Human Papillomavirus Vaccination and Human Papillomavirus–Related Cancer Rates

Key Points Question Are there disparities in human papillomavirus (HPV) vaccination initiation and up-to-date rates and HPV-related cancer incidence across counties and health service regions (HSRs) in Texas? Findings In this cross-sectional study with more than 54.7 million participants, county- and HSR-level HPV vaccination series initiation rates and up-to-date status as well as the incidence of HPV-related cancer varied widely. The counties in the northern region of Texas had a higher incidence of HPV-related cancers and lower HPV vaccination rates compared with those in other regions. Meaning The finding that North Texas had lower HPV vaccination series initiation and up-to-date status with a higher HPV-related cancer burden than other regions raises concern, as this may indicate continued widening of existing health disparities between North Texas and other regions.


Introduction
The United States has a high human papillomavirus (HPV) disease burden, with more than 42 million people infected with disease-associated HPV types and 13 million people acquiring a new infection in 2018. 1 Additionally, approximately 30 700 HPV-attributable cancer cases are newly diagnosed in the United States each year. 2 With the introduction of the HPV vaccine in 2006, HPV-associated infections, warts (HPV types 6 and 11), and cancers (HPV types 16 and 18) became preventable. 3The HPV 9-valent vaccine that is now available for use in the United States protects against 9 high-risk (HR) HPV types (6, 11, 16, 18, 31, 33, 45, 52, and 58) and is recommended as a 2-dose series for individuals aged 9 to 14 years or a 3-dose series for ages 15 to 26 years. 4The HPV vaccination series has been found to be highly effective, with efficacy rates close to 100% in preventing the development of HPV-associated cancers among individuals without prior infection of the HPV vaccine types. 5Despite its safety and high efficacy, national HPV vaccination rates are well below the Healthy People 2030 goal of 80% coverage. 6mpared with other US regions, Southern states, including Texas, have lower HPV vaccination series initiation, up-to-date, and completion rates and higher incidence rates (IRs) of cervical cancer, a well-known HPV-related cancer. 7,8In female individuals in Texas, an estimated 83% of HPV-related cancer incidence is attributable to HR-HPV infection, while in male individuals, the estimate is 74%, 8 indicating a need for increased HPV vaccination initiation, completion, and coverage as well as HPV-related cancer surveillance.According to the National Immunization Survey-Teen in 2022, the estimated HPV vaccination coverage among teenagers aged 13 to 17 years in Texas is 58.5%, which is below the national estimate of 62.6% for the same age group. 9Texas ranks 48th in HPV vaccination series completion and 44th in HPV vaccination series initiation (Ն1 dose) among US states for eligible adolescents and young adults, 10,11  Disparities in HPV vaccination and HPV-related cancer incidence also exist within areas of Texas.
Between 2013 and 2017, 3200 incident cases of HPV-related cancers were diagnosed annually, with higher IRs in rural than urban regions (13.0 vs 11.7 per 100 000, respectively). 8HPV vaccination coverage in Texas regions also varied among teenagers aged 13 to 17 years in 2017, with percentages of vaccine initiation ranging from 53% to 85% and up-to-date vaccination ranging from 30% to 51% across 6 distinct regions. 13[16][17] Given the HPV vaccination disparities within Texas as well as the low rates of vaccination coverage in Texas compared with the national estimates, 13 we sought to examine the Texas countyand health services region (HSR)-specific proportion of children and teenagers aged 9 to 17 years who initiated and were up to date for HPV vaccination series and to examine the HPV-related cancer IR among adults.The aims of this study were to provide county-specific data for Texas on HPV vaccination uptake and up-to-date status and HPV-related cancer incidence to inform targeted interventions.

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Human Papillomavirus Vaccination and Human Papillomavirus-Related Cancer Rates

Study Population
Our study population consists of (1) children and teenagers aged 9 to 17 years who received at least 1 dose (initiated) and were up to date (all vaccine recommended doses) for the HPV vaccination series and (2) HPV-related cancer IR among adults aged 20 years and older across Texas.The state of Texas has 254 counties, which is the highest number for any US state.Texas Department of State Health Services (DSHS) grouped the 254 counties in the state into 11 Public Health Regions served by 8 regional offices, which are HSR 1, HSR 2/3, HSR 4/5N, HSR 6/5S, HSR 7, HSR 8, HSR 9/10, and HSR 11 (eFigure in Supplement 1).The roles of the HSRs include the organizing and provision of comprehensive public health services to Texas residents. 18Other roles of HSRs of Texas are resource sharing, provision of direct support to county and local public health agencies, and leadership and coordination of public health emergency preparedness and response.Each county is assigned to 1 of the 8 HSRs for administrative purposes.HSR 1, with 41 counties, has the highest number of counties, and HSR 11, with 19 counties, has the lowest number of counties. 19The University of Texas Medical Branch institutional review board reviewed this study and classified it as exempt because it used publicly available deidentified county-and state-level data.This report follows the Strengthening the Reporting of Observational Studies in Epidemiology (STROBE) reporting guideline.

Calculation of HPV Vaccination Coverage
We calculated HPV vaccination coverage with cumulative number of children and teenagers aged 9

Calculation of HPV-Related Cancer IRs
We used the direct method 21 to estimate the mean yearly age-adjusted HPV-related cancer IRs.
Multiple diagnoses of the same HPV-related cancer for any patient in a single year period were used as only 1 diagnosis.We applied the mean annual HPV-related cancer IR derived from years 2016 to 2020 to the US 2000 standard population weights to obtain our mean annual age-adjusted cancer

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IRs. 22 In addition, we carried out a Spearmen correlation matrix between HPV vaccination initiation, HPV vaccination up-to-date status, and HPV-related cancer incidence across all counties, separately by sex.

Geospatial Variation
For assessment of geospatial patterns of the HPV metrics of interest through univariate mapping, HPV vaccination series initiation, HPV vaccination up-to-date status, and HPV-related cancer rates were divided into terciles.Each tercile was color coded with increasingly darker colors indicating increased incidence of HPV-related cancers. 14Bivariate choropleth maps were thereafter generated to show concurrent county-level HPV vaccine initiation prevalence and HPV-related cancer IR for each sex, in which 3 terciles of HPV vaccine initiation and 3 terciles of HPV-related cancer incidence were separated into 9 values to allow for greater variability in the values of displayed variables. 14,23l geospatial analyses were done in ArcGIS Pro software version 3.2 (Esri).(Figure 1).HPV vaccination initiation among male individuals increased from 5.8% in 2011 to 39.3% in 2022 (Figure 1).The up-to-date HPV vaccination status also increased for female participants from 0% in 2006 to 17.1% in 2022 and from 2.2% to 16.6% for male participants.

A
The mean county-level HPV vaccination initiation rates for 2021 to 2022 ranged from 6.3% to 69.1% for females (62.8-percent point spread) and from 7.0% to 77.6% for males (70.6-percent point spread) (Figure 2).More counties and HSRs in North Texas were found to have HPV vaccination initiation and up-to-date estimates in the lowest tercile for both female (6.3%-32.9%)and male (7.0%-29.6%)individuals compared with other regions.
In Texas in 2022, 16.6% of male individuals and 17.1% of female individuals aged 9 to 17 years were up to date with their HPV vaccination series.Across all the counties studied, the mean 2021 and 2022 proportion of children and teenagers aged 9 to 17 years old who had up-to-date status for HPV vaccination series ranged from 2.1% to 34.8% for male participants and from 1.6% to 30.4% for female participants.Most of the counties with up-to-date HPV vaccination status in the lowest tercile for both male (2.1%-14.2%)and female (1.6%-14.5%)individuals were in North Texas (Figure 2).
The Texas yearly mean age-adjusted HPV-related cancer IR for years 2016 to 2020 was 22.1 per 100 000 female individuals and 14.3 per 100 000 male individuals.The county-level HPV-related cancer IR ranged from 0 to 154.2 per 100 000 for female individuals and 0 to 64.9 per 100 000 for male individuals (Figure 3).Most counties that had HPV-related cancer IRs within the highest tercile for female individuals (23.8 to 154.2 per 100 000) were in North Texas.Similarly, most counties with the highest tercile of HPV-related cancer IRs for male individuals (16.4 to 64.9 per 100 000) were in North Texas (Figure 3).Complete results of county-level HPV vaccination initiation and up-to-date estimates as well as HPV-related cancer IRs are available online in eTable 1 in Supplement 1 for female individuals and eTable 2 in Supplement 1 for male individuals.For HSRs, HSR 2/3 (35.7% and 33.7%) and HSR 4/5N (36.0% and 33.3%) had lower HPV vaccination initiation rates for both female and male children and teenagers compared with other HSRs (Figure 1).HSR 9/10 (46.5% and 46.4%) and HSR 11 (43.9% and 43.5%) had higher HPV vaccination rate for both female and male children and teenagers compared with other HSRs as well as the state average rate (40.9%) (Figure 1).
The HPV-related cancer IRs as well as HPV vaccination initiation rate across the counties were examined concurrently in bivariate choropleth maps (Figure 3).Up-to-date (male) Up-to-date (female) Up-to-date (state average) Initiated (male) Initiated (female) Initiated (state average) coded dark purple had the highest rates of vaccination and the lowest rates of HPV-related cancer.
South Texas had the lowest incidence of HPV-related cancers for both female (Յ17.2 per 100 000) and male (Յ10.6 per 100 000) individuals and the most counties with high HPV vaccination initiation (Ն41.7%for female individuals; Ն38.9% for male individuals) and up-to-date rates (Ն19.8%for female individuals; Ն17.8% for male individuals) (Figure 3 and Figure 4).Complete results of a Spearmen correlation matrix between HPV vaccination initiation, HPV vaccination up-todate status, and HPV-related cancer incidence across all counties, separately by sex, are available in eTable 3 in Supplement 1 for female individuals and eTable 4 in Supplement 1 for male individuals.
to 17 years who initiated or were up-to-date as the numerator for the rate and the annual total population of children and teenagers aged 9 to 17 years from the DSHS as the denominator.Based on the years that Centers for Disease Control and Prevention's Advisory Council on Immunization Practices recommended the HPV vaccine universally, HPV vaccination rates by county and HSR region were calculated for female individuals from 2006 to 2022 and for male individuals from 2011 to 2022.Excel version XX (Microsoft) was used to carry out the temporal trend analyses.
total of 32 270 243 children and teenagers (65.8% female individuals and 34.2% male individuals) and 22 490 105 individuals aged 20 years and older (50.7% female individuals and 49.3% male individuals) were included.HPV vaccination series initiation among children and teenagers aged 9 to 17 years in the state of Texas increased among female individuals from 0% in 2006 to 40.9% in 2022 Some of the counties and HSRs in Texas are doing well in terms of coverage, whereas others are lagging.Overall, HSR 2/3 and HSR 4/5N and more counties in North Texas are far behind regarding HPV vaccination uptake compared with East, West, and South regions.

Figure 2 .
Figure 2. Human Papillomavirus Vaccine Initiation and Up-to-Date Estimates Among Female and Male Individuals From 2021 to 2022, by County Initiation (female) A highlighting the state's low HPV vaccination rates.Available statistics indicate that the total population estimates of individuals aged 12 to 17 years in Texas for year 2022 was 2 635 339 compared with 1 525 176 for Florida, 1 378 121 for New York, 937 432 for Pennsylvania, and 25 810 168 for the rest of the United States, 12 which makes it important to raise HPV vaccination coverage rate among this age group in Texas.

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The counties color coded hot pink had the highest rate of HPV-related cancer and the lowest level of vaccine initiation, while counties Downloaded from jamanetwork.comby guest on 09/13/2024 Figure 1.Human Papillomavirus Vaccine Initiation and Up-to-Date Estimates Among Female and Male Individuals From 2006 to 2022, by Texas Health Service Region