A feasibility study assessing knowledge, vaccine hesitancy, and completion rates of free HPV vaccination in low-income uninsured adults

ABSTRACT

Background: Human Papillomavirus (HPV) vaccination rates remain low in the U.S., particularly among minorities and low-income, uninsured patients. We report preliminary data on a pilot study program providing education and free HPV vaccination at a clinic serving low-income uninsured adults.

Methods: From October 2020 through October 2022, we assessed HPV vaccination knowledge, awareness, and prevalence of hesitancy towards receiving the vaccine among low-income uninsured patients age 18-45. The Parents Attitudes about Childhood Vaccines (PACV) survey was modified and used to evaluate vaccine hesitancy. An educational video on HPV was shown to patients declining vaccination.

Results: 43 patients were enrolled. 69.8% had heard of the HPV vaccine and 85.7% were non-hesitant based on PACV scores of 0-49. Black participants had a statistically significant higher PACV score (more hesitant) than White participants. Familiarity with the HPV vaccine correlated with lower PACV scores. Only 27% completed all three HPV vaccine doses.

Discussion: The availability of an education program together with free HPV vaccination are not sufficient to achieve adequate vaccination rates in low-income, uninsured adults. Innovative, culturally sensitive education and supportive interventions, in addition to access to free HPV vaccination, are warranted in order to improve vaccination rates in this underserved population.

Clinical trials.gov Identifier: NCT04474821

KEYWORDS:

• human papillomavirus (HPV)
• vaccine
• patient education
• disparities
• low-income

Introduction

The Human Papillomavirus (HPV) is a prevalent virus usually causing a self-limiting sexually transmitted infection, affecting approximately 85% of people in their lifetime [1]. In the U.S. alone, approximately 14 million new infections occur yearly [2]. Persistent infections with certain HPV strains are associated with cervical, oropharyngeal, anal, vaginal, vulvar, and penile cancers, making it a serious public health concern worldwide[3]. HPV types 16 & 18 are responsible for more than 90% of HPV-associated cancers [4].

The HPV 9-valent vaccine, Gardasil 9, was approved by the Food and Drug Administration (FDA) in 2014 for females aged 9 through 26 years of age and males aged 9 through 15 for the prevention of genital warts and precancerous lesions associated with the nine most common carcinogenic HPV serotypes [5]. The approval was extended to males ages 16 through 26 in 2015, and to all adults 27 through 45 years of age in 2018 [6]. The Centers of Disease Control and Prevention (CDC) recommends routine HPV vaccination for all adolescents through 26 years of age [7]. Vaccination against HPV is effective at preventing HPV-associated cancers, yet the national HPV vaccination rates remains low in the U.S., with only 58.6% of adolescents being up to date in their HPV vaccinations in 2020 [8,9]. Given the high percentage of adults who are not up to date on HPV vaccination, efforts towards facilitating catch up HPV vaccination among adult (up to age 45) underserved patients are needed.

One impediment to HPV vaccine uptake is lack of awareness [10]. Despite previous national efforts towards increasing awareness about HPV vaccination, there is still low uptake of HPV vaccination in the U.S. [9, 11, 12]. In addition, awareness of HPV among the male population is necessary since the CDC estimates that 72% of all male oropharyngeal cancers are HPV-related [13]. It is imperative to increase HPV knowledge in underserved populations, such as racial/ethnic minorities, low income populations, individuals with low educational attainment, and the uninsured/underinsured, which exhibit lower HPV vaccine completion rates, contributing to the existing disparities in HPV-related cancers outcomes [12,14,15]. There is a need for studies that address the reasons and potential solutions for lack of HPV awareness and higher vaccine hesitancy among these underserved populations.

Vaccine hesitancy is defined as a state of indecision and uncertainty about vaccination before a decision is made to act or not to act. Many factors contribute to higher vaccine hesitancy in populations including the power of digital media platforms, decline in the trust of experts, healthcare education levels, emergence of alternative treatments, and political polarization [16]. In 2019, the World Health Organization (WHO) identified vaccine hesitancy as one of the top ten threats to global health [17]. A validated survey tool to assess vaccine hesitancy is the Parents Attitudes about Childhood Vaccines (PACV), a self-administered survey constructed with qualitative methodology to identify vaccine-hesitant parents [18]. In a systematic review of 116 studies that assessed parental vaccine attitudes and beliefs in childhood vaccination, the PACV was the most used standard questionnaire, highly encouraged for its further use as it encompasses four content domains that are essential to identify vaccine hesitancy: immunization behavior, beliefs about vaccine safety and efficacy, attitudes about vaccine mandates and exemptions, and trust in medical providers [18,19]. We adapted the PACV survey tool to assess vaccine hesitancy in the studied population.

Volunteers in Medicine (VIM) is a free healthcare clinic that serves low-income, uninsured working patients in Jacksonville, Florida. VIM provides healthcare using volunteer physicians, nurse practitioners, nurses, pharmacists, office staff, and students. A previous Mayo Clinic study performed at VIM assessed the awareness and knowledge of HPV, HPV vaccines, and HPV-related cancers among this clinic population. This 2014 study demonstrated a statistically significant lower awareness of HPV (50.3% vs 63.6%) and the HPV vaccine (32.1% vs 62.7%) as compared with the national population (HINTS national study, p < 0.0001) [14]. As a result of this study, VIM and Mayo Clinic collaborated with Merck pharmaceuticals to develop a free HPV vaccination program and an HPV video education program for patients at VIM to increase awareness and acceptance of the HPV vaccine. The study sought to assess the updated level of knowledge and awareness of the HPV vaccine among VIM patients while evaluating for correlation between the PACV score with the willingness to receive and complete free HPV vaccination after an educational video on HPV.

We hypothesized that: (1) the awareness of the HPV vaccine will be lower in males as compared with females and in racial and ethnic minorities compared to White patients, (2) the average PACV score of participants interested in the HPV vaccine will be lower (less hesitancy) than in participants who are not interested in the HPV vaccine, and (3) the acceptance and completion rates of HPV vaccination will increase following an educational video on HPV and HPV vaccination.

Material and methods

Design and setting

This education interventional pilot study was performed at VIM, which serves low-income working uninsured patients who reside or work in Jacksonville, Florida (Duval County), USA. The COVID-19 pandemic affected the recruitment process due to VIM closing for in-person appointments, which led to some recruitments taking place by phone. Patients were accrued from October 19, 2020, through October 6, 2022. Pre-intervention and Post-intervention surveys were completed to determine vaccine hesitancy and the effectiveness of the education intervention.

Process

Initial plans were to recruit 300 patients in person among VIM clinic patients age 18–45 with no history of HPV vaccination, but the recruitment process had to change to via phone as a result of the COVID pandemic, which limited the number of patients who were able to participate in the trial. Eligible patients were identified by VIM personnel and contacted via phone to ascertain their interest in participating in the study. Each participant received information explaining the study via phone with those interested having an in person visit with the study coordinator and a self-administered survey in their language of preference (Spanish or English). The survey assessed knowledge about HPV, HPV-related cancers, and HPV vaccination as well as vaccination hesitancy (PACV survey). Demographic information was also collected from each participant (gender, race/ethnicity, age, marital status, educational level, employment status, number of children). After completing this first survey, the participants observed a short, 3-minute educational program regarding HPV, its risk factors, and HPV vaccination. This educational video was developed by the authors and was presented to the participants immediately after the completion of the initial survey. Following the educational program and during the same visit, a second survey was handed out to verify the participants’ willingness to come back and receive the HPV vaccine. HPV vaccination was provided free to patients as part of a Merck patient assistance program. Mayo Clinic Cancer Center provided to VIM the refrigeration equipment needed to preserve the vaccines. As part of this program, additional Merck products were made available to their VIM patient population for free.

Participants demographics

Adult patients ages 18–45 who attended a clinic appointment at VIM with no history of HPV vaccination were offered participation in this study. The ability to read in English or Spanish was also required. Gender was classified as male or female, and race/ethnicity as either Black, White, Latino or Other Race. Level of education was categorized as high school/GED or less, some college/2-year degree, 4-year college, and more than 4-year college. Income was classified as $30,000 or less, $30,001-$50,000, and $50,001 or more.

Vaccine hesitancy: PACV survey

In the initial survey, there were 15 questions derived from the PACV questionnaire. These questions were scored to assign a PACV score to each participant to assess vaccine hesitancy.For each question, there was a hesitant response, a neutral response, and a non-hesitant response. Hesitant responses were given a score of 2, neutral responses were given a score of 1, and non-hesitant responses were given a score of 0. The raw total PACV score was calculated by summing each item answered as previously published (18). The raw score was then adjusted to a scale of 0–100 using simple linear transformation, accounting for items with missing values, as previously published and previously validated (18). A score from 0–49 was considered non-hesitant, and a score from 50–100 was considered hesitant. Participants with no children were asked to answer the questions related to their children hypothetically.

Analysis

Descriptive data and bivariate analysis were employed for comparison between HPV/vaccine awareness and interest, PACV score, and vaccine hesitancy in terms of the diverse demographic data. In addition, p-values for numeric variables were extracted from Kruskal–Wallis Rank Sum Test. Categorical variables results were taken from the Fisher’s exact test. P-values <0.05 were considered significant. β values, 95% confidence intervals, and p-values were conducted from univariate linear regression models to compare average PACV scores with different participant demographics, including age, sex, race, education level, whether they had children, awarenenss of HPV vaccine and interest in HPV vaccination. β values were interpreted as the change in the mean value of the outcome variable PACV score corresponding to presence of the given variable.

Ethics and consent

This study was approved by the Mayo Clinic Institutional Review Board as a minimal risk study (IRB# 18-010455). Informed consent to participate was obtained from all subjects by Mayo Clinic research personnel. Research personnel reviewed with each subject an IRB approved consent and privacy authorization form in either English and Spanish prior to participation, and after review, was signed by both the subject to document their permission to take part in the research and by the person obtaining consent that the research study was explained and all questions were answered to the best of their ability.

Results

To assess knowledge and awareness regarding HPV and its vaccine, a total of 43 participants were surveyed from the Volunteers in Medicine Clinic (Table 1). From this cohort, 79.1% identified as female and 20.9% identified as male. 39.5% identified as Black or African American, 34.9% identified as White, 14% identified as Latino, and 11.6% identified as other race. The mean age of this 43-participant cohort was 38.5 years with a median of 40 years. More than half had at least some college education, and more than 75% had a household income of less than $50,000. Results found that 38/43 (88.3%) of the participants had heard of HPV, with 78.9% of this group being female. A total of 8/9 (88.9%) of male participants had heard of HPV, and 30/34 (88.2%) of female participants had heard of HPV before. Out of the 5 participants that had not heard about HPV, all had a household income of less than $30,000. Regarding the HPV vaccine, 30/43 (69.8%) participants were knowledgeable about an HPV vaccine. Of the male participants, only (4/9) 44.4% knew of the existence of an HPV vaccine, but 26/34 (60.4%) of female participants were knowledgeable of the HPV vaccine. Of the 13 participants that had not heard of the HPV vaccine, all of them had a household income of less than $50,000. There was a statistically significant association (p = 0.015) between the PACV score and HPV vaccine awareness, where participants who were familiar with the HPV vaccine had more non-hesitant PACV scores compared to participants who were not familiar.

Table 1. Demographics by vaccine awareness.

Variable	Have not heard of vaccine (N = 13)	Have heard of vaccine (N = 30)	Total (N = 43)	P-value
Age				0.791
Median (Range)	40.0 (29.0, 45.0)	40.0 (22.0, 45.0)	40.0 (22.0, 45.0)
Mean (SD)	38.9 (5.4)	38.3 (5.7)	38.5 (5.5)
Gender				0.102
Female	8 (61.5%)	26 (86.7%)	34 (79.1%)
Male	5 (38.5%)	4 (13.3%)	9 (20.9%)
Race				0.962
Black	5 (38.5%)	12 (40.0%)	17 (39.5%)
Latino	2 (15.4%)	4 (13.3%)	6(14.0%)
Other Race	2 (15.4%)	3 (10.0%)	5 (11.6%)
White	4 (30.8%)	11 (36.7%)	15(34.9%)
Education				0.146
High school / GED or less	3 (23.1%)	10 (33.3%)	13 (30.2%)
Some college/2-year degree	7 (53.8%)	8 (26.7%)	15 (34.9%)
4-year college	0 (0.0%)	7 (23.3%)	7 (16.3%)
More than 4-year college	3 (23.1%)	5(16.7%)	8 (18.6%)
Have Children				0.742
No	5 (38.5%)	10 (33.3%)	15 (34.9%)
Yes	8 (61.5%)	20 (66.7%)	28 (65.1%)
Income				0.153
$30,000 or less	11 (84.6%)	16(53.3%)	27 (62.8%)
$30,001-$50,000	2 (15.4%)	9 (30.0%)	11(25.6%)
$50,001 or more	0 (0.0%)	5 (16.7%)	5 (11.6%)
Interested in Vaccine				1.00
No	3 (23.1%)	6 (20.0%)	9 (21.4%)
Yes	10 (76.9%)	23(76.7%)	33 (78.6%)
PACV Score				0.015
Median (Range)	39.0 (7.0, 67.0)	21.5 (0.0, 61.0)	25.0 (0.0, 67.0)
Mean (SD)	38.7 (16.6)	23.4 (17.5)	28.0 (18.5)

In terms of HPV vaccine interest before and after an educational video, only 3 female participants changed their minds (7.1%) following the educational video. Two female participants that expressed disinterest toward the HPV vaccine saw the video and decided to undergo vaccination, but another female participant declined HPV vaccination after seeing the video, having said before the video that she was interested. Of the female participants, 78.8% (26/33) were interested in the vaccine, and 77.8% (7/9) of male participants were interested in the vaccine. Black participants were more likely to decline the vaccine, with 35.3% declining vaccination. All 9 participants that were not interested in the vaccine had an income of less than of less than $50,000.

85.7% of evaluable patients were considered non-hesitant based on PACV scores and 19.4% of this subset (7/36) declined vaccination. A higher percentage (33%, 2/ 6) of participants that were considered vaccine hesitant, declined vaccination. Of the 33 participants that were interested in the HPV vaccine, 48.5% had a PACV scores consistent with least hesitancy with values equal or less than 24, 39.4% had a PACV score in between 25-49, and only 12.1% (4/33) had a PACV score consistent with vaccine hesitancy of more than or equal to 50 (Table 2).

Table 2. Demographics by PACV score.

PACV Score	Vaccine non-hesitant Score 0–49 (% total)	Vaccine hesitant Score 50 or More (% total)
Number of Participants (%)	36 (85.7)	6 (14.3)
	N (%)	N (%)
Sex
Female	28 (77.8)	5 (83.3)
Male	8 (22.2)	1 (16.7)
Race/Ethnicity
Black	15 (41.7)	3 (50.0)
White	12 (33.3)	1 (16.7)
Latino/Hispanic	5 (13.9)	1 (16.7)
Other	4 (11.1)	1 (16.7)
Education
High school/GED or less	13 (36.1)	1 (16.7)
Some college or 2-year degree	12 (33.3)	2 (33.3)
4-year college degree	5 (13.9)	2 (33.3)
More than 4-year college degree	6 (16.7)	1 (16.7)
Have Children
Yes	21 (58.3)	4 (66.7)
No	15 (41.7)	2 (33.3)
Household Income
$30,000 or less	24 (66.7)	3 (50.0)
$30,001-$50,000	9 (25.0)	2 (33.3)
$50,001-or more	3 (8.3)	1 (16.7)
Interested in Vaccine
Yes	29 (80.6)	4 (66.7)
No	7 (19.4)	2 (33.3)

The average PACV score was reviewed for comparisons between sex, race/ethnicity, and participants interested in the HPV vaccine or not (Table 2). Male participants had a higher PACV score (more hesitancy) on average when compared to female participants. White participants had the lowest average PACV score (less hesitancy), and participants that were interested in the vaccine had a lower average PACV score than those that were not interested. A univariable linear regression model was used to evaluate the association of PACV score between age, gender, race, education, having children or not, HPV vaccine awareness and interest (Table 3). There was a significant statistical difference between the PACV score of White and Black participants (Black patients had higher scores, more hesitancy, p = 0.012). In addition, there was a statistically significant difference between HPV vaccine awareness, where participants who had heard of the vaccine beforehand had a lower PACV score (less hesitancy) compared to participants who had not heard of the vaccine (p = 0.015).

Table 3. Univariable linear regression model evaluating association of PACV score with variables.

Term	β (95% CI)	P value
Age	0.46 (−0.58 - 1.5)	0.38
Male	8.85 (−5.03-22.74)	0.21
Race: Latino vs Black	−6.51 (−23.16-10.14)	0.43
Race: Other vs Black	3.42 (−14.42-21.26)	0.70
Race: White vs Black	−16.24 (−28.66 - −3.82)	0.012
Some college/2-year degree vs High School / GED or less	−1.77 (−16.34-12.81)	0.81
4-year college vs High School / GED or less	−6.91 (−24.94-11.12)	0.44
More than 4-year college vs High School / GED or less	−0.14 (−17.43-17.14)	0.99
Have Children	10.85 (−0.74-22.45)	0.07
Heard of HPV Vaccine	−15.33 (−26.9 - −3.75)	0.011
Interested in Vaccine	−11.36 (−25.23-2.5)	0.11

β = regression coefficient; CI = confidence interval.

P-values <0.05 are considered significant and shown in bold.

Discussion

HPV vaccine awareness of working, uninsured adults (18-45 year old) from the VIM clinic was higher than expected when compared to our previous 2014 study [14]. In the 2014 study, 32.1% of the eligible 296 participants were knowledgeable of the HPV vaccine [14]. In the present study conducted from October 2020 through October 2022, 30/43 (69.7%) eligible participants were knowledgeable of the vaccine. Nonetheless, a recent study conducted at the University of Texas-MD Anderson to assess HPV and HPV vaccine awareness during a 10-year period (2008-2018) stated that HPV-related awareness had declined during that period in the US general population, where the lowest awareness was found among racial minorities, male patients, rural residents, those aged 65 years or older, and those with the lowest educational and socioeconomic status [20]. Also, a recent analysis of HINTS-5 dataset (Health Information National Trends Survey) involving an older population (15, 637 participants with a median age 58), showed that HPV awareness was significantly lower among individuals with lower educational attainment (less than high school) [21]. Our study demonstrated that all 13 participants that had not heard of the HPV vaccine beforehand had an income of less than $50,000, which is consistent with previous studies showing less awareness in lower socioeconomic status patients. Participants who had heard of the HPV vaccine beforehand had a statistically significant lower PACV score (less hesitancy) (Table 1; p = 0.015). This opens the possibility that exposure to information about the HPV vaccine, whether through TV advertisements or high-quality recommendations from physicians, could be helpful in lowering general hesitancy towards the HPV vaccine.

Most participants were considered non-hesitant by their PACV score, and as expected, most of these non-hesitant participants were interested in receiving the HPV vaccination. Despite most patients being non-hesitant by PACV score and agreeing to vaccination, a minority of them completed the three free HPV vaccination doses. There were many favorable factors for patients to get vaccinated in terms of the accessibility and education. However, only two patients out of the ten (20%) that had declined vaccination changed their minds to undergo vaccination after viewing the educational video. The availability of free HPV vaccination and education are not sufficient to achieve adequate vaccination rates in low-income uninsured adults. We hypothesize that the COVID-19 global pandemic during the time period of our study adversely affected completion rates of the full 3 dose HPV vaccine series. Other contributing factors may include the need for follow up for a multi-dose vaccine regimen, misconceptions about the effectiveness of the HPV vaccine at the older age group of 18-45, and decline in trust of vaccination in general.

This preliminary study can guide future interventions aimed at increasing awareness of HPV and completion of HPV vaccination among low income racially and ethnically diverse populations. Our preliminary findings of low percentage of HPV vaccination completion despite the availability of free HPV vaccination and the suggestion of greater vaccine hesitancy among Black patients and those with no awareness of HPV, would suggest that the development of culturally sensitive expanded education efforts and interventions aimed at facilitating the completion of the recommended 3 doses of the HPV vaccine will be critical for these efforts. The lower prevalence of HPV vaccination among black women age 19–26 in the USA compared to white women further supports the need for initiatives that will adress this disparity [22]. The experience with COVID vaccine hesitancy among Blacks in the USA at the beginning of the COVID pandemic and the eventual improvement of COVID vaccination rates among Blacks demonstrates that education on the benefits of vaccination can overcame these disparities [23].

Our study has several important limitations. A follow up study involving a larger patient population is needed to confirm the findings of this preliminary study, given the relatively small size of the studied cohort. Second, our data suggesting increased awareness of HPV in this study population compared to those studied by our group in 2014 could have been because the current study was performed during the COVID-19 pandemic, which did raise the awareness for vaccines in general. Also, the fact that most of the recruitment for the current study took place via phone may had created bias favoring participation in the trial of patients with already some interest in HPV vaccination, a significant difference from the 2014 VIM study. Asking participants with no children to answer the PACV questions related to their willingness to have their children vaccinated hypothetically may had introduced some bias in the PACV results. Lastly, the participants in this study had a median age of 40, and therefore additional studies with younger adults (ages 18-26) will be needed to determinate if similar findings are seen in the younger age group.

Conclusions

The availability of an education program and free HPV vaccination was not sufficient in overcoming barriers to HPV vaccination in this racially and ethnically diverse low income underserved patient populaion. Vaccine hesitancy was higher among Black patients and among those who had not heard of the HPV vaccine. Additional innovative and culture sensitive education and supportive interventions are needed in this low income uninsured adult patient population in order to increase the acceptance and completion rates of HPV vaccination.

Ethics approval and consent to participate

• Informed consent to participate was obtained from all subjects by Mayo Clinic research personnel.

• This study was approved by the Mayo Clinic Institutional Review Board as a minimal risk study (IRB# 18-010455).

• A research participation consent and privacy authorization form was reviewed with all subjects, in either English or Spanish, and signed by both the subject agreeing to participate and the research personnel who obtained the consent.

Competing interests

Dr.Colon-Otero is the local Principal Investigator for a Merck clinical trial. Authors report no other direct or indirect conflicts of interest with the reported work.

Authors' contributions: Each author made substantial contributions to this study and approved this manuscript

• HDC – interpretation of data and drafted initial manuscript

• LPS – acquisition and analysis

• VF – design, acquisition, and analysis

• SCL – design, acquisition, and analysis

• MH – interpretation, edited and substantially revised manuscript

• KM – interpretation, edited and substantially revised manuscript

• CD – design, acquisition, analysis

• ZL – analysis of data

• GCO – design, analysis, interpretation, editing, and substantial revision of manuscript

Authors' information

• HDC – Medical student at University of Puerto Rico, Summer research intern at Mayo Clinic

• LPS – Senior Program Coordinator – Research, Department of Clinical Trials and Biostatistics, Mayo Clinic Florida

• VF – Physician, Medical Director of Volunteers in Medicine

• SCL – Clinical Research Coordinator – Community Based Research, Mayo Clinic Florida

• MH – Physician, Department of Medicine, Community Internal Medicine, Program Director Internal Medicine Residency Program, Mayo Clinic Florida

• KM – Physician, Department of Medicine, Division of Hospital Internal Medicine, Mayo Clinic Florida

• CD – Physician, Department of Gynecology, Mayo Clinic Florida, and Volunteer Physician at Volunteers in Medicine (VIM)

• ZL – Principle Biostatistician, Clinical Trials and Biostatistics, Mayo Clinic Florida

• GCO – Physician, Department of Medicine, Division of Hematology / Oncology, Mayo Clinic Florida, and Dean of Mayo Clinic Alix School of Medicine (MCASOM) Florida Campus

Availability of data and materials

The datasets used and/or analyzed during the current study are available from the corresponding author on reasonable request.

Additional information

Funding

This work was supported by NIH Office of the Director: [Grant Number UL1 TR002377]; National Cancer Institute: [Grant Number CA15083]; National Institutes of Health: [Grant Number UL1 TR002377].