The issue of vaccine hesitancy is not a new one. For as long as there have been vaccines, there have been skeptics who distrusted the efficacy and safety of vaccination, and who have shared misinformation about their value. Celebrities such as Jenny McCarthy (Gottlieb, 2016; Largent, 2012) and news media norms of balance have given such skeptics increased attention (Clarke, 2008; Dixon and Clarke, 2013). Such misinformation can be a major driver of vaccine hesitancy (Enders et al., 2022; Lee et al., 2022). We define misinformation as any information that counters the current best evidence and expert consensus on the topic (Vraga and Bode, 2020; see also Nyhan and Reifler, 2010; Southwell et al., 2022). Given the strong scientific and medical consensus on vaccines, there is often a clear distinction between what is true versus false (i.e., misinformation).

What makes recent years unique in terms of vaccine hesitancy and the spread of misinformation is the emergence of social media. Social media allows for a democratization of voices, with user-generated content appearing alongside (and often with equal prominence to) official scientific and medical voices. Social media, moreover, can be both insular and porous, allowing diverse views to compete, but also for individuals to often identify and interact primarily with those who share their views (Jones-Jang and Chung, 2022; Schmidt et al., 2018), a phenomenon that has been called the ‘echo chamber.’ Thus, misinformation can often live much longer in sheltered corners of social media than it might if subjected to greater public scrutiny. Existing studies have demonstrated that many social media platforms are rife with vaccine misinformation (Suarez-Lledo and Alvarez-Galvez, 2021), which is concerning because misinformation often outperforms accurate information in terms of popularity and reach (Vosoughi et al., 2018). For these reasons, the WHO included vaccine hesitancy as one of the top 10 health challenges facing the globe in 2019, even before the emergence of COVID-19 upended public health (WHO, 2019).

COVID-19 created a perfect storm in terms of preexisting vaccine hesitancy and a media environment that was well suited to amplify concerns and misinformation about the development of a COVID-19 vaccine that did not have decades of clear evidence of its specific safety and efficacy. For those who have been engaged in understanding and reducing vaccine hesitancy toward other vaccines, this raises two questions. First, is hesitancy towards the relatively new COVID vaccine – which was developed based on decades of evidence for other vaccines – associated with hesitancy toward other, more established vaccines? Second, is exposure to COVID-19 vaccine misinformation on social media associated with hesitancy toward other vaccines?

We answer these questions in the context of the human papillomavirus (HPV) and hepatitis B (HBV) vaccines because the former has been received with hesitancy by some segments of the public (Saulsberry et al., 2019), as was COVID-19. This is due in part to the politicization of these vaccines. We also include HBV vaccination to determine whether the impact extends to other cancer-related vaccines.

For our first research question, namely whether COVID-19 vaccine hesitancy, intention, or uptake (COVID constructs) are empirically associated with HPV or HBV vaccine hesitancy, intention, or uptake (HPV or HBV constructs), only 7 of the 322 reports reviewed met our criteria. All studies were cross-sectional in nature and examined the associations between hesitancy, intention, or uptake for COVID-19 and HPV vaccines, but not the HBV vaccine. Five of the seven studies found significant associations after adjustment for covariates (i.e., potential confounders), and one found an association in unadjusted analyses.

Three of seven cross-sectional studies framed their questions in terms of whether COVID-19 constructs impacted HPV constructs. In January 2021, Shimizu et al., 2022 conducted a survey of 1257 Japanese caregivers with daughters aged 12–16 y, recruited via a registered research panel. Among other potential determinants of intention to obtain the HPV vaccine for one’s child, the authors measured intention to obtain a COVID-19 vaccine for their child and oneself once the vaccine became available if side effects were ‘common’ (i.e., not serious). Models were adjusted for demographics, health literacy, media contact, and perceptions and beliefs. Odds of HPV vaccine intention were higher among caregivers who intended to vaccinate their child (odds ratio [OR] = 4.16, 95% CI: 2.79–6.19) and themselves (OR = 1.96, 95% CI: 1.29–3.00) against COVID-19. In March 2021, Tsui et al., 2023 conducted a survey of 357 parents of adolescents aged 9–17 y who were participating in an academic enrichment program for low-income, first-generation, racial or ethnic minority families in Los Angeles, CA, USA. Among other potential determinants of HPV vaccine hesitancy, the authors measured intention to obtain a COVID-19 vaccine for their children once it became available. In unadjusted models, the odds of HPV vaccine hesitancy were higher among parents who reported being only somewhat likely (OR = 1.58, 95% CI: 0.75–3.31), not too likely (OR = 2.86, 95% CI: 1.16–7.05), or not likely at all (OR = 15.7, 95% CI: 4.45–55.70) to get their children vaccinated against COVID-19, relative to parents who were very likely to do so. Only the latter association remained significant in models adjusting for covariates, including medical mistrust and exposure to negative information about the HPV vaccine. COVID-19 vaccine intent for children was not associated with HPV vaccine initiation for the youngest child in the family. Using electronic health record data as of November 2021, Coronado and colleagues (2023) examined the association between initiation of the COVID-19 and HPV vaccines among over 40,000 Kaiser Permanente Northwest members aged 12–17 y who lived in Oregon or southwest Washington, USA. Adjusting for age, sex, race, ethnicity, insurance status, urban/rural status, and having a clinic visit in the past year, having initiated the COVID-19 vaccine was associated with greater odds of having initiated the HPV vaccine (OR = 4.01, 95% CI: 3.80–4.23). Not surprisingly, given the cross-sectional study design, having initiated the HPV vaccine also was associated with greater odds of having initiated the COVID-19 vaccine (OR = 4.02, 95% CI: 3.81–4.24).

Four of the cross-sectional studies exclusively framed their questions in terms of whether HPV constructs impacted COVID-19 constructs but were again cross-sectional in nature. Between November and December 2020, Berenson et al., 2021 surveyed 342 women aged 18–45 y who were recruited from reproductive clinics in South Texas, USA. Adjusting for other factors, women had greater intention to receive a doctor-recommended COVID-19 vaccine if they had previously received the HPV vaccine (OR = 2.26, 95% CI: 1.07–4.79). Between March and April 2021, Phan et al., 2022 conducted a survey of 513 caregivers recruited from a pediatric healthcare system in the mid-Atlantic United States. Caregivers were diverse with respect to race, ethnicity, socioeconomic status, and rurality/urbanity. History of child’s receipt of at least one dose of the HPV vaccine if aged 13–20 y was not associated with caregiver intention to vaccinate their children against COVID-19. Between February and March 2021, Kecojevic and colleagues (2021) surveyed 457 students attending a public university in New Jersey, USA. In unadjusted analyses, being vaccinated against ‘other infectious diseases,’ with HPV given as an example, was not associated with being vaccinated against COVID-19; however, this variable was associated with greater intention to become vaccinated against COVID-19 (OR = 2.84, 95% CI: 1.84– 4.37). This association became nonsignificant when adjusting for covariates. Between November and December 2021, Ogaz and colleagues (2023) recruited 1039 UK men who have sex with men aged 16 and older from social networking and dating applications to complete surveys. Known HPV vaccination was associated with completed COVID-19 vaccination (OR = 3.32, 95% CI: 1.43–7.75), adjusting for age, ethnicity, gender, sexual orientation, education, employment, relationship status, risk for severe COVID-19 illness based on a medical condition, COVID-19 infection, and self-worth.

Two additional studies did not fully meet criteria for our first research question because they lacked a statistical comparison of the relationship between COVID-19 and HPV (or HBV) constructs, but did not explore COVID-19 and HPV constructs in relation to one another. In each study, parents were recruited via an online research panel. Between September and October 2020, Olagoke et al., 2022 conducted a survey of 342 parents of adolescents aged 11–17 y who had never been vaccinated against HPV. To meet eligibility criteria, parents had to identify as Christian and live in the United States. In regression analyses adjusting for sociodemographic variables, perceived vulnerability of one’s child to HPV (β = 0.32, 95% CI: 0.21–0.44) and perceived response efficacy of the HPV vaccine (β = 0.41, 95% CI: 0.28–0.53) were independently associated with greater intent to vaccinate one’s child against COVID-19, while perceived severity of HPV was not associated with this outcome (β = 0.16, 95% CI: –0.01 to 0.32). All three HPV constructs – perceived vulnerability of one’s child to HPV (β = 0.37, 95% CI: 0.25–0.48), perceived response efficacy of the HPV vaccine (β = 0.46, 95% CI: 0.33–0.59), and perceived severity of HPV (β = 0.21, 95% CI: 0.05–0.38) – were independently associated with parents’ intention to vaccinate oneself against COVID-19. Although intention to vaccinate one’s child against HPV was measured, it was not examined as a predictor of COVID-19 vaccination intentions. In the second study, performed in August 2021, Manganello et al., 2023 conducted a survey of 452 parents of children aged 9–14 y living in different communities across the United States. Among parents who would be likely to vaccinate their child against COVID-19, 75% would also be likely to vaccinate their child against HPV. Conversely, among parents who would be likely to vaccinate their child against HPV, 58% would also be likely to vaccinate their child against COVID-19. Although no statistical test was conducted, results suggested that there was greater hesitancy for the COVID-19 vaccine than the HPV vaccine among parents who were accepting of the contrasting vaccine.

Turning to our second research question, our review found that none of the 72 studies reviewed met all three criteria for our second research question, that is, whether exposure to COVID-19 vaccine misinformation on social media was associated with HPV or HBV vaccine hesitancy, intention, or uptake. Studies identified as potential candidates by our literature search generally described COVID-19 vaccine misinformation on social media, without examining whether exposure to misinformation on social media was associated with HPV or HBV vaccine hesitancy, intention, or uptake among individuals within social media networks.

Our research suggests that there is a dearth of published peer-reviewed research studies addressing the question of whether COVID-19 vaccine hesitancy or misinformation spills over to hesitancy toward HPV/HBV vaccines. In our review of studies containing keywords related to both COVID-19 and HPV or HBV vaccine hesitancy, intention, or uptake (RQ1), only seven studies examined the empirical association between COVID-19 and HPV constructs. Moreover, these studies were all cross-sectional in nature, so that any association between vaccine hesitancy, intention, or uptake for both vaccines that was uncovered does not inform the directionality of this effect. However, knowing there is a relationship between hesitancy, intention, or uptake for the COVID-19 and HPV vaccines is instructive. This suggests that there is a potential spillover that should be examined through longitudinal research. Since COVID-19 vaccine has been politicized in the United States (Motta, 2021), it is important to further our understanding of how COVID-19 vaccine hesitancy may not only be associated with but also impact attitudes toward other vaccines, including those that protect against cancer. Of note, no studies tested the association between COVID-19 constructs and HBV constructs.

Additionally, there were no peer-reviewed studies that explored the empirical association between exposure to COVID-19 misinformation on social media and HPV and HBV hesitancy, intention, or uptake (RQ2). This lack of research is very concerning, especially since so much of the populace relies on social media as a primary information source (Pew, 2022), and social media use is associated with vaccine hesitancy for multiple vaccines (Dunn et al., 2017; Jennings et al., 2021). This area is prime for new empirical research, and such findings can inform policymaking and regulations to ensure that social media platform policies address health information to promote public health. In addition, previous research in other domains (e.g., climate change) has found that there can be a reinforcing spiral between science skepticism and information consumption behaviors over time (Feldman et al., 2014). Thus, those who are skeptical of vaccines may seek confirmation of their (inaccurate) beliefs and become even more skeptical over time, as predicted by the ideological health spirals model (Young and Bleakley, 2020).

Additional research directions

Innovative, ongoing work in computational methods, epidemiology, and communication research can be leveraged to understand vaccine spillover effects (e.g., COVID-19 vaccine hesitancy leading to HPV hesitancy) and how social media misinformation may contribute to such spillover. For example, we need more sophisticated methods to map how misinformation, refutation of misinformation, and accurate information about different vaccines propagates through a social network. One method is to form a tree structure with an initial source of information depicted as the root (Figure 1; Ma et al., 2017; Wu et al., 2015). Individuals who share misinformation, refutation of misinformation, and accurate information are depicted through different colors throughout the tree structure. Different actors within the social networks may choose to further spread misinformation, refute misinformation, or deliver accurate information. Those who refute misinformation are of particular interest. These are the individuals who may be able to interrupt the spread of misinformation within a network.

Figure 1

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To our knowledge, however, investigators have not examined the spread of both vaccine misinformation and refutation in a social network, and whether exposure to both types of information influences vaccine hesitancy, intentions, or uptake. Given the pervasiveness of social media, and the reliance on one’s social media network members to inform decision-making, this type of research is urgently needed. In addition, based on our review, investigators have not attempted to link exposure to COVID-19 vaccine misinformation in a social media network to individual-level HPV or HBV vaccine hesitancy, intention, or uptake.

Other future research directions could involve exploring differences in the spread of misinformation on different social media platforms, testing individual and community differences in vulnerability to misinformation spread through social media, and modeling the impact of exposure to misinformation for one vaccine on hesitancy for other vaccines. For example, does the social media platform (e.g., Twitter, Facebook, Instagram, TikTok) impact vaccine hesitancy differently? Does COVID-19 misinformation impact its recipients in different ways depending on the source from which they received it? Are some people more susceptible to believing vaccine misinformation and how can we assess their vulnerability? What is the direction of spillover with respect to hesitancy for two vaccines (e.g., COVID-19 vaccine hesitancy impacting HPV vaccine hesitancy or vice versa)? Putting these pieces together involves developing and testing a comprehensive model that includes social media exposure, vaccine hesitancy, and vaccine uptake for multiple vaccines. Ideally, data would be collected over an extended period of time.

In conclusion, our systematic review underscores the need for longitudinal research examining potential spillover effects between hesitancy for different vaccines. This is especially urgent with new vaccines in development to prevent or treat cancer, where uptake can save lives (Winstead, 2022). Additionally, our review did not identify any studies that empirically examined whether COVID-19 vaccine misinformation on social media relates to HPV or HBV vaccine hesitancy, intention, or uptake. Tracking people’s interaction with misinformation on social media, and its refutation, holds promise for providing novel insights into which people are active participants in misinformation spread, and which are active in stopping its spread (Khan et al., 2023). This understanding can help in developing strategies to encourage vaccine uptake by suppressing the efforts of those who spread misinformation and accelerating the efforts of those who spread the truth. Such prevention strategies are only likely to be effective when there is a foundation of rigorous research to guide efforts.

A systematic literature review was conducted via the Ovid Medline and APA PsychInfo databases. These public databases cover published studies associated with biomedicine and health (Ovid Medline) and psychological, social, and behavioral sciences (PsychInfo). We developed a multistep search strategy (see Table 1) to identify the articles that potentially met the criteria to answer two research questions: (1) Is COVID-19 vaccine hesitancy, intention, or uptake associated with HPV or HBV vaccine hesitancy, intention, or uptake? (2) Is exposure to COVID-19 vaccine misinformation on social media associated with HPV or HBV vaccine hesitancy, intention, or uptake? Search steps #1–5 each consisted of keywords for one dimension of the research questions (e.g., mis-/disinformation; social media). The bottom two rows of Table 1 show how steps #1–5 were used in combination to address the research questions. Two members of the research team independently completed the multistep search in each database and achieved consistent results on October 22, 2022. A bridge search was performed in June 2023 to incorporate all published articles through May 31, 2023. Search steps for the first research question yielded 398 total records (PsychInfo, n = 314; Medline, n = 84); search steps for the second research question yielded 95 total records (PsychInfo, n = 88, Medline: n = 7) (see Table 1).

Figure 2 summarizes the process of identifying relevant peer-reviewed articles using terminology from the 2020 PRISMA guidelines. Record refers to the title and/or abstract of an article indexed in a database, whereas report refers to the electronic document containing detailed information about a study (e.g., a journal article, dissertation, etc.) (Page et al., 2021).

Figure 2 with 2 supplements see all

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For the first research question, 380 reports were eligible for assessment after removing duplicate (n = 8) or incomplete (n = 9) records and one report that was unable to be retrieved. To meet the criteria for inclusion, the full paper was reviewed to ensure that the study was an empirical study published in an academic journal and (1) measured COVID-19 vaccine hesitancy, intention, or uptake; (2) measured HPV or HBV vaccine hesitancy, intention, or uptake; and (3) tested the statistical association between both measures. For the purposes of this review, we defined an empirical study as one that had measures of observable data. Based on these criteria, a further 56 reports were excluded that were commentaries, reviews, opinion pieces, book chapters, simulation modeling, meta-analyses, or animal studies. Two additional studies were removed that were non-English-language reports, leaving a total of 322 articles classified as eligible for full review. The reports were divided among seven members of the research team to code independently after first meeting to discuss assessment criteria and reaching consensus on the first 16 reports.

For the second research question, 90 reports were eligible for assessment after removing duplicate records (n = 4) and a retracted article (n = 1). To meet the criteria for inclusion, a study had to be an English-language empirical study published in an academic journal and (1) measure exposure to COVID-19 vaccine misinformation (or disinformation, conspiracy theories, rumors, or fake news) on social media; (2) measure HPV or HBV vaccine hesitancy, intention, or uptake; and (3) test the statistical association between both measures. Based on these criteria, a further 18 reports were excluded, leaving a total of 72 articles classified as eligible for full review. Two members of the research team coded all remaining 72 articles after five members of the research team first met to discuss assessment criteria and reach consensus on reports.

Data regarding the articles reviewed is available at: https://doi.org/10.5061/dryad.fttdz08zw.

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Decision letter after peer review:

Thank you for submitting your article "HPV and HBV vaccine hesitancy, intention and uptake in the era of social media and COVID-19: A review" for consideration by eLife. Your article has been reviewed by 2 peer reviewers, and I oversaw the evaluation in my dual role of Reviewing Editor and Senior Editor. The reviewers have opted to remain anonymous.

Essential revisions:

As is customary in eLife, the reviewers have discussed their critiques with one another and with the Editors. The decision was reached by consensus. What follows below is my edited compilation of the essential and ancillary points provided by reviewers in their critiques and in their interaction post-review. Please submit a revised version that addresses these concerns directly. Although we expect that you will address these comments in your response letter, we also need to see the corresponding revision clearly marked in the text of the manuscript. Some of the reviewers' comments may seem to be simple queries or challenges that do not prompt revisions to the text. Please keep in mind, however, that readers may have the same perspective as the reviewers. Therefore, it is essential that you amend or expand the text to clarify the narrative accordingly.

Reviewer #1:

This study reviews the literature on cancer vaccine hesitancy in relation to more recent COVID-19 vaccine hesitancy. The review is sound and the conclusions are warranted.

Recommendations for the authors:

Be sure to highlight the fact that many studies are not causal, meaning that it remains very unclear if exposure to misinformation causes anti-vaxx or misinformed beliefs, and it remains unclear if false beliefs lead to vaccine refusal. People could be seeking out and believing ideas that comport with actions they would have taken anyway. There has been a well-organized anti-vaxx movement for more than twenty years and many people were vaccine-hesitant long before COVID and HPV vaccines.

Reviewer #2:

This paper presents a review to address questions of COVID-19 vaccine hesitancy and its relationship to HPV and HBV vaccine hesitancy, in addition to the influence of social media misinformation on vaccine intentions and uptake. While these are important issues to be addressed, there are several methodological constraints that limit the overall impact of the findings and conclusions. The review search strategy is limited to public databases, Psychinfo and Medline. Other databases could have been addressed as well. A better-defined systematic review would have more clearly defined the search strategy. There is no mention of following PRISMA guidelines. The search strategy as presented lacks details, such as the procedure or individual records. Were titles and abstracts removed as a first step prior to final record selection? These gaps may ultimately have led to the few articles meeting the inclusion criteria for the first question and no articles addressing the second question. In the Results section, a brief description of several studies' limitations was provided, but in the methods, it was indicated that cross-sectional correlational studies were to be targeted, but the lack of longitudinal studies was highlighted as a significant gap. The Discussion section is short on implications and more of a 'Future Directions'. Finally, there is an extensive Future Research Directions on the role of social media that is based on no findings from the systematic and more of a polemic on its role in facilitating the dissemination of misinformation on vaccines. While this is interesting, the model presented in Figure 2 on the links among misinformation propagators and refuters does not really add to the overall impact of the paper, which should be based on the findings.

Recommendations for the authors:

1. Introduction could be more concise and pointed, and many of the statements made are not directly relevant to the research questions.

2. Expand the search strategy using consultation from a librarian and under PRIMA guidelines and registration. This will strengthen the fundamental search strategies and might aid in modifying the two objectives of the study.

3. The Methods should be more clearly defined in a stepwise fashion, e.g., including first a title and abstract screening to identify articles for full-text review.

4. Be clear in the limits of your investigation- only cross-sectional studies and/or longitudinal studies and support these inclusion criteria.

5. In the discussion, please ensure that the implications of summarized studies are made clear, especially regarding any studies ultimately discovered regarding the role of social media information if found in a more expanded systematic review.

6. Finally, ensure that the future directions are based soundly on the findings and any additional innovative ideas that spring from the author's own insights or experience.

Essential revisions:

As is customary in eLife, the reviewers have discussed their critiques with one another and with the Editors. The decision was reached by consensus. What follows below is my edited compilation of the essential and ancillary points provided by reviewers in their critiques and in their interaction post-review. Please submit a revised version that addresses these concerns directly. Although we expect that you will address these comments in your response letter, we also need to see the corresponding revision clearly marked in the text of the manuscript. Some of the reviewers' comments may seem to be simple queries or challenges that do not prompt revisions to the text. Please keep in mind, however, that readers may have the same perspective as the reviewers. Therefore, it is essential that you amend or expand the text to clarify the narrative accordingly.

Reviewer #1:

This study reviews the literature on cancer vaccine hesitancy in relation to more recent COVID-19 vaccine hesitancy. The review is sound and the conclusions are warranted.

Recommendations for the authors:

Be sure to highlight the fact that many studies are not causal, meaning that it remains very unclear if exposure to misinformation causes anti-vaxx or misinformed beliefs, and it remains unclear if false beliefs lead to vaccine refusal. People could be seeking out and believing ideas that comport with actions they would have taken anyway. There has been a well-organized anti-vaxx movement for more than twenty years and many people were vaccine-hesitant long before COVID and HPV vaccines.

We thank the reviewer for these suggestions. We have greatly revised the discussion to clearly state that the cross-sectional nature of our studies does not allow us to discern the directionality of any association between COVID-19 vaccine hesitancy, intention, or uptake, COVID-19 misinformation exposure on social media, and HPV/HBV vaccine hesitancy, intention, or uptake. We acknowledge that people skeptical of vaccines may be seeking out confirmation of their beliefs but also point to existing literature suggesting that this can create a self-reinforcing cycle and that is theorized to apply to COVID-19 behaviors. We believe this represents a more clear theoretical model for any association between vaccine beliefs and online behaviors, as well as reinforces the practical importance of empirically testing this relationship.

In addition, we acknowledge in the introduction of the manuscript that vaccine hesitancy is not new or novel, although we point to the ways in which we think social media may be exacerbating vaccine hesitancy and spillover.

Reviewer #2:

This paper presents a review to address questions of COVID-19 vaccine hesitancy and its relationship to HPV and HBV vaccine hesitancy, in addition to the influence of social media misinformation on vaccine intentions and uptake. While these are important issues to be addressed, there are several methodological constraints that limit the overall impact of the findings and conclusions.

The review search strategy is limited to public databases, Psychinfo and Medline. Other databases could have been addressed as well.

Reviewer #2 expresses concern that our use of only two public databases – PsychInfo and Medline – may limit our results. We deliberately selected these two databases to identify a comprehensive set of studies associated with the topic. Medline is the National Library of Medicine’s leading database, containing citations from 5,200 journals worldwide in biomedicine and health (https://www.nlm.nih.gov/medline/medline_overview.html).

PsychInfo is a top indexing database for psychological, social, and behavioral sciences and is used to supplement the findings from PubMed by capturing research that investigates the psychological factors that play a role in vaccine hesitancy. Studies are often cross-referenced between both databases.

We deliberately selected public (rather than proprietary) databases to ensure the reproducibility of our results. Moreover, this database selection allowed for a more refined search strategy to focus on empirical published peer-reviewed articles, excluding unpublished, grey literature, pre-publications, or dissertations.

We excluded Google Scholar from our database search as it does not offer a clear denominator as part of the search (i.e., it does not show us the total number of studies with text that contains key words), meaning it is unable to follow PRISMA guidelines. Google Search also uses a proprietary algorithm for producing results, which could change without any advance notification and thus undermine the reproducibility of our results.

We have added a sentence to our methods briefly describing why we chose these two databases.

A better-defined systematic review would have more clearly defined the search strategy. There is no mention of following PRISMA guidelines.

We have now clarified in the text (p. 9) that PRISMA guidelines were followed as part of our search and selection strategy. This is also clarified in the legend for Figure 2, which includes the PRISMA table describing the identification of relevant peer reviewed articles for this review.

The search strategy as presented lacks details, such as the procedure or individual records. Were titles and abstracts removed as a first step prior to final record selection? These gaps may ultimately have led to the few articles meeting the inclusion criteria for the first question and no articles addressing the second question.

Thank you for raising this concern. We have clarified the search strategy and review process in the text of the paper and in our figures. Specifically, we note that we carefully reviewed the full text of articles that contained the specified key words from our search strings, as opposed to only reviewing the titles and abstracts of articles. This maximized the likelihood that studies that met our criteria were not overlooked in our review.

In the Results section, a brief description of several studies' limitations was provided, but in the methods, it was indicated that cross-sectional correlational studies were to be targeted, but the lack of longitudinal studies was highlighted as a significant gap.

We have ensured that our methods has no language suggesting that our search was limited to cross-sectional correlational studies. Our search was designed to include all peer reviewed empirical studies that investigated the relationship between COVID-19 and HPV/HBV vaccine hesitancy, intention, or uptake. Our review found that few such studies existed and all were correlational in nature, which we discuss as a limitation of the research.

The Discussion section is short on implications and more of a 'Future Directions'.

We agree with the reviewer than in our previous draft, the implications of the summarized studies were insufficiently described. We have expanded our Discussion section to describe key takeaways from our systematic review for both RQ1 regarding spillover effects between COVID-19 vaccination and HPV/HBV vaccination and RQ2 regarding a possible relationship between COVID-19 misinformation on social media and HPV/HBV vaccination attitudes. We clearly indicate that the first paragraph addresses the implications of our findings for RQ1, while our second paragraph directly relates to RQ2 to facilitate readers’ comprehension of what we see as the main contributions of our review.

Finally, there is an extensive Future Research Directions on the role of social media that is based on no findings from the systematic and more of a polemic on its role in facilitating the dissemination of misinformation on vaccines. While this is interesting, the model presented in Figure 2 on the links among misinformation propagators and refuters does not really add to the overall impact of the paper, which should be based on the findings.

We appreciate this constructive critique. We now more clearly delineate between conclusions that are based soundly on the findings versus ideas that are based on the current work and expertise of authors. Specifically, our discussion first describes future research based on the systematic review to allow us to define necessary future research based on what our systematic review revealed about the state of the literature with regards to vaccine hesitancy and misinformation. We then elaborate on additional research directions to offer more innovative research ideas based on our own expertise in the interdisciplinary fields of computer science, epidemiology, and communication. This includes a shortened and greatly revised description of how we think Figure 1 represents an innovative method for studying the question of the implications of social media misinformation for vaccine attitudes and behaviors. We think these revisions greatly clarify the contribution of our work and thank the reviewer for this suggestion.

Recommendations for the authors:

1. Introduction could be more concise and pointed, and many of the statements made are not directly relevant to the research questions.

We have streamlined the introduction to more narrowly focus on our research questions.

2. Expand the search strategy using consultation from a librarian and under PRIMA guidelines and registration. This will strengthen the fundamental search strategies and might aid in modifying the two objectives of the study.

We appreciate the encouragement to consider the best search strategy approach for our systematic review. We have described the rationale for our decision to limit our searches to the PubMed and PychInfo databases in our response to Reviewer #2, comment 1.

In response to Reviewer #2’s comments, we now more clearly identify our use of PRISMA guidelines in our search strategy. In accordance with best practices, we performed a bridge search through May 31, 2023 to incorporate any materials published between our previous search (on October 22, 2022) and our revisions. Using the same review process as described in the paper, we identified an additional 3 studies for RQ1 that met our criteria of empirically investigating the link between COVID-19 and HPV/HBV vaccine hesitancy, intention, or uptake, and 0 studies for RQ2 that met our criteria of empirically testing the relationship between exposure to COVID-19 vaccine misinformation on social media and HPV/HBV vaccine hesitancy, intention, or uptake.

We have revised the PRISMA figure to reflect the results across both research questions and describe the results of the bridge search in our methods section. Our revised Results section reports on the results of all of these studies identified in both the original and bridge searches.

3. The Methods should be more clearly defined in a stepwise fashion, e.g., including first a title and abstract screening to identify articles for full-text review.

Because our search yielded so few articles that potentially met criteria, there was no need to have a step of only reviewing titles and abstracts. We were able to review to review the full text of all articles that potentially met criteria for research questions one and two. We have revised our methods section to be clearer about our search and review strategy.

4. Be clear in the limits of your investigation- only cross-sectional studies and/or longitudinal studies and support these inclusion criteria.

We have ensured that our methods has no language suggesting that our search was limited to cross-sectional correlational studies. Our search was designed to include all peer reviewed empirical studies that investigated the relationship between COVID-19 and HPV/HBV vaccine hesitancy, intention, or uptake. Our review found that few such studies existed and all were correlational in nature, which we discuss as a limitation of the research.

5. In the discussion, please ensure that the implications of summarized studies are made clear, especially regarding any studies ultimately discovered regarding the role of social media information if found in a more expanded systematic review.

Please see our comments above with regards to the changes to the Discussion section to clarify the implications of our summarized studies.

6. Finally, ensure that the future directions are based soundly on the findings and any additional innovative ideas that spring from the author's own insights or experience.

Please see our comments above about the revisions to the future direction section, with special attention paid to distinguishing between those results based on the findings versus those that are based on our insights and experiences.

Author details

1. Emily K Vraga

   Hubbard School of Journalism and Mass Communication, University of Minnesota, Minneapolis, United States

   Contribution

   Conceptualization, Formal analysis, Supervision, Investigation, Methodology, Writing – original draft, Project administration, Writing - review and editing

   For correspondence

   ekvraga@umn.edu

   Competing interests

   No competing interests declared

   "This ORCID iD identifies the author of this article:" 0000-0002-3016-3869

2. Sonya S Brady

   Division of Epidemiology and Community Health, University of Minnesota School of Public Health, Minneapolis, United States

   Contribution

   Conceptualization, Data curation, Supervision, Investigation, Methodology, Writing – original draft, Project administration, Writing - review and editing

   Competing interests

   No competing interests declared

3. Chloe Gansen

   Hubbard School of Journalism and Mass Communication, University of Minnesota, Minneapolis, United States

   Contribution

   Formal analysis, Investigation, Visualization, Writing – original draft, Writing - review and editing

   Competing interests

   No competing interests declared

4. Euna Mehnaz Khan

   Department of Computer Science and Engineering, College of Science and Engineering, University of Minnesota, Minneapolis, United States

   Contribution

   Formal analysis, Investigation, Visualization, Writing – original draft

   Competing interests

   No competing interests declared

   "This ORCID iD identifies the author of this article:" 0000-0002-0030-7841

5. Sarah L Bennis

   Division of Epidemiology and Community Health, University of Minnesota School of Public Health, Minneapolis, United States

   Contribution

   Formal analysis, Investigation

   Competing interests

   No competing interests declared

6. Madalyn Nones

   Division of Epidemiology and Community Health, University of Minnesota School of Public Health, Minneapolis, United States

   Contribution

   Formal analysis, Investigation

   Competing interests

   No competing interests declared

7. Rongwei Tang

   Hubbard School of Journalism and Mass Communication, University of Minnesota, Minneapolis, United States

   Contribution

   Formal analysis, Investigation

   Competing interests

   No competing interests declared

   "This ORCID iD identifies the author of this article:" 0000-0003-3441-276X

8. Jaideep Srivastava

   Department of Computer Science and Engineering, College of Science and Engineering, University of Minnesota, Minneapolis, United States

   Contribution

   Conceptualization, Supervision, Methodology, Writing - review and editing

   Competing interests

   No competing interests declared

9. Shalini Kulasingam

   Division of Epidemiology and Community Health, University of Minnesota School of Public Health, Minneapolis, United States

   Contribution

   Conceptualization, Formal analysis, Supervision, Investigation, Methodology, Writing – original draft, Project administration, Writing - review and editing

   Competing interests

   No competing interests declared

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