Parent-Centered Versus Parent-Adolescent Dyad Interventions to enhance HPV Vaccination Uptake in Children and Adolescents: A Systematic Review and Meta- analysis

Parent-Centered Versus Parent-Adolescent Dyad Interventions to enhance HPV Vaccination Uptake in Children and Adolescents: A Systematic Review and Meta- analysis | Research Square window.SnipcartSettings = { analytics: { enabled: false } }; (function() { var accessVector = localStorage.getItem('access_vector') || ''; window.dataLayer = window.dataLayer || []; if (accessVector) { window.dataLayer.push({ user: { profile: { profileInfo: { snid: accessVector } } } }); } })(); (function(w,d,s,l,i){w[l]=w[l]||[];w[l].push({'gtm.start':new Date().getTime(),event:'gtm.js'});var f=d.getElementsByTagName(s)[0],j=d.createElement(s),dl=l!='dataLayer'?'&l='+l:'';j.async=true;j.src='https://www.googletagmanager.com/gtm.js?id='+i+dl;f.parentNode.insertBefore(j,f);})(window,document,'script','dataLayer','GTM-K279D39R'); Browse Preprints In Review Journals COVID-19 Preprints AJE Video Bytes Research Tools Research Promotion AJE Professional Editing AJE Rubriq About Preprint Platform In Review Editorial Policies Our Team Advisory Board Help Center Sign In Submit a Preprint Cite Share Download PDF Research Article Parent-Centered Versus Parent-Adolescent Dyad Interventions to enhance HPV Vaccination Uptake in Children and Adolescents: A Systematic Review and Meta- analysis Phelele Bhengu, CS Wiysonge, P Kuodi, J L Tamuzi, AV Mazingisa, and 4 more This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-6221575/v1 This work is licensed under a CC BY 4.0 License Status: Posted Version 1 posted You are reading this latest preprint version Abstract Introduction: The human papillomavirus (HPV) vaccine is pivotal in preventing HPV-related cancers, yet vaccine uptake rates vary significantly. This study assesses the efficacy of parent-adolescent dyad and parent-centered interventions on enhancing HPV vaccine uptake across different doses and over time. Methods The study systematically searched Cochrane, PubMed, Web of Science, and Scopus databases from inception until the day of the search, synthesizing data to compare intervention effectiveness across HPV vaccination stages and time intervals. It assessed HPV vaccine uptake among children and adolescents aged 9–18 years after parent or parent-adolescent dyad interventions, alongside completion rates. Meta-analyses, utilizing random-effects models, were conducted for each outcome. Results For the first dose, parent-adolescent dyad interventions indicated a potential, though uncertain, increase in uptake (odds ratio [OR] 1.43, 95% confidence interval [CI]: 0.84, 2.42), while parent-centered interventions showed a significant, consistent improvement (OR 1.14, 95% CI: 1.08, 1.19). The second dose benefited markedly from dyad interventions (OR 3.75, 95% CI: 1.04, 13.52), with parent-centered interventions also demonstrating effectiveness (OR 1.27, 95% CI: 1.08, 1.48). For doses three and above, dyad interventions suggested a strong impact (OR 1.77, 95% CI: 1.13, 2.77), albeit with variability for parent-centered strategies (OR 1.13, 95% CI: 0.41, 3.11). Over time, interventions consistently improved uptake, particularly notable at 6 and 12 months for initial doses and showing long-term improvements in completing the series. Conclusion The study underscores the differential yet significant impact of parent-adolescent dyad and parent-centered interventions on HPV vaccine uptake across various doses and over time. These findings highlight the importance of tailored, dynamic public health strategies that engage both parents and adolescents to enhance HPV vaccination rates, supporting broader efforts to mitigate HPV-related health outcomes. Figures Figure 1 Figure 2 Figure 3 Figure 4 Introduction Human papillomavirus (HPV) is one of the most common sexually transmitted infections, with a high prevalence worldwide ,common among young women who are more prone to recurrent infections and health related complications 1 . Globally, an estimated 630,000 HPV-related cancers are diagnosed each year, 84% of which are cervical cancers which is the fourth most common cancer in women. 1 Most of these malignancies (84%) occur in low- and middle-income countries (LMICs). 2 Young women under 25 are particularly susceptible to HPV with a global prevalence of 19.2%, increasing to 43.9% in Sub-Saharan Africa. 3 HPV is particularly a major issue in East and Southern Africa, where cervical cancer rates are 36–40 per 100,000 women, three to four times higher than the global average. 3 HPV vaccines were initially approved and introduced in three-dose vaccination schedules. Subsequently, immunogenicity and effectiveness studies led to the approval of a two-dose vaccination schedules for young immune-competent adolescents. However, people living with HIV and other immunocompromised people should receive at least two doses, with three doses highly recommended 4 .The effectiveness of the HPV vaccine increases with each dose, with evidence indicating that while a single dose gives acceptable protection, two- and three-dose regimens provide better and longer-lasting immunity 5 . Meta-analyses demonstrate that increased vaccine uptake leads to greater reductions in HPV prevalence and associated illnesses 6 . Inequalities in access to screening and treatment contribute to the global cervical disease disparity. To address this public health concern, vaccination programs have been implemented to prevent the spread and advancement of HPV-caused cancers. 2 As of 2023, a total of 107 of the 194 WHO Member States had introduced HPV vaccination, with the research and acceptance of HPV more prevalent in the United States and Europe. 7 However, global HPV vaccination coverage remains low due to limited awareness, accessibility challenges, cultural hesitations, and integration issues in immunization programs, compounded by misconceptions and stigma. Addressing these barriers through educational campaigns and emphasizing the vaccine's cancer prevention role is crucial for increasing uptake and overcoming healthcare inequalities. Some of the strategies recommended to enhance HPV vaccination uptake in children and adolescents include parent-centered interventions and parent-adolescent dyad interventions. 2 The nuanced dynamics of health decision-making within families regarding HPV vaccination are underscored by the comparison between parent-centered and parent-adolescent dyad interventions. Parent-centered approaches aim to directly address parental hesitancy by providing necessary information and motivation, thus overcoming barriers to vaccine uptake 8 . In contrast, dyad interventions promote shared decision-making and open dialogue between parents and adolescents, acknowledging their different roles and perspectives in the vaccination decision process 8 . Studies indicate that such an approach not only addresses parental confidence but also accommodates the varying factors influencing decision-making within family dynamics 9 . In practice, both strategies might be used together to emphasize the importance of context-sensitive methods to enhance HPV vaccination rates, for a broader public health effort to mitigate HPV-related diseases. A comparison of these strategies will offer healthcare providers and policymakers useful insights into the most effective interventions for increasing HPV vaccination uptake in children and adolescents. This systematic review aimed to comprehensively assess the effectiveness of interventions targeting parents and parent-adolescent dyads in increasing HPV vaccination uptake to guide policy and practice. Methods Protocol We developed a protocol for the systematic review according to Preferred Reporting Items for Systematic Reviews and Meta-analysis (PRISMA) guidelines and registered it on the PROSPERO platform 10 , 11 , registration number CRD42023431934. Information sources We searched the following databases for relevant literature from inception until the day of the search: Cochrane, PubMed, Web of Science, and Scopus. We also searched the WHO International Clinical Trials Registry Platform for active trials, as well as the reference lists of included research and related reviews for other relevant studies. Furthermore, we searched the abstracts of recent conferences of key scientific associations connected to vaccination and HPV virology for new or pending information that has not yet been published in peer-reviewed journals. Search strategy We developed a search strategy following guidelines by Cochrane's highly sensitive search guidelines. 12 We developed a comprehensive search strategy with the assistance of a librarian. The following search terms will be used: "HPV vaccination," "parent-cantered interventions," "parent-adolescent dyad interventions," "children," "adolescents," "uptake," "barriers," and "facilitators." The literature search was conducted between June 2023 and August 2023. Study eligibility criteria We considered randomized trials, non-randomized trials, interrupted time-series studies, and controlled before-after studies that met the Cochrane Effective Practice and Organization of Care (EPOC) quality criteria. 13 Only cluster-randomized controlled trials with at least two intervention and two control clusters were considered. Interrupted time series studies were only considered if their outcomes were measured at least three times. Only controlled before-and-after studies with at least two intervention groups and at least two similar control groups were considered. We excluded systematic reviews, observational designs and studies that are not centered on parents or parent-adolescent dyads such as interventions focusing on providers or health systems improvement etc. We also excluded studies not reporting separate data for female girls between 9–18 years. Participants The participants were girls aged 9 to 18 years eligible for WHO-recommended HPV vaccines and their parents or their legal guardians. The comparison group included individuals who received standard HPV vaccination services without any additional parent or parent-adolescent dyad interventions. We excluded boys from this study because they are not currently included as a primary target for HPV vaccination in Africa. According to WHO, the vaccination of secondary targets, such as boys and older females, should only be considered if feasible and afordable 4 . Types of interventions The interventions considered for inclusion included: educational programs, counseling sessions, SMS, phone call, email reminders or any other types of reminders, and other strategies targeting parents and parent-adolescent dyads to increase awareness and knowledge about HPV vaccination, addressing concerns about HPV vaccine safety or adverse effects, and promoting vaccination uptake. Examples of target interventions included: interventions to improve communication with adolescents or their parents (or both) about adolescent HPV vaccination, financial and non-financial incentives for adolescents or their parents (or both); and mandatory vaccination. Outcome of interest The primary outcome measure was the proportion of children and adolescents between 9–18 years who receive at least one dose of HPV vaccine after parent or parent-adolescent dyad interventions compared to the standard HPV vaccination program. The secondary outcome measure was the proportion of children and adolescents between 9–18 years who completed the recommended HPV vaccine series after parent or parent-adolescent dyad interventions compared to the standard HPV vaccination program. Other secondary outcome measures included factors influencing HPV vaccination uptake, including parental knowledge, attitudes, and barriers. Selection process PB and AM, independently screened titles and abstracts of reviews for potential eligibility following predefined inclusion and exclusion criteria. Following this, full texts of potentially eligible studies were retrieved. Differences between the two reviewers were resolved by discussion and consensus. Data collection process PB and PK independently extracted data from included studies and assessed the quality of included studies into a predesigned data extraction form. In instances where there were discrepancies in the data extracted between the first and the second reviewers, a third reviewer was consulted. Data items The following data points were extracted: 1) study characteristics; author identification, contacts, and institutional affiliation(s), date of publication, title of the study, study design, setting, study objectives, study participants and characteristics, duration of follow-up and study outcomes, funding sources and disclosures by the authors. 2) review specific objectives; type of intervention, type of comparator, and type of outcomes measured. Risk of bias assessment Two review authors assessed the risk of bias in each included paper separately by addressing seven specific domains: random sequence generation, random allocation concealment, participant and personnel blinding, result assessment blinding, insufficient outcome data, selective outcome reporting, and other issues. 14 Two review authors independently described what the study reported for each domain and then decided the risk of bias for that domain by assigning a judgement of "low risk" of bias, "high risk" of bias, or "unclear risk." The review's authors then compared the results of their independent assessments of bias risk and corrected any discrepancies. Synthesis methods We conducted a meta-analysis for individual studies using Stata software (V.18, Stata Corp, College Station, Texas, USA). Pooled statistics were reported as odds ratios (OR) and their 95% confidence intervals (95%CI). The random-effect with a restricted maximum likelihood method was used compare the subgroups interventions including parent-adolescent dyad or parent centered across different doses for improving HPV vaccine uptake among adolescents aged 9–18 years. In the same line, we pooled studies including both parent-adolescent dyad or parent centered interventions vs, control groups (no interventions) to compare HPV vaccine uptake across different doses among adolescents aged 9–18 years. Statistical heterogeneity was assessed using the I 2 and Chi 2 statistics. An I 2 value under 40% suggests statistical heterogeneity might not be important between included studies. Subgroup analysis was performed for the primary outcome on the basis of type of intervention, gender, vaccine dose, type of intervention, and vaccine effectiveness over time. In order to investigate heterogeneity between subgroups, a meta-regression model was built using parents ’age, HPV dose timing, parents’ education levels and their health insurance status. Publication bias was assessed using the Egger regression and Begg’s tests. Furthermore, the Galbraith and Abbe plots were also used to assess publication bias. Results Result of search: The literature search produced a total of 606 published documents. Overall, 576 items were obtained from electronic databases, with an additional 30 entries discovered through a Google Scholar search. No other unique records were discovered on organizational websites. Of the overall output, 441 full-text publications were determined to be eligible for inclusion in the systematic review. Figure 1 depicts the screening and selection procedures for this systematic review. The supplementary Table contains a summary of the quality assessment of the nine papers selected for inclusion in this systematic review. Overall, 9 out of 432 studies met the criteria. Characteristics of included studies Included studies comprised of longitudinal and randomized controlled trials. All the studies included were from one geographical location, the USA. Five studies reported dyadic interventions whereas four included studies reported non-dyadic interventions. They were carried out in a range of settings, including community clinics, school-based health centers, and medical facilities. Intervention types included education materials, reminder magnets, parent health messages, narrative intervention videos, fact sheet library and decision aids. Characteristics of the included studies are summarized in Supplemental Table 1. Risk of bias in studies A summary of the risk of bias in the included studies is shown in Supplemental Fig. 1. 15 Briefly, identified risk of bias was related to missing outcome data for three studies, unsuccessful randomization for one study, outcome measurement for one study, and selective reporting of results for one study. Effect of parent-adolescent dyad and parent-centered interventions on HPV vaccine uptake across different doses The analyses of interventions across HPV vaccine doses reflect a nuanced effect of various strategies (Fig. 2 ). For the first dose, parent-adolescent dyad interventions showed an OR of 1.43 (95% CI: 0.84, 2.42), suggesting a favorable but uncertain increase in uptake (Fig. 2 A). Parent-centered interventions, on the other hand, had a statistically significant and more reliable effect, with an OR of 1.14 (95% CI: 1.08, 1.19), pointing to a consistent enhancement in vaccine initiation. For the second dose, dyad interventions were notably effective, with an OR of 3.75 (95% CI: 1.04, 13.52), indicating a substantial likelihood of increased uptake, albeit with considerable variability (Fig. 2 B). Parent-centered interventions also showed a significant effect, with an OR of 1.27 (95% CI: 1.08, 1.48), denoting a meaningful increase in the odds of receiving the second dose. The overall effect of interventions for Dose 2 revealed a significant pooled OR of 1.29 (95% CI: 1.23, 1.34), demonstrating the efficacy of interventions at this stage. For Dose 3 and above, parent-adolescent dyad interventions were again beneficial, with an OR of 1.77 (95% CI: 1.13, 2.77), suggesting a strong impact on series completion (Fig. 2 C). Conversely, parent-centered interventions had a non-significant OR of 1.13 (95% CI: 0.41, 3.11), with a wide confidence interval that underscores the uncertainty of their effect on later doses. The overall effect for these doses was an OR of 1.35 (95% CI: 0.82, 2.24), presenting a trend towards improved uptake but without statistical significance, reflecting potential variability and the need for more targeted research to ascertain the true effect of interventions on full series vaccination. When assessing the collective impact of interventions across all HPV vaccine doses, the pooled analysis offers a clearer understanding and sheds light on the progressive enhancement of the intervention's effectiveness after each dose (Fig. 3 ). The combined effect across Dose 1, Dose 2, and Dose ≥ 3 yields a pooled OR of 1.17 (95% CI: 1.01, 1.36), signifying a statistically significant 17% increase in the odds of vaccine uptake due to interventions. This overall effect, though modest, is consistent and significant, supporting the beneficial role of interventions in enhancing HPV vaccine coverage across the entire vaccination series. Efficacy of interventions over time on HPV vaccine uptake The efficacy of interventions to improve the uptake of the HPV vaccine over time displays varied results across the different dosing schedules (Fig. 4 ). In the first dose, a significant early impact was observed at the 3-month interval with an OR of 1.26 (95% CI: 0.51, 3.15), suggesting more than a twofold increase in the likelihood of vaccination initiation (Fig. 4 A). However, the wide confidence interval implies a high level of uncertainty. By 6 months, the increase in uptake becomes statistically significant with an OR of 1.16 (95% CI: 1.08, 1.25), indicative of a 16% improvement in odds. At 12 months, the interventions' effect remains positive and significant with an OR of 1.10 (95% CI: 1.04, 1.17), pointing to a sustained influence on vaccine initiation over time.For the second dose, the 3-month data showed a non-significant trend towards increased uptake with an OR of 1.41 (95% CI: 0.71, 2.82) (Fig. 4 B). This potential 41% rise in uptake solidifies by the 6-month mark, as evidenced by a significant OR of 1.28 (95% CI: 1.07, 1.53), reflecting a consistent 28% increase in the odds of receiving the vaccine. The overall time effect for the second dose reveals a cumulative positive impact, with an OR of 1.29 (95% CI: 1.08, 1.53), representing a nearly 29% improvement across the observed period. When assessing the third dose and beyond, initial data at 3 months indicated an OR of 0.50 (95% CI: 0.09, 2.75), which was not statistically significant and highly variable (Fig. 4 C). Nevertheless, by 11–12 months, the interventions seem to yield a significant and consistent effect with an OR of 1.13 (95% CI: 1.07, 1.20), suggesting a 13% increase in vaccine series completion. The overall effect for Dose 3 and above aligns with this finding, maintaining an OR of 1.13 (95% CI: 1.07, 1.20), corroborating the long-term effectiveness of the interventions to enhance vaccine uptake over time. Factors influencing HPV vaccination The meta-regression analysis shows the significant influence of parental education and the timing of vaccine doses on HPV vaccination uptake among adolescents (Supplemental Table 2). Notably, adolescents whose parents had a high school or higher level of education exhibited a statistically significant 13% increase in vaccine uptake, indicating a robust and positive effect. Conversely, extended intervals between HPV vaccine doses are linked to an 8% reduction in uptake, with this negative association being statistically significant. The parent’s age and health insurance status show no significant direct impact on vaccination rates, with health insurance displaying a marginal negative effect (P-value = 0.059) suggesting a nuanced influence. Publication bias Publication bias was evaluated through Egger regression and Begg tests, pooling results across all doses. The analysis revealed non-significant findings for both tests, with z = 1.77 (P = 0.08) for Egger regression and z = 0.69 for Begg test, indicating minimal publication bias. Discussion This systematic review and meta-analysis investigated the comparative effectiveness of parent and adolescent dyadic interventions versus non-dyadic interventions in promoting the initiation and completion of HPV vaccination. Additionally, we examined various factors influencing HPV vaccination uptake. Parent-centered interventions consistently enhanced vaccine initiation and completion across all doses, affirming their effectiveness. Dyad interventions exhibited a significant increase in the uptake of the second dose, with a trend towards improving completion rates for subsequent doses, albeit with some uncertainty. Over time, the influence of these interventions not only persisted but also strengthened, indicating that such strategies could be critical in augmenting long-term vaccine uptake. Finally, our findings highlight the critical roles of socio-economic factors, especially parental education, and logistical elements like dose timing, in shaping vaccination behaviors and public health interventions. Our findings are in harmony with existing scholarly discussions, emphasizing the nuanced influence of various interventions on HPV vaccine uptake 7 . In line with previous research, our analysis points to the critical roles that parent-centered and parent-adolescent dyad interventions play in enhancing vaccine compliance, especially at crucial points in the vaccination series where the risk of discontinuation is high 25 . This combination of parental influence and dyadic communication in decision-making is identified as key in overcoming obstacles to completing the vaccine series, mirroring the variability and context-specific efficacy of such interventions as noted in comparative analyses 25 . The lack of significance observed in the uptake of the first dose may be attributed to disagreements among dyad members regarding the individual responsible for making the final decision concerning HPV decision. However, the persistence of the dyadic approach, emphasizing combined parental involvement and adolescent awareness, might explain the significant increase in uptake observed with the second dose. This suggests that continued dyadic engagement over time could be key to overcoming initial hesitations and achieving notable success in vaccination efforts. Furthermore, the consistent efficacy of parent-directed strategies throughout the vaccination series reflects the outcomes of previous studies demonstrated the utility of educational and reminder-based interventions directed at parents in improving vaccine adherence 26 . This highlights the significant influence parents have on health care decisions for adolescents and establishes the importance of targeted, parent-focused methods in improving public health metrics. Consequently, consideration of local cultural norms, existing health beliefs, and communication dynamics within families is crucial for the successful implementation of these interventions. For example, in some cultures, the topic of a vaccine against a sexually transmitted infection may be met with stigma or discomfort, potentially impacting the willingness of parents or adolescents to engage with the intervention or to get vaccinated 27 . Further research is necessary to disentangle the specific elements of interventions that contribute to their success or lack thereof. Qualitative studies exploring the subjective experiences of families participating in these interventions could provide valuable insights into the mechanisms at play. The analysis indicates that while dyad interventions are particularly effective at addressing specific points of attrition within the vaccination series, parent-centered interventions lay a solid groundwork for sustained vaccine uptake across all doses. Collectively, these findings validate the complex nature of successful vaccination strategies and stress the necessity of tailored interventions in navigating the complexities of health behavior change 28 . The findings from this analysis have profound implications for both policy formulation and healthcare practice. They highlight the necessity for public health policies to integrate interventions that engage both parents and adolescents, particularly emphasizing the significance of dyad interventions at crucial vaccination stages such as the second dose to mitigate attrition. The demonstrated success of parent-centered strategies across the vaccination series mandates their inclusion as foundational elements in vaccination campaigns, suggesting that fostering parental involvement could be instrumental in enhancing vaccine coverage. Furthermore, the evidence of sustained intervention efficacy over time advocates for persistent, long-term public health initiatives rather than transient campaigns 29 . This long-term perspective is essential for maintaining and improving vaccine uptake rates. Policymakers are thus encouraged to champion policies that support the comprehensive implementation of these evidence-based strategies, ensuring that HPV vaccination programs are equipped to achieve maximal reach and impact. In practical terms, healthcare providers are urged to adopt these insights into their routine practice, leveraging the proven effectiveness of parent-adolescent engagement to facilitate informed decision-making and increase vaccination rates 30 . This involves not only the dissemination of tailored educational materials and reminders but also fostering open, inclusive dialogues that address the concerns and expectations of both parents and adolescents. By aligning intervention strategies with these detailed insights into vaccine uptake dynamics, public health initiatives can more accurately target the multifaceted barriers to vaccination, paving the way for a significant reduction in HPV-related health burdens. The analysis from meta-regression illustrates the importance of tailored interventions in HPV vaccine uptake, suggesting policy and practice recommendations that consider the timing of vaccine doses and the pivotal role of education. Strategies to enhance vaccine uptake should not only address intervention content but also focus on delivery and timing, ensuring they are adapted to diverse populations' needs. Incorporating educational components into vaccination programs could empower parents with the knowledge to make informed decisions about their children's health as has been demonstrated previously 31 , 32 . Strengthens and Limitations The strength of this study lies in its comprehensive analysis of the impact of parent-adolescent dyad and parent-centered interventions on HPV vaccine uptake. By systematically evaluating these interventions across doses and time intervals, the study provides a nuanced understanding of how specific strategies can enhance vaccine coverage. Including a wide range of studies ensures a robust examination of intervention outcomes, offering valuable insights into the effectiveness of engaging both parents and adolescents in the vaccination process. Additionally, the longitudinal assessment of vaccine uptake over time contributes significantly to the existing literature on HPV vaccination strategies and public health policy formulation. However, the study faces limitations, including the lack of direct head-to-head comparisons between dyadic and non-dyadic interventions. Instead, studies primarily compare dyadic or non-dyadic interventions with standard care, revealing a gap in the literature. Wide confidence intervals in some analyses, particularly for parent-adolescent dyad interventions, suggest variability and uncertainty in the estimated effects, indicating a need for more targeted research. Furthermore, heterogeneity among included studies in population demographics, intervention delivery methods, and healthcare settings may limit generalizability. Despite these limitations, the study offers valuable insights into HPV vaccination uptake dynamics, highlighting areas for future research and policy development to enhance vaccination strategies. Future research should expand geographical scope and include diverse populations, particularly from low- and middle-income countries (LMICs), while qualitative research can complement quantitative findings by exploring reasons behind parental hesitancy or refusal, providing a more comprehensive understanding of barriers to HPV vaccine uptake. Conclusion This study highlights the critical role of parent-adolescent dyad and parent-centered interventions in enhancing HPV vaccine uptake, revealing varying degrees of effectiveness across different doses and over time. Our findings advocate for tailored public health strategies, emphasizing sustained engagement with both parents and adolescents. Integrating diverse approaches into vaccination programs can significantly elevate coverage and combat HPV-related diseases. Ongoing research is essential to understand intervention mechanisms and implementation strategies, particularly in low- and middle-income countries facing cultural barriers to vaccination efforts. Declarations Ethics approval Ethics approval was not necessary for this study as we used publicly available data Availability of data and materials The datasets generated and/or analyzed during the current study are not publicly available but are available from the corresponding author upon reasonable request. Competing interests The authors declare that they have no competing interests. Funding N/A Acknowledgments The work reported herein was made possible through support by the South African Medical Research Council (SAMRC) through its Division of Research Capacity Development under the Bongani Mayosi National Health Scholars Programme from funding received from the Public Health Enhancement Fund / South African National Department of Health. This research is also supported by the SAMRC, through Cochrane South Africa project code 43500. The content hereof is the sole responsibility of the authors and does not necessarily represent the official views of the SAMRC. Authors' contributions PB and PDMCK led the protocol writing and data extraction process and wrote the first draft of the manuscript. PB and AV participated in the article screening process. PK and PB designed the data extraction tools and participated in the data extraction process. JLT, PB and PK oversaw statistical analysis and critically reviewed the manuscript. MS, PDMCK, CSW, DN, SC, critically reviewed the manuscript and contributed to results interpretation. All authors read and approved the final manuscript. References Stelzle D, Tanaka LF, Lee KK, et al. Estimates of the global burden of cervical cancer associated with HIV. Lancet Glob Health 2020; published online Nov 16. DOI: S2214-109X (20)30459-9 Hull R, Mbele M, Makhafola T, Hicks C, Wang SM, Reis RM, Mehrotra R, Mkhize‑Kwitshana Z, Kibiki G, Bates DO, Dlamini Z. Cervical cancer in low and middle‑income countries. Oncology letters. 2020 Sep 1;20(3):2058-74. Regasa T, Sendo EG, Deressa JT. Human Papillomavirus Knowledge, Perception, and Willingness to Receive Vaccination Among Female University Students in Addis Ababa University, Ethiopia, 2022: A Cross-Sectional Study. SAGE Open Nursing. 2023 Aug; 9:23779608231193554. World Health Organization (WHO). Human Papillomavirus (HPV) vaccines: WHO Position Paper (2022 update). Weekly Epidemiological Record 2022;97:645-672. Meites E. Use of a 2-dose schedule for human papillomavirus vaccination—updated recommendations of the Advisory Committee on Immunization Practices. MMWR. Morbidity and mortality weekly report. 2016;65. Drolet, Mélanie, et al, "Population-level impact and herd effects following the introduction of human papillomavirus vaccination programmes: updated systematic review and meta-analysis." The Lancet 394.10197 (2019): 497-509. Asempah E, Ikpebe E. Accelerating HPV vaccination in Africa for health equity. Global Health Research and Policy. 2024 Sep 19;9(1):37. Singh P, Dhalaria P, Kashyap S, Soni GK, Nandi P, Ghosh S, Mohapatra MK, Rastogi A, Prakash D. Strategies to overcome vaccine hesitancy: a systematic review. Systematic reviews. 2022 Apr 26;11(1):78. Edwards D, Bennett CL, Kelly D. Interventions that improve HPV vaccination uptake and intention: an umbrella review summary. HPV World. 2024 Jan 31. Moher, D., Shamseer, L., Clarke, M. et al. Preferred reporting items for systematic review and meta-analysis protocols (PRISMA-P) 2015 statement. Syst Rev 4, 1 (2015). doi.org/10.1186/2046-4053-4-1 Booth, A., Clarke, M., Dooley, G. et al. The nuts and bolts of PROSPERO: an international prospective register of systematic reviews. Syst Rev 1, 2 (2012). https://doi.org/10.1186/2046-4053-1-2. (EPOC, 2017). Implications for practice. In EPOC Resources for Review Authors. Cochrane Effective Practice and Organisation of Care (EPOC). Available online: https://epoc.cochrane.org/resources/epoc-resources-review-authors/ (accessed on 10 June 2023). Lefebvre C, Manheimer E, Glanville J. Searching for studies. Cochrane handbook for systematic reviews of interventions: Cochrane book series. 2008 Sep 26:95-150. doi.org/10.1002/9780470712184.ch6 Higgins JPT, Thomas J, Chandler J, Cumpston M, Li T, Page MJ, Welch VA (editors). Cochrane Handbook for Systematic Reviews of Interventions version 6.3 (updated February 2022). Cochrane, 2022. Available from www.training.cochrane.org/handbook. McGuinness, LA, Higgins, JPT. Risk-of-bias VISualization (robvis): An R package and Shiny web app for visualizing risk-of-bias assessments. Res Syn Meth. 2020; 1- 7. https://doi.org/10.1002/jrsm.1411 Ma GX, Zhu L, Tan Y, Zhai S, Lin TR, Zambrano C, Siu P, Lai S, Wang MQ. A multilevel intervention to increase HPV vaccination among Asian American adolescents. Journal of community health. 2022 Feb 1:1-8. Paskett ED, Krok-Schoen JL, Pennell ML, Tatum CM, Reiter PL, Peng J, Bernardo BM, Weier RC, Richardson MS, Katz ML. Results of a multilevel intervention trial to increase human papillomavirus (HPV) vaccine uptake among adolescent girls. Cancer Epidemiology, Biomarkers & Prevention. 2016 Apr 1;25(4):593-602. Winer RL, Gonzales AA, Noonan CJ, Buchwald DS. A cluster-randomized trial to evaluate a mother–daughter dyadic educational intervention for increasing HPV vaccination coverage in American Indian girls. Journal of community health. 2016 Apr; 41:274-81. Tiro JA, Sanders JM, Pruitt SL, Stevens CF, Skinner CS, Bishop WP, Fuller S, Persaud D. Promoting HPV vaccination in safety-net clinics: a randomized trial. Pediatrics. 2015 Nov 1;136(5):850-9. Coley S, Hoefer D, Rausch-Phung E. A population‐based reminder intervention to improve human papillomavirus vaccination rates among adolescents at routine vaccination age. Vaccine. 2018 Aug 6;36(32):4904-9. Rickert VI, Auslander BA, Cox DS, Rosenthal SL, Rupp RE, Zimet GD. School-based HPV immunization of young adolescents: effects of two brief health interventions. Human vaccines & immunotherapeutics. 2015 Feb 1;11(2):315-21. Lee H, Kim M, Cooley ME, Kiang PN, Kim D, Tang S, Shi L, Thiem L, Kan P, Peou S, Touch C. Using narrative intervention for HPV vaccine behavior change among Khmer mothers and daughters: A pilot RCT to examine feasibility, acceptability, and preliminary effectiveness. Applied Nursing Research. 2018 Apr 1; 40:51-60 Dempsey AF, Pyrznawoski J, Lockhart S, Barnard J, Campagna EJ, Garrett K, Fisher A, Dickinson LM, O’Leary ST. Effect of a health care professional communication training intervention on adolescent human papillomavirus vaccination: a cluster randomized clinical trial. JAMA pediatrics. 2018 May 1;172(5): e180016-. Bennett AT, Patel DA, Carlos RC, Zochowski MK, Pennewell SM, Chi AM, Dalton VK. Human papillomavirus vaccine uptake after a tailored, online educational intervention for female university students: a randomized controlled trial. Journal of Women's Health. 2015 Nov 1;24(11):950-7. Chang J, Ipp LS, de Roche AM, Catallozzi M, Breitkopf CR, Rosenthal SL. Adolescent-parent dyad descriptions of the decision to start the HPV vaccine series. Journal of pediatric and adolescent gynecology. 2018 Feb 1;31(1):28-32. Winer, R.L., Gonzales, A.A., Noonan, C.J. et al. A Cluster-Randomized Trial to Evaluate a Mother–Daughter Dyadic Educational Intervention for Increasing HPV Vaccination Coverage in American Indian Girls. J Community Health 41, 274–281 (2016). https://doi.org/10.1007/s10900-015-0093-2 Ko LK, Taylor VM, Mohamed FB, Do HH, Gebeyaw FA, Ibrahim A, Ali AA, Winer RL. “We brought our culture here with us”: A qualitative study of perceptions of HPV vaccine and vaccine uptake among East African immigrant mothers. Papillomavirus Research. 2019 Jun 1; 7:21-5. Jallah JK, Anjankar A, Nankong FA. Public Health Approach in the Elimination and Control of Cervical Cancer: A Review. Cureus. 2023 Sep 1;15(9):e44543. doi: 10.7759/cureus.44543. PMID: 37789997; PMCID: PMC10544705. Larson HJ, Toledo AH. Nurturing, nudging and navigating the increasingly precarious nature of cooperation in public health: the cases of vaccination and organ donation. Global Discourse. 2023 Nov 1;13(3-4):290-315. Steenstra I, Murali P, Perkins R, Joseph N, Paasche-Orlow M, Bickmore T. Changing Parent Attitudes Towards HPV Vaccination by Including Adolescents in Multiparty Counseling using Virtual Agents. InProceedings of the 23rd ACM International Conference on Intelligent Virtual Agents 2023 Sep 19 (pp. 1-8). López N, Garcés-Sánchez M, Panizo MB, de la Cueva IS, Artés MT, Ramos B, Cotarelo M. HPV knowledge and vaccine acceptance among European adolescents and their parents: a systematic literature review. Public health reviews. 2020 Dec; 41:1-24. Zhang X, Wang Z, Ren Z, Li Z, Ma W, Gao X, Zhang R, Qiao Y, Li J. HPV vaccine acceptability and willingness-related factors among Chinese adolescents: a nation-wide study. Human Vaccines & Immunotherapeutics. 2021 Apr 3;17(4):1025-32. Additional Declarations No competing interests reported. Supplementary Files Supplementalsmaterials.docx Cite Share Download PDF Status: Posted Version 1 posted You are reading this latest preprint version Research Square lets you share your work early, gain feedback from the community, and start making changes to your manuscript prior to peer review in a journal. As a division of Research Square Company, we’re committed to making research communication faster, fairer, and more useful. We do this by developing innovative software and high quality services for the global research community. Our growing team is made up of researchers and industry professionals working together to solve the most critical problems facing scientific publishing. Also discoverable on Platform About Our Team In Review Editorial Policies Advisory Board Help Center Resources Author Services Accessibility API Access RSS feed Manage Cookie Preferences © Research Square 2026 | ISSN 2693-5015 (online) Privacy Policy Terms of Service Do Not Sell My Personal Information {"props":{"pageProps":{"initialData":{"identity":"rs-6221575","acceptedTermsAndConditions":true,"allowDirectSubmit":true,"archivedVersions":[],"articleType":"Research Article","associatedPublications":[],"authors":[{"id":428463498,"identity":"f3e5ee7c-6eb4-43a8-8e0a-c982a5026faf","order_by":0,"name":"Phelele Bhengu","email":"data:image/png;base64,iVBORw0KGgoAAAANSUhEUgAAAZAAAAAyAQMAAABI0h/eAAAABlBMVEX///8AAABVwtN+AAAACXBIWXMAAA7EAAAOxAGVKw4bAAAA6klEQVRIiWNgGAWjYBACAwkGBmYGBgkeNvYG0rTYyPHxHADzidaSZiwnkUCkFnPp3mOPCyoOJ7ZJvk6T5qn5w8DffoD5ww88WiznnEs3nnEGqEU6d5s0zzEDBokzCQyGPfgcdiPHTJq3DaqFtwHosBsMDAk8BLX8AznsLESLPFDLwT8EtTSkGbNJ8EK0GNxgYGzGZ4vljBxzY55jNnJsPLmbLeccM+YxPJPYzCyDR4u5RI7ZY54aCR759rMbb7ypkZOTO3748Mc3eLQAARuMwQKMIwagkxgb8GtA0sL8gZDSUTAKRsEoGJkAAImeRYoq5jmwAAAAAElFTkSuQmCC","orcid":"","institution":"University of Cape Town","correspondingAuthor":true,"prefix":"","firstName":"Phelele","middleName":"","lastName":"Bhengu","suffix":""},{"id":428463499,"identity":"ca3e751c-b3c8-4a43-a8d1-aebf9039be80","order_by":1,"name":"CS Wiysonge","email":"","orcid":"","institution":"Cochrane South Africa","correspondingAuthor":false,"prefix":"","firstName":"CS","middleName":"","lastName":"Wiysonge","suffix":""},{"id":428463500,"identity":"369913b0-742f-463d-991a-247aaa8e61df","order_by":2,"name":"P Kuodi","email":"","orcid":"","institution":"University of Global Health Equity (UGHE)","correspondingAuthor":false,"prefix":"","firstName":"P","middleName":"","lastName":"Kuodi","suffix":""},{"id":428463501,"identity":"6b723fd5-f8d7-4049-9ce4-4a537806b34e","order_by":3,"name":"J L Tamuzi","email":"","orcid":"","institution":"Stellenbosch University","correspondingAuthor":false,"prefix":"","firstName":"J","middleName":"L","lastName":"Tamuzi","suffix":""},{"id":428463502,"identity":"59ae52f4-703a-47f0-9344-76acb253cc27","order_by":4,"name":"AV Mazingisa","email":"","orcid":"","institution":"Cochrane South Africa","correspondingAuthor":false,"prefix":"","firstName":"AV","middleName":"","lastName":"Mazingisa","suffix":""},{"id":428463503,"identity":"26e240cf-8439-4de7-8bda-5d276da1eb29","order_by":5,"name":"D Ndwandwe","email":"","orcid":"","institution":"Cochrane South Africa","correspondingAuthor":false,"prefix":"","firstName":"D","middleName":"","lastName":"Ndwandwe","suffix":""},{"id":428463504,"identity":"84d0dfc1-42a4-44b3-960b-acce4d802079","order_by":6,"name":"S Cooper","email":"","orcid":"","institution":"Cochrane South Africa","correspondingAuthor":false,"prefix":"","firstName":"S","middleName":"","lastName":"Cooper","suffix":""},{"id":428463505,"identity":"818511c4-c29b-4546-ae23-bd50c43b8fe1","order_by":7,"name":"PDMC Katoto","email":"","orcid":"","institution":"Stellenbosch University","correspondingAuthor":false,"prefix":"","firstName":"PDMC","middleName":"","lastName":"Katoto","suffix":""},{"id":428463506,"identity":"fb759135-1fdc-4e07-b690-59119972c821","order_by":8,"name":"M Shey","email":"","orcid":"","institution":"University of Cape Town","correspondingAuthor":false,"prefix":"","firstName":"M","middleName":"","lastName":"Shey","suffix":""}],"badges":[],"createdAt":"2025-03-13 15:53:25","currentVersionCode":1,"declarations":"","doi":"10.21203/rs.3.rs-6221575/v1","doiUrl":"https://doi.org/10.21203/rs.3.rs-6221575/v1","draftVersion":[],"editorialEvents":[],"editorialNote":"","failedWorkflow":false,"files":[{"id":78657847,"identity":"5780a363-141a-4ee3-bccd-c1045f470d9c","added_by":"auto","created_at":"2025-03-17 09:41:07","extension":"png","order_by":1,"title":"Figure 1","display":"","copyAsset":false,"role":"figure","size":24947,"visible":true,"origin":"","legend":"\u003cp\u003eFlowchart of the literature search and selection process.\u003c/p\u003e","description":"","filename":"1.png","url":"https://assets-eu.researchsquare.com/files/rs-6221575/v1/ae95984896a58ac00db5143e.png"},{"id":78657849,"identity":"68d7a447-d354-4ff9-b7b4-3bfab97daf4b","added_by":"auto","created_at":"2025-03-17 09:41:07","extension":"png","order_by":2,"title":"Figure 2","display":"","copyAsset":false,"role":"figure","size":77040,"visible":true,"origin":"","legend":"\u003cp\u003e\u003cstrong\u003eImpact of parent-centered and parent-adolescent dyadic interventions on HPV vaccination uptake across different doses. \u003c/strong\u003ePanels A, B, and C illustrate the effects on vaccine uptake following the first, second, and three or more doses, respectively.\u003c/p\u003e","description":"","filename":"2.png","url":"https://assets-eu.researchsquare.com/files/rs-6221575/v1/a1eac3a5126550991645ef1d.png"},{"id":78657848,"identity":"f3bb367e-6a66-4197-b1bb-a8293702a379","added_by":"auto","created_at":"2025-03-17 09:41:07","extension":"png","order_by":3,"title":"Figure 3","display":"","copyAsset":false,"role":"figure","size":79486,"visible":true,"origin":"","legend":"\u003cp\u003e\u003cstrong\u003eImpact of either parent-centered or parent-adolescent dyadic interventions on HPV vaccination uptake across different doses. \u003c/strong\u003ePanels A, B, and C illustrate the effects on vaccine uptake following the first, second, and three or more doses, respectively.\u003c/p\u003e","description":"","filename":"3.png","url":"https://assets-eu.researchsquare.com/files/rs-6221575/v1/01fac8ff06af74839ebb711e.png"},{"id":78658563,"identity":"c922b2c7-607a-452c-8779-bddf41053da5","added_by":"auto","created_at":"2025-03-17 09:49:07","extension":"png","order_by":4,"title":"Figure 4","display":"","copyAsset":false,"role":"figure","size":73127,"visible":true,"origin":"","legend":"\u003cp\u003e\u003cstrong\u003eImpact of either parent-centered or parent-adolescent dyadic interventions on HPV vaccination uptake over time. \u003c/strong\u003ePanels A, B, and C illustrate the effects on vaccine uptake over time following the first, second, and three or more doses, respectively.\u003c/p\u003e","description":"","filename":"4.png","url":"https://assets-eu.researchsquare.com/files/rs-6221575/v1/315e9b1a9b3e8d954bd1d657.png"},{"id":88966279,"identity":"fe824ede-5f54-44b5-b396-0286c98c9b14","added_by":"auto","created_at":"2025-08-13 08:55:14","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":1145093,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-6221575/v1/a49f2714-3d7f-4218-babd-ebc1b5747fae.pdf"},{"id":78659593,"identity":"300576a7-1b09-4963-b7d1-6b69ad9632c5","added_by":"auto","created_at":"2025-03-17 09:57:07","extension":"docx","order_by":1,"title":"","display":"","copyAsset":false,"role":"supplement","size":386286,"visible":true,"origin":"","legend":"","description":"","filename":"Supplementalsmaterials.docx","url":"https://assets-eu.researchsquare.com/files/rs-6221575/v1/66dd732a51e3b90244f9e58e.docx"}],"financialInterests":"No competing interests reported.","formattedTitle":"Parent-Centered Versus Parent-Adolescent Dyad Interventions to enhance HPV Vaccination Uptake in Children and Adolescents: A Systematic Review and Meta- analysis","fulltext":[{"header":"Introduction","content":"\u003cp\u003eHuman papillomavirus (HPV) is one of the most common sexually transmitted infections, with a high prevalence worldwide ,common among young women who are more prone to recurrent infections and health related complications\u003csup\u003e\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e\u003c/sup\u003e. Globally, an estimated 630,000 HPV-related cancers are diagnosed each year, 84% of which are cervical cancers which is the fourth most common cancer in women.\u003csup\u003e\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e\u003c/sup\u003e Most of these malignancies (84%) occur in low- and middle-income countries (LMICs).\u003csup\u003e\u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e\u003c/sup\u003e Young women under 25 are particularly susceptible to HPV with a global prevalence of 19.2%, increasing to 43.9% in Sub-Saharan Africa.\u003csup\u003e\u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e\u003c/sup\u003e HPV is particularly a major issue in East and Southern Africa, where cervical cancer rates are 36\u0026ndash;40 per 100,000 women, three to four times higher than the global average.\u003csup\u003e\u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e\u003c/sup\u003e\u003c/p\u003e \u003cp\u003eHPV vaccines were initially approved and introduced in three-dose vaccination schedules. Subsequently, immunogenicity and effectiveness studies led to the approval of a two-dose vaccination schedules for young immune-competent adolescents. However, people living with HIV and other immunocompromised people should receive at least two doses, with three doses highly recommended\u003csup\u003e\u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e\u003c/sup\u003e.The effectiveness of the HPV vaccine increases with each dose, with evidence indicating that while a single dose gives acceptable protection, two- and three-dose regimens provide better and longer-lasting immunity\u003csup\u003e\u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e\u003c/sup\u003e. Meta-analyses demonstrate that increased vaccine uptake leads to greater reductions in HPV prevalence and associated illnesses\u003csup\u003e\u003cspan citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e\u003c/sup\u003e.\u003c/p\u003e \u003cp\u003eInequalities in access to screening and treatment contribute to the global cervical disease disparity. To address this public health concern, vaccination programs have been implemented to prevent the spread and advancement of HPV-caused cancers.\u003csup\u003e\u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e\u003c/sup\u003e As of 2023, a total of 107 of the 194 WHO Member States had introduced HPV vaccination, with the research and acceptance of HPV more prevalent in the United States and Europe.\u003csup\u003e\u003cspan citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e\u003c/sup\u003e However, global HPV vaccination coverage remains low due to limited awareness, accessibility challenges, cultural hesitations, and integration issues in immunization programs, compounded by misconceptions and stigma. Addressing these barriers through educational campaigns and emphasizing the vaccine's cancer prevention role is crucial for increasing uptake and overcoming healthcare inequalities.\u003c/p\u003e \u003cp\u003eSome of the strategies recommended to enhance HPV vaccination uptake in children and adolescents include parent-centered interventions and parent-adolescent dyad interventions.\u003csup\u003e\u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e\u003c/sup\u003e The nuanced dynamics of health decision-making within families regarding HPV vaccination are underscored by the comparison between parent-centered and parent-adolescent dyad interventions. Parent-centered approaches aim to directly address parental hesitancy by providing necessary information and motivation, thus overcoming barriers to vaccine uptake\u003csup\u003e\u003cspan citationid=\"CR8\" class=\"CitationRef\"\u003e8\u003c/span\u003e\u003c/sup\u003e. In contrast, dyad interventions promote shared decision-making and open dialogue between parents and adolescents, acknowledging their different roles and perspectives in the vaccination decision process\u003csup\u003e\u003cspan citationid=\"CR8\" class=\"CitationRef\"\u003e8\u003c/span\u003e\u003c/sup\u003e. Studies indicate that such an approach not only addresses parental confidence but also accommodates the varying factors influencing decision-making within family dynamics\u003csup\u003e\u003cspan citationid=\"CR9\" class=\"CitationRef\"\u003e9\u003c/span\u003e\u003c/sup\u003e. In practice, both strategies might be used together to emphasize the importance of context-sensitive methods to enhance HPV vaccination rates, for a broader public health effort to mitigate HPV-related diseases. A comparison of these strategies will offer healthcare providers and policymakers useful insights into the most effective interventions for increasing HPV vaccination uptake in children and adolescents. This systematic review aimed to comprehensively assess the effectiveness of interventions targeting parents and parent-adolescent dyads in increasing HPV vaccination uptake to guide policy and practice.\u003c/p\u003e"},{"header":"Methods","content":"\u003cdiv id=\"Sec3\" class=\"Section2\"\u003e \u003ch2\u003eProtocol\u003c/h2\u003e \u003cp\u003eWe developed a protocol for the systematic review according to Preferred Reporting Items for Systematic Reviews and Meta-analysis (PRISMA) guidelines and registered it on the PROSPERO platform\u003csup\u003e\u003cspan citationid=\"CR10\" class=\"CitationRef\"\u003e10\u003c/span\u003e,\u003cspan citationid=\"CR11\" class=\"CitationRef\"\u003e11\u003c/span\u003e\u003c/sup\u003e, registration number CRD42023431934.\u003c/p\u003e \u003c/div\u003e\n\u003ch3\u003eInformation sources\u003c/h3\u003e\n\u003cp\u003eWe searched the following databases for relevant literature from inception until the day of the search: Cochrane, PubMed, Web of Science, and Scopus. We also searched the WHO International Clinical Trials Registry Platform for active trials, as well as the reference lists of included research and related reviews for other relevant studies. Furthermore, we searched the abstracts of recent conferences of key scientific associations connected to vaccination and HPV virology for new or pending information that has not yet been published in peer-reviewed journals.\u003c/p\u003e\n\u003ch3\u003eSearch strategy\u003c/h3\u003e\n\u003cp\u003eWe developed a search strategy following guidelines by Cochrane's highly sensitive search guidelines.\u003csup\u003e\u003cspan citationid=\"CR12\" class=\"CitationRef\"\u003e12\u003c/span\u003e\u003c/sup\u003e We developed a comprehensive search strategy with the assistance of a librarian. The following search terms will be used: \"HPV vaccination,\" \"parent-cantered interventions,\" \"parent-adolescent dyad interventions,\" \"children,\" \"adolescents,\" \"uptake,\" \"barriers,\" and \"facilitators.\" The literature search was conducted between June 2023 and August 2023.\u003c/p\u003e\n\u003ch3\u003eStudy eligibility criteria\u003c/h3\u003e\n\u003cp\u003eWe considered randomized trials, non-randomized trials, interrupted time-series studies, and controlled before-after studies that met the Cochrane Effective Practice and Organization of Care (EPOC) quality criteria.\u003csup\u003e\u003cspan citationid=\"CR13\" class=\"CitationRef\"\u003e13\u003c/span\u003e\u003c/sup\u003e Only cluster-randomized controlled trials with at least two intervention and two control clusters were considered. Interrupted time series studies were only considered if their outcomes were measured at least three times. Only controlled before-and-after studies with at least two intervention groups and at least two similar control groups were considered. We excluded systematic reviews, observational designs and studies that are not centered on parents or parent-adolescent dyads such as interventions focusing on providers or health systems improvement etc. We also excluded studies not reporting separate data for female girls between 9\u0026ndash;18 years.\u003c/p\u003e\n\u003ch3\u003eParticipants\u003c/h3\u003e\n\u003cp\u003eThe participants were girls aged 9 to 18 years eligible for WHO-recommended HPV vaccines and their parents or their legal guardians. The comparison group included individuals who received standard HPV vaccination services without any additional parent or parent-adolescent dyad interventions. We excluded boys from this study because they are not currently included as a primary target for HPV vaccination in Africa. According to WHO, the vaccination of secondary targets, such as boys and older females, should only be considered if feasible and afordable\u003csup\u003e\u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e\u003c/sup\u003e.\u003c/p\u003e \u003cdiv id=\"Sec8\" class=\"Section2\"\u003e \u003ch2\u003eTypes of interventions\u003c/h2\u003e \u003cp\u003eThe interventions considered for inclusion included: educational programs, counseling sessions, SMS, phone call, email reminders or any other types of reminders, and other strategies targeting parents and parent-adolescent dyads to increase awareness and knowledge about HPV vaccination, addressing concerns about HPV vaccine safety or adverse effects, and promoting vaccination uptake. Examples of target interventions included: interventions to improve communication with adolescents or their parents (or both) about adolescent HPV vaccination, financial and non-financial incentives for adolescents or their parents (or both); and mandatory vaccination.\u003c/p\u003e \u003c/div\u003e\n\u003ch3\u003eOutcome of interest\u003c/h3\u003e\n\u003cp\u003eThe primary outcome measure was the proportion of children and adolescents between 9\u0026ndash;18 years who receive at least one dose of HPV vaccine after parent or parent-adolescent dyad interventions compared to the standard HPV vaccination program. The secondary outcome measure was the proportion of children and adolescents between 9\u0026ndash;18 years who completed the recommended HPV vaccine series after parent or parent-adolescent dyad interventions compared to the standard HPV vaccination program. Other secondary outcome measures included factors influencing HPV vaccination uptake, including parental knowledge, attitudes, and barriers.\u003c/p\u003e\n\u003ch3\u003eSelection process\u003c/h3\u003e\n\u003cp\u003ePB and AM, independently screened titles and abstracts of reviews for potential eligibility following predefined inclusion and exclusion criteria. Following this, full texts of potentially eligible studies were retrieved. Differences between the two reviewers were resolved by discussion and consensus.\u003c/p\u003e \u003cdiv id=\"Sec11\" class=\"Section2\"\u003e \u003ch2\u003eData collection process\u003c/h2\u003e \u003cp\u003ePB and PK independently extracted data from included studies and assessed the quality of included studies into a predesigned data extraction form. In instances where there were discrepancies in the data extracted between the first and the second reviewers, a third reviewer was consulted.\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec12\" class=\"Section2\"\u003e \u003ch2\u003eData items\u003c/h2\u003e \u003cp\u003eThe following data points were extracted: 1) study characteristics; author identification, contacts, and institutional affiliation(s), date of publication, title of the study, study design, setting, study objectives, study participants and characteristics, duration of follow-up and study outcomes, funding sources and disclosures by the authors. 2) review specific objectives; type of intervention, type of comparator, and type of outcomes measured.\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec13\" class=\"Section2\"\u003e \u003ch2\u003eRisk of bias assessment\u003c/h2\u003e \u003cp\u003eTwo review authors assessed the risk of bias in each included paper separately by addressing seven specific domains: random sequence generation, random allocation concealment, participant and personnel blinding, result assessment blinding, insufficient outcome data, selective outcome reporting, and other issues.\u003csup\u003e\u003cspan citationid=\"CR14\" class=\"CitationRef\"\u003e14\u003c/span\u003e\u003c/sup\u003e Two review authors independently described what the study reported for each domain and then decided the risk of bias for that domain by assigning a judgement of \"low risk\" of bias, \"high risk\" of bias, or \"unclear risk.\" The review's authors then compared the results of their independent assessments of bias risk and corrected any discrepancies.\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec14\" class=\"Section2\"\u003e \u003ch2\u003eSynthesis methods\u003c/h2\u003e \u003cp\u003eWe conducted a meta-analysis for individual studies using Stata software (V.18, Stata Corp, College Station, Texas, USA). Pooled statistics were reported as odds ratios (OR) and their 95% confidence intervals (95%CI). The random-effect with a restricted maximum likelihood method was used compare the subgroups interventions including parent-adolescent dyad or parent centered across different doses for improving HPV vaccine uptake among adolescents aged 9\u0026ndash;18 years. In the same line, we pooled studies including both parent-adolescent dyad or parent centered interventions vs, control groups (no interventions) to compare HPV vaccine uptake across different doses among adolescents aged 9\u0026ndash;18 years. Statistical heterogeneity was assessed using the I\u003csup\u003e\u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e\u003c/sup\u003e and Chi\u003csup\u003e\u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e\u003c/sup\u003e statistics. An I\u003csup\u003e\u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e\u003c/sup\u003e value under 40% suggests statistical heterogeneity might not be important between included studies. Subgroup analysis was performed for the primary outcome on the basis of type of intervention, gender, vaccine dose, type of intervention, and vaccine effectiveness over time. In order to investigate heterogeneity between subgroups, a meta-regression model was built using parents \u0026rsquo;age, HPV dose timing, parents\u0026rsquo; education levels and their health insurance status. Publication bias was assessed using the Egger regression and Begg\u0026rsquo;s tests. Furthermore, the Galbraith and Abbe plots were also used to assess publication bias.\u003c/p\u003e \u003c/div\u003e"},{"header":"Results","content":"\u003cdiv id=\"Sec16\" class=\"Section2\"\u003e \u003ch2\u003eResult of search:\u003c/h2\u003e \u003cp\u003eThe literature search produced a total of 606 published documents. Overall, 576 items were obtained from electronic databases, with an additional 30 entries discovered through a Google Scholar search. No other unique records were discovered on organizational websites. Of the overall output, 441 full-text publications were determined to be eligible for inclusion in the systematic review. Figure\u0026nbsp;\u003cspan refid=\"Fig1\" class=\"InternalRef\"\u003e1\u003c/span\u003e depicts the screening and selection procedures for this systematic review. The supplementary Table contains a summary of the quality assessment of the nine papers selected for inclusion in this systematic review. Overall, 9 out of 432 studies met the criteria.\u003c/p\u003e\u003c/div\u003e \u003cdiv id=\"Sec17\" class=\"Section2\"\u003e \u003ch2\u003eCharacteristics of included studies\u003c/h2\u003e \u003cp\u003eIncluded studies comprised of longitudinal and randomized controlled trials. All the studies included were from one geographical location, the USA. Five studies reported dyadic interventions whereas four included studies reported non-dyadic interventions. They were carried out in a range of settings, including community clinics, school-based health centers, and medical facilities. Intervention types included education materials, reminder magnets, parent health messages, narrative intervention videos, fact sheet library and decision aids. Characteristics of the included studies are summarized in Supplemental Table\u0026nbsp;1.\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec18\" class=\"Section2\"\u003e \u003ch2\u003eRisk of bias in studies\u003c/h2\u003e \u003cp\u003eA summary of the risk of bias in the included studies is shown in Supplemental Fig.\u0026nbsp;1.\u003csup\u003e\u003cspan citationid=\"CR15\" class=\"CitationRef\"\u003e15\u003c/span\u003e\u003c/sup\u003e Briefly, identified risk of bias was related to missing outcome data for three studies, unsuccessful randomization for one study, outcome measurement for one study, and selective reporting of results for one study.\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec19\" class=\"Section2\"\u003e \u003ch2\u003eEffect of parent-adolescent dyad and parent-centered interventions on HPV vaccine uptake across different doses\u003c/h2\u003e \u003cp\u003eThe analyses of interventions across HPV vaccine doses reflect a nuanced effect of various strategies (Fig.\u0026nbsp;\u003cspan refid=\"Fig2\" class=\"InternalRef\"\u003e2\u003c/span\u003e). For the first dose, parent-adolescent dyad interventions showed an OR of 1.43 (95% CI: 0.84, 2.42), suggesting a favorable but uncertain increase in uptake (Fig.\u0026nbsp;\u003cspan refid=\"Fig2\" class=\"InternalRef\"\u003e2\u003c/span\u003eA). Parent-centered interventions, on the other hand, had a statistically significant and more reliable effect, with an OR of 1.14 (95% CI: 1.08, 1.19), pointing to a consistent enhancement in vaccine initiation.\u003c/p\u003e \u003cp\u003eFor the second dose, dyad interventions were notably effective, with an OR of 3.75 (95% CI: 1.04, 13.52), indicating a substantial likelihood of increased uptake, albeit with considerable variability (Fig.\u0026nbsp;\u003cspan refid=\"Fig2\" class=\"InternalRef\"\u003e2\u003c/span\u003eB). Parent-centered interventions also showed a significant effect, with an OR of 1.27 (95% CI: 1.08, 1.48), denoting a meaningful increase in the odds of receiving the second dose. The overall effect of interventions for Dose 2 revealed a significant pooled OR of 1.29 (95% CI: 1.23, 1.34), demonstrating the efficacy of interventions at this stage.\u003c/p\u003e \u003cp\u003eFor Dose 3 and above, parent-adolescent dyad interventions were again beneficial, with an OR of 1.77 (95% CI: 1.13, 2.77), suggesting a strong impact on series completion (Fig.\u0026nbsp;\u003cspan refid=\"Fig2\" class=\"InternalRef\"\u003e2\u003c/span\u003eC). Conversely, parent-centered interventions had a non-significant OR of 1.13 (95% CI: 0.41, 3.11), with a wide confidence interval that underscores the uncertainty of their effect on later doses. The overall effect for these doses was an OR of 1.35 (95% CI: 0.82, 2.24), presenting a trend towards improved uptake but without statistical significance, reflecting potential variability and the need for more targeted research to ascertain the true effect of interventions on full series vaccination.\u003c/p\u003e \u003cp\u003eWhen assessing the collective impact of interventions across all HPV vaccine doses, the pooled analysis offers a clearer understanding and sheds light on the progressive enhancement of the intervention's effectiveness after each dose (Fig.\u0026nbsp;\u003cspan refid=\"Fig3\" class=\"InternalRef\"\u003e3\u003c/span\u003e). The combined effect across Dose 1, Dose 2, and Dose\u0026thinsp;\u0026ge;\u0026thinsp;3 yields a pooled OR of 1.17 (95% CI: 1.01, 1.36), signifying a statistically significant 17% increase in the odds of vaccine uptake due to interventions. This overall effect, though modest, is consistent and significant, supporting the beneficial role of interventions in enhancing HPV vaccine coverage across the entire vaccination series.\u003c/p\u003e\u003c/div\u003e \u003cdiv id=\"Sec20\" class=\"Section2\"\u003e \u003ch2\u003eEfficacy of interventions over time on HPV vaccine uptake\u003c/h2\u003e \u003cp\u003eThe efficacy of interventions to improve the uptake of the HPV vaccine over time displays varied results across the different dosing schedules (Fig.\u0026nbsp;\u003cspan refid=\"Fig4\" class=\"InternalRef\"\u003e4\u003c/span\u003e). In the first dose, a significant early impact was observed at the 3-month interval with an OR of 1.26 (95% CI: 0.51, 3.15), suggesting more than a twofold increase in the likelihood of vaccination initiation (Fig.\u0026nbsp;\u003cspan refid=\"Fig4\" class=\"InternalRef\"\u003e4\u003c/span\u003eA). However, the wide confidence interval implies a high level of uncertainty. By 6 months, the increase in uptake becomes statistically significant with an OR of 1.16 (95% CI: 1.08, 1.25), indicative of a 16% improvement in odds. At 12 months, the interventions' effect remains positive and significant with an OR of 1.10 (95% CI: 1.04, 1.17), pointing to a sustained influence on vaccine initiation over time.For the second dose, the 3-month data showed a non-significant trend towards increased uptake with an OR of 1.41 (95% CI: 0.71, 2.82) (Fig.\u0026nbsp;\u003cspan refid=\"Fig4\" class=\"InternalRef\"\u003e4\u003c/span\u003eB). This potential 41% rise in uptake solidifies by the 6-month mark, as evidenced by a significant OR of 1.28 (95% CI: 1.07, 1.53), reflecting a consistent 28% increase in the odds of receiving the vaccine. The overall time effect for the second dose reveals a cumulative positive impact, with an OR of 1.29 (95% CI: 1.08, 1.53), representing a nearly 29% improvement across the observed period. When assessing the third dose and beyond, initial data at 3 months indicated an OR of 0.50 (95% CI: 0.09, 2.75), which was not statistically significant and highly variable (Fig.\u0026nbsp;\u003cspan refid=\"Fig4\" class=\"InternalRef\"\u003e4\u003c/span\u003eC). Nevertheless, by 11\u0026ndash;12 months, the interventions seem to yield a significant and consistent effect with an OR of 1.13 (95% CI: 1.07, 1.20), suggesting a 13% increase in vaccine series completion. The overall effect for Dose 3 and above aligns with this finding, maintaining an OR of 1.13 (95% CI: 1.07, 1.20), corroborating the long-term effectiveness of the interventions to enhance vaccine uptake over time.\u003c/p\u003e\u003c/div\u003e \u003cdiv id=\"Sec21\" class=\"Section2\"\u003e \u003ch2\u003eFactors influencing HPV vaccination\u003c/h2\u003e \u003cp\u003eThe meta-regression analysis shows the significant influence of parental education and the timing of vaccine doses on HPV vaccination uptake among adolescents (Supplemental Table\u0026nbsp;2). Notably, adolescents whose parents had a high school or higher level of education exhibited a statistically significant 13% increase in vaccine uptake, indicating a robust and positive effect. Conversely, extended intervals between HPV vaccine doses are linked to an 8% reduction in uptake, with this negative association being statistically significant. The parent\u0026rsquo;s age and health insurance status show no significant direct impact on vaccination rates, with health insurance displaying a marginal negative effect (P-value\u0026thinsp;=\u0026thinsp;0.059) suggesting a nuanced influence.\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec22\" class=\"Section2\"\u003e \u003ch2\u003ePublication bias\u003c/h2\u003e \u003cp\u003ePublication bias was evaluated through Egger regression and Begg tests, pooling results across all doses. The analysis revealed non-significant findings for both tests, with z\u0026thinsp;=\u0026thinsp;1.77 (P\u0026thinsp;=\u0026thinsp;0.08) for Egger regression and z\u0026thinsp;=\u0026thinsp;0.69 for Begg test, indicating minimal publication bias.\u003c/p\u003e \u003c/div\u003e"},{"header":"Discussion","content":"\u003cp\u003eThis systematic review and meta-analysis investigated the comparative effectiveness of parent and adolescent dyadic interventions versus non-dyadic interventions in promoting the initiation and completion of HPV vaccination. Additionally, we examined various factors influencing HPV vaccination uptake. Parent-centered interventions consistently enhanced vaccine initiation and completion across all doses, affirming their effectiveness. Dyad interventions exhibited a significant increase in the uptake of the second dose, with a trend towards improving completion rates for subsequent doses, albeit with some uncertainty. Over time, the influence of these interventions not only persisted but also strengthened, indicating that such strategies could be critical in augmenting long-term vaccine uptake. Finally, our findings highlight the critical roles of socio-economic factors, especially parental education, and logistical elements like dose timing, in shaping vaccination behaviors and public health interventions.\u003c/p\u003e \u003cp\u003eOur findings are in harmony with existing scholarly discussions, emphasizing the nuanced influence of various interventions on HPV vaccine uptake\u003csup\u003e\u003cspan citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e\u003c/sup\u003e. In line with previous research, our analysis points to the critical roles that parent-centered and parent-adolescent dyad interventions play in enhancing vaccine compliance, especially at crucial points in the vaccination series where the risk of discontinuation is high\u003csup\u003e\u003cspan citationid=\"CR25\" class=\"CitationRef\"\u003e25\u003c/span\u003e\u003c/sup\u003e. This combination of parental influence and dyadic communication in decision-making is identified as key in overcoming obstacles to completing the vaccine series, mirroring the variability and context-specific efficacy of such interventions as noted in comparative analyses\u003csup\u003e\u003cspan citationid=\"CR25\" class=\"CitationRef\"\u003e25\u003c/span\u003e\u003c/sup\u003e.\u003c/p\u003e \u003cp\u003eThe lack of significance observed in the uptake of the first dose may be attributed to disagreements among dyad members regarding the individual responsible for making the final decision concerning HPV decision. However, the persistence of the dyadic approach, emphasizing combined parental involvement and adolescent awareness, might explain the significant increase in uptake observed with the second dose. This suggests that continued dyadic engagement over time could be key to overcoming initial hesitations and achieving notable success in vaccination efforts. Furthermore, the consistent efficacy of parent-directed strategies throughout the vaccination series reflects the outcomes of previous studies demonstrated the utility of educational and reminder-based interventions directed at parents in improving vaccine adherence\u003csup\u003e\u003cspan citationid=\"CR26\" class=\"CitationRef\"\u003e26\u003c/span\u003e\u003c/sup\u003e. This highlights the significant influence parents have on health care decisions for adolescents and establishes the importance of targeted, parent-focused methods in improving public health metrics.\u003c/p\u003e \u003cp\u003eConsequently, consideration of local cultural norms, existing health beliefs, and communication dynamics within families is crucial for the successful implementation of these interventions. For example, in some cultures, the topic of a vaccine against a sexually transmitted infection may be met with stigma or discomfort, potentially impacting the willingness of parents or adolescents to engage with the intervention or to get vaccinated\u003csup\u003e\u003cspan citationid=\"CR27\" class=\"CitationRef\"\u003e27\u003c/span\u003e\u003c/sup\u003e. Further research is necessary to disentangle the specific elements of interventions that contribute to their success or lack thereof. Qualitative studies exploring the subjective experiences of families participating in these interventions could provide valuable insights into the mechanisms at play.\u003c/p\u003e \u003cp\u003eThe analysis indicates that while dyad interventions are particularly effective at addressing specific points of attrition within the vaccination series, parent-centered interventions lay a solid groundwork for sustained vaccine uptake across all doses. Collectively, these findings validate the complex nature of successful vaccination strategies and stress the necessity of tailored interventions in navigating the complexities of health behavior change\u003csup\u003e\u003cspan citationid=\"CR28\" class=\"CitationRef\"\u003e28\u003c/span\u003e\u003c/sup\u003e. The findings from this analysis have profound implications for both policy formulation and healthcare practice. They highlight the necessity for public health policies to integrate interventions that engage both parents and adolescents, particularly emphasizing the significance of dyad interventions at crucial vaccination stages such as the second dose to mitigate attrition. The demonstrated success of parent-centered strategies across the vaccination series mandates their inclusion as foundational elements in vaccination campaigns, suggesting that fostering parental involvement could be instrumental in enhancing vaccine coverage.\u003c/p\u003e \u003cp\u003eFurthermore, the evidence of sustained intervention efficacy over time advocates for persistent, long-term public health initiatives rather than transient campaigns\u003csup\u003e\u003cspan citationid=\"CR29\" class=\"CitationRef\"\u003e29\u003c/span\u003e\u003c/sup\u003e. This long-term perspective is essential for maintaining and improving vaccine uptake rates. Policymakers are thus encouraged to champion policies that support the comprehensive implementation of these evidence-based strategies, ensuring that HPV vaccination programs are equipped to achieve maximal reach and impact. In practical terms, healthcare providers are urged to adopt these insights into their routine practice, leveraging the proven effectiveness of parent-adolescent engagement to facilitate informed decision-making and increase vaccination rates\u003csup\u003e\u003cspan citationid=\"CR30\" class=\"CitationRef\"\u003e30\u003c/span\u003e\u003c/sup\u003e. This involves not only the dissemination of tailored educational materials and reminders but also fostering open, inclusive dialogues that address the concerns and expectations of both parents and adolescents. By aligning intervention strategies with these detailed insights into vaccine uptake dynamics, public health initiatives can more accurately target the multifaceted barriers to vaccination, paving the way for a significant reduction in HPV-related health burdens.\u003c/p\u003e \u003cp\u003eThe analysis from meta-regression illustrates the importance of tailored interventions in HPV vaccine uptake, suggesting policy and practice recommendations that consider the timing of vaccine doses and the pivotal role of education. Strategies to enhance vaccine uptake should not only address intervention content but also focus on delivery and timing, ensuring they are adapted to diverse populations' needs. Incorporating educational components into vaccination programs could empower parents with the knowledge to make informed decisions about their children's health as has been demonstrated previously\u003csup\u003e\u003cspan citationid=\"CR31\" class=\"CitationRef\"\u003e31\u003c/span\u003e,\u003cspan citationid=\"CR32\" class=\"CitationRef\"\u003e32\u003c/span\u003e\u003c/sup\u003e.\u003c/p\u003e \u003cdiv id=\"Sec24\" class=\"Section2\"\u003e \u003ch2\u003eStrengthens and Limitations\u003c/h2\u003e \u003cp\u003eThe strength of this study lies in its comprehensive analysis of the impact of parent-adolescent dyad and parent-centered interventions on HPV vaccine uptake. By systematically evaluating these interventions across doses and time intervals, the study provides a nuanced understanding of how specific strategies can enhance vaccine coverage. Including a wide range of studies ensures a robust examination of intervention outcomes, offering valuable insights into the effectiveness of engaging both parents and adolescents in the vaccination process. Additionally, the longitudinal assessment of vaccine uptake over time contributes significantly to the existing literature on HPV vaccination strategies and public health policy formulation. However, the study faces limitations, including the lack of direct head-to-head comparisons between dyadic and non-dyadic interventions. Instead, studies primarily compare dyadic or non-dyadic interventions with standard care, revealing a gap in the literature. Wide confidence intervals in some analyses, particularly for parent-adolescent dyad interventions, suggest variability and uncertainty in the estimated effects, indicating a need for more targeted research. Furthermore, heterogeneity among included studies in population demographics, intervention delivery methods, and healthcare settings may limit generalizability. Despite these limitations, the study offers valuable insights into HPV vaccination uptake dynamics, highlighting areas for future research and policy development to enhance vaccination strategies. Future research should expand geographical scope and include diverse populations, particularly from low- and middle-income countries (LMICs), while qualitative research can complement quantitative findings by exploring reasons behind parental hesitancy or refusal, providing a more comprehensive understanding of barriers to HPV vaccine uptake.\u003c/p\u003e \u003c/div\u003e"},{"header":"Conclusion","content":"\u003cp\u003eThis study highlights the critical role of parent-adolescent dyad and parent-centered interventions in enhancing HPV vaccine uptake, revealing varying degrees of effectiveness across different doses and over time. Our findings advocate for tailored public health strategies, emphasizing sustained engagement with both parents and adolescents. Integrating diverse approaches into vaccination programs can significantly elevate coverage and combat HPV-related diseases. Ongoing research is essential to understand intervention mechanisms and implementation strategies, particularly in low- and middle-income countries facing cultural barriers to vaccination efforts.\u003c/p\u003e "},{"header":"Declarations","content":"\u003cp\u003e\u003cstrong\u003eEthics approval\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eEthics approval was not necessary for this study as we used publicly available data\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAvailability of data and materials\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe datasets generated and/or analyzed during the current study are not publicly available but are available from the corresponding author upon reasonable request.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eCompeting interests\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe authors declare that they have no competing interests.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eFunding\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eN/A\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAcknowledgments\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe work reported herein was made possible through support by the South African Medical Research Council (SAMRC) through its Division of Research Capacity Development under the Bongani Mayosi National Health Scholars Programme from funding received from the Public Health Enhancement Fund / South African National Department of Health. This research is also supported by the SAMRC, through Cochrane South Africa project code 43500. The content hereof is the sole responsibility of the authors and does not necessarily represent the official views of the SAMRC.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAuthors\u0026apos; contributions\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003ePB and PDMCK led the protocol writing and data extraction process and wrote the first draft of the manuscript. PB and AV participated in the article screening process. PK and PB designed the data extraction tools and participated in the data extraction process. JLT, PB and PK oversaw statistical analysis and critically reviewed the manuscript. MS, PDMCK, CSW, DN, SC, critically reviewed the manuscript and contributed to results interpretation. All authors read and approved the final manuscript.\u003c/p\u003e"},{"header":"References","content":"\u003col\u003e\n\u003cli\u003eStelzle D, Tanaka LF, Lee KK, et al. Estimates of the global burden of cervical cancer associated with HIV. Lancet Glob Health 2020; published online Nov 16. DOI: S2214-109X (20)30459-9 \u003c/li\u003e\n\u003cli\u003eHull R, Mbele M, Makhafola T, Hicks C, Wang SM, Reis RM, Mehrotra R, Mkhize‑Kwitshana Z, Kibiki G, Bates DO, Dlamini Z. Cervical cancer in low and middle‑income countries. Oncology letters. 2020 Sep 1;20(3):2058-74.\u003c/li\u003e\n\u003cli\u003eRegasa T, Sendo EG, Deressa JT. Human Papillomavirus Knowledge, Perception, and Willingness to Receive Vaccination Among Female University Students in Addis Ababa University, Ethiopia, 2022: A Cross-Sectional Study. SAGE Open Nursing. 2023 Aug; 9:23779608231193554.\u003c/li\u003e\n\u003cli\u003eWorld Health Organization (WHO). Human Papillomavirus (HPV) vaccines: WHO Position Paper (2022 update). Weekly Epidemiological Record 2022;97:645-672. \u003c/li\u003e\n\u003cli\u003eMeites E. Use of a 2-dose schedule for human papillomavirus vaccination\u0026mdash;updated recommendations of the Advisory Committee on Immunization Practices. MMWR. Morbidity and mortality weekly report. 2016;65.\u003c/li\u003e\n\u003cli\u003eDrolet, M\u0026eacute;lanie, et al, \u0026quot;Population-level impact and herd effects following the introduction of human papillomavirus vaccination programmes: updated systematic review and meta-analysis.\u0026quot; \u003cem\u003eThe Lancet\u003c/em\u003e 394.10197 (2019): 497-509. \u003c/li\u003e\n\u003cli\u003eAsempah E, Ikpebe E. Accelerating HPV vaccination in Africa for health equity. Global Health Research and Policy. 2024 Sep 19;9(1):37.\u003c/li\u003e\n\u003cli\u003eSingh P, Dhalaria P, Kashyap S, Soni GK, Nandi P, Ghosh S, Mohapatra MK, Rastogi A, Prakash D. Strategies to overcome vaccine hesitancy: a systematic review. Systematic reviews. 2022 Apr 26;11(1):78.\u003c/li\u003e\n\u003cli\u003eEdwards D, Bennett CL, Kelly D. Interventions that improve HPV vaccination uptake and intention: an umbrella review summary. HPV World. 2024 Jan 31.\u003c/li\u003e\n\u003cli\u003eMoher, D., Shamseer, L., Clarke, M. et al. Preferred reporting items for systematic review and meta-analysis protocols (PRISMA-P) 2015 statement. Syst Rev 4, 1 (2015). doi.org/10.1186/2046-4053-4-1\u003c/li\u003e\n\u003cli\u003eBooth, A., Clarke, M., Dooley, G. et al. The nuts and bolts of PROSPERO: an international prospective register of systematic reviews. Syst Rev 1, 2 (2012). https://doi.org/10.1186/2046-4053-1-2.\u003c/li\u003e\n\u003cli\u003e(EPOC, 2017). Implications for practice. In EPOC Resources for Review Authors. Cochrane Effective Practice and Organisation of Care (EPOC). Available online: https://epoc.cochrane.org/resources/epoc-resources-review-authors/ (accessed on 10 June 2023).\u003c/li\u003e\n\u003cli\u003eLefebvre C, Manheimer E, Glanville J. Searching for studies. Cochrane handbook for systematic reviews of interventions: Cochrane book series. 2008 Sep 26:95-150. doi.org/10.1002/9780470712184.ch6 \u003c/li\u003e\n\u003cli\u003eHiggins JPT, Thomas J, Chandler J, Cumpston M, Li T, Page MJ, Welch VA (editors). Cochrane Handbook for Systematic Reviews of Interventions version 6.3 (updated February 2022). Cochrane, 2022. Available from www.training.cochrane.org/handbook.\u003c/li\u003e\n\u003cli\u003eMcGuinness, LA, Higgins, JPT. Risk-of-bias VISualization (robvis): An R package and Shiny web app for visualizing risk-of-bias assessments. Res Syn Meth. 2020; 1- 7. https://doi.org/10.1002/jrsm.1411\u003c/li\u003e\n\u003cli\u003eMa GX, Zhu L, Tan Y, Zhai S, Lin TR, Zambrano C, Siu P, Lai S, Wang MQ. A multilevel intervention to increase HPV vaccination among Asian American adolescents. Journal of community health. 2022 Feb 1:1-8.\u003c/li\u003e\n\u003cli\u003ePaskett ED, Krok-Schoen JL, Pennell ML, Tatum CM, Reiter PL, Peng J, Bernardo BM, Weier RC, Richardson MS, Katz ML. Results of a multilevel intervention trial to increase human papillomavirus (HPV) vaccine uptake among adolescent girls. Cancer Epidemiology, Biomarkers \u0026amp; Prevention. 2016 Apr 1;25(4):593-602.\u003c/li\u003e\n\u003cli\u003eWiner RL, Gonzales AA, Noonan CJ, Buchwald DS. A cluster-randomized trial to evaluate a mother\u0026ndash;daughter dyadic educational intervention for increasing HPV vaccination coverage in American Indian girls. Journal of community health. 2016 Apr; 41:274-81.\u003c/li\u003e\n\u003cli\u003eTiro JA, Sanders JM, Pruitt SL, Stevens CF, Skinner CS, Bishop WP, Fuller S, Persaud D. Promoting HPV vaccination in safety-net clinics: a randomized trial. Pediatrics. 2015 Nov 1;136(5):850-9.\u003c/li\u003e\n\u003cli\u003eColey S, Hoefer D, Rausch-Phung E. A population‐based reminder intervention to improve human papillomavirus vaccination rates among adolescents at routine vaccination age. Vaccine. 2018 Aug 6;36(32):4904-9.\u003c/li\u003e\n\u003cli\u003eRickert VI, Auslander BA, Cox DS, Rosenthal SL, Rupp RE, Zimet GD. School-based HPV immunization of young adolescents: effects of two brief health interventions. Human vaccines \u0026amp; immunotherapeutics. 2015 Feb 1;11(2):315-21.\u003c/li\u003e\n\u003cli\u003eLee H, Kim M, Cooley ME, Kiang PN, Kim D, Tang S, Shi L, Thiem L, Kan P, Peou S, Touch C. Using narrative intervention for HPV vaccine behavior change among Khmer mothers and daughters: A pilot RCT to examine feasibility, acceptability, and preliminary effectiveness. Applied Nursing Research. 2018 Apr 1; 40:51-60\u003c/li\u003e\n\u003cli\u003eDempsey AF, Pyrznawoski J, Lockhart S, Barnard J, Campagna EJ, Garrett K, Fisher A, Dickinson LM, O\u0026rsquo;Leary ST. Effect of a health care professional communication training intervention on adolescent human papillomavirus vaccination: a cluster randomized clinical trial. JAMA pediatrics. 2018 May 1;172(5): e180016-.\u003c/li\u003e\n\u003cli\u003eBennett AT, Patel DA, Carlos RC, Zochowski MK, Pennewell SM, Chi AM, Dalton VK. Human papillomavirus vaccine uptake after a tailored, online educational intervention for female university students: a randomized controlled trial. Journal of Women\u0026apos;s Health. 2015 Nov 1;24(11):950-7.\u003c/li\u003e\n\u003cli\u003eChang J, Ipp LS, de Roche AM, Catallozzi M, Breitkopf CR, Rosenthal SL. Adolescent-parent dyad descriptions of the decision to start the HPV vaccine series. Journal of pediatric and adolescent gynecology. 2018 Feb 1;31(1):28-32.\u003c/li\u003e\n\u003cli\u003eWiner, R.L., Gonzales, A.A., Noonan, C.J. et al. A Cluster-Randomized Trial to Evaluate a Mother\u0026ndash;Daughter Dyadic Educational Intervention for Increasing HPV Vaccination Coverage in American Indian Girls. J Community Health 41, 274\u0026ndash;281 (2016). https://doi.org/10.1007/s10900-015-0093-2\u003c/li\u003e\n\u003cli\u003eKo LK, Taylor VM, Mohamed FB, Do HH, Gebeyaw FA, Ibrahim A, Ali AA, Winer RL. \u0026ldquo;We brought our culture here with us\u0026rdquo;: A qualitative study of perceptions of HPV vaccine and vaccine uptake among East African immigrant mothers. Papillomavirus Research. 2019 Jun 1; 7:21-5.\u003c/li\u003e\n\u003cli\u003eJallah JK, Anjankar A, Nankong FA. Public Health Approach in the Elimination and Control of Cervical Cancer: A Review. Cureus. 2023 Sep 1;15(9):e44543. doi: 10.7759/cureus.44543. PMID: 37789997; PMCID: PMC10544705.\u003c/li\u003e\n\u003cli\u003eLarson HJ, Toledo AH. Nurturing, nudging and navigating the increasingly precarious nature of cooperation in public health: the cases of vaccination and organ donation. Global Discourse. 2023 Nov 1;13(3-4):290-315.\u003c/li\u003e\n\u003cli\u003eSteenstra I, Murali P, Perkins R, Joseph N, Paasche-Orlow M, Bickmore T. Changing Parent Attitudes Towards HPV Vaccination by Including Adolescents in Multiparty Counseling using Virtual Agents. InProceedings of the 23rd ACM International Conference on Intelligent Virtual Agents 2023 Sep 19 (pp. 1-8).\u003c/li\u003e\n\u003cli\u003eL\u0026oacute;pez N, Garc\u0026eacute;s-S\u0026aacute;nchez M, Panizo MB, de la Cueva IS, Art\u0026eacute;s MT, Ramos B, Cotarelo M. HPV knowledge and vaccine acceptance among European adolescents and their parents: a systematic literature review. Public health reviews. 2020 Dec; 41:1-24.\u003c/li\u003e\n\u003cli\u003eZhang X, Wang Z, Ren Z, Li Z, Ma W, Gao X, Zhang R, Qiao Y, Li J. HPV vaccine acceptability and willingness-related factors among Chinese adolescents: a nation-wide study. Human Vaccines \u0026amp; Immunotherapeutics. 2021 Apr 3;17(4):1025-32.\u003c/li\u003e\n\u003c/ol\u003e"}],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":false,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":true,"hideJournal":true,"highlight":"","institution":"","isAcceptedByJournal":false,"isAuthorSuppliedPdf":false,"isDeskRejected":"","isHiddenFromSearch":false,"isInQc":false,"isInWorkflow":false,"isPdf":false,"isPdfUpToDate":true,"isWithdrawnOrRetracted":false,"journal":{"display":true,"email":"[email protected]","identity":"researchsquare","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":true,"externalIdentity":"","sideBox":"","snPcode":"","submissionUrl":"/submission","title":"Research Square","twitterHandle":"researchsquare","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"","reportingPortfolio":"","inReviewEnabled":false,"inReviewRevisionsEnabled":true},"keywords":"","lastPublishedDoi":"10.21203/rs.3.rs-6221575/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-6221575/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003ch2\u003eIntroduction:\u003c/h2\u003e \u003cp\u003eThe human papillomavirus (HPV) vaccine is pivotal in preventing HPV-related cancers, yet vaccine uptake rates vary significantly. This study assesses the efficacy of parent-adolescent dyad and parent-centered interventions on enhancing HPV vaccine uptake across different doses and over time.\u003c/p\u003e\u003ch2\u003eMethods\u003c/h2\u003e \u003cp\u003eThe study systematically searched Cochrane, PubMed, Web of Science, and Scopus databases from inception until the day of the search, synthesizing data to compare intervention effectiveness across HPV vaccination stages and time intervals. It assessed HPV vaccine uptake among children and adolescents aged 9\u0026ndash;18 years after parent or parent-adolescent dyad interventions, alongside completion rates. Meta-analyses, utilizing random-effects models, were conducted for each outcome.\u003c/p\u003e\u003ch2\u003eResults\u003c/h2\u003e \u003cp\u003eFor the first dose, parent-adolescent dyad interventions indicated a potential, though uncertain, increase in uptake (odds ratio [OR] 1.43, 95% confidence interval [CI]: 0.84, 2.42), while parent-centered interventions showed a significant, consistent improvement (OR 1.14, 95% CI: 1.08, 1.19). The second dose benefited markedly from dyad interventions (OR 3.75, 95% CI: 1.04, 13.52), with parent-centered interventions also demonstrating effectiveness (OR 1.27, 95% CI: 1.08, 1.48). For doses three and above, dyad interventions suggested a strong impact (OR 1.77, 95% CI: 1.13, 2.77), albeit with variability for parent-centered strategies (OR 1.13, 95% CI: 0.41, 3.11). Over time, interventions consistently improved uptake, particularly notable at 6 and 12 months for initial doses and showing long-term improvements in completing the series.\u003c/p\u003e\u003ch2\u003eConclusion\u003c/h2\u003e \u003cp\u003eThe study underscores the differential yet significant impact of parent-adolescent dyad and parent-centered interventions on HPV vaccine uptake across various doses and over time. These findings highlight the importance of tailored, dynamic public health strategies that engage both parents and adolescents to enhance HPV vaccination rates, supporting broader efforts to mitigate HPV-related health outcomes.\u003c/p\u003e","manuscriptTitle":"Parent-Centered Versus Parent-Adolescent Dyad Interventions to enhance HPV Vaccination Uptake in Children and Adolescents: A Systematic Review and Meta- analysis","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2025-03-17 09:41:02","doi":"10.21203/rs.3.rs-6221575/v1","editorialEvents":[{"type":"communityComments","content":0}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"researchsquare","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":true,"externalIdentity":"","sideBox":"","snPcode":"","submissionUrl":"/submission","title":"Research Square","twitterHandle":"researchsquare","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"","reportingPortfolio":"","inReviewEnabled":false,"inReviewRevisionsEnabled":true}}],"origin":"","ownerIdentity":"8584be14-6805-46ae-9896-cc5b0b33f745","owner":[],"postedDate":"March 17th, 2025","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"posted","subjectAreas":[],"tags":[],"updatedAt":"2025-08-13T08:54:25+00:00","versionOfRecord":[],"versionCreatedAt":"2025-03-17 09:41:02","video":"","vorDoi":"","vorDoiUrl":"","workflowStages":[]},"version":"v1","identity":"rs-6221575","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-6221575","identity":"rs-6221575","version":["v1"]},"buildId":"8U1c8b4HqxoKbykW_rLl7","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}