What are the barriers and enablers to the uptake of the HPV vaccine in Romania, Bulgaria and Croatia? A mixed methods systematic review

Abstract

Introduction

Eradication of human papillomavirus (HPV) is a global public health priority. It is linked to approximately 5% of all cancers, causing almost all cases of cervical cancer, nearly 90% of anal cancers and a significant proportion of oropharyngeal, penile, vaginal and vulval cancers.

HPV vaccination can provide protection when 90% coverage is reached. However, many countries are yet to achieve this threshold. Uptake in Romania, Bulgaria and Croatia has been low historically, and although rates are increasing, vaccine coverage remains significantly lower than the recommended WHO rate of 90%. This systematic review sought to identify the barriers and enablers to HPV vaccine uptake in these three countries.

Methods

The Joanna Briggs Institute (JBI) convergent integrated methodological framework for mixed methods systematic reviews was employed. Seven databases were searched from inception to April 2024. No restrictions were imposed on language or setting. All included studies were critically appraised with JBI Critical Appraisal tools. Data extraction was performed using standardised tools with an emphasis on equity, followed by data transformation and data synthesis. Each stage was conducted by two independent reviewers. Bronfenbrenner’s socio-ecological model was applied as a theoretical lens.

Results

A total of 402 findings from 31 studies were extracted and aggregated to form 65 categories. These were further combined in a meta-synthesis which yielded 13 synthesised findings. The meta synthesis identified commonalities across each country’s findings: attitudes towards HPV vaccination were characterised by distrust and misconceptions; knowledge deficits existed particularly in relation to gender neutral provision; and a lack of consensus among health professionals concerning the efficacy and safety of the vaccine impacted intention and uptake.

Conclusions

Barriers and enablers to HPV vaccine uptake centred on knowledge and trust. Public health interventions that address the concerns of young people, parents and health professionals are pivotal to improving HPV vaccine coverage across the three countries. Contemporaneous research to further explore the social, cultural and political factors that impede acceptance of the HPV vaccine is also required.

PROSPERO registration number

CRD42024523200.

WHAT IS ALREADY KNOWN ON THIS TOPIC

• If human papillomavirus vaccine coverage of 90% is achieved among girls and boys, eradication of cervical cancer and a significant reduction in anal, oropharyngeal, penile, vaginal and vulval cancers is possible. However, vaccine coverage rates are suboptimal in Romania, Bulgaria and Croatia.

WHAT THIS STUDY ADDS

• The findings of this review identified nuanced political, historical and policy contexts that have given rise to distrust, knowledge deficits and a lack of consensus among health professionals regarding the efficacy and safety of the vaccine.

HOW THIS STUDY MIGHT AFFECT RESEARCH, PRACTICE OR POLICY

• This review has identified clear areas of focus for public health policy and practice to target the particular behavioural and social drivers of enhanced vaccination uptake in these countries.

Introduction

Human papillomavirus (HPV) types 16 and 18 are linked to approximately 5% of all cancers worldwide.¹ HPV causes almost all cases of cervical cancer, nearly 90% of anal cancers and a significant proportion of oropharyngeal, penile, vaginal and vulval cancers,² with cervical cancer alone estimated to cause 350 000 deaths in 2022.³ Eradication of HPV is, therefore, a global public health priority.³

HPV vaccination can provide protection against the most high-risk HPV infections if a 90% vaccine coverage rate (VCR) in girls and boys is reached, ideally prior to sexual debut.⁴ However, HPV VCRs differ significantly, with many countries not reaching the required coverage.⁵ In Romania, since 2023 girls and boys, aged 11–18, have been able to access the vaccine and women up to age 45 can claim reimbursement at 50%. In Bulgaria HPV vaccination became free of charge for specific groups of females in 2012 and in 2025 it was made available for boys and the target age group of girls was expanded.⁶ In Croatia, HPV vaccination has recently been made available free of charge for boys and girls aged 10–15 with a free catch-up programme available. However, vaccine coverage remains significantly lower than the recommended WHO rate of 90%.⁴

As part of a wider European Union-funded project, HPV Protect,⁷ this mixed methods systematic review sought to identify barriers and enablers to HPV vaccine uptake in Romania, Bulgaria and Croatia. Our searches of the literature, PROSPERO, the Cochrane Library and Joanna Briggs Institute (JBI) Evidence Synthesis confirmed that no similar reviews have previously been undertaken.

Methods

This review used the JBI convergent integrated methodological framework for mixed methods systematic reviews.⁸ A priori protocol (online supplemental file 1) was registered with PROSPERO (CRD42024523200) and the review was conducted in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) guidelines.⁹ Stakeholder engagement with in-country consultants was integral to each stage of the review.

The search strategy (online supplemental file 2) was conducted by an information specialist with search terms informed by expert stakeholders. Seven databases were searched for primary research papers (Medline (Ovid), EMBASE (Ovid), PsycINFO (Ovid), Ovid Emcare, CINAHL (EBSCO), Web of Science, Scopus). No restrictions were imposed on language or date. Forward and backward citation tracking were completed using the Citationchaser application¹⁰ to retrieve any relevant studies not identified during database searching.

All identified records were collated and uploaded into EndNote V.20 and duplicates removed. Following de-duplication, citations were imported into Rayyan¹¹ and titles and abstracts were independently screened by two reviewers. Full texts of studies with potential to meet eligibility criteria were retrieved and assessed independently against the inclusion criteria. Conflicts were resolved through discussion between reviewers.

Eligibility criteria

Inclusion criteria, informed by our subject specialists, were determined using the Population, phenomenon of Interest and Context (PICo) framework¹²:

Population: All population groups.

Phenomenon of Interest: Barriers and enablers to HPV vaccine uptake.

Context: Any setting in Romania, Bulgaria and Croatia.

The review considered original quantitative, qualitative and mixed methods research. There were no restrictions on the type of study design or sample size. Conference abstracts, book chapters, editorials, reviews, study protocols, dissertations and theses were ineligible for inclusion. Studies were also excluded if they were concerned with the perceptions of Romanian, Bulgarian and Croatian expatriates as their experiences were not considered current.

Quality appraisal

All studies that met the inclusion criteria went forward to critical appraisal, conducted independently by two reviewers using the appropriate JBI tools.¹³ Disagreements were resolved through discussion. Regardless of methodological quality, all studies underwent data extraction and synthesis.

Reflexivity

Reflexive practice was embedded in the team’s research practice. We were a culturally diverse team with differing professional interests and representation from the three countries which led to meaningful consideration of equality, diversity and inclusion (EDI) and sociocultural factors that impact access to and uptake of the HPV vaccine. EDI was also prioritised methodologically.^14–17

Data extraction and synthesis

For the first phase of data extraction, the review team developed standardised data extraction proformas (online supplemental file 3) which were piloted and adjusted accordingly to capture demographic information and other relevant study characteristics required to meet the review’s aim. For each country, data were extracted by one researcher and checked for accuracy by in-country consultants.

The second phase of data extraction involved the separate extraction of qualitative and quantitative findings. All relevant qualitative findings and accompanying illustrations were extracted. For quantitative studies, all relevant numerical results and accompanying narrative text addressing the review aim were extracted verbatim where possible. Where accompanying narrative text was not available, a descriptive textual representation of the numerical results was developed. In accordance with the JBI convergent integrated approach,¹⁸ quantitative findings were then transformed into textual descriptions or ‘qualitised data’ to facilitate integration with the qualitative evidence (online supplemental file 3). Each finding was then assigned a level of credibility in accordance with JBI guidance¹⁹:

• Unequivocal: findings accompanied by an illustration that was beyond reasonable doubt and therefore not open to challenge.

• Credible: findings accompanied by an illustration lacking clear association with it and therefore open to challenge.

• Not supported: findings were not supported by the data.

Integration was conducted independently by two reviewers and checked by two additional reviewers. Only findings rated as unequivocal or credible were included in the integration process. Qualitative findings and quantitative findings transformed into textual descriptions (‘qualitised data’) were assembled and subjected to repeated detailed examination to identify categories based on similarity in meaning. Categories were aggregated to produce integrated findings that addressed the review question (online supplemental file 4). Finally, a narrative description summarising each integrated finding was produced.

Assessment of certainty of the evidence is currently not recommended for JBI mixed methods systematic reviews due to the impact of data transformation and/or integration on the grading process.¹⁹

Theoretical framework

Throughout, it was important to identify how macro, meso and micro factors interacted to influence an individual’s access to and uptake of the HPV vaccine. To assist an understanding of this process Bronfenbrenner’s²⁰ socio-ecological model was applied. The model proposes five levels of influence specific to health behaviour (figure 1): intrapersonal factors that are unique to the individual; the microsystem which is concerned with interpersonal processes and proximal contexts (family, peers); the mesosystem which is a system of microsystems that interrelate and are of particular significance to the individual (eg, school); the exosystem which includes distal contexts such as the individual’s local community context, media, local and central government and the macrosystem which refers to institutional patterns of culture and sub-culture such as political, social and educational systems. The model asserts that the individual is situated at the centre of this ‘layered’ social system, with all the nested, interrelated layers of the system interacting and influencing their development in a reciprocal manner. The chronosystem, which refers to the socio-historical context including the influence of policy, is an integral part of the model.

Figure 1. Socio-ecological model.²⁰.

Results

Study inclusion

580 records were identified as potentially relevant to the review (figure 2). Following removal of duplicates, 264 unique records (online supplemental file 5) underwent title and abstract screening. The remaining 62 records (online supplemental file 6) underwent full-text assessment. Those that did not meet the inclusion criteria were excluded (online supplemental file 7). Forward and backward citation analysis was conducted on the included studies, resulting in 905 additional records. Of these, 34 records were shortlisted and 33 were excluded as they did not meet the inclusion criteria (online supplemental file 8).

Figure 2. Flow of studies through the review.⁹.

Methodological quality

The critical appraisal scores for methodological quality of selected studies are presented in online supplemental file 9. The cross-sectional studies scored between 5 and 7, out of a possible score of 8, with the majority failing to identify confounding factors and all failing to consider strategies to deal with such factors. Inappropriate statistical analysis was identified in four studies.^21–24 The quality of qualitative publications varied considerably, with scores ranging from 2 to 10 out of a potential score of 10. The lowest scoring paper²⁵ lacked evidence of methodological congruity. Common areas of weakness across the majority of qualitative studies included a lack of reported reflexivity and reference to research ethics.

Characteristics of included studies

Each country’s findings were nuanced, reflecting their particular political, historical and policy contexts. For this reason and to support policymakers and practitioners in the development of public health interventions, the findings of this review are presented separately for each country.

In total, 31 studies, across 32 publications (Brunton et al²⁶ and Petrova et al²⁷ reported on the same study) met the inclusion criteria. The studies were conducted in Romania (n=20), Bulgaria (n=3) and Croatia (n=7), and one study²⁸ reported on data from both Romania and Croatia; the data from this latter study were disaggregated and reported on separately for each county. The included studies encompassed a range of quantitative (n=20), qualitative (n=8) and mixed methods (n=3) designs. The characteristics of included studies are presented in online supplemental file 3.

Bulgaria

Three Bulgarian studies, across four publications, were included in the review, with two publications^26,27 reporting on the same study. Two studies were qualitative,^26,27,29 one was cross-sectional.³⁰ Participant characteristics and EDI considerations are detailed in online supplemental file 3. Across the studies there was a lack of consideration of male populations, socio-economic status, religion, ethnicity and locale.

Croatia

Of the Croatian studies, seven were cross-sectional^{22,24,31–35} and one was qualitative and part of a wider European study.²⁸ Participant characteristics and EDI considerations are detailed in online supplemental file 3. The geographical location of participants was wide ranging and there was a mix of female and male participants. A broad age range was represented, along with a range of educational backgrounds, professional groups, students and parents. Consideration was given to socio-economic status in three studies.^32,34,35 None referred to ethnicity but three^24,32,33 reported on religiosity. One study³² reported on locale with 38% of participants in rural areas and 62% in urban environments.

Romania

Of the 21 studies reporting findings from Romania, 12 were cross-sectional,^{21,23,36–45} 6 were qualitative^28,46–50 (1 of which was conducted across Europe²⁸ and 3 were mixed methods).^25,51,52 Participant characteristics and EDI considerations are detailed in online supplemental file 3. The geographical location of participants was wide ranging. Nine Romanian studies had all female participants^{36–39,42,43,46,47,51} and eight had a mix of female and males.^{21,23,28,40,41,44,45,52} The age range was 17–65+ years for all but six studies^{25,44,45,48–50} in which participant age was not stated. All but seven studies^41,46–51 outlined participants’ level of education, which ranged from no education/schooling to doctorate. Where detailed, participants’ occupations were wide ranging. Socio-economic status was detailed in six studies,^{25,36,38,40,42,47} with the majority of participants on lower incomes. Only two studies^43,47 detailed ethnicity. Participants in seven studies^{23,25,36,37,39,44,52} were from urban areas and three^38,42,43 involved those from rural areas.

Findings of the review

To identify the barriers and enablers to HPV vaccine uptake in Romania, Bulgaria and Croatia, a total of 402 findings from 31 studies were extracted and aggregated to form 65 categories (online supplemental file 4). These were further combined in a meta-synthesis which yielded 13 synthesised findings. The numbers of findings which informed the categories and, in turn, the synthesised findings are presented in table 1.

Table 1. Composition of synthesised findings and categories by country.

Bulgaria	Findings (N) n=31 Credibility U: n=29 C: n=1 NS: n=1*	Synthesised finding 1 Comprising 11 findings from 3 studies across 4 papers26,27,29,30
		Category 1 Findings n=4 from 1 study across 2 papers26,27	Category 2 Findings n=4 from 2 studies across 3 papers26,27,29	Category 3 Findings n=3 from 1 study26,27,29,30
		Synthesised finding 2 Comprising 9 findings from 2 studies across 3 papers27,28,31
		Category 4 Findings n=3 from 1 study across 2 papers26,27	Category 5 Findings n=4 from 1 study30	Category 6 Findings n=2 from 1 study26
		Synthesised finding 3 Comprising 10 findings from 2 studies30,31
		Category 7 Findings n=7 from 2 studies30,31	Category 8 Findings n=3 from 1 study30
Croatia	Findings (N) n=57 Credibility U: n=56 NS: n=1*	Synthesised finding 1 Comprising 16 findings from 4 studies23,33–35
		Category 1 Findings n=4 from 1 study23	Category 2 Findings n=5 from 2 studies23,35	Category 3 Findings n=4 from 1 study33	Category 4 Findings n=3 from 1 study34
		Synthesised finding 2 Comprising 15 findings from 5 studies23,25,29,32,34
		Category 5 Findings n=8 from 5 studies23,25,29,32,34	Category 6 Findings n=7 from 2 studies25,32
		Synthesised finding 3 Comprising 25 findings from 6 studies22,31–35
		Category 7 Findings n=2 from 1 study23	Category 8 Findings n=4 from 2 studies23,33	Category 9 Findings n=6 from 2 studies23,33	Category 10 Findings n=5 from 4 studies32,34–36
		Category 11 Findings n=5 from 1 study33	Category 12 Findings n=3 from 1 study32
Romania	Findings (N) n=314 Credibility U: n=297 C: n=3 NS: n=14*	Synthesised finding 1 Comprising 52 findings from 13 studies26,29,38,40,41,45–52
		Category 1 Findings n=8 from 5 studies26,45,46,49,52	Category 2 Findings n=17 from 5 studies47–50,52	Category 3 Findings n=8 from 5 studies37,39,47,48,50	Category 4 Findings n=14 from 7 studies29,45,47–49,51,52
		Category 5 Findings n=5 from 3 studies26,40,41
		Synthesised finding 2 Comprising 14 findings from 4 studies26,40,41,45
		Category 6 Findings n=6 from 2 studies40,41	Category 7 Findings n=3 from 3 studies26,40,41	Category 8 Findings n=3 from 3 studies26,40,45	Category 9 Findings n=2 from 1 study26
		Synthesised finding 3 Comprising 67 findings from 10 studies22,24,26,37–39,41–43,46
		Category 10 Findings n=2 from 1 study41	Category 11 Findings n=17 from 5 studies26,37–39,43	Category 12 Findings n=17 from 3 studies26,37,39	Category 13 Findings n=11 from 4 studies26,37,39,43
		Category 14 Findings n=9 from 2 studies24,46	Category 15 Findings n=11 from 3 studies22,41,42
		Synthesised finding 4 Comprising 58 findings from 11 studies22,26,38,40–45,49,50
		Category 16 Findings n=33 from 1 study50	Category 17 Findings n=3 from 1 study45	Category 18 Findings n=8 from 5 studies26,38,41,43,44	Category 19 Findings n=6 from 6 studies22,40,42,43,45,49
		Category 20 Findings n=3 from 3 studies45,49,50	Category 21 Findings n=2 from 1 study26	Category 22 Findings n=3 from 1 study45
		Synthesised finding 5 Comprising 40 findings from 9 studies22,24,26,39–42,45,46
		Category 23 Findings n=5 from 2 studies40,41	Category 24 Findings n=8 from 2 studies40,41	Category 25 Findings n=4 from 2 studies40,41	Category 26 Findings n=4 from 2 studies40,41
		Category 27 Findings n=8 from 2 studies26,39	Category 28 Findings n=4 from 3 studies22,45,46	Category 29 Findings n=4 from 3 studies24,45,46	Category 30 Findings n=3 from 2 studies42,46
		Synthesised finding 6 Comprising 15 findings from 5 studies22,24,26,43,53
		Category 31 Findings n=6 from 4 studies22,24,26,43	Category 32 Findings n=3 from 2 studies22,24	Category 33 Findings n=3 from 1 study24	Category 34 Findings n=3 from 1 study53
		Synthesised finding 7 Comprising 54 findings from 10 studies24,38–42,44,47,49,51
		Category 35 Findings n=12 from 1 study24	Category 36 Findings n=3 from 1 study42	Category 37 Findings n=2 from 2 studies39,49	Category 38 Findings n=7 from 4 studies38–40,47
		Category 39 Findings n=4 from 4 studies40,41,44,49	Category 40 Findings n=7 from 1 study38	Category 41 Findings n=3 from 2 studies40,49	Category 42 Findings n=4 from 3 studies40,49,51
		Category 43 Findings n=5 from 3 studies39,40,49	Category 44 Findings n=4 from 2 studies40,42	Category 45 Findings n=3 from 1 study41

^*Excluded from meta-aggregation.

C, credible; NS, not supported; U, unequivocal.

Bulgaria

Synthesised finding 1: attitudes towards HPV vaccination in Bulgaria were characterised by distrust

This synthesis revealed that the HPV vaccine was viewed with distrust in Bulgaria and there was a lack of access to reliable information.

Category 1: There was a lack of balanced information available to young women in the Bulgarian language

A lack of unbiased information available in the Bulgarian language was seen as a barrier to HPV vaccine uptake by young women.

Category 2: Constructions of state control and distrust served as a barrier to HPV vaccination uptake in Bulgaria

Among participants, there was widespread suspicion that pharmaceutical companies paid doctors to promote the vaccine. Young women were also distrustful of doctors.

Category 3: There was a lack of reliable information available to Bulgarian parents

Parents had limited access to reliable information about HPV and the HPV vaccine. General practitioners attributed this as well as negative information about the vaccine online and in the media to Bulgaria’s low VCRs.

Synthesised finding 2: decision making about HPV vaccine intent and take-up in Bulgaria was based on cost-benefit analyses

This synthesis revealed that decision making regarding HPV vaccine intention and uptake in Bulgaria was based on an analysis of perceived benefits versus fiscal concerns and perceived risks.

Category 4: Young Bulgarian women’s decision making about HPV vaccination was based on fiscal considerations and risk analyses

Free access to the vaccine in Bulgaria was unavailable at the time of this research, but the findings indicated that young women could be excluded from access to the vaccine if it was expensive. It was also identified that young women’s decision making was informed by their perceived risk of contracting HPV and the benefit of the vaccine.

Category 5: Bulgarian parents had concerns about the safety and efficacy of the HPV vaccine

General practitioners reported that parents lacked confidence in the vaccine’s safety and efficacy and were fearful of complications. The general practitioners believed that this negatively impacted uptake.

Category 6: HPV vaccination was perceived as a personal and social responsibility by young Bulgarian women

Uptake of the vaccine was perceived by some women as a right. It was also perceived by young women as a responsible thing to do.

Synthesised finding 3: there was a lack of consensus among health professionals in Bulgaria regarding the efficacy and safety of the HPV vaccine

This synthesis revealed that health professionals in Bulgaria had differing perspectives on the safety and efficacy of the HPV vaccine.

Category 7: Health professionals in Bulgaria had mixed perceptions of the vaccine

Some health professionals were convinced of the benefits of the vaccine but others lacked confidence in it, with some rejecting it. Although health professionals promoted the vaccine publicly, some refused vaccination for their own children.

Category 8: Health professionals in Bulgaria tried to address concerns about the HPV vaccine

Health professionals used scientific facts to overcome concerns and reduce uncertainty and in so doing aimed to explain away the ‘myths’ surrounding the vaccine.

Croatia

Synthesised finding 1: inequalities in HPV vaccine take-up and intention are prevalent in Croatia with widespread knowledge deficits regarding the role of the HPV vaccine for males

This synthesis revealed that HPV vaccine intent and uptake in Croatia varies across groups and that knowledge deficits exist regarding the role of the HPV vaccine for males.

Category 1: Croatian parents and health professionals were more likely to intend to vaccinate their daughters than their sons

Parental support for HPV vaccination was influenced by a child’s biological sex, regardless of whether the parent was a health professional or not, with intention identified as lower for sons.

Category 2: Confusion existed among Croatian health professionals and parents regarding the relevance of the HPV vaccine for males

There were knowledge deficits regarding the role of the HPV vaccine for males among parents and health professionals and HPV vaccination intention was lower for sons among parents.

Category 3: Some Croation young people experienced disparities in HPV vaccination messaging and take-up based on their biological sex

Young women were more likely to have a positive attitude and to be more open to having the vaccine compared with young men, although knowledge levels about HPV appeared consistent between young women and men.

Category 4: Some Croatian young women’s HPV vaccination decision-making was influenced by their mothers, but others made the decision independently

For some girls, their mothers were influential in their decision making about HPV vaccine uptake but others made the decision for themselves.

Synthesised finding 2: Confidence in the safety and efficacy of the HPV vaccine varies which impacted intention and take-up across Croatia

This synthesis revealed that perceptions concerning the safety and efficacy of the HPV vaccine were variable and this impacted vaccine intent and uptake.

Category 5: Croatian parents, girls and health professionals lacked confidence in the safety and efficacy of the HPV vaccine which impacted behaviours

It was found that parents, girls and health professionals lacked confidence in the safety and effectiveness of the vaccine which negatively impacted their support for vaccination. Doctors did not uniformly vaccinate their own children against HPV.

Category 6: Croatian nurses held more negative or ambivalent views regarding the HPV vaccine than doctors

In comparison to doctors, nurses had more concerns about the vaccine and were less likely to recommend it.

Synthesised finding 3: attitudes towards HPV vaccination in Croatia are influenced by knowledge, experience, economic considerations and beliefs

This synthesis revealed that attitudes towards HPV vaccination in Croatia were influenced by a myriad of factors.

Category 7: Experience of HPV positively influenced Croatian parent’s attitudes towards HPV vaccination

Personal experience of HPV positively influenced parental attitudes towards vaccination and knowing an individual with HPV associated disease impacted vaccination intention.

Category 8: Knowledge of HPV positively influenced Croatian parents’ and emerging adults’ attitudes towards HPV vaccination

Knowledge of the virus and transmission risks promoted positive attitudes towards vaccination among parents and emerging adults. Beliefs regarding non-sexual HPV transmission impacted parental (healthcare professionals and non-healthcare professionals) support for HPV vaccination. Awareness of HPV infection and cervical cancer risk among emerging adults decreased vaccine hesitancy.

Category 9: Croatian parents, emerging adults and health professionals believed that promiscuity increased HPV risk which negatively influenced their attitudes towards vaccination

It was widely held by parents that promiscuity and risky sexual behaviour increased HPV risk and this negatively impacted support for HPV vaccination. Religiosity increased HPV vaccine hesitancy among emerging adults.

Category 10: Croatian parents, health professionals and the general public were aware of the HPV vaccine and they knew that it was available, but cost could be a barrier

Parents, health professionals and citizens had heard of the vaccine and knew that it was available. However, it was identified that cost would be a barrier for girls.

Category 11: Non-modifiable factors appeared to have no bearing on HPV vaccine hesitancy among Croatian emerging adults

Age, years and level of formal education, relationship status and locale appeared not to influence HPV vaccine hesitancy.

Category 12: Croatian doctors’ sources of information about HPV and knowledge varied in quality

Doctors’ sources of information were of variable quality. Although they were largely knowledgeable about target populations, knowledge about vaccination against cervical dysplasia was mixed.

Romania

Synthesised finding 1: unsupported beliefs served as a barrier to HPV vaccine uptake in Romania

This synthesis revealed that unsubstantiated beliefs had a negative impact on HPV vaccine uptake in Romania.

Category 1: HPV risk was perceived as modifiable and the HPV vaccine was viewed as unnecessary

Alternatives to the HPV vaccine such as personal protective methods, limited sexual activity and treatment were perceived as viable alternatives to vaccination, with the HPV vaccine being presented as unnecessary.

Category 2: Distrust in stakeholders fueled suspicion around the vaccine

People were suspicious of the reasons for providing the vaccine. This perception appeared to be exacerbated by it becoming free of charge. People felt that the vaccine was experimental and connected to state control.

Category 3: Religious beliefs and acceptance of predetermined health outcomes deterred vaccine uptake

Religious beliefs and acceptance of the inevitability of HPV infection and cancer were linked to vaccine refusal with some believing in destiny or ‘God’s will’ and a lack of control over cancer.

Category 4: There was widespread concern that the vaccine would harm children

The vaccine was framed as posing a risk to children with some people linking it to adverse health outcomes such as diminished fertility, (other) cancers and autism as well as other non-specific side-effects. Moral risks were also highlighted in relation to the vaccine potentially promoting promiscuity.

Category 5: Fear of side effects related to the HPV vaccine were associated with refusal

Fear of side effects related to the vaccine was a barrier to HPV vaccine uptake among women and teenage girls and for some adolescents, parental concerns about safety presented a barrier to uptake.

Synthesised finding 2: practical concerns and a lack of knowledge surrounding the HPV vaccine were associated with vaccine hesitancy in Romania

This synthesis revealed that practical concerns and a lack of knowledge surrounding the HPV vaccine were associated with vaccine hesitancy in Romania.

Category 6: Insufficient knowledge was a barrier to uptake among teenage girls

Some teenage girls reported barriers to uptake of the vaccine being linked to confusion about the timing of vaccination in relation to sexual debut, a lack of knowledge about the vaccine in general and concerns regarding its efficacy.

Category 7: Fear of injections was a barrier to uptake

Fear of needles and pain was a barrier to uptake among a minority of women and adolescents.

Category 8: Financial concerns were a barrier to uptake

The cost of the vaccine would deter some women and teenagers from having it. The majority of physicians felt that the vaccine should be free of charge. This is now the case in Romania.

Category 9: Lack of time and issues with accessing the vaccine were barriers to uptake

Not knowing where to access the HPV vaccine and a lack of time posed barriers to uptake for a minority of women.

Synthesised finding 3: knowledge of the virus, transmission and vaccination varied across different groups in Romania

Category 10: There were gendered differences in knowledge levels among young people

Girls were more likely than boys to be aware of HPV and the vaccine.

Category 11: Women’s understanding of HPV was variable

Some women understood HPV and its potential link to cervical cancer but others were unclear about symptoms and the virus’s potential impact on both men and women.

Category 12: Women had gaps in their knowledge of HPV transmission

Women’s knowledge of HPV transmission varied, with some confusion evident regarding sexual and non-sexual transmission routes.

Category 13: Women had gaps in their knowledge of the HPV vaccine

Most women were unclear about the availability of the HPV vaccine. Many were also unaware of the gender neutral offer. HPV-vaccinated women were confused about follow-up and ongoing screening.

Category 14: The public had some knowledge of HPV and the HPV vaccine

Citizens were aware of HPV and its link to cervical cancer but knowledge regarding transmission and vaccination varied.

Category 15: Young people had gaps in knowledge of HPV

Young people had differing levels of HPV-related knowledge and were unclear regarding viral transmission. Nearly half of young people knew that HPV causes cervical cancer, but the majority were unaware that HPV also causes cancers in men.

Synthesised finding 4: low levels of knowledge relating to HPV and the vaccine were driven by multiple factors in Romania

This synthesis revealed that low levels of HPV-related knowledge were underpinned by a range of factors.

Category 16: Media coverage about HPV vaccination was inconsistent

HPV vaccine messaging in the media was heterogenous and sometimes incomplete. Few reports addressed vaccinating boys and information about vaccine efficacy was often incorrectly presented. Concerns surrounding insufficient vaccine testing were highlighted with media reports more likely to recommend vaccine refusal.

Category 17: Levels of knowledge of HPV infection and vaccine varied across physicians

Knowledge varied between doctors but appeared to be positively associated with increased experience.

Category 18: Predictors of knowledge regarding HPV infection and vaccination were nuanced

A variety of individual, social and structural factors contributed to low levels of knowledge about HPV and the vaccine in Romania. Education, income, healthcare accessibility, age at sexual debut and family relationships played significant roles, but predictors of knowledge were inconsistent across different groups.

Category 19: Information on HPV and the vaccine was perceived as insufficient

There was a consensus across health professionals, young people, mothers and the general population that information concerning the HPV virus and the vaccine was lacking.

Category 20: The general public were dissatisfied with the government’s educational campaign

Governmental educational campaigns were not perceived as intended with widespread dissatisfaction among the public and physicians.

Category 21: HPV knowledge deficits in women reflected poor knowledge levels among health professionals

Doctors asserted that if health professionals were more knowledgeable about HPV they would be better able to educate the general population which would, in turn, positively impact VCR.

Category 22: There was a lack of consensus regarding the vaccination programme in Romania among physicians

Physicians had mixed opinions on whether the vaccine should be mandatory or optional, but the majority agreed on the age at which vaccination should occur.

Synthesised finding 5: information sources for HPV and the vaccine varied across different demographic groups in Romania

This synthesis revealed that information sources for HPV and the vaccine varied across different demographic groups in Romania.

Category 23: The internet and television were the most commonly cited information sources for young people

Young people relied largely on digital and broadcast media for HPV and vaccine information.

Category 24: The family was an underutilised source of information for young people

While some young people saw family as a potential source of information, most did not discuss HPV with them.

Category 25: Health professionals were a trusted but underutilised source of information for young people

Healthcare professionals were considered a reliable source of information, but young people rarely turned to them for information.

Category 26: Schools were a limited information source for young people

Schools played only a small role in HPV-related education, despite some young people seeing school as a potential source of information.

Category 27: Women’s HPV information sources were widespread

Women learnt about HPV through a variety of sources such as health professionals, the internet and television.

Category 28: Health professionals’ HPV information sources varied

Health professionals accessed a variety of HPV-related information sources including some that were not scientifically based.

Category 29: Health professionals were used as a resource for HPV and HPV vaccination information

Health professionals were considered by some as a good resource for HPV and HPV vaccination information, but physicians did not see themselves as the best method of dissemination.

Category 30: Few parents, young people and doctors used their healthcare provider as an information source for HPV and HPV vaccination information

Health providers rarely proactively discussed HPV and the vaccine with patients and, where appropriate, their parents.

Synthesised finding 6: a minority of the population were vaccinated or intended to be vaccinated against HPV despite high levels of confidence in the vaccine

This synthesis revealed that a minority of the Romanian population were vaccinated or intended to be vaccinated against HPV, despite high levels of confidence in the vaccine.

Category 31: A minority of people had received the HPV vaccine or intended to do so

Reports suggested that a minority had accepted the vaccine and, likewise, only a minority intended to do so.

Category 32: More females than males had received the HPV vaccination

There were notable gender disparities favouring females in relation to vaccine take-up.

Category 33: The general public believed that the HPV vaccine poses no risks

The vaccine was considered to be safe among parents and the general population and most parents in this study would recommend HPV vaccination.

Category 34: Health professionals had confidence in the HPV vaccine

Health professionals in the study that informed this category had a high level of confidence in the vaccine and the majority were willing to recommend it.

Synthesised finding 7: HPV vaccine intent was influenced by a broad spectrum of personal and institutional factors

This synthesis revealed that HPV vaccine intent was influenced by a broad spectrum of personal and institutional factors.

Category 35: Predictors of HPV vaccination decisions among parents were varied

Predictors of parental HPV vaccination decision making varied across studies and were sometimes contradictory.

Category 36: Predictors of HPV vaccination decisions among young people were based on multiple factors

Anticipated inaction regret, perceived vaccine effectiveness and safety, previous refusal, perceived susceptibility, perceived severity, knowledge, anticipated worry, concerns about infecting others, gender and sexual history were related to vaccine intent and acceptability in young people.

Category 37: Health professionals influenced vaccine intent

Health professionals impacted vaccine intent both positively and negatively depending on the message conveyed.

Category 38: Friends, relatives and authority figures influenced HPV vaccine decision making

Decision making among mothers, adult women, younger women and teenage girls regarding HPV vaccine uptake was influenced by people who they perceived as significant such as parents, relatives, friends and authority figures.

Category 39: Educational campaigns influenced HPV vaccine decision making

Educational information about the HPV vaccine appeared to positively influence HPV vaccine decision making.

Category 40: Vaccine intent was associated by a complex interplay of factors

Vaccine intent was shaped by individuals’ engagement with the topic and how they framed HPV vaccination.

Category 41: People who were in favour of HPV vaccination relied on factual evidence

Engagement with objective biomedical evidence appeared to be linked to positive attitudes towards the HPV vaccine.

Category 42: People who were in favour of HPV vaccination framed the risks associated with refusal as greater than the risks posed by the vaccine

Those in favour of vaccination perceived any potential vaccine-related risks to be outweighed by those risks associated with not being vaccinated. For example, cancer was positioned as a risk associated with non-vaccination by pro-vaccination parents.

Category 43: People who were in favour of HPV vaccination held positive attitudes towards it

Those in support of the HPV vaccine held positive attitudes towards it compared with those who were hesitant.

Category 44: Young people who were in favour of HPV vaccination held positive attitudes towards vaccination in general

Young people who were generally pro-vaccination had positive attitudes towards the HPV vaccine. For example, there was a significant correlation between influenza and HPV vaccine intent among young people.

Category 45: HPV vaccine take-up among adolescents appeared to be shaped by a mix of personal and social factors

Young people’s willingness to have the HPV vaccine appeared to be influenced by a wide variety of factors such as age at sexual debut, their household income and relationships with family members.

Discussion

This review sought to identify the barriers and enablers to HPV vaccine uptake in Romania, Bulgaria and Croatia against a backdrop of suboptimal vaccine coverage.

Each country’s findings were nuanced, reflecting their particular political, historical and policy contexts. There was an imbalance in the number of included studies across the three countries, with the majority focusing on Romanian populations. There was variation in methodological rigour and a lack of consideration of male populations, socio-economic status, religion, ethnicity and locale in Bulgaria, and ethnicity in Romania and Croatia. However, the meta-synthesis identified commonalities across the findings of all three countries. Attitudes towards HPV vaccination were characterised by distrust and misconceptions about both the virus and the vaccine; knowledge deficits existed particularly in relation to gender neutral provision; and a lack of consensus among health professionals concerning the efficacy and safety of the vaccine impacted intention and uptake. Findings from stakeholder engagement and structured consultation with opinion leaders, conducted in parallel to this review, suggest that these barriers persist. In Romania, a recent cross-sectional study⁵³ of family physicians has identified that both physician and public attitudes toward HPV vaccination are only moderately positive, which limits vaccine uptake and the success of prevention efforts.

Application of Bronfenbrenner’s²⁰ socio-ecological model demonstrates the importance of attending to the microsystem which is concerned with interpersonal processes and proximal contexts such as the attitude of family and peers towards the HPV vaccine.^33,37,39,46 Similarly, the evidence suggests that the impact of the mesosystem, the system of microsystems that interrelate and are of particular significance, such as messages conveyed about the HPV vaccine through schools and the healthcare system, require attention in order to promote vaccination uptake.^{22,24,25,29–31,38,44,48} Equally, the exosystem which includes distal contexts such as the local community context,^37–39,46 media,⁴⁹ local and central government policy and the macrosystem, which includes political, social and educational systems, all impact HPV vaccine uptake. Finally, the chronosystem, or the socio-historical context, is an additional integral aspect which influences HPV vaccine uptake with, for example, wider discourses around state control,^{26,27,29,46,48,49,51} vaccine hesitancy,^39,41,48 health beliefs^47,48 and young people’s sexual decision-making^22,25,40 potentially impacting intentions and uptake of HPV vaccination.

All of these nested, interrelated layers interact and influence the uptake of the vaccine. While acknowledging the included studies’ methodological limitations and Bulgaria and Croatia’s sparse evidence base, the meta synthesis suggests that interventions need to be multifaceted and nuanced in taking account of local context. It also highlights that knowledge deficits among health professionals and the public regarding the efficacy and safety of the HPV vaccine require attention. In operationalising these findings, the WHO’s Behavioural and Social Drivers of Vaccination framework,⁵⁴ which draws on the work of Brewer et al⁵⁵ highlights four categories of drivers for vaccination (figure 3). Thinking and feeling pertains to individual level factors, such as perceived disease risk and confidence in the vaccine. Social processes refer to social norms, including the opinions of community leaders or the recommendation of healthcare workers. Thinking and feeling and social processes lead to motivation, which is the intention to be vaccinated. If there is motivation to be vaccinated, practical issues, like affordability and ease of access impact uptake. All of these factors were evidenced in the current review. Combined with Bronfenbrenner’s²⁰ socio-ecological model, this framework could inform an effective approach to increasing HPV vaccine uptake across these three countries. However, to measure the impact of such interventions, better VCR monitoring mechanisms are required.

Figure 3. The WHO Behavioural and Social Drivers of Vaccination framework (2022, p.2). License: CC BY-NC-SA 3.0 IGO.

A notable limitation of the current body of literature pertaining to Romania, Bulgaria and Croatia was its lack of attention to ethnicity. The findings of a systematic review⁵⁶ that specifically addressed racial/ethnic disparities in HPV vaccination were similar to those of the current review, with uptake reflecting a lack of support for the vaccine from health professionals, limited knowledge of HPV and HPV vaccination, and concerns about safety. Rani et al’s⁵⁷ systematic review of public education interventions and their impact on the uptake of HPV vaccination found that minority group interventions that provided individually tailored messages, addressed misconceptions, removed barriers and engaged parents and community members improved HPV vaccine acceptance.

Two Romanian studies^39,40 identified that school-based education was an underused resource that young people would welcome. This is a currently under-researched area of focus across the three countries and elsewhere. Ampofo et al’s⁵⁸ systematic review highlighted the lack of research regarding the benefits of school-based education in improving knowledge and behaviours towards HPV vaccination internationally. However, their findings⁵⁸ suggest that printed education materials focused on HPV-related content and face-to-face active approaches may positively impact risk perceptions. Gobbo et al’s⁵⁹ systematic review identified a positive impact of peer intervention on vaccine take-up. In examining parental interventions aimed at increasing HPV vaccine uptake, Mohamed et al’s⁶⁰ systematic review concluded that parent-based interventions do not increase uptake, but reminder and recall systems have the potential to improve initiation and completion, arguing that behavioural theories and pharmacy-based HPV vaccination appear to be underused.

A recurring theme across the Romanian and Bulgarian study findings was the role of health professionals in influencing HPV vaccine uptake.^29,30,38,48 Constable et al⁶¹ conducted a review of the literature which identified specific communication strategies employed by healthcare professionals in promoting uptake of the HPV vaccine. Similarly, Efua et al⁶² demonstrated that health professionals can improve HPV vaccine uptake through the use of bespoke strategies.

Limitations

The findings of this review need to be contextualised by the small number of Bulgarian and Croatian studies that were identified for inclusion and variations in the quality of reporting across all the included studies which may adversely affect confidence in the findings of the review. These factors highlight the need for better quality research and large-scale trials in the future, including the needs of under-represented groups. In addition, the majority of studies were dated and undertaken prior to recent policy changes regarding free access to the HPV vaccine for both girls and boys in these countries. It is important to note that HPV awareness and prevention policy has been advancing over the past 2 years, although at different speeds. Romania has recently adopted a national HPV prevention programme to include boys as well as girls, age 10–14, in vaccination programmes using 9-valent vaccines. Romania has expanded reimbursement for vaccines for boys and girls and catch up to age 26. Partial reimbursement has also been introduced which is positive given the current high burden of cervical cancer. In Bulgaria HPV vaccination was made available for boys and girls in 2025. Croatia had already been providing gender neutral vaccination and has focused on improving vaccine uptake. Mandatory vaccination has also been debated. These changes show a shift in political ambition to improve the prevention profile in Southeast Europe. This is evidenced in the latest HPV Prevention Policy Atlas⁶³ which shows that 89% of European countries now have national vaccination programmes, and 87% also support a gender-neutral approach. However, the infrastructure for vaccine delivery may be inequitable and public health education campaigns still vary widely in their focus and efficacy.

Conclusions

Barriers and enablers to HPV vaccine uptake centred on knowledge and trust. Years of life lost and productivity costs due to HPV-related cancers are significant in Romania, Bulgaria and Croatia.⁶⁴ The HPV vaccine offers a powerful tool against these cancers, but success is contingent on a VCR of 90%.⁴ By September 2023, over 280 million doses of the HPV vaccine had been administered worldwide and safety and efficacy have been demonstrated.^65,66 Public health interventions that draw on this data to challenge the misconceptions about the vaccine are of paramount importance in increasing these countries’ HPV VCRs. In addition, evidence identified in this review supports the need for better quality monitoring mechanisms and further contemporary and culturally-competent⁶⁷ research to understand the social, cultural and political factors that impede acceptance of the HPV vaccine.

Data availability statement

All data relevant to the study are included in the article or uploaded as supplementary information.