The causal relationship between infection with human papillomavirus (HPV) and subsequent development of cervical cancer is well established.1,2 Prophylactic HPV vaccines were subsequently developed to prevent infection with high risk HPV strains accounting for the majority of cervical cancers.3,4 Studies have demonstrated that, when administered before exposure, these vaccines are approximately 98% effective at preventing strain-specific, HPV-related, high-grade cervical intraepithelial neoplasia.3,4
Despite the demonstrated efficacy of the prophylactic HPV vaccines in preventing HPV associated cervical cancers, vaccine uptake has been suboptimal.5 A Centers for Disease Control and Prevention report of the National Immunization Survey–Teen in 2016 reported that only 65.1% and 43.0% of females aged 13–17 had received 1 dose and 3 doses of the prophylactic HPV vaccine, respectively.6 Strategies to increase prophylactic HPV vaccine uptake will not only help protect individual patients, but also likely lead to the attainment of herd immunity.7
Minorities and women of low socioeconomic status have been identified as being at increased risk of infection with HPV.8 In addition, minority women are less likely to receive the HPV vaccine, leaving this population of women with increased vulnerability to cervical cancer.9,10 Given the burden of HPV infection among this population and generalized low vaccine uptake, it is critical to identify reasons for poor vaccine uptake to develop targeted interventions aimed at increasing vaccine acceptance. We aim to determine whether educational interventions targeting knowledge deficits among a group of young women can increase HPV vaccine acceptability.
An exploratory phase of this study was first completed to explore barriers and motivators to vaccine uptake to facilitate the later development of targeted interventions aimed at increasing HPV vaccine acceptability. To determine baseline acceptance of the prophylactic HPV vaccine and barriers to acceptance among the intended population, a cross-sectional survey of 200 women and semi-structured qualitative interviews of 15 women were completed between May 2013 and January 2014 at Obstetrics and Gynecology clinics affiliated with the University of Pennsylvania Healthcare System. In this exploratory phase of the study, inclusion criteria included: 1) presentation for gynecologic care to a University of Pennsylvania–affiliated clinic; 2) age between 12 and 34 years, inclusive; and 3) ability to read and write in English. Age restrictions for this exploratory phase were selected to capture data on women eligible for vaccination at the time the first prophylactic HPV vaccine received approval from the U.S. Food and Drug Administration. Exclusion criteria included: 1) known history or current diagnosis of cervical cancer and 2) current pregnancy.
Women who agreed to enroll in the exploratory phase of this study completed a survey that collected data on age, race, socioeconomic status, obstetric and gynecologic history, family history, knowledge about the prophylactic HPV vaccine, acceptance of the prophylactic HPV vaccine, and vaccine uptake. At the time of study design and implementation, a well-validated questionnaire about knowledge and acceptability of the HPV vaccine did not exist. Knowledge of the prophylactic HPV vaccine was assessed using responses to eight statements (Table 1), and a total knowledge score (0–8) was calculated as the unweighted sum of correct responses. Knowledge statements had three potential responses: “agree,” “disagree” and “I don't know.” Acceptability of the prophylactic HPV vaccine was determined by responses to the statement, “I would be willing to accept the HPV vaccine today.” Using the same responses as the knowledge statements, those who responded “agree” to this statement were categorized as acceptors and those who responded “disagree” or “I don't know” were categorized as nonacceptors.
Fifteen of the 200 women who completed the survey were randomly selected to participate in semi-structured qualitative interviews. All interviews were completed by telephone and responses were recorded at the time of each interview. Participating women were asked questions assessing knowledge of the vaccine, motivators and influences driving acceptance and nonacceptance, and preferred learning styles (Appendix 1, available online at http://links.lww.com/AOG/B444). Interviews were completed until thematic saturation (recurrence of similar themes with limited new data obtained from additional interviews) was achieved. A $20 gift card stipend was provided to interview participants only.
Data from the exploratory phase of this study then were used to identify themes driving acceptance and nonacceptance. Educational interventions (one handout and one video) targeting these themes, using preferred learning styles ascertained in the exploratory phase and providing motivational messaging were created. The educational content of each intervention was reviewed to ensure that it was consistent with an eighth-grade reading level. Two subject matter experts reviewed the content of each intervention to ensure accuracy and that the same content was conveyed in each intervention. Content of both interventions was piloted among five women receiving care at participating clinics to ensure acceptability and ease of use before finalization.
After the development of these educational interventions, a single-institution, randomized, controlled trial was completed at Obstetrics and Gynecology clinics affiliated with the University of Pennsylvania Healthcare System that historically have primarily served minority women. Women were enrolled and randomized as outlined in Figure 1. Inclusion criteria included: 1) presentation for gynecologic or obstetric care to a University of Pennsylvania–affiliated clinic; 2) age between 12 and 26 years, inclusive; and 3) ability to read and write in English. Age restrictions for this phase were selected to capture data on those currently eligible for the prophylactic HPV vaccine. Exclusion criteria included: 1) known history or current diagnosis of cervical cancer, 2) prior initiation or completion of the HPV vaccine series, and 3) presentation to clinic for HPV vaccination.
Authors' Data Sharing Statement
- Will individual participant data be available (including data dictionaries)? No.
- What data in particular will be shared? Not available.
- What other documents will be available? Not available.
- When will data be available (start and end dates)? Not applicable.
- By what access criteria will data be shared (including with whom, for what types of analyses, and by what mechanism)? Not applicable.
Eligible women were approached in clinic for recruitment and those who provided written consent to enrollment were randomized using a simple 1:1:1 randomization schedule generated by STATA 14.2. Randomization resulted in assignment to one of three study arms by study staff: control (no educational intervention), educational handout (one-page handout), or educational video (approximately eight-minute video). After completion of their randomization arm, all women completed the same survey as used in the exploratory phase. The primary outcome for this study was acceptability of the prophylactic HPV vaccine, as defined in the exploratory phase. The secondary study outcome was prophylactic HPV vaccine knowledge, as defined in the exploratory phase. Additional data were collected on utility of the educational interventions.
A sample size calculation was completed for the primary aim of this study. From the exploratory phase, baseline acceptability of the prophylactic HPV vaccine was determined to be 51%. Using a type I error of 0.025 to account for comparing each intervention arm with the control arm and 80% power, 84 women were needed in each of the three study arms to detect a 20% difference in vaccine acceptability among arms.
Standard descriptive statistics were employed. Nonparametric continuous variables were reported as median (interquartile range) and categorical variables were reported as frequencies (percent). In the exploratory phase, Chi-square and Wilcoxon rank sum tests were used to compare categorical and continuous characteristics, respectively, between acceptors and nonacceptors. In the randomized, controlled trial phase, Chi-square and Kruskal-Wallis tests were used to compare categorical and continuous characteristics, respectively, between study arms.
Two-sided P-values less than 0.05 and less than 0.025 were designated as statistically significant for all analyses in the exploratory and randomized, controlled trial phases, respectively. STATA 14.2 was used. Institutional review board approval (Protocol# 817883 for exploratory phase and Protocol# 826486 for randomized, controlled trial phase) was obtained by the University of Pennsylvania. The randomized, controlled trial phase of this study was registered at clinicaltrials.gov (www.clinicaltrials.gov, NCT03337269).
In the exploratory phase of this study of survey participants, 51.0% (n=102) of women reported willingness to accept the HPV vaccine. Despite this, only 41.0% (n=82) and 19.0% (n=38) of women initiated and completed the vaccine series, respectively. Vaccine acceptors were more likely than nonacceptors to have Medicaid insurance (58.6% vs 43.8%, P=.02) and to have more children (0 vs 1, P=.04; Table 1). There was no difference in age, race, highest level of education, household income, or family history of cervical cancer between vaccine acceptors and nonacceptors.
Baseline knowledge of the prophylactic HPV vaccine varied between vaccine acceptors and nonacceptors in the exploratory phase. Vaccine acceptors were more likely than nonacceptors to correctly understand the role of the prophylactic HPV vaccine in preventing cervical cancer (51% vs 22.4%, P<.01; Table 2). They were also more likely to correctly understand the role for ongoing cervical cancer surveillance with the Pap test (72.5% vs 54.1%), the route of spread of HPV (49.0% vs 38.8%), and the ability to obtain the prophylactic HPV vaccine after sexual debut (87.3% vs 71.4%) in comparison with nonacceptors (all P=.02). Median total knowledge score was 6 (interquartile range 5–7) among acceptors and 4 (interquartile range 4–6) among nonacceptors (P<.01).
Fifteen of the 200 survey participants were randomly selected to complete a semi-qualitative, structured interview. Themes driving acceptance and nonacceptance of the prophylactic HPV vaccine were identified using the semi-qualitative structured interviews of the exploratory phase (Appendix 1, http://links.lww.com/AOG/B444). Vaccine acceptors commonly identified the vaccine's role in preventing cervical cancer as a reason for vaccine acceptance, whereas nonacceptors commonly identified a lack of understanding of the purpose of the vaccine as a reason for nonacceptance. Additionally, vaccine acceptors commonly identified their health care professional as being most influential in their decision for vaccine acceptance, whereas nonacceptors identified lack of information as the most important factor in decision-making. Most women in both groups identified their preferred learning style as reading or watching educational material.
After identification of knowledge deficits based on the exploratory survey and semi-structured interviews, targeted educational interventions were created and tested in a randomized, controlled trial. A total of 256 women were enrolled between March 13, 2017, and August 15, 2017. Women were randomized to one of three study arms: control (n=85), educational handout (n=84), or educational video (n=87). No differences with respect to age, race, insurance type, number of children, highest level of education, household income, or family history of cervical cancer were identified among study arms (Table 3). The majority of women identified themselves as black (80.6%, n=207) and almost half indicated that they had a household income less than $25,000 (48.3%, n=123).
Significant differences in HPV vaccine acceptability were identified among participants after completion of their respective randomization and educational interventions (Table 4). Women in the educational video arm reported the highest vaccine acceptance rates at 51.7% (n=45) compared with 33.3% (n=28) in the educational handout arm (P=.02), and 28.2% (n=24) in the control arm (P<.01). Women in both the educational video and handout arms reported that the interventions helped them learn about the HPV vaccine (97.7% vs 92.9%, P=.15). However, the video intervention was more likely to be helpful for deciding on whether to accept the HPV vaccine (86.2% vs 70.2%, P<.01). No differences were noted among study arms regarding the belief that vaccines can be harmful (P=.14) or that participants try to obtain all types of recommended vaccines (P=.73).
Women randomized to an educational intervention arm had higher median HPV vaccine knowledge scores than those in the control arm after completion of their assigned educational intervention (Table 5). The highest median HPV vaccine knowledge score was obtained in the educational video arm with a median score of 6 (interquartile range 5–7) followed by the educational handout arm with a median score of 5 (interquartile range 4–6) and the control arm with median score of 3 (interquartile range 1–4) (P<.01). In addition, those in the educational video arm were more likely to respond correctly to all eight knowledge statements (all P<.01).
Vaccine acceptors were more likely than nonacceptors to have greater knowledge of the prophylactic HPV vaccine in the exploratory phase of this study. Additionally, in semi-structured qualitative interviews, a lack of knowledge or understanding of the vaccine was commonly reported by vaccine nonacceptors as a reason for nonacceptance. Given common themes of poor understanding of the HPV vaccine among nonacceptors, educational interventions targeting knowledge deficits were developed.
In the randomized, controlled trial phase of this study, it was demonstrated that implementation of educational interventions targeting knowledge deficits surrounding the prophylactic HPV vaccine improves vaccine acceptability and knowledge. Greater acceptability was reported among the educational video arm (51.7%, n=45) than among the educational handout arm (33.3%, n=28; P=.02) and the control arm (28.2%, n=24; P<.01). Similarly, the highest HPV vaccine knowledge scores were achieved among those women in the educational video arm.
The current study supports earlier findings reporting lack of knowledge of the prophylactic HPV vaccine as a barrier to uptake.11–15 However, from the present study, we demonstrated that by developing educational interventions targeting specific knowledge deficits within a population, acceptability and knowledge of the prophylactic HPV vaccine can be improved. Although previous studies have demonstrated that other educational interventions (ie, in-person talks, videos) can increase knowledge and, in some cases, acceptability of the HPV vaccine, they have not used targeted interventions and have not compared multiple educational interventions to determine which is most effective.11,16,17 Both the educational video and handout contained the same information and motivational messaging; however, the educational video demonstrated greater improvement in vaccine acceptability and assisting women in deciding whether or not to accept the prophylactic HPV vaccine.
Importantly, most women in the randomized, controlled trial phase of the study were minorities of low socioeconomic status, a group previously identified as being at increased risk for HPV infection8 and nonreceipt of the HPV vaccine.9,10 Previous studies have also demonstrated that racial disparities exist surrounding HPV vaccine knowledge18 and have identified a need for ongoing efforts to decrease such health care disparities within the United States.19 This study demonstrates that educational interventions can increase HPV vaccine knowledge and acceptability among this high risk population. Additional efforts are needed to determine whether such interventions can increase prophylactic HPV vaccine uptake among this population to decrease disparities among women receiving the HPV vaccine.
It is also important to note that the HPV vaccine acceptance rate among the control arm of the randomized, controlled trial phase (28.2%) was substantially lower than the acceptance rate among women in the exploratory phase of this study (51.0%). Furthermore, HPV vaccine acceptance rates among women in the exploratory phase and those in the educational video arm of the randomized, controlled trial phase (51.7%) were similar. It is possible that this difference in baseline acceptance is a result of the completion of national and local campaigns aimed at increasing HPV vaccine uptake between when the two phases of the current trial were conducted. Such campaigns likely capture women who are more willing to accept the vaccine and, as such, women who did not participate in such campaigns and remained eligible for the current study may have a greater likelihood of nonacceptance of the HPV vaccine.
This study has both strengths and limitations. The primary strength of this study is its randomized, controlled trial design. Additionally, the exploratory phase was used to identify themes driving nonacceptance of the vaccine and to guide development of educational interventions. Main limitations of the study include potential selection bias and generalizability. As previously noted, given the median age of women enrolled in this study and the completion of campaigns aimed at increasing vaccine uptake, it is likely that these women may have already refused the vaccine and have a strong predilection to decline the vaccine. Despite this potential limitation, a difference in vaccine acceptability and knowledge was detected. Additionally, all participants were recruited from a single tertiary care center and, as such, the ability to generalize our findings beyond the target population may be limited.
Given the efficacy of the prophylactic HPV vaccines, it is important to focus future efforts on increasing initiation and completion of the vaccine series. Additional studies are also warranted to determine what interventions will most effectively increase prophylactic HPV vaccine uptake among young men, as this vaccine is also approved among this population.
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