Barriers and Factors Associated with HPV Vaccination Among American Indians and Alaska Natives: A Systematic Review

Abstract

American Indian and Alaska Native (AI/AN) persons bear a disproportionate burden of human papillomavirus (HPV)-associated cancers and face unique challenges to HPV vaccination. We undertook a systematic review to synthesize the available evidence on HPV vaccination barriers and factors among AI/AN persons in the United States. We searched fourteen bibliographic databases, four citation indexes, and six gray literature sources from July 2006 to January 2021. We did not restrict our search by study design, setting, or publication type. Two reviewers independently screened the titles and abstracts (stage 1) and full-text (stage 2) of studies for selection. Both reviewers then independently extracted data using a data extraction form and undertook quality appraisal and bias assessment using the modified Mixed Methods Appraisal Tool. We conducted thematic synthesis to generate descriptive themes. We included a total of 15 records after identifying 3017, screening 1415, retrieving 203, and assessing 41 records. A total of 21 unique barriers to HPV vaccination were reported across 15 themes at the individual (n=12) and clinic or provider (n=3) levels. At the individual level, the most common barriers to vaccination--safety and lack of knowledge about the HPV vaccine--were each reported in the highest number of studies (n=9; 60%). The findings from this review signal the need to develop interventions that target AI/AN populations to increase the adoption and coverage of HPV vaccination. Failure to do so may widen disparities.

INTRODUCTION

Human papillomavirus (HPV), the most common sexually transmitted infection,¹ causes certain cancers collectively known as HPV-associated cancers. In the United States (US), over 45,000 new cases of HPV-associated cancer cases occur annually.² The burden of HPV-associated cancers is disproportionately higher among American Indians and Alaska Natives (AI/AN). From 2013 to 2017, the incidence rate (per 100,000) for all HPV-associated cancers was significantly higher among AI/AN women (15.9) than non-Hispanic White women (13.7), highlighting the disparity in disease burden.³

Vaccines to prevent HPV-associated cancers have been available since 2006 for girls and since 2009 for boys in the US. However, in 2019, only 71.1% of AI/AN adolescents aged 13 to 17 years had initiated, and 57.5% were up to date with HPV vaccination nationally.⁴ Previous systematic reviews have identified several factors and barriers associated with HPV vaccination.^5–11 However, some factors, such as insurance coverage,^8,12,13 and barriers, such as the cost of the HPV vaccine,^5–7 may not apply to the AI/AN context. In addition, reviews have centered on specific racial and ethnic groups, including African Americans and Latinos.^14,15 However, no review on HPV vaccination barriers and factors has focused on the AI/AN population. Even reviews that have assessed racial factors and disparities in vaccination did not include AI/AN persons.^16–18 Furthermore, data on HPV vaccination factors for AI/AN persons are combined with other racial groups in the analysis of national surveys,^19–22 making it challenging to discern vaccination factors unique to AI/AN communities.

In the absence of a review focused on the AI/AN population and given the elevated burden of HPV-associated cancers and unique challenges AI/AN communities face, we undertook this review to synthesize the available evidence on HPV vaccination barriers and factors. The objective of this systematic review was to identify and assess factors that (i) are barriers to HPV vaccination, (ii) support or enhance HPV vaccination, and (iii) are found not to be associated with HPV vaccination among AI/AN persons in the US.

METHODS

We developed and published the protocol for this systematic review using the Preferred Reporting Items for Systematic Reviews and Meta-Analyses for Protocols 2015 (PRISMA-P 2015).^23,24 The systematic review is registered in PROSPERO (CRD42020156865). We also adhered to the PRISMA 2020 guidelines and report our review according to their recommendations (see Supplementary File A).²⁵

Eligibility criteria.

We included studies published in English that assessed HPV vaccination barriers and factors among AI/AN persons in the US, except territories, covering the period from July 1, 2006 to January 05, 2021. We did not restrict by study design (except existing reviews), setting, or publication type.

Information sources.

We followed and reported the information sources, search strategy, and record management using PRISMA-S guidelines.²⁶ To minimize the risk of bias and maximize the inclusion of relevant studies, we searched fourteen bibliographic databases, four citation indexes, and six gray literature sources. A list of sources searched is presented in Table 1. We also undertook complementary searching activities, including citation chaining and searching.

TABLE 1.

Sources searched for systematic review of human papillomavirus vaccination barriers or factors, July 2006-January 2021.

Name	Interface/Platform	Search executed (# of records*)	Total # of records*
Database and Citation Index
MEDLINE and Epub Ahead of Print, In-Process and Other Non-Indexed Citations	Ovid	July 8, 2019 (n = 364) Search updated: October 3, 2019 (n = 34) December 16, 2020 (n = 82)	480
PubMed	https://www.ncbi.nlm.nih.gov/pubmed/	July 22, 2019 (n = 428) Search updated: October 3, 2019 (n = 18) December 16, 2020 (n = 43)	489
Embase	Ovid	July 8, 2019 (n = 348) Search updated: October 3, 2019 (n = 9) December 16, 2020 (n = 95)	452
Cochrane Central Register of Controlled Trials (CENTRAL)	Ovid	October 4, 2019 (n = 7) Search updated: December 16, 2020 (n = 2)	9
CINAHL Complete	EBSCO	July 22, 2019 (n = 31) Search updated: December 16, 2020 (n = 9)	40
ERIC	Ovid	July 22, 2019 (n = 87) Search updated: December 16, 2020 (n = 19)	106
PsycINFO	Ovid	July 8, 2019 (n = 154) Search updated: December 16, 2020 (n = 31)	185
SocINDEX	EBSCO	July 22, 2019 (n = 34) Search updated: December 16, 2020 (n = 52)	86
Bibliography of Native North Americans	EBSCO	July 22, 2019 (n = 6) Search updated: December 16, 2020 (n = 0)	6
Social Work Abstracts	EBSCO	July 22, 2019 (n = 11) Search updated: December 16, 2020 (n = 11)	22
Native Health Database	https://hslic-nhd.health.unm.edu/	December 22, 2019 (n = 0) Search updated: January 5, 2021 (n = 0)	0
Indigenous Studies Portal (iPortal)	https://iportal.usask.ca/	December 23, 2019 (n = 3) Search updated: January 5, 2021 (n = 0)	3
Arctic Health Publications Database	https://arctichealth.org/	December 23, 2019 (n = 1) Search updated: January 5, 2021 (n = 0)	1
Science Citation Index Expanded (SCI-Expanded)	Web of Science	July 8, 2019 (n = 313) Search updated: December 16, 2020 (n = 116)	429
Social Sciences Citation Index (SSCI)	Web of Science
Arts & Humanities Citation Index (A&HCI)	Web of Science
Emerging Sources Citation Index	Web of Science
Scopus	https://www.scopus.com/home.uri	July 22, 2019 (n = 56) Search updated: December 16, 2020 (n = 285)	341
Grey Literature
Dissertation
Dissertations and Theses	ProQuest	October 4, 2019 (n = 212) Search updated: December 17, 2020 (n = 41)	253
Abstracts and Conferences
Northern Light Life Sciences Conference Abstracts	Ovid	July 22, 2019 (n = 65) Search updated: December 16, 2020 (n = 15)	80
PapersFirst	FirstSearch	October 4, 2019 (n = 1) Search updated: December 17, 2020 (n = 0)	1
Proceedings	FirstSearch	October 4, 2019 (n = 33) Search updated: December 17, 2020 (n = 0)	33
Preprints
OSF Preprints	https://osf.io/preprints/	December 24, 2020 (n = 0) Search updated: January 5, 2021 (n = 0)	0
Reports
Tribal Epidemiology Centers	https://tribalepicenters.org/12-tecs/	January 5, 2020 (n = 1) Search updated: January 5, 2021 (n = 0)	1

Abbreviations:

CINAHL, Cumulative Index to Nursing and Allied Health; ERIC, Education Resources Information Center.

Notes:

^*Number of records prior to screening. May include duplicate records.

Search strategy.

We selected the information sources and developed the search strategy in consultation with an experienced health sciences librarian. We used controlled vocabulary terms and keywords, such as synonyms and trade names, to capture key concepts. To strike a balance between comprehensiveness and precision, we used truncation and proximity searching to ensure comprehensiveness, and set appropriate limits and removed duplicates to achieve precision. We piloted the search strategy in three Ovid databases (MEDLINE, Embase, PsycINFO), and Web of Science Core Collection’s Social Sciences Citation Index, Science Citation Index-Expanded, Arts & Humanities Citation Index, and Emerging Sources Citation Index. We refined the search terms, if needed. The refined search strategy for all sources with interface and coverage has been published previously.²⁴ We also updated our search to include newer literature from December 2020 to January 2021.

Selection process.

We screened and selected studies in two stages. In stage 1, two reviewers used the following keywords to screen titles and abstracts: HPV vaccine or vaccination, American Indian, Alaska Native, Native American, race or racial. In stage 2, we developed, piloted, and revised a screening and selection form to screen the full-text of records included in stage 1. The two reviewers resolved discrepancies through discussions and consulted a third reviewer to aid decision-making and achieve resolution when needed.

Data collection process and data items.

We developed and piloted a data extraction form by adapting questions from the Cochrane Collaboration’s intervention reviews for RCTs and non-RCTs,²⁷ Strengthening the Reporting of Observational Studies in Epidemiology (STROBE) guideline for quantitative studies,²⁸ and Standards for Reporting Qualitative Research (SRQR) guideline.²⁹ The data extraction form and the included data items are provided in a previous publication.²⁴

Quality appraisal and bias assessment.

We used a modified Mixed Methods Appraisal Tool (MMAT) (version 2018) to assess the methodological quality of included studies.³⁰ We selected the tool because it covers different study designs, has improved content validity, and has high inter-rater reliability.³⁰ We added five questions to the MMAT and expanded the scope to include methodological and reporting criteria. The first three questions (Are the data collection and analysis methods appropriate? Are the limitations of the study adequately described? Are there any ethical concerns or conflict of interest?) are a requirement of several reporting guidelines.^28,29,31 The remaining two questions were adapted from the CONSIDER statement to assess whether AI/AN stakeholders were involved in the research process and whether a culturally appropriate methodology was used.³² Similar to screening and selecting studies, the two reviewers undertook independent quality and bias assessment, with disagreements being resolved through discussion and in consultation with the third reviewer when needed.

Data synthesis.

We did not undertake a meta-analysis due to the unavailability of individual data and heterogeneity in study designs and measures. However, we assessed HPV vaccination barriers and factors at the individual and clinic or provider levels. When available, we reported measures of frequency and association.

For thematic synthesis, we reviewed each study included in our final review and extracted data about barriers and factors related to and unrelated to HPV vaccination. Two reviewers verified the extracted data and resolved any discrepancies. In addition, the reviewers assessed similarities and differences and organized and grouped the data into related areas to construct descriptive themes.

RESULTS

Study selection.

From July 2006 to January 2021, we identified 3,017 records from databases and citation indexes and one record from the gray literature. After removing duplicate, non-English, and non-US records, we screened 1,415, retrieved 203, and assessed 41 records. For the final review, we included a total of 15 records^33–47 after excluding records that did not address HPV vaccination barriers or factors (n=14) or did not include data by AI/AN race (n=10), and excluding conference abstracts if they were later published as full-text articles (n=2). Figure 1 shows a PRISMA 2020 flow diagram with the results of the search and selection process.

Figure 1:

PRISMA 2020 flow diagram.

Study characteristics.

Key characteristics of the included studies are presented in Table 2. Of the 15 studies, nine assessed HPV vaccination barriers or factors at the individual level,^33–41 five studies assessed barriers at the clinic or provider level,^42–46 and one study included both levels.⁴⁷ Four studies used quantitative research methodology,^34,35,42,43 four used qualitative methodology,^33,36,38,40 six used both qualitative and quantitative approaches,^{37,39,44–47} and one was a cluster-randomized trial.⁴¹ Most studies were published as full-text articles (n=12), but our final review also included one dissertation,³⁴ one presentation,⁴⁰ and one abstract.⁴² Two studies focused on AN adolescents³⁸ and parents³⁹ and one study included provider surveys and interviews from IHS in Alaska.⁴⁵

TABLE 2.

Characteristics of included studies (n=15).

							HPV vaccination
Author (year)	Publication Type	Study Period	State or Location	Method	Size (% female)	Population	Barriers	Factors
Individual-level
Bowen (2014)33	Article	2009–2010	CT, MA, ME, NH, RI, VT	Qualitative (focus group)	50 (100%)	Parents	Yes	Yes
Bowker (2017)34	Dissertation	2017	SD	Quantitative (survey)	89 (100%)	Young adults (18–25 years)	Yes	Yes
Buchwald (2013)35	Article	2007–2009	SD	Quantitative (survey)	351 (100%)	Adults (18–65 years)	Yes	Yes
Hodge (2014)36	Article	2009	AZ & CA	Qualitative (focus group)	53 (60.4%)	College students (18–26 years)	No	Yes
Hodge (2011)37	Article	2009	AZ & CA	Quantitative (survey) & Qualitative (focus group)	57 (59.6%)	College students (18–26 years)	No	Yes
Kemberling (2011)38	Article	2008	AK	Qualitative (interviews)	79 (100%)	Adolescents (11–18 years)	Yes	Yes
Toffolon-Weiss (2008)39	Article	2007	AK	Quantitative (survey) & Qualitative (focus group)	80 (>80%)	Parents	Yes	Yes
White (2018)40	Presentation	–*	WA	Qualitative (focus group)	9 (–*)	Parents & Young adults (18–26 years)	Yes	Yes
Winer (2016)41	Article	2007–2013	AZ	Cluster-randomized trial	97 (100%)	Parents & Adolescents (9–12 years)	Yes	Yes
Clinic- or Provider-level
Bruegl (2016)42	Abstract	–*	–*	Quantitative (survey)	60 (–*)	Physicians	Yes	Yes
Duvall (2012)43	Article	2009–2010	WA	Quantitative (survey)	31 IHS or tribal clinics (–*)	–*	No	Yes
Jacobs-Wingo (2017)44	Article	2013–2015	5 IHS regions	Quantitative (survey) & Intervention study	19 I/T/U facilities (–*)	–*	Yes	Yes
Jim (2012)45	Article	2009–2010	12 IHS areas	Quantitative (survey) & Qualitative (semi-structured interview)	Survey: 268 (74.6%) Interview: 51 (78.4%)	Healthcare provider	No	Yes
Kashani (2019)46	Article	2006–2015	MI	Qualitative (semi-structured interview) & Secondary data analysis	Interview: 14 (–*) Data: 684,509 adolescents (49.9%)	Providers and public health professionals	Yes	Yes
Both
Schmidt-Grimminger (2013)47	Article	2009	SD	Quantitative (survey) & Qualitative (focus group)	73 (–*)	Tribal and IHS health providers, young adults (19–26 years), adolescents (14–18 years), and parents.	No	Yes

Notes:

^*Data not specified or not applicable.

Abbreviations: IHS, Indian Health Service; I/T/U, Indian Health Service, tribally-operated, and urban Indian healthcare facilities.

U.S. State: AK, Alaska; AZ, Arizona; CA, California; CT, Connecticut; MA, Massachusetts; ME, Maine; MI, Michigan; NH, New Hampshire; RI, Rhode Island; SD, South Dakota; VT, Vermont; WA, Washington.

Participant characteristics.

At the individual level, studies assessed HPV vaccination barriers or factors among AI/AN adolescents (n=2), young adults or college students (n=4), adults (n=1), and parents (n=3). Most participants at the individual level were female. The proportion of females was 100% in five studies,^{33–35,38,41} >80% in one study,³⁹ and approximately 60% in two studies.^36,37 One study did not specify the sex of the participants.⁴⁸ At the clinic or provider level, five studies assessed factors or barriers among healthcare providers, public health professionals, and staff from the Indian Health Service (IHS), Tribal and Urban Indian (I/T/U) facilities.^42–46

Quality assessment.

We have included a summary table of the quality and risk of bias assessment for each study according to the modified MMAT in Supplementary File B. All qualitative studies, except one,⁴⁵ met every methodological quality criterion of MMAT. Conversely, the methodological quality for quantitative studies varied. For example, only two studies (22.2%) adequately addressed the risk of nonresponse bias,^34,43 and two studies (22.2%) clearly described the target population and sample.^34,44

Across all studies, information addressing the additional questions on the modified MMAT was not uniformly reported. We could not ascertain information about conflicts of interest for nine studies,^{33,34,36–40,42,47} indicating the need for authors and journals to be more transparent. In addition, nine studies did not specify whether and how they considered the physical, social, economic, and cultural environment of the AI/AN stakeholders and participants,^{33,35–37,40,42,43,45,46} making it challenging to evaluate the context and implications for AI/AN communities.

Barriers associated with HPV vaccination.

We have summarized barriers and factors related to and unrelated to HPV vaccination in concise (Table 3) and detailed (Supplementary File C) tables.

TABLE 3.

Summary of barriers and factors associated with HPV vaccination among American Indians and Alaska Natives.

HPV vaccination	Population	Themes (n)*	Key Findings	Studies
Barriers
	Parents
		Safety (n=7)	Parents or caregivers expressed concerns about side effects and long-term safety.	Bowen (2014), Jacobs-Wingo (2017), Jim (2012), Kashani (2019), Schmidt-Grimminger (2013), Toffolon-Weiss (2008), Winer (2016)
		Knowledge (n=6)	Parents or caregivers lacked awareness and knowledge of the HPV vaccine. They also expressed confusion and misconceptions about the HPV vaccine.	Bowen (2014), Bruegl (2016), Duvall (2012), Jacobs-Wingo (2017), Kashani (2019), Winer (2016)
		Sexual activity (n=5)	Some parents or caregivers believed that the HPV vaccine increases sexual activity. Some parents refused the vaccine because they believed that their child was not sexually active, while some parents believed that their child was already sexually active.	Jacobs-Wingo (2017), Jim (2012), Schmidt-Grimminger (2013), White (2018), Winer (2016)
		Mistrust (n=4)	Parents expressed mistrust of the HPV vaccine and the medical system.	Bowen (2014), Duvall (2012), Toffolon-Weiss (2008), White (2018)
		Vaccine efficacy (n=2)	Parents expressed concerns about the efficacy of the HPV vaccine.	Bruegl (2016), Jim (2012)
		Cost (n=1)	Physician perceived barriers to vaccination uptake included concerns about vaccine cost.	Bruegl (2016)
		Clinic access issues (n=1)	One of the top five barriers to vaccination was clinic access issues.	Jacobs-Wingo (2017)
		Moral or religious reasons (n=1)	57% of providers from I/T/U facilities reported that parent opposition to the vaccine was for moral or religious reasons.	Jim (2012)
	Young adults
		Knowledge (n=3)	College students and young adults showed a lack of knowledge about HPV and HPV vaccine.	Bowker (2017), Hodge (2014), Hodge (2011)
		Cultural barriers (n=2)	Some college students explained that discussing HPV may be considered taboo culturally.	Hodge (2014), Hodge (2011)
		Risk perception (n=2)	Some college students held poor personal risk perception, and getting vaccinated against HPV was not seen as important.	Hodge (2014), Hodge (2011)
		Safety (n=1)	Female college students reported the fear of short- or long-term side effects.	Hodge (2011)
		Funding (n=1)	Providers from I/T/U facilities reported funding to be the main barrier for young adults.	Jim (2012)
		Access issues (n=1)	College students shared that not all American Indian persons have access to IHS clinics or providers due to distance or rural location.	Hodge (2011)
	Adolescents
		Side effects (n=1)	Older Alaska Native teens were concerned about the vaccine side effects.	Kemberling (2011)
		Vaccine efficacy (n=1)	Older Alaska Native teens cited doubts about vaccine efficacy.	Kemberling (2011)
		Afraid of shots (n=1)	Younger Alaska Native teens reported that being afraid of shots was the reason for not wanting to be vaccinated.	Kemberling (2011)
	Healthcare providers
		Provider recommendation (n=2)	Lack of provider recommendations were reported as important barriers to vaccination.	Kashani (2019), Schmidt-Grimminger (2013)
		Resource constraints (n=1)	IHS providers reported lack of time and provider shortages as potential barriers.	Schmidt-Grimminger (2013)
		Funding (n=1)	Some clinics cited an overall lack of funding as a barrier to administering the HPV vaccine.	Duvall (2012)
Factors
	Parents
		Provider trust (n=1)	Healthcare provider influence and trust (39%) was the most important factor for receiving the HPV vaccination.	White (2018)
		HPV vaccine education (n=1)	Mothers who received an HPV vaccine education intervention were more likely to initiate HPV vaccination (adjusted RR: 2.6; 95% CI: 1.4, 4.9) compared with the control group.	Winer (2016)
		HPV knowledge (n=1)	Parents’ level of HPV knowledge was associated with willingness to vaccinate their child against HPV (OR: 1.2–1.5; p<.00–.05).	Buchwald (2013)
	Young adults
		Provider trust (n=1)	Healthcare provider influence and trust (36%) was the most important factor for receiving the HPV vaccination.	White (2018)
		Cultural practices (n=1)	Lakota women aged 18–25 who participated in the Hunkapi (Making of Relative) were two and a half times more likely to receive the HPV vaccine (OR: 2.58; 95% Cl: 1.07, 6.62).	Bowker (2017)
	Healthcare providers
		None
Factors not found to be associated
	Young adults
		Ceremonial practices (n=1)	Some ceremonial practices among Lakota women aged 18–25 were not associated with HPV vaccination.	Bowker (2017)
		Language (n=1)	Speaking or understanding the Lakota language was not associated with HPV vaccination.	Bowker (2017)

Abbreviations:

AN, Alaska Native; AI, American Indian; HPV, human papillomavirus; IHS, Indian Health Service; I/T/U, IHS, Tribal and Urban Indian.

Notes:

^*Indicates number of studies.

Twenty-one unique barriers to HPV vaccination were reported across 15 themes at the individual (n=12) and clinic or provider (n=3) levels. The most common barriers to vaccination—safety concerns^{33,37–39,41,44–47} and lack of knowledge^{33,34,36,37,41–44,46} about the HPV vaccine—were each reported in the highest number of studies (n=9; 60%). In these studies, AI/AN parents, young adults, and adolescents expressed concerns about the side effects and long-term safety of the HPV vaccine. They also lacked knowledge about the HPV vaccine, including lack of awareness, confusion, and misconceptions about the vaccine. For example, in a survey of Lakota women aged 18 to 25 years, 42.7% of participants believed that the HPV vaccine is only available for women, and 21.3% thought it was only for women under 18.³⁴ Among other commonly noted barriers, AI/AN parents expressed mistrust of the vaccine and medical system in four studies^33,39,40,43 and believed that the HPV vaccine could encourage earlier or riskier sexual behavior in three studies.^44,45,47

At the provider or clinic level, studies reported funding issues or resource constraints as barriers.^43,47 In a survey of 31 tribal and IHS clinics, 39% cited an overall lack of funding as a barrier to administering the HPV vaccine.⁴³ In another study, IHS providers reported lack of time and provider shortages as potential barriers for vaccine administration.⁴⁷

Factors associated with HPV vaccination.

We identified four studies elucidating factors associated with HPV vaccination across four themes: HPV knowledge,³⁵ HPV education,⁴¹ provider trust,⁴⁰ and cultural practices.³⁴ First, HPV knowledge is an essential factor for vaccination. In a survey of rural AI women in the Northern Plains, knowledge about HPV was associated with willingness to vaccinate their child, underscoring the influence of educational interventions to increase vaccination rates.³⁵ Mothers who received educational presentations on HPV as a part of a cluster-randomized trial were more likely to initiate (adjusted RR: 2.6; 95% CI: 1.4, 4.9) and complete (adjusted RR: 4.0; 95% CI: 1.2, 13.1) HPV vaccination in their daughters.⁴¹ In addition, 39% of parents and 36% of young adults in a focus group cited healthcare provider influence and trust as the most important factor for receiving the HPV vaccine.⁴⁰

Factors not associated with HPV vaccination.

Among Lakota women aged 18 to 25 years, participating in ceremonial practices, such as Hunkapi (making of relative), increased the likelihood of HPV vaccination (odds ratio [OR]: 2.58; 95% Cl: 1.07, 6.62).³⁴ However, other ceremonial practices, such as Inipi (rite of purification), Isnati (womanhood ceremony), and Wiwanyag Wachipi (Sundance), were not associated with HPV vaccination.³⁴ In the same population, speaking or understanding the Lakota language was not associated with HPV vaccination.³⁴

DISCUSSION

This systematic review provides an extensive synthesis of evidence to identify and summarize the barriers and factors to HPV vaccination at the individual and clinic level among AI/AN persons in the US. The results of this review revealed several barriers in this population, the most prominent of which were safety concerns, lack of knowledge about the vaccine, and medical and vaccine mistrust.

We found that concerns about safety and side effects are a major obstacle to HPV vaccination; this finding is consistent with systematic reviews in other populations.^7,49–54 In previous reviews, adolescents,^7,51,52 young adults,^7,50 parents,^49,53 and racial and ethnic minorities⁵⁴ have shared safety concerns about the HPV vaccine, all of whom perceive it as an impediment to vaccination. Furthermore, in line with other systematic reviews,^9,51–54 we found a lack of awareness and knowledge coupled with confusion and misconceptions about the HPV vaccine. HPV and HPV vaccine knowledge is associated with vaccination, as seen in one of the studies included in the review.³⁵ In addition, an HPV educational presentation directed at Hopi mothers led to a higher HPV vaccine initiation and completion rate among their daughters.⁴¹ Therefore, to address the knowledge gaps and safety concerns, the development and dissemination of strong public health education campaigns tailored to the population are critical.

Another prominent reason for non-vaccination was medical and vaccine mistrust, which extended to drug companies, healthcare providers, and overall medical professionals in one study.³³ Mistrust among AI/AN communities stems from multiple factors and has roots in historical events, including historical trauma and distrust.^33,55 Therefore, it is critical for healthcare and public health systems and professionals to engage, address the long-standing historical and contemporary concerns, and establish trust with AI/AN communities.⁵⁶ Building and maintaining trust will also translate into higher vaccination coverage, as seen in a study involving AI/AN parents of adolescent children, who reported that healthcare provider influence and trust was the most important factor for receiving the HPV vaccination for their children.⁴⁰

Additionally, the cost of the HPV vaccine has been reported as a barrier in other systematic reviews.^5,6 However, barring one study in our review,⁴² we did not find vaccination costs to be a barrier to HPV vaccination, primarily because the AI/AN persons can receive the HPV vaccine at no cost and are entitled to federally funded health care under treaties negotiated between Tribal Nations and the US government. HPV vaccines are often funded through the Vaccines for Children (VFC) program.

Limitations

Per PRISMA 2020 guidelines,²⁵ limitations of this systematic review include limitations related to the included studies and the review process itself. The evidence from studies included in our review are subject to at least five limitations. First, based on the assessment using the modified MMAT, the quality of the studies included in our review was variable, highlighting methodological concerns. For example, most quantitative studies failed to adequately address the potential for selection bias and measurement error. Similarly, some qualitative studies did not use a theoretical framework or apply theory to inform the study design. Second, the reporting in some of the studies was inadequate, which limited our assessment. Specifically, some studies did not adequately describe study limitations, discuss ethical concerns, or describe how tribal communities were engaged as partners in the design and conduct of the research. Third, close to half of the studies included in our review were conducted before 2010, which may influence our results about vaccine knowledge, as these studies were completed only a few years after the vaccine’s introduction in 2006. As barriers or factors to HPV vaccination may evolve, we did not emphasize evidence found in newer studies compared with older studies. Fourth, although we did not assess for publication bias, only one study in our review reported factors that were not associated with HPV vaccination. Lastly, our research question did not allow us to differentiate between those who were hesitant and those who refused the HPV vaccine, as these differences may require different approaches and interventions.

Our review process also has some limitations that merit consideration. First, we excluded studies that included AI/AN populations, but did not provide data on barriers or factors by AI/AN status. Second, we could not report a pooled proportion of HPV vaccination among AI/AN adolescents due to missing coverage estimates and varying age groups and study participants. Third, information regarding our outcomes and key characteristics was unavailable for some studies; however, we did not contact the authors to obtain this information or seek further clarification. Lastly, and more importantly, we combine AI and AN persons into a single category of AI/AN in this review. In doing so, we are combining culturally and geographically distinct groups, which differ in traditions, languages, lifestyles, and laws. Aggregating AI and AN persons may mask important differences in HPV vaccination barriers and factors unique to each population, highlighting the value of examining these groups separately. The disaggregation of data in other U.S. populations, such as Asian American and Native Hawaiian and Pacific Islander (NHPI) persons, has shown variation in cancer risk factors and outcomes.⁵⁷ For example, when data on HPV vaccine initiation was disaggregated for Asian and NHPI women, it was found that adult Asian women aged 18 to 26 years reported a higher HPV vaccine initiation than adult NHPI women.⁵⁸ Our review does not disaggregate AI groups from AN groups and fails to capture the diversity and heterogeneity between and within AI and AN communities. Therefore, our findings need to be interpreted in this context, thus limiting the generalizability of this review.

Conclusions

Identifying and understanding barriers and factors associated with HPV vaccination can increase vaccination coverage and ultimately reduce the incidence of HPV-associated cancers. Evidence from this review provides priority areas for improving HPV vaccination coverage in AI/AN persons, such as safety concerns and lack of vaccine knowledge. Our findings also signal the need for health systems, providers, and public health professionals to establish or strengthen trust with AI/AN communities. Additionally, and closely related, any intervention aimed at benefiting an AI/AN community must be sensitive to its culture and tradition to ensure engagement and adoption of HPV vaccination. Failure to do so may increase vaccine hesitancy and widen health disparities in this population.