Barriers, supports, and effective interventions for uptake of human papillomavirus- and other vaccines within global and Canadian Indigenous peoples: a systematic review protocol

Background Despite the existence of human papilloma virus (HPV) vaccines with demonstrated safety and effectiveness and funded HPV vaccination programs, coverage rates are persistently lower and cervical cancer burden higher among Canadian Indigenous peoples. Barriers and supports to HPV vaccination in Indigenous peoples have not been systematically documented, nor have interventions to increase uptake in this population. This protocol aims to appraise the literature in Canadian and global Indigenous peoples, relating to documented barriers and supports to vaccination and interventions to increase acceptability/uptake or reduce hesitancy of vaccination. Although HPV vaccination is the primary focus, we anticipate only a small number of relevant studies to emerge from the search and will, therefore, employ a broad search strategy to capture literature related to both HPV vaccination and vaccination in general in global Indigenous peoples. Methods Eligible studies will include global Indigenous peoples and discuss barriers or supports and/or interventions to improve uptake or to reduce hesitancy, for the HPV vaccine and/or other vaccines. Primary outcomes are documented barriers or supports or interventions. All study designs meeting inclusion criteria will be considered, without restricting by language, location, or data type. We will use an a priori search strategy, comprised of key words and controlled vocabulary terms, developed in consultation with an academic librarian, and reviewed by a second academic librarian using the PRESS checklist. We will search several electronic databases from date of inception, without restrictions. A pre-defined group of global Indigenous websites will be reviewed for relevant gray literature. Bibliographic searches will be conducted for all included studies to identify relevant reviews. Data analysis will include an inductive, qualitative, thematic synthesis and a quantitative analysis of measured barriers and supports, as well as a descriptive synthesis and quantitative summary of measures for interventions. Discussion To our knowledge, this study will contribute the first systematic review of documented barriers, supports, and interventions for vaccination in general and for HPV vaccination. The results of this study are expected to inform future research, policies, programs, and community-driven initiatives to enhance acceptability and uptake of HPV vaccination among Indigenous peoples. Systematic review registration PROSPERO Registration Number: CRD42017048844 Electronic supplementary material The online version of this article (10.1186/s13643-018-0692-y) contains supplementary material, which is available to authorized users.

(Continued from previous page) Discussion: To our knowledge, this study will contribute the first systematic review of documented barriers, supports, and interventions for vaccination in general and for HPV vaccination. The results of this study are expected to inform future research, policies, programs, and community-driven initiatives to enhance acceptability and uptake of HPV vaccination among Indigenous peoples.
Enhancing HPV vaccination is a potentially high-impact, low-cost opportunity for cancer risk reduction among Indigenous peoples. As part of a tri-phase study in First Nations people to (1) establish baseline HPV vaccination rates, (2) systematically identify and validate the barriers and supports to HPV vaccination, and (3) comprehensively map documented and reported supports and barriers to HPV vaccination to develop a theory-informed, context-appropriate knowledge translation intervention, this synthesis aims to identify documented barriers, supports, and intervention strategies for HPV vaccination in Canadian and global Indigenous populations.

Vaccine acceptability, hesitancy, and uptake
Despite its success as a public health intervention [27][28][29][30][31][32][33][34], vaccination in many countries still falls short of levels needed to ensure community protection [30,[35][36][37]. Even where vaccination rates are high, ongoing acceptance remains a vulnerability [35], as evidenced by significant variability among different groups within high vaccinecoverage countries [30,37]. Measuring vaccination rates can be challenging, requiring different metrics to quantify impact. "Vaccine coverage" (e.g., the proportion of the target population who have received the vaccine) is the typical population-level measure of protection [30,[37][38][39], while "vaccine acceptability" and "uptake" are more common, individual-level measures. "Vaccine acceptability" reflects individuals' willingness to accept vaccination, typically assessed as attitudes, beliefs, and/or intentions [40]. A more commonly used term, "vaccine hesitancy", refers to a delay in acceptance or refusal of vaccines despite the availability of vaccine services [41]. "Vaccine uptake" reflects the behavior of getting vaccinated [37]. Understanding the barriers and supports to vaccine acceptability/hesitancy, moving from acceptance to uptake, and uptake from multiple perspectives (e.g., recipient, parents/guardians, health care providers, policy makers) [25], is a critical first step to tailoring strategies to enhance vaccination [37,42].

HPV vaccine-specific barriers, supports, and effective interventions
In Canada, the HPV vaccine was introduced into national and regional vaccination programs targeting preadolescents in school settings [54], to prevent cancers caused by HPV [55,56]. Vaccines preventing HPV infection demonstrate long-term effectiveness and acceptable safety profiles [24]. However, a number of issues specific to the HPV vaccine influence its acceptability and uptake in the general population; these factors are well described in systematic reviews [25,26,[57][58][59][60][61] and include knowledge and perceived risk of HPV disease, misinformation about vaccine safety, cost, misperceptions that the vaccine induces sexual promiscuity, and multi-dose vaccine series delivery. Additional challenges in the school setting include the information and consent process, vaccination setting, and student anxiety regarding privacy and pain during vaccination [62]. In high-income countries, access to and receipt of the HPV vaccine is determined by factors that influence policy makers, health care professionals, and parental decision-making, including financial constraints, social norms and values concerning sexual activity, and trust in vaccination programs and health care providers [61]. Further, barriers, and supports may be context-specific; for example, access to HPV vaccine may be facilitated by universal coverage health care systems or hindered by parents' cultural or religious perceptions about sexual activity [61]. Much of the literature reports barriers and supports to HPV vaccine acceptability, as reported by parents, health care providers, and policy makers [25], rather than vaccine recipients. This gap in self-reported data hinders effective, evidence-and theoryinformed intervention mapping [63].
A recent systematic review [25] summarized the nature and frequency of adolescent females' self-reported barriers to HPV vaccination. These factors included cost, perceived lack of need, concerns about safety and side effects, perceived efficacy, perceived relative benefit, vaccination logistics, fear of needles, vaccine novelty, perception that sexual inactivity precludes the need for vaccination, negative physician-related recommendations, social norms, inability to discuss the vaccine with parents, lack of awareness or information, anti-vaccination views, subjective norms, pregnancy (or trying to conceive), self-efficacy, mistrust of pharmaceutical companies, and the perception that alternative strategies are available. Cost and the perception that HPV vaccination leads to increased sexual activity were previously identified as vaccination barriers [60]. Adolescent females' self-reported supports to HPV vaccination included perceived benefit, positive health care provider recommendations, social norms, parental endorsement, perceived risk, cost-free access, subjective norms, perceived severity, positive attitude toward vaccine or reported personal importance of vaccine, self-efficacy, and vaccine efficacy [25,60].
Although a recent systematic review reported a lack of consistency and detailed reporting of interventions to increase HPV vaccine uptake [64], it found that the nature and magnitude of effect for national and international strategies (e.g., single and multifaceted behavioral [targeted at patient, provider and patient-provider] and environmental [local and national level policies]) were documented. It also revealed that environmental interventions (e.g., school-based vaccine administration) achieved the highest vaccination rates, but noted a lack of data for differentiating subpopulations. The need was underscored for specific strategies and interventions to target underserved populations, including Indigenous youth [64,65].
Barriers and supports to HPV vaccine acceptability and uptake in indigenous peoples HPV vaccine coverage levels in the general population of pre-adolescents may hide sub-populations with lower coverage, including Indigenous peoples who are known to have higher HPV infection rates [2,11,66], lower cervical cancer screening rates [13,14,67], higher rates of invasive cervical cancer [15,68], higher rates of cervical cancer-related hospitalizations [16], and lower rates of cervical cancer survival [17,18,69]. There is a paucity of data on HPV vaccination coverage in Indigenous peoples; however, it is well known that other childhood vaccinations in these groups are typically below that of the general population [52,[70][71][72][73][74][75][76]. Ongoing work in Canada [77] and Australia [78] strives to accurately track coverage levels, but an important companion to this work is a more detailed understanding of the barriers and supports to vaccination in Indigenous peoples. Moreover, generic interventions aimed at improving vaccine uptake in the general population of pre-adolescent children may require modifications or redesign for Indigenous peoples [79,80], particularly given the multijurisdictional complexities in health services delivery for those living on reserve. In addition, context and pragmatics (e.g., differing HPV vaccination programs in municipal schools versus on-reserve schools) may impact coverage levels [81].
The evidence compiled thus far on the barriers, supports, and interventions for HPV vaccination reveals considerable gaps in data for Indigenous peoples. Even so, any evidence on vaccination in this population may provide important guidance for future work. To our knowledge, this will be the first synthesis of the barriers, supports, and interventions for improving vaccination and HPV vaccination in Indigenous peoples. Synthesislevel knowledge in this area is expected to support Indigenous peoples, researchers, clinicians, policy makers, and communities in their efforts to ameliorate welldocumented and disproportionate burdens of disease that persist in Indigenous populations worldwide.

Methods/design
Aims Because we anticipate only a small number of relevant studies on HPV vaccination to emerge from the search, we will employ a broad search strategy to capture literature related to both HPV vaccination and vaccination in general among Indigenous peoples in Canada and globally. This systematic review will locate, gather, and critically appraise the global literature in Indigenous peoples [77], relating to (a) documented barriers and supports to vaccination and specifically HPV vaccination (V/HPV-V) and (b) interventions to increase acceptability and uptake or reduce hesitancy of V/HPV-V.
The design of this mixed methods [82][83][84] systematic review protocol and search strategy was guided by the Cochrane Handbook for Systematic Reviews [85], the Preferred Reporting Items for Systematic Review and Meta-Analysis (PRISMA) [86] and protocols (PRISMA-P) [87], and ENTREQ [88] reporting guidelines. Because our study will generate both quantitative and qualitative data, we propose segregated analyses on each data set [89]; qualitative data will be managed using NVivo10 [90] and quantitative data will be captured and managed in MS Excel and analyzed using STATA v13.1 [91]. This study protocol was registered with the International Prospective Register of Systematic Reviews on March 1, 2017 (PROSPERO CRD42017048844). Any protocol amendments will be discussed as the review proceeds and documented using a protocol addendum in the final report [92,93] (see Additional file 1).

Research questions
Primary questions of interest are:  [69,94,95]. Study participants may include vaccine recipients, youth, parents, grandparents, guardians, and Elders and/or knowledge holders, health care providers, policy-makers, decision-makers, and community leaders, without restricting by sex or age. Draft inclusion-exclusion criteria were developed (Table 1) and refined using key articles identified from preliminary search findings. Eligible studies will (a) include global Indigenous peoples and (b) discuss barriers or supports and/or interventions to improve uptake/ acceptability or to reduce vaccine hesitancy for V/HPV-V. Studies will be excluded if they do not (a) include global Indigenous peoples or include subpopulation(s) of one or more global Indigenous peoples comprising more than 50% of study participants, or for which separate analyses for global Indigenous peoples or subpopulation(s) are not presented; (b) discuss barriers, supports or interventions for enhancing acceptability or uptake or reducing hesitancy for V/HPV-V; (c) report extractable data; or (d) report original research.

Outcome measures
Primary outcomes are documented barriers or supports or interventions that increase or enhance acceptability/ uptake or interventions to reduce hesitancy for V/HPV-V. Secondary outcomes will investigate these same factors, specific to youth (< 18 years) in Canadian and global Indigenous peoples. For this review, we define barriers as single or multilevel factors that are negatively associated with, or hinder the acceptability or uptake of V/HPV-V or increase hesitancy. Supports include single or multilevel factors that are positively associated with, or enhance the acceptability and uptake of V/HPV-V or reduce hesitancy. Vaccination acceptability is defined as individuals' willingness to accept vaccination (typically measured by assessing attitudes, beliefs, and/or intention to be vaccinated) and vaccine uptake is defined as the behavior of getting vaccinated [40]. Vaccine hesitancy refers to a delay in acceptance or refusal of vaccines despite the availability of such services [41]. In order to optimize the capture of literature, vaccination intervention is defined as a singular or multilevel, simple and/or complex strategy(ies) used in the design or execution of vaccination or used to increase or enhance vaccine acceptability, uptake or to reduce vaccine hesitancy. Vaccination is defined as the act of introducing a vaccine into the body to produce immunity to a specific disease [96]. Study outcomes will be segregated into three main variable groups: study characteristics, barriers and supports, and vaccination interventions (acceptability, uptake, hesitancy).

Study type
All study designs meeting inclusion criteria will be considered, without restricting by language, location, or data type (i.e., qualitative, quantitative, and mixed methods studies are eligible).

Data sources and search strategy
A comprehensive search of the literature will use an a priori search strategy (draft MEDLINE search strategy in Table 1) comprised of key words and controlled vocabulary terms (Medical Subject Headings or MeSH terms). The core search strategy was developed in MEDLINE, in partnership with an academic librarian (HG) and submitted to a second academic librarian (YL) for independent peer review using the Peer Review of Electronic Search Strategies (PRESS) checklist [97]. PRESS feedback was integrated and the finalized strategy translated for use with the remaining databases. We will search several electronic databases ( (Table 2).

Gray literature search strategy
A search will be employed to identify original research that is not reported in peer-reviewed journal articles. The search and Level 1 screening process will be conducted concurrently, with two researchers searching a pre-defined group of government, agency, and Canadian and global Indigenous websites to locate relevant gray literature ( Table 3). Combinations of the following combinations will be used: (1) Indigenous or Aboriginal or Indian, and (2) Vaccine or Vaccination or Immunization or Immunize or Immunization or Immunize or HPV or Human papillomavirus. Terms will be combined using "and" or "&". Websites and resources that pertain to (1) Indigenous populations and (2) discuss barriers/supports or interventions to improve vaccination or HPV vaccination will be retained for screening. The title, URL, and data accessed for all websites/resources identified through this search will be entered into an Excel spreadsheet. Questionable resources will be retained for screening. All websites/resources identified in the search will be screened to determine if they meet the inclusion criteria (Table 1). Bibliographic searches will be conducted for all included studies and additional papers identified. We will also contact known provincial, national, and international experts working in this area

Preliminary findings
A search of key national and international websites that register, fund, or publish knowledge syntheses failed to locate an existing synthesis to address our review questions. We identified several helpful systematic reviews in the areas of vaccine hesitancy [41,60,98], acceptability [60,99], inequity of HPV vaccine uptake [100], barriers and facilitators to HPV vaccination in young women [25,57,61,101,102], and identification and assessment of interventions to improve HPV vaccine uptake [64,79,80,103]. We identified several tangential emergent syntheses through the PROSPERO International Prospective Register of Systematic Reviews pertaining to parental-reported barriers and facilitators to HPV vaccination [104], hesitancy toward HPV vaccine [105], the effects of mass media interventions on enhancing childhood vaccine uptake [106], health care provider recommendation of HPV vaccine in boys and young men [107,108], and individual and environmentallevel factors influencing HPV vaccination [107]. A relevant review of specific subpopulations that included Canadian or global Indigenous peoples was not located. The core database search was conducted in MEDLINE using the Ovid interface, including in-process and e-pub-ahead-ofprint records, without restrictions, and generated a total of 2096 citations after de-duplication. A search filter for identifying literature for Canadian Indigenous peoples was added to the core MEDLINE search and feedback from PRESS review integrated [109].

Study selection
Search strategy findings will be cataloged using Endnote™ X8.0 and duplicates removed manually. For inclusion, studies must involve one or more global Indigenous peoples and discuss barriers or supports to V/HPV-V and/or interventions to increase uptake/acceptability or reduce V/HPV-V hesitancy, as per study eligibility criteria. We will exclude studies that do not: a) involve a global Indigenous population (or a subpopulation comprising ≥ 50% of study participants), b) discuss barriers or supports to V/ HPV-V; c) discuss V/HPV-V interventions or interventions that enhance the acceptability or uptake of V/HPV-V or reduce V/HPV-V hesitancy, d) report extractable data, or e) report original research.
Title and abstract screening (Level 1) Prior to commencing Level 1 (title and abstract) screening [89], we will calibrate screening among reviewers on a random sample (5% of the total number of citations) [83]. All citations will then be screened independently and in duplicate by two investigators [GN/KJM/MSB/NB/SG/ CC/RVR] and discrepancies discussed until consensus is reached or, failing consensus, referred to a third reviewer for final resolution. Overall screening concordance will be calculated using the Kappa statistic [110]. Only those studies meeting screening inclusion/exclusion criteria will be retrieved for full text Level 2 [89] review. To pass Level 1 screening, studies must discuss one or more global indigenous peoples and barriers or supports to V/HPV-V or vaccination interventions to increase acceptability and uptake or reduce hesitancy for V/HPV-V.
Full-text review and data abstraction (Level 2) The anticipated outcomes of interest are barriers and supports to V/HPV-V (qualitative and quantitative data, if measured) and interventions to enhance V/HPV-V acceptability or uptake or reduce hesitancy (qualitative and quantitative data, if measured), in Canadian and global Indigenous peoples and, secondarily, in Canadian Indigenous youth (< 18 years). Where multiple citations occur, data will be combined to create a full description of the study. Should a lack of clarity about multiple citations arise, information will be sought from authors and studies excluded where discrepancies remain unresolved. We will calibrate full text screening among reviewers using the same methods described for Level 1. The full text of each included citation will be reviewed independently and in duplicate by two investigators [CC/GN/ KJM/MSB/NB/SG/SM/RVR/CB] and discrepancies resolved by a third investigator.   A draft data abstraction tool will be generated in MS Excel [111], based on the Data Collection Checklist from the Cochrane EPOC [112]. A subsection of the tool will be developed to assess the included intervention studies, specifically. We will use a set of a priori variables generated from preliminary findings (Table 4), combined with several items adapted from the Community Guide's Data Abstraction Framework (CGDA) [113] and the Standards for Reporting Implementation Studies Statement (StaRI) [114]. The abstraction tool will be pilot-tested by reviewers on a random sample of included articles and revised until consensus is reached on key variables and definitions.

Methodological quality
Methodological quality will be assessed using a universal appraisal tool (Quality Assessment Tool for Reviewing Studies with Diverse Designs -QATSDD) developed for the assessment of quality in diverse study designs [115]. The 4-point tool scoring system will be applied to each item, allowing an overall quality assessment for each study using one set of criteria. Team members will independently pilot the quality assessment tool using two to three included studies. The team will review discrepancies and discuss to consensus at a weekly team meeting before proceeding. Two investigators [CC/GN/KJM/ MSB/NB/SG/SM/RVR/CB] will assess methodological quality in all included studies, independently and in duplicate. Discrepancies will be noted and discussed until consensus, or failing consensus, referred to a third investigator. Quality scores will be reported as combined reviewer scores across the 16 items and the total score for each study and then summarized and used to fully describe the nature and characteristics of included studies in the analysis. Quality assessment scores will be presented in tabular format for all included studies to highlight the strengths and weaknesses of the evidence base. Quality assessments will be used to 1) describe and characterize the methodological rigor and scientific quality of included studies; and 2) provide context for the interpretation of findings, formulation of conclusions, and/or recommendations arising from the review. Extreme outlier scores will be discussed by the team and depending on the issues identified, may be excluded to avoid the influence of significantly flawed studies on statistical and/or conceptual analyses, as appropriate.
A secondary quality analysis of the included effective intervention studies will be undertaken using the domains of the Consolidated Framework for Implementation Research (CFIR) [116]. The main purpose of this quality analysis is to gather and assess, where available, detail about the presence and nature of the individuallevel factors and contextual, intervention or implementation process factors for implementation, using a robust framework.

Data analysis
The overall study flow will be reported using a PRISMA diagram [86], providing a summary of citation numbers, sources, exclusions/rationale, and final number of included studies. Data analysis of abstracted variables will consist of two main sections with several subsections [82], including: (1) an inductive, qualitative, thematic synthesis [117] of all documented barriers and supports and (2) a quantitative analysis of measured barriers and supports found to be statistically significant, summarized as mean proportion and standard deviation of participants reporting the barrier or support (or other relevant aggregate measures as appropriate) or ranked by frequency of reported barriers or supports. The thematic analysis will proceed using a step-wise, iterative approach. Team members will review each study independently, and in duplicate. Line-by-line coding of identified barriers and/or supports will be conducted on   each study, and we will note similarities and differences in codes and discuss any discrepancies to consensus at weekly team meetings. Subsequent studies will be subjected to the same analysis, contributing text to existing (or generating new) themes, as appropriate. Once the coding process is complete, the team will review each of the barrier and support themes and sub themes, refine their definitions if necessary, and examine the text within them for consistency, code interrelations and to identify any potential conceptual hierarchies. All changes to codes, conceptual re-alignments, discussions and decisions will be documented as part of the study audit trail. We will report a summary of emerging themes, sub themes, definitions and linkages to studies in which themes arise. We anticipate the ability to provide both a descriptive synthesis and quantitative summary of relevant measures for interventions; however, recent reviews examining barriers and supports in the area of HPV vaccination revealed a level of heterogeneity among studies precluding meta-analysis [25]. All included studies describing interventions will be assessed using the Community Guide's Data Abstraction Framework [118] with interventions categorized and frequencies reported by type and intensity.
We plan to report findings pertaining to Canadian Indigenous and global Indigenous peoples separately, contingent on the volume of eligible literature identified in each group. We will report results for HPV vaccines separately from results arising from studies of other vaccines, given the characteristics and contextual factors associated with HPV compared with other vaccines and target populations. A draft analysis plan and anticipated products of the synthesis are outlined in Table 5.

Discussion
To date, we have not located a systematic review describing the barriers and supports to HPV vaccination or one that gathered and assessed effective interventions to increase acceptability and uptake of HPV vaccines in Indigenous peoples. Previous systematic reviews have been limited to vaccine efficacy in Indigenous peoples [119][120][121]. In addition to identifying studies that describe the barriers and supports to vaccination and interventions to increase vaccination acceptability and uptake in Indigenous peoples, the proposed systematic review will also aim to identify studies that specifically describe the barriers and supports to HPV vaccination and interventions that have been shown to increase acceptability and uptake of the HPV vaccine. While there is some evidence to suggest that tailoring vaccine strategies to the needs and preferences of adolescents using technology interventions may be promising, it is unclear how these findings relate to Canadian Indigenous youth. We have *denotes subcategories will be generated inductively • What is the quality of the eligible literature? (QATSDD tool) • What, if any, themes arise in the literature describing barriers and supports to vaccine or HPV vaccine in Canadian and global Indigenous peoples?
• To describe articles that report barriers and/ or supports to HPV and other vaccines • To establish the quality of included articles (item and total study scores) • To analyze and (where possible) group barriers and facilitators meaningfully across studies • To analyze any themes among barriers and supports to vaccine or HPV vaccine that are specific to Canadian Indigenous populations • To statistically analyze measured barriers and supports across studies (should they be deemed appropriate for meta-analysis)

Quantitative Analysis
• What, if any, barriers and supports to vaccine or HPV vaccine in Canadian and global Indigenous peoples are statistically significant?
2: To identify and assess the documented effective interventions to increase acceptability, uptake or reduce hesitancy of vaccination, and HPV vaccination, in Canadian and global Indigenous peoples Descriptive statistics, narrative summary • What interventions are documented to increase vaccine or HPV vaccine acceptability and uptake and reduce hesitancy in Canadian and global Indigenous populations?
• What is the quality of the eligible literature? (QATSDD tool) • What, is the nature of vaccine or HPV acceptability, hesitancy and uptake in Canadian and global Indigenous peoples?
• To describe articles that report effective strategies for increasing vaccine or HPV vaccine acceptability, uptake or reducing hesitancy in Canadian and global Indigenous peoples • To establish the quality of included articles (item and total study scores) • To describe quantitatively and qualitatively (thematic synthesis) the nature and characteristics of interventions to increase vaccine or HPV vaccine acceptability and uptake or reducing hesitancy in Canadian and global Indigenous peoples  • To describe and systematically assess interventions to increase acceptability and uptake, and reduce hesitancy of vaccination and HPV vaccination in youth (< 18 years) within Canadian and global Indigenous peoples, and report findings using the domains/subdomains of the CFIR framework.
chosen to focus on HPV vaccination because, despite wide-spread availability, uptake of HPV vaccination between Indigenous and non-Indigenous youth remains unequal [19]. This finding is similar to that found in non-Indigenous populations in the USA where only 65% of girls and 56% of boys initiate a HPV vaccination series and fewer (43% and 32%, respectively) complete the series [64]. The approach we propose will allow us to synthesize existing evidence of HPV vaccine-specific barriers, supports, and effective interventions that may provide insights into vaccination practices that better meet the needs of Indigenous peoples. While the importance of multiple [79,80,122] and/or tailored [123,124] (versus singular) interventions in some target groups remains a matter of debate in the implementation literature [125], multiple strategies focused on increasing HPV vaccination rates in non-Indigenous peoples have been shown to be effective [80,[126][127][128][129][130][131][132]. Furthermore, interventions tailored to address specific barriers to HPV vaccination or to address contextual differences may be required [133,134]. It is unlikely, given the apparent state of the literature, that detailed information is available about contextual influences on HPV vaccination barriers and supports and HPV vaccination acceptability/hesitancy and uptake.
We have chosen to include global Indigenous peoples [133,134] and anticipate that this review may suggest that Indigenous peoples, regardless of country, may experience similar barriers and supports to vaccination acceptability/hesitancy and uptake. With this in mind, we chose a broad definition of Indigenous peoples to help generate results that are relevant to many stakeholders. Given the dearth of literature in this area, we will consider all study designs meeting inclusion criteria, without restriction by language, location, or data type. We anticipate only a small number of relevant studies to emerge from the search and, hence, have used a broad, less restrictive search strategy that aims to capture literature related to V/HPV-V among Indigenous peoples.
The results of this study are expected to inform future research, policies, programs, and community-driven initiatives to enhance acceptability and uptake of vaccination among Indigenous peoples. Specifically, this review will identify and describe the documented barriers, supports, and interventions for V/HPV-V. These will provide a foundation to inform the development of new vaccination strategies among Indigenous peoples. We anticipate the review will identify the nature of evidence gaps and highlight areas requiring further study.

Dissemination and knowledge translation plan
To our knowledge, this study will contribute the first systematic review of the global literature in this area. We will take an integrated knowledge translation [135,136] approach to guide our synthesis in close partnership with First Nation knowledge holders and others who will help interpret, structure, and disseminate findings to relevant research, clinical, Indigenous, policy, and decision maker groups. We anticipate there may be important regional, group, and contextual differences present in the data that will require tailored dissemination ( (2016), unpublished) and plan to co-present findings with First Nation partners. We anticipate strong receptivity for study findings and will utilize a translation process that is informed by the Knowledge-to-Action framework [137,138] but is deliberately inductive to ensure knowledge systems, contexts, and the unique needs of our knowledge users are considered [77]. This process will extend from the analysis and interpretation of review findings through the conceptualization, mapping, and execution of vaccination strategies [139][140][141]. In closing, the intent of this synthesis is to assess the global literature pertaining to barriers and supports to V/HPV-V and identify effective interventions to enhance acceptability and uptake of V/HPV-V, in Canadian and global Indigenous peoples. We anticipate that this synthesis will provide numerous stakeholder groups with a better understanding of the current state of the literature in this area and help inform the development of interventions that encourage V/HPV-V acceptability and uptake and reduce hesitancy in Canadian and global Indigenous peoples.  Availability of data and materials Data sharing is not applicable to this article as no datasets were generated or analyzed during the current study.
Authors' contributions KJM was involved with study conception and design, developed the protocol (search strategy, inclusion/exclusion criteria, quality assessment and data extraction), reviewed and approved the final manuscript. KJM also registered the protocol with PROSPERO. SM was involved with study conception and design, developed the protocol (search strategy, inclusion/ exclusion criteria, quality assessment and data extraction), reviewed and approved the final manuscript. MSB was involved with study conception and design, developed the protocol (search strategy, inclusion/exclusion criteria, quality assessment and data extraction), reviewed and approved the final manuscript. NB was involved with study conception and design, developed the protocol (search strategy, inclusion/exclusion criteria, quality assessment and data extraction), reviewed and approved the final manuscript. HG was involved with study conception and design, developed the protocol (search strategy, inclusion/exclusion criteria, quality assessment and data extraction), reviewed and approved the final manuscript. SG was involved with study conception and design, developed the protocol (search strategy, inclusion/ exclusion criteria, quality assessment and data extraction), reviewed, and approved the final manuscript. LB was involved with study conception and design, reviewed and approved the final manuscript. BH was involved with study conception and design, reviewed, and approved the final manuscript. CH was involved with study conception and design, reviewed, and approved the final manuscript. JG was involved with study conception and design, reviewed and approved the final manuscript. AC was involved with study conception and design, reviewed, and approved the final manuscript. CB was involved with study conception and design, reviewed and approved the final manuscript. RR was involved with study conception and design, reviewed and approved the final manuscript. RH was involved with study conception and design, reviewed and approved the final manuscript. JK was involved with study conception and design, reviewed and approved the final manuscript. CB was involved with study conception and design, reviewed, and approved the final manuscript. RAB was involved with study conception and design, reviewed, and approved the final manuscript. AL was involved with study conception and design, reviewed, and approved the final manuscript. GN was involved with study conception and design, developed the protocol (search strategy, inclusion/exclusion criteria, quality assessment and data extraction), reviewed, and approved the final manuscript. GN is the guarantor of the protocol. All authors read and approved the final manuscript.