Factors associated with HPV vaccine acceptance and hesitancy in Africa: a systematic review protocol

Abstract

Introduction

Human papillomavirus (HPV) infection is the most prevalent sexually transmitted infection worldwide. HPV vaccination is an important tool to prevent and control HPV infection and its complications. Despite carrying the severe burden of disease, HPV vaccine coverage in Africa remains low. The aim of the current review is to evaluate the factors associated with HPV vaccination acceptance among adolescent men and women, young men and women, parents/caregivers, men who have sex with men, healthcare workers and programme managers in Africa.

Methods and analysis

We will include peer-reviewed quantitative studies. We will search PubMed, Scopus, PsycInfo, Web of Science and Cochrane Central Register of Controlled Trials, with no language restriction, to identify eligible studies. Two review authors will independently screen the titles and abstracts of the search output in Covidence to select potentially eligible studies. The same two reviewers will independently screen the full-text of all identified potentially eligible articles to identify studies meeting inclusion criteria. Two review authors will independently extract data from eligible studies using a predefined data extraction form. Two review authors will independently assess the risk of bias in each included study, using the Effective Public Health Practice Project ‘Quality Assessment Tool for Quantitative Studies’. We will assess the quality of evidence using the method for Grading of Recommendations Assessment, Development and Evaluation.

Ethics and dissemination

Ethical approval is not required for this study because we will use already published data. The results of this review will be disseminated through peer-reviewed publication and conference presentation.

PROSPERO registration number

CRD42023475810.

Correspondence to Dr Edison Johannes Mavundza; [email protected]

STRENGTHS AND LIMITATIONS OF THIS STUDY

• We will include studies conducted among all individuals eligible for human papillomavirus vaccination, including all stakeholders involved in vaccination processes.

• This study will employ a rigorous methodology that involves an established framework, a search strategy and a selection process.

• We will use the Grading of Recommendations Assessment, Development and Evaluation approach to assess the certainty of the evidence.

• We will only include studies conducted in Africa; this may limit generalisability of our findings.

Introduction

Human papillomavirus (HPV) infection is the most prevalent sexually transmitted infection worldwide.¹ It is estimated that approximately 75% of sexually active men and women will acquire HPV infection in their lifetime.² HPV infections are most prevalent in young adults, as sexual risk behaviours are greatest in this age group. Sexually active young women, in particular, carry the highest risk of infection, with studies documenting rates as high as 68%–71%.³ Due to their sexual practices such as receptive anal intercourse,^{4 5} men who have sex with men (MSM) are also at high risk of HPV infection and associated diseases.^4–9 There are more than 200 HPV types that are classified into low-risk and high-risk types.^{2 10 11} High-risk HPV types include HPV-16, -18, -31, -33, -35, -39, -45, -51, -52, -56, -58 and -59, whereas low-risk HPV types include HPV-6, -11, -40, -42, -43, -44, -54, -61 and -72.²

Although most HPV infections are transient and asymptomatic, persistent infection with high-risk HPV types may result in cancers, including cervical, anal, vulvar, vaginal, penile and oropharyngeal cancers^12–14 and genital warts.¹⁴ Cervical cancer, the fourth most common cancer in women worldwide, is the most common cancer associated with HPV infection,¹⁰ with an estimated 6 04 127 cases and 341 831 deaths in 2020.² Low and middle-income countries (LMICs), especially in sub-Saharan Africa (SSA), carry the severe burden of the disease.¹⁵ SSA accounts for 20% of cases and 25% of deaths from cervical cancer worldwide,¹⁶ with women of low socioeconomic status bearing the greatest burden.¹⁷ The burden is mainly caused by the lack of preventive services such as vaccination or cytological screening (ie, Pap smears) programmes.^18–20 Although countries in the Middle East and North Africa (MENA) are very conservative,^21–23 HPV infection and related cancers are prevalent in this region. However, the prevalence of HPV in the MENA region is very low compared with other regions globally.^22–24 HPV infection is also responsible for an estimated 90%, 60% and 70% of anal, penile and oropharyngeal cancer in men, respectively.^{7 19 25}

Vaccination is one of the most effective public health interventions used for controlling and eliminating life-threatening infectious diseases.²⁶ It is estimated that vaccines save approximately 2–3 million lives worldwide each year.²⁷ Vaccination has been regarded as one of the greatest public health achievements of the 20th century.^28–31 HPV vaccination is an important tool to prevent and control HPV infection and its complications.¹³ However, HPV vaccines are most effective when administered before sexual debut and first exposure to HPV.³² The first HPV vaccine was licensed in 2006.^{10 33} Currently, there are six licensed HPV vaccines that are used across the world: Cervarix, Cecolin and Walrinvax, the bivalent vaccines; Gardasil and Cervarax, the quadrivalent vaccines; and Gardasil9, the nonavalent vaccine.^{17 33} Evidence has shown that all six vaccines are safe, highly immunogenic and effective in preventing HPV infection and its sequelae.¹⁷ All vaccines are licensed for use in women and men, except for Cecolin and Walrinvax, which are licensed for women only.³³ HPV vaccination is currently recommended for adolescent men and women aged 9–14 years in a one or two-dose series and as a three-dose series for young men and women aged 15 years or older and immunocompromised individuals, including those living with HIV.³³

Since the licensing of the first vaccine in 2006, many countries across the world have introduced HPV vaccines in their national immunisation programmes to prevent cervical cancer.^34–36 As of December 2022, 172 of the 194 WHO Member States were considered to have partially or fully introduced national HPV vaccination programmes.³³ Despite carrying the severe burden of HPV infection and its associated diseases, very few LMICs have introduced HPV vaccination programmes. As of 2019, HPV vaccination programmes have been introduced by more than 80% and 41% of high-income countries and LMICs, respectively.^{17 37} As of December 2019, there were only 17 countries that have introduced HPV vaccination in their national immunisation programmes,³⁸ including Libya, Lesotho, Rwanda, Uganda, Zambia, Malawi, South Africa, Botswana, Mauritius and Seychelles.^{10 39–41} Due to the stigma related to HPV as a sexually transmitted infection, most of the countries in the MENA region have not yet introduced HPV vaccination programmes. Currently, Libya and the United Arab Emirates are the only countries that included HPV vaccine in their health programmes.^{22 24} Of the 172 countries that have introduced HPV vaccination programmes worldwide, 47 (24%) targeted both men and women.³³ Some of these countries include Argentina, Austria, Australia, Canada, Isarel, New Zealand, the United Kingdom and the USA.^{5 8 36 42 43}

Despite being available for about 17 years, proven safety, efficacy, recommendation by WHO, as well as the programmes implemented by many countries to promote vaccination, HPV vaccine uptake remains low, compared with other childhood and adolescent vaccines.⁴⁴ In 2019, it was estimated that only 4% of men and 15% of women were fully vaccinated worldwide.⁴³ In SSA, female HPV vaccine coverage was estimated to be 20% in 2019.³⁷ Numerous barriers to HPV vaccination have been identified, including lack of healthcare provider recommendations, concerns about safety, concerns about side effects and a general lack of awareness and knowledge about HPV vaccination.⁴⁵ Vaccine hesitancy is considered an important driver contributing to low levels of vaccination coverage in many settings.^{29 46} Vaccine hesitancy is defined as a delay in acceptance or a refusal of vaccination despite the availability of vaccination services.^47–49 It is influenced by factors such as complacency (the person does not see a need and value for the vaccine), confidence (individual’s confidence in the vaccine) and convenience (access to vaccines).^50–52 Resistance to vaccinations is not a new phenomenon; it dates back to the era of smallpox vaccination.⁵³ In 2019, the WHO identified vaccine hesitancy as one of the top 10 threats to global health.^{34 54}

For the vaccination programme to be successful, a high level of acceptability and uptake in the relevant population is required.^{34 36 55} There is, therefore, an urgent need for the evaluation of the factors associated with HPV vaccination acceptance. In Africa, two systematic reviews on factors associated with HPV vaccination acceptance were published in 2014.^{18 56} However, the reviews included both qualitative and quantitative studies, conducted only in SSA, and published up to 2013. One review included studies only conducted among adults and parents,¹⁸ while the other one focused on studies among adolescents, parents/guardians and healthcare workers.⁵⁶ These limitations justify the need for a comprehensive systematic review that will include studies conducted in the whole of Africa, among all individuals eligible for HPV vaccination, and other key stakeholders. The aim of the current review is to evaluate the factors associated with HPV vaccination acceptance among adolescent men and women, young men and women, parents/caregivers, MSM, healthcare workers and programme managers in Africa. Both parents/caregivers, healthcare workers and vaccination programme managers play a significant role in the acceptance and uptake of HPV vaccination. The healthcare workers’ recommendation for vaccination is the strongest predictor of vaccine uptake.^{18 57 58} Studies have shown that individuals who receive a recommendation for the HPV vaccination are more likely to initiate vaccination.^58–60 Since most HPV vaccination target mainly young adolescents, parents/caregivers make the decision to vaccinate these adolescents.⁶¹ Their decision-making affects the success of HPV vaccination programmes.^{61 62} The findings of this review will help to promote acceptability and uptake of HPV vaccination in Africa, by developing and implementing interventions tailored to address identified factors.

Objectives

The objective of the review is to identify, evaluate and synthesise quantitative studies investigating the factors associated with HPV vaccine acceptance among adolescent men and women, young men and women, MSM, parents or caregivers, healthcare workers and programme managers in Africa.

Methodology

This systematic review will be conducted as per the Preferred Reporting Items for Systematic Reviews and Meta Analyses (PRISMA) guidelines.⁶³ The study will be conducted from November 2024 to November 2025.

Eligibility criteria

We will include quantitative studies that investigated the factors that are associated with HPV vaccine acceptance in Africa, irrespective of their setting. The eligible studies would be those that were conducted among all individuals eligible for HPV vaccination, parents or caregivers, healthcare workers and programme managers. Finally, eligible studies should report one of our primary or secondary outcomes. Our primary outcome will include HPV vaccine acceptance rates while our secondary outcomes will include factors associated with HPV vaccine acceptance, namely sociodemographic factors, HPV vaccine attitudes, level of awareness and knowledge of HPV vaccines and risk understanding of HPV. We will exclude studies that do not meet our eligibility criteria.

Search strategy

We have developed a comprehensive search strategy for searching electronic databases. We will search the following databases with no language restriction: PubMed, Scopus, PsycInfo, Web of Science and Cochrane Central Register of Controlled Trials. We have provided the search strategy for one database, PubMed, in table 1. We will search databases since the introduction of HPV vaccine in 2006, until the day of the search. We will also search the reference lists of included studies and related reviews for other relevant studies.

Table 1

PubMed search strategy

Search	Query
#1	Facilitator*[tiab] OR barrier*[tiab] OR predictor*[tiab] OR factor*[tiab] OR determinant*[tiab] OR motivator*[tiab] OR challenge*[tiab]
#2	“papillomavirus vaccine”[tiab] OR “papilloma virus vaccine”[tiab] OR “HPV vaccination”[tiab] OR “HPV vaccine”[tiab] OR “HPV immunization”[tiab] OR “HPV immunization”[tiab] OR “papillomavirus vaccination”[tiab] OR “Papilloma virus vaccination”[tiab] OR “papillomavirus immunization”[tiab] OR “papilloma virus immunization”[tiab] OR “papillomavirus immunization”[tiab] OR “papilloma virus immunization”[tiab] OR (Papillomavirus [Mesh]) OR (Papillomavirus Vaccines [Mesh]) OR (papilloma* [tiab]) OR (HPV [tiab])
#3	(“Uterine Cervical Dysplasia”[Mesh]) OR (“Uterine Cervical Neoplasms”) OR (HSIL*[tiab]) OR (“high grade squamous intraepithelial”[tiab]) OR (cancer*[tiab]) OR 7 (tumor[tiab]) OR (tumors[tiab]) OR (tumoral*[tiab]) OR (neoplas*[tiab]) OR (tumour*[tiab]) OR (dysplasia*[tiab]) OR (dysplastic[tiab]) OR (carcino*[tiab]) OR (adenosquam*[tiab]) OR(adenocarcinoma*[tiab])
#4	uptake[tiab] OR receipt OR initiation OR completion OR complete OR initiate OR receive OR “vaccin* refusal”[MeSh] OR “vaccin* acceptance
#5	Africa [all fields] OR Southern Africa [all fields] OR West Africa[all fields] OR Western Africa[all fields] OR Central Africa[all fields] OR West African[all fields] OR East African[all fields] OR South African[tiab] OR Central African[tiab] OR Mauritania [all fields] OR Senegal [all fields] OR Gambia [all fields] OR Guinea-bissau [all fields] OR Mali [all fields] OR Guinea [all fields] OR Sierra leone [all fields] OR Liberia [all fields] OR Cote d’ivoire [all fields] OR Nigeria [all fields] OR Niger [all fields] OR Chad [all fields] OR Burkina faso [all fields] OR Ghana [all fields] OR Togo [all fields] OR Benin [all fields] OR Equatorial Guinea [all fields] OR Sao Tome and Principe [all fields] OR Congo [all fields] OR Rwanda [all fields] OR Burundi [all fields] OR Uganda [all fields] OR Djibouti [all fields] OR Seychelles [all fields] OR Comoros[all fields] OR Mauritius [all fields] OR Malawi [all fields] OR Swaziland [all fields] OR Lesotho [all fields] OR Central African Republic [all fields] OR Cameroon [all fields] OR Gabon [all fields] OR Sudan [all fields] OR South Sudan [all fields] OR Eritrea [all fields] OR Ethiopia [all fields] OR DRC [all fields] OR Democratic Republic of Congo [all fields] OR Kenya [all fields] OR Somalia [all fields] OR Tanzania [all fields] OR Angola [all fields] OR Zambia [all fields] OR Namibia [all fields] OR Zimbabwe [all fields] OR Botswana [all fields] OR Mozambique [all fields] OR Madagascar [all fields] OR South Africa[all fields]

Selection of studies

Two review authors (AJ and EJM) will independently screen titles and abstracts of the search output in Covidence to identify potentially eligible studies. Disagreements between the two authors will be resolved by discussion and consensus. We will obtain the full texts of all potentially eligible studies. The two review authors (AJ and EJM) will screen the full text of all potentially eligible studies to identify studies meeting inclusion criteria. Disagreement between the two authors will be resolved by discussion and consensus. A third author (SC) will arbitrate any unresolved disagreements.

Data extraction and management

Two review authors (AJ and EJM) will extract data from each included study using a structured and standardised data extraction form. Data to be extracted will include study, participants and outcome details. Differences between the two authors will be resolved by discussion and consensus.

Risk of bias assessment

Two review authors (AJ and EJM) will independently assess risk of bias in each included study using the Effective Public Health Practice Project ‘Quality Assessment Tool for Quantitative Studies’.⁶⁴ We will evaluate selection bias (representativeness of sample, participation rate), data collection method (validity, reliability) and study design using a rating rubric to classify each study as either having a low, moderate or high risk of bias. Studies with no ‘high risk of bias’ ratings will be classified as having low risk of bias, studies with one ‘high risk of bias’ rating will be classified as having high risk of bias and studies with ‘moderate risk of bias’ rating will be classified as moderate risk of bias.

Assessment of reporting biases

Should it be possible to pool 10 studies or more, we will generate and assess a funnel plot for possible publication biases and interpret the results appropriately.

Data analysis

To measure HPV vaccine acceptance, we will convert acceptance ratings to a 0–100 scale, determine mean HPV vaccine acceptance for each study, and then calculate the overall mean HPV acceptance. We will perform a meta-analysis on studies that investigated similar factors associated with HPV vaccine acceptance, while a subgroup analysis will be conducted if there are different factors among studies. We will use V.4 of the Comprehensive Meta-Analysis Software to measure effect sizes for each variable. A random effect model will be used to counterbalance for clinical and methodological differences among studies. The study authors will combine coefficients throughout the studies for each variable to determine an estimate of their association with HPV vaccine acceptance. To evaluate the degree of heterogeneity, we will use the I² index and measure homogeneity of associations in the included studies. Where it is not possible to meta-analyse estimates, we will use narrative synthesis to analyse our data.

Summary of findings and GRADE

The certainty of the evidence (high, moderate, low and very low) will be evaluated by two review authors independently using the five Grading of Recommendations Assessment, Development and Evaluation (GRADE) domains (risk of bias, consistency of effect, imprecision, indirectness and publication bias).⁶⁵ The methods and recommendations defined in Section 8.5 and Chapter 12 of the Cochrane Handbook for Systematic Reviews of interventions,⁶⁶ the Effective Practice and Organisation of Care worksheets,⁶⁷ and GRADEpro software (GRADEpro GDT) will be used to assess the quality of evidence. Disagreements on certainty ratings will be resolved by discussion, and an explanation for decisions to downgrade or upgrade will be provided.

Data availability

All data used in this review will be available on request.

Reporting results of the review

We will use a PRISMA flow diagram to report the final number of included articles in the review. Two review authors (AJ and EJM) will conduct a meta-analysis on the rates of HPV vaccination data extracted from the eligible articles. The meta-analysis results will be presented through forest plots, and GRADE results will be presented through a summary of findings tables.

Expert consultation

To confirm our findings and analysis, an expert in the field of HPV vaccine acceptance will be consulted.

Patient and public involvement

None.

Ethics and dissemination

The methods applied to conduct this review will consist of reviewing and collecting evidence from secondary data, and thus, no ethical approval is required. Conducting this study is imperative in identifying research gaps in the currently available body of evidence. Therefore, this research will impact current research on HPV vaccine acceptance in Africa. The results that will be produced from this review will be disseminated to the public through peer-reviewed publications and conferences.

We would like to acknowledge the South African Medical Research Council for allowing the use of the office space and facilities to conduct this project.

Ethics statements

Patient consent for publication

Not applicable.

Footnote

Collaborators Not applicable.

Contributors EJM and AJ wrote the first draft of the protocol. SC, DEN and CSW critically examined the intellectual content of the paper. EJM is the guarantor for this review.

Funding The authors have not declared a specific grant for this research from any funding agency in the public, commercial or not-for-profit sectors.

Competing interests CSW serves on the Editorial Advisory Board of BMJ Open.

Patient and public involvement Patients and/or the public were not involved in the design, or conduct, or reporting, or dissemination plans of this research.

Provenance and peer review Not commissioned; externally peer-reviewed.

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