PMID: 29569498

25. Ortiz RR, Smith A, Coyne-Beasley T. A systematic literature review to examine the potential for social media to impact HPV vaccine uptake and awareness, knowledge, and attitudes about HPV and HPV vaccination. Hum Vaccin Immunother. 2019;15(7-8):1465-75. https://doi.org/10.1080/21645515.2019.1581543 PMID: 30779682

26. Bruel S, Cochard J, Espinouse S, Frappé P. Revue de la littérature sur les interventions en milieu scolaire concernant la vaccination anti-HPV. Sante Publique. 2020;32(1):29-41. https://doi.org/10.3917/spub.201.0029

27. Lefevere E, Theeten H, Hens N, De Smet F, Top G, Van Damme P. From non school-based, co-payment to school-based, free Human Papillomavirus vaccination in Flanders (Belgium): a retrospective cohort study describing vaccination coverage, age-specific coverage and socio-economic inequalities. Vaccine. 2015;33(39):5188-95. https://doi.org/10.1016/j.vaccine.2015.07.088 PMID: 26254978

28. Musto R, Siever JE, Johnston JC, Seidel J, Rose MS, McNeil DA. Social equity in Human Papillomavirus vaccination: a natural experiment in Calgary Canada. BMC Public Health. 2013;13(1):640. https://doi.org/10.1186/1471-2458-13-640 PMID: 23837819

29. Chyderiotis S, Sicsic J, Raude J, Bonmarin I, Jeanleboeuf F, Le Duc Banaszuk AS, et al. Optimising HPV vaccination communication to adolescents: A discrete choice experiment. Vaccine. 2021;39(29):3916-25. https://doi.org/10.1016/j.vaccine.2021.05.061 PMID: 34088507

30. Ministère de la culture (MDC). Langues et usages des langues dans les consommations culturelles en France. [Languages and language usages in cultural consumption in France]. Paris: MDC; 13 Mar 2023. French. Available from: https://www.culture.gouv.fr/Thematiques/Etudes-et-statistiques/Publications/Collections-de-synthese/Culture-etudes-2007-2023/Langues-et-usages-des-langues-dans-les-consommations-culturelles-en-France-CE-2023-3

License, supplementary material and copyright

This is an open-access article distributed under the terms of the Creative Commons Attribution (CC BY 4.0) Licence. You may share and adapt the material, but must give appropriate credit to the source, provide a link to the licence and indicate if changes were made.

Any supplementary material referenced in the article can be found in the online version.

This article is copyright of the authors or their affiliated institutions, 2023.