Human papillomavirus vaccinations at recommended ages: How a middle school-based educational and vaccination program increased uptake in the Rio Grande Valley

ABSTRACT

Human papillomavirus (HPV) vaccination is recommended for U.S. adolescents at ages 11–12 requiring two or three doses depending on if the vaccine series started before age 15. The objective was to compare HPV vaccination rates among medically underserved, economically disadvantaged, students in rural middle school districts (Rio Grande Valley [RGV], Texas) by age of initiation (≤ age 11 years vs. age 12 years and older). This quasi-experimental study included 1,766 students (884 females; 882 males) who received at least one HPV vaccine dose through our school-based vaccination program between 08/2016-06/2022. Summary statistics were stratified by age at initiation and gender. The overall HPV up-to-date (UTD) rate was 59.7% (95% Confidence Interval: 57.4–62.0%). The median age at HPV UTD (range) was 12 years (9–19) and median interval between HPV vaccine doses (range) was 316 days (150–2,855). Most students received the HPV vaccine bundled with other vaccinations (72.4%, 1,279/1,766). There was a higher HPV UTD rate among students who initiated the HPV vaccine on or before age 11 than those who initiated on or after age 12 (73.6% versus 45.1%, respectively). The median age of HPV UTD was age 12 for those initiating on or before 11 years versus age 13 for those initiating on or after 12 years of age. Initiating the HPV vaccine at age ≤11 years increased completion of the HPV vaccine series. Improving HPV vaccine coverage and introduction of pan-gender vaccination programs will significantly decrease HPV-related diseases in the RGV.

KEYWORDS:

• Human papillomavirus vaccine
• adolescent health
• human papillomavirus-related cancers and diseases
• school-based vaccination
• provider recommendation
• Rio Grande Valley

Introduction

HPV vaccination rates remain suboptimal¹ despite the evidence supporting the human papillomavirus (HPV) vaccine as a safe and effective strategy for reducing the morbidity and mortality of HPV-associated diseases at the population-level.^2–12 Routine HPV vaccination in the United States (US) has been recommended for females since 2006 and 2011 for males aged 9–26 years. Although HPV vaccination is recommended for adolescents aged 11–12, it can be initiated as early as 9 years of age.¹³ If HPV vaccination rates rose to 80%, 53,000 more cervical cancer cases would be prevented over the lifetime of those aged ≤12 years.^14,15

Texas continues to have a 10% lower HPV vaccine uptake than the rest of the nation. Texas ranks 47^th in terms of HPV UTD vaccinations out of 50 states and the District of Columbia.¹⁶ Due to HPV-associated cancers and lower HPV vaccination rates,^10–17–20 offering the HPV vaccine at no cost is important in rural, medically underserved settings in Texas, such the Rio Grande Valley (RGV). The RGV consists of four counties bordering Mexico (Cameron, Hidalgo, Starr and Willacy Counties) with some of the worst health and economic disparities in the nation.²¹ Hispanics are at higher risk for HPV-associated cancers. Culturally appropriate interventions and survey methods are needed to increase HPV uptake and improve efforts in engaging with this population.^22–25

Introduction of the HPV vaccine in a school-based setting provides a rare opportunity to build and strengthen adolescent health.¹² Research has shown that parents play a pivotal role in HPV vaccine uptake²⁶ and healthcare providers play crucial roles in ensuring its administration.^27–34 The target age group (ages 11–12) presents particular challenges including more scrutiny of HPV vaccines than traditional childhood vaccines, e.g., age, sexual activity, and safety concerns.¹² The study objective is to evaluate how a community-based education and school-based HPV vaccination program increased HPV vaccination rates among medically underserved, economically disadvantaged, students in rural middle school districts (Rio Grande Valley [RGV], Texas) by age of initiation (≤ age 11 years vs. age 12 years and older).

Methods

This quasi-experimental study is part of a larger funded project evaluating an intervention program to increase HPV vaccine uptake in the RGV (Texas) to meet the 2016 National Immunization Survey – Teen HPV vaccination rates (initiation: 49.3%; completion: 32.9%)^35–37 To be included in this study, students had to receive at least one HPV vaccine dose from our school-based vaccination program (vaccination events). The study outcomes included HPV vaccine initiation and HPV up-to-date (UTD) status. HPV vaccine initiation was defined as receipt of the first dose of the HPV vaccine series. HPV UTD was defined as receipt of ≥ 3 doses if initiated after age 15 years or had immunocompromising conditions or receipt of 2 doses if initiated before age 15 years, with the minimum interval of 5 months between the first and second dose.³⁸

As described previously, the intervention combined community-based HPV education with school-based vaccinations ^35–37 at middle schools to increase HPV vaccine uptake in the RGV. The intervention addressed factors affecting HPV vaccine uptake (e.g., social norms, knowledge, health provider recommendations and risk perception, accessibility, schedule, costs, bundling vaccines).^{18,26,27,31,32,36,39,40,41} The physician-led educational events started in August 2016 in Cameron, Hidalgo, and Starr counties (located in a 15-mile radius encompassing the original intervention site, the Rio Grande City Independent School District [RGCISD] in Starr County) while the PSJA ISD school-based vaccination program (Hidalgo County) began in June 2019 with total enrollment of 6,481 students.³⁶ Approval for this program was obtained from the University of Texas Medical Branch’s Institutional Review Board, and RGCCISD, PSJA ISD, Roma Independent School District (Roma ISD) and Zapata County Independent School District (Zapata County ISD) School Boards. Informed consent was required for middle school students to be vaccinated.

The study period was from 1 September 2016 to 30 June 2022. Between June 2019 and June 2022, the school-based vaccination was implemented in PSJA ISD (starting with largest student enrollment schools in closest proximity to RGCCISD: August 2019 for Phase 1 [3 middle schools]; August 2020 for Phase 2 [3 middle schools]; and February 2021 for Phase 3 [2 middle schools]).³⁶ In August 2020, the school-based vaccination program was implemented in 2 middle schools in Roma ISD (Starr County) and 1 middle school in Zapata County ISD. Students were recruited through the four school districts. We collaborated with community and public health organizations to actively promote the school-based HPV vaccination program through stakeholder/PTA/school board meetings, social media, and radio. Although the target population included RGCCISD, PSJA ISD, Roma ISD, and Zapata County ISD middle school students, students who came to vaccination events that met the age criteria received HPV vaccinations. HPV vaccine series were initiated and completed during the school year at back-to-school events, progress report nights, and preview events. Up to 5 reminder letters, texts, and phone calls for subsequent doses were sent to the parents/guardians of children who initiated HPV vaccination. To ensure on-time vaccination and adherence to the dosing schedule, catch-up vaccination was scheduled through nearby clinics when requested by parents and subsequent events for missed doses.

We continued to strengthen our implementation strategies by having physicians addressing the audience, targeting female and male middle school students at the recommended ages (aged 11–12 years of age), bundling the HPV vaccine with recommended vaccines (e.g., flu, Meningococcal, Meningitis B, Tetanus, Diphtheria [TD], or Tetanus, Diphtheria, and Pertussis [TDAP] and Hepatitis A vaccines), addressing previously identified barriers, and extending the study area for school-based vaccinations from RGCCISD to PSJA ISD, Roma ISD, and Zapata County ISD.^{26,27,31,32,35–42} Prior to coronavirus disease 2019 (COVID-19), school-based vaccination events were held in the nurses’ offices, conference rooms, nearby clinics at parents’ requests, and community events. When the COVID-19 pandemic hit in the middle of the first year of the school-based vaccination program and caused school closures, adaptions were made. We held outside events with social distancing, limited in-person activities, increased online activities, and provided more frequent stakeholder engagement through teleconference, navigational services, and mobile van vaccinations.³⁶

The HPV vaccination data was refreshed quarterly. It was collected from the vaccine vendor and school immunization records and reconciled with Immtrac2, Texas Immunization Registry. The registry is secure and confidential, and safely consolidates and stores immunization records from multiple sources in one centralized system. Summary statistics were computed and stratified by gender, age of initiation (9, 10, 11, 12, 13, 14+), and vaccination year. Assuming a small effect size (W = 0.1) and equal sample size in the two groups (Age of Initiation: ≤11 years vs. 12+ years) using Power Analysis and Sample Size (PASS 2022), a sample size of 786 achieves 80% power to detect a small effect size (W = 0.1) using Chi-Square Test with a significance level (alpha) of 0.05. SAS version 9.4 (SAS Institute Inc, Cary, NC) was used in conducting all analyses. Statistical significance was set at α|=|.05 (two-sided).

Results

Table 1 displays the demographic characteristics of the study population and HPV vaccination rates by gender. At baseline, 6,481 students were enrolled at PSJA ISD. Among 1,766 middle school students (females n = 884; males n = 882) who received at least one HPV vaccine dose through our school-based vaccination program, most were from RGCCISD (47.8%; 844/1,766) and PSJA ISD (46.8%; 827/1,766). Most middle school students initiated the HPV vaccine at age 11 (39.5%, 698/1,766) or age 12 (30.5%, 539/1,766) (Table 1). The overall HPV UTD rate was 59.7% (95% Confidence Interval: 57.4–62.0%). Overall, the median age at HPV UTD (range) was 12 years (9–19). The median days between HPV vaccine doses (range) was 316 days (150–2,855). Among the 1,766 middle school students who received the HPV vaccine, 72.4% (1,279/1,766) had received the HPV vaccine bundled with other recommended vaccinations (Table 1). The percentage of students who received their HPV vaccine with other recommended vaccinations were similar across female and male students (72.3% vs. 72.6%).

Table 1. Students’ Characteristics and HPV Vaccination Rates by Gender.

	All Students N = 1766		Females N = 884		Males N = 882
	n	%	n	%	n	%
All	1766
Females	884	50.1%	884	100.0%
Males	882	49.9%			882	100.0%
Age at HPV Vaccine Initiation
9	101	5.7%	53	6.0%	48	5.4%
10	105	5.9%	55	6.2%	50	5.7%
11	698	39.5%	375	42.4%	323	36.6%
12	539	30.5%	243	27.5%	296	33.6%
13	189	10.7%	85	9.6%	104	11.8%
14+	134	7.6%	73	8.3%	61	6.9%
HPV UTD*	1054	59.7%	546	61.8%	508	57.6%
Age at HPV UTD
Mean Age at UTD (SD)	12.6 (1.4)		12.5 (1.4)		12.6 (1.4)
Median Age at UTD (Min, Max)	12 (9, 19)		12 (9, 19)		12 (9, 18)
Days Between HPV Vaccine Doses
Mean (SD)	477.2 (398.8)		475.6 (403.8)		479.0 (393.8.8)
Median (Min, Max)	316 (150, 2855)		304 (151, 2855)		333 (150, 2843)
Received Other Vaccinations Bundled with the HPV Vaccine
No	487	27.6%	245	27.7%	242	27.4%
Yes	1279	72.4%	639	72.3%	640	72.6%
School District
PSJA ISD	827	46.8%	425	48.1%	402	45.6%
RGCCISD	844	47.8%	411	46.5%	433	49.1%
Roma ISD	91	5.2%	45	5.1%	46	5.2%
Zapata County ISD	4	0.2%	3	0.3%	1	0.1%

Note: UTD or Completion receipt of >  = 3 doses or receipt 2 doses if initiated < age 15 years, and the time between the first and last dose was at least 5 months.

Most students initiated the HPV vaccine at ≤ age 11 years (n = 904) (Table 2). Regardless of gender, a higher percentage of students who initiated the HPV vaccine at age 9, age 10 or age 11 were HPV UTD compared to those who initiated at age 12 or older (Figure 1). Almost 74% (665/904) of those who initiated the HPV vaccine at ≤ age 11 completed the HPV vaccine (results not shown). As shown in Table 2, HPV UTD was highest among middle school students who initiated the HPV vaccine at age 11 years (39.5%). A higher percentage of females were HPV UTD compared to males (30.9% versus 28.8%, respectively). A total of 195 students had received ≥3 HPV vaccine doses (11.0%; n = 195). Overall, 12.9% (114/884) of females who initiated the HPV vaccine received ≥3 HPV vaccine doses, while 9.2% (81/882) of males who initiated the HPV vaccine received ≥3 HPV vaccine doses.

Figure 1. HPV UTD status by age at initiation.

Table 2. Summary of HPV Vaccine Initiation and HPV UTD by Gender.

	All Students who Received at Least 1 HPV Dose from Vaccination Events N = 1,766				Females N = 844				Males N = 842
	Initiated HPV Vaccine		HPV UTD		Initiated HPV Vaccine		HPV UTD		Initiated HPV Vaccine		HPV UTD
	n	%	n	%	n	%	n	%	n	%	n	%
Gender
All	1766	100.0%	1054	59.7%
Females	884	50.1%	546	30.9%	884	100.0%	546	61.8%
Males	882	49.9%	508	28.8%					882	100.0%	508	57.6%
Age at Initiation
9	101	5.7%	63	3.6%	53	6.0%	36	4.1%	48	5.4%	27	3.1%
10	105	5.9%	67	3.8%	55	6.2%	34	3.8%	50	5.7%	33	3.7%
11	698	39.5%	535	30.3%	375	42.4%	293	33.1%	323	36.6%	242	27.4%
12	539	30.5%	287	16.3%	243	27.5%	135	15.3%	296	33.6%	152	17.2%
13	189	10.7%	79	4.5%	85	9.6%	34	3.8%	104	11.8%	45	5.1%
14+	134	7.6%	23	1.3%	73	8.3%	14	1.6%	61	6.9%	9	1.0%
Received ≥3 doses			195	11.0%			114	12.9%			81	9.2%

Note: UTD or Completion receipt of >  = 3 doses or receipt 2 doses if initiated < age 15 years, and the time between the first and last dose was at least 5 months.

Table 3 shows students who initiated the HPV vaccine on or before age 11 had a higher HPV UTD (completion) rate than those who initiated the HPV vaccine on or after age 12 (73.6% versus 45.1%, respectively). The median age of HPV UTD or completion was age 12 for those initiating on or before 11 years old, and age 13 for those initiating on or after 12 years of age. The median (range) days between HPV vaccine doses was longer among those who initiated the HPV vaccine on or before age 11 years (358 days, 158–2,855) compared to those who initiated on or after age 12 years (268 days, 153, 2,016).

Table 3. HPV Vaccine Completion by Age at Initiation.

	Total N = 1766	Age of Initiation ≤11 years N = 904	Age of Initiation 12+ Years N = 862
Completion Rate	1054 (59.7)	665 (73.6)	389 (45.1)
Age of Completion
Mean (SD)	12.6 (1.4)	12.1 (1.3)	13.4 (1.2)
Median (Min, Max)	12 (9, 19)	12 (9, 19)	13 (12, 18)
Days between initiation and completion
Mean (SD)	477.2 (398.8)	522.2 (432.8)	400.4 (318.9)
Median (Min, Max)	316 (150, 2855)	358 (150, 2855)	268 (153, 2016)

Discussion

Areas with higher incidence and mortality of HPV-related diseases and cancers, lower rates of Pap test screening and lower levels of HPV vaccination make these areas up at risk for continued higher rates of HPV-related cancers and diseases. This study provides information on how community-based HPV education and school-based vaccination program can influence HPV vaccine initiation and completion rates. Hence, potentially decrease future HPV-related disease prevalence in the area.

A total of 1,776 middle school students received at least one dose through our vaccination events. Almost 74% (665/904) of those who initiated the HPV vaccine at ≤ age 11 completed the HPV vaccine. We had students completing their HPV vaccination series at the recommended ages. Overall, the HPV UTD rate was 59.7% (95% Confidence Interval: 57.4–62.0%).

The results provide evidence supporting how initiation of the HPV vaccine series prior to age 11 improves population-level HPV vaccination coverage and timely completion of the series within a school year. The median age at HPV UTD (range) was 12 years (9–19). Most students initiated the HPV vaccine at ≤ age 11 years (n = 904). If they initiated the HPV vaccine series at younger ages (age 9, 10, or 11), they had higher rates of HPV UTD. The interval between vaccine doses were also in line in HPV vaccine guidelines and bundling with other vaccines increased HPV vaccine uptake. The median interval between HPV vaccine doses (range) was 316 days (150–2,855). Among students who received the HPV vaccine through our intervention, 72.4% (1,279/1,766) had received the HPV vaccine bundled with other recommended vaccinations.

Improving the timeliness of HPV vaccination is critical for protecting adolescents prior to HPV exposure. Adherence to the recommended dosing schedule for HPV vaccine is also important for adequate immune response and expected protection from HPV-associated diseases.⁴³ Since younger adolescents have a better immunologic response to the HPV vaccine, this may translate into improved effectiveness.⁴⁴ Emphasizing routine administration of the HPV vaccination at age 11–12 has shown to increase parents’ preference for on-time vaccination and improves adherence to the dose scheduling.^43,45 Previous research has shown that framing recommendations involving fewer doses before age 15 may discourage on-time HPV vaccination and suggest to parents that routine HPV vaccine administration extends to this age.⁴⁵

Our study supports the importance of simplifying the messaging for HPV vaccination and recommending HPV vaccine initiation at younger ages.^43,45 We emphasized HPV vaccination as cancer prevention and discuss the improved effectiveness of HPV vaccination at younger ages. Our study contributes to previous research by examining HPV vaccination rates on and before age 11 and 12 years and older through a school-based education and vaccination program in the RGV. Our findings suggest that adherence to the recommended dosing schedule remains relatively low among older adolescents. Therefore, findings from this research are important for the improvement in removing barriers to on-time vaccination and adherence to the HPV vaccine schedule.^46,47

Our results must be considered in light of certain limitations. Limited information was collected on students and parents, such as students’ race and ethnicity and other socioeconomic status (SES), parents’ education and income levels, country of birth or knowledge and confidence in the HPV vaccines. Therefore, examination of rates by these important characteristics cannot be undertaken. We do not have complete information on students’ insurance, which may be important for examining access to care. This population is transient with some students changing schools during our study. For simplification, we followed our baseline cohort. Some students may have received the HPV vaccine outside the school settings through their local providers. If parents failed to report the HPV vaccine status to the schools, we would be unable to account for those in our study. The vendor and schools shared updated information, but it may not capture all vaccines received.⁴⁷ In addition, we suspect that the increased HPV vaccine uptake at the intervention school may be due to more motivation to share updated records because of onsite events, more exposure to study personnel, and better access to vaccinations. Future studies should explore issues, such as inadequate school-based health centers and vaccine billing as barriers for school-based HPV programs.⁴⁸

Conclusions

Initiating the HPV vaccine at age ≤11 years increased completion of the HPV vaccine series. Our community-based education and school-based intervention program provides the HPV vaccine in an alternative setting (schools), increases access and support through education and outreach, and encourages on-time HPV vaccination and completion. Improving HPV vaccine coverage and introduction of pan-gender vaccination programs will significantly decrease HPV-related diseases in the RGV. Given the positive influence of healthcare providers on parental decisions to vaccinate, future studies should target under recommended groups, men and Hispanics, to increase knowledge and awareness about HPV, the HPV vaccine, and HPV-associated cancers and promote greater HPV vaccine uptake and reduce parental hesitancy.

List of abbreviations

ACIP	=	Advisory Committee on Immunization Practices
CDC	=	Centers for Disease Control and Prevention
COVID-19	=	Coronavirus Disease 2019
HPV	=	Human Papillomavirus
PSJA ISD	=	Pharr-San Juan-Alamo Independent School District
RGV	=	Rio Grande Valley
RGCCISD	=	Rio Grande City Consolidated Independent School District
Roma ISD	=	Roma Independent School District
TDAP	=	Tetanus, Diphtheria (TD), or Tetanus, Diphtheria, and Pertussis
U.S.	=	United States
UTD	=	Up-to-date
VFC	=	Vaccines for Children
Zapata County ISD	=	Zapata County Independent School District

Author contributions

All authors contributed to the conceptualization of this manuscript. AMR and TQD wrote the first draft of the manuscript, and all authors contributed to the editing and finalization of the manuscript.

Acknowledgments

The authors are incredibly grateful for the support and assistance from the School Superintendents and School Boards for RGCCISD, PSJA ISD, Roma ISD, and Zapata County ISD, faculty/staff, school nurses, parents, and the RGV community (Cameron. Hidalgo, and Starr Counties) in implementing this project. We also thank Iris L. Tijerina, Iris I. Rivera, Nadia Garces, Maria F. Lincoln, and Jesus Moralez from the University of Texas Medical Branch for their work and involvement in this project.

Disclosure statement

No potential conflict of interest was reported by the author(s).

Additional information

Funding

The content is solely the responsibility of the authors and does not necessarily represent the official views of the Cancer Prevention Institute of Texas or the National Institutes of Health. AMR and KFK received grant funding from The Cancer Prevention Research Institute of Texas (CPRIT) [grant numbers PP160097, 2016; PP190023, 2019; P200057, 2020]. This study was conducted with the support of the Institute for Translational Sciences at the University of Texas Medical Branch, supported in part by a Clinical and Translational Science Award from the National Center for Advancing Translational Sciences, National Institutes of Health [grant number UL1 TR001439] and The University of Texas MD Anderson Cancer Center’s HPV Vaccination Initiative. Neither NIH, MD Anderson’s HPV Vaccination Initiative nor CPRIT have roles in the development of this article (i.e., in the study design; in the collection, analysis, and interpretation of data; in the writing of the report; or in the decision to submit the paper for publication).