The National Cancer Institute defines cancer health disparities as the adverse differences in incidence, prevalence, survivorship, and cancer-related morbidity among population groups.1 Hispanic and black women have the highest rates of cervical cancer incidence and mortality when compared with white women in the United States. A recent analysis revealed an even larger racial disparity in the mortality gap: cervical cancer death rates were found to be 10.1 per 100,000 black women compared with 4.7 per 100,000 white women when correcting for hysterectomy.2 These disparities underscore the need for population-level cancer prevention strategies.2–6
Immunization against human papillomavirus (HPV) has the opportunity to provide primary prevention among all racial and ethnic groups; however, HPV vaccine coverage in the United States remains low.7,8 Human papillomavirus vaccination has been shown to be safe and highly effective.7 Centers for Disease Control and Prevention (CDC) national guidelines call for routine vaccine administration to girls at age 11–12 years and is recommended at ages 9 through 26 years.8,9
Barriers to HPV vaccine series initiation and completion have been identified. Socioeconomic factors include health care provider recommendation, education level of parents, lack of receiving other adolescent vaccinations, insurance status, and race and ethnicity.10–14 Acculturation, defined as the process by which certain groups adopt the attitudes, values, and practices of a host society, may be an important factor in health care utilization.15–18 English proficiency and preferred interview language have been used as a proxy for acculturation.19,20
The primary objective of this study was to compare HPV vaccine completion rates by race and ethnicity in an integrated health care system. Our secondary objective was to determine an association between acculturation and the likelihood of vaccine completion among the diverse Hispanic population in northern California.
MATERIALS AND METHODS
A retrospective cohort study was conducted among female adolescents and young women who initiated the HPV vaccine series in the Kaiser Permanente Northern California system between January 1, 2008, and December 31, 2012. We collected data from electronic medical records of female members of Kaiser Permanente Northern California who received an initial dose of the recombinant quadrivalent vaccine (HPV-4) at ages 11–26 years as per National CDC guidelines between 2008 and 2012.8 Inclusion criteria were continuous enrollment in the Kaiser Permanente health care plan 1 year before and 1 year after administration of the index vaccination dose as well as administration of each vaccine dose at a Kaiser Permanente Northern California facility. Exclusion criteria were history of cervical dysplasia or neoplasia at the time of vaccine initiation as well as insufficient or lapsed health plan enrollment.
Kaiser Permanente Northern California is a large community-based health care system for which all visits are captured in the integrated electronic medical record system. Vaccine administrations were identified from the Kaiser Immunization and Tracking System. Health plan enrollment history and demographic data, including age, race or ethnicity, preferred written and spoken language, and whether an interpreter was required, were extracted from Kaiser Permanente Northern California electronic administrative databases. Racial and ethnic groups were assigned using a hierarchical algorithm, in which anyone identified as Hispanic ethnicity was categorized as Hispanic. Among those remaining in the cohort, if more than one race was reported, mutually exclusive categories were assigned in the following order: black, Asian or Pacific Islander, Native American, white, or unknown. Relevant medical history was identified from inpatient and outpatient diagnoses documented in health plan utilization data sources and disease registries. The cohort member's preferred written and spoken language was used as a proxy for acculturation. The degree of acculturation among Hispanic females was categorized as high (English was preferred spoken and written language and interpreter was not required), moderate (Spanish-speaking, not requiring an interpreter, with Spanish or English as preferred written language), or low (Spanish-speaking, requiring an interpreter, and with Spanish the preferred written language).
All cohort members were HPV-4 vaccine initiators. The primary outcome was the completion of the HPV vaccine series. Given national CDC guidelines at the time of our study, vaccine completion was defined as the completion of at least three vaccine injections for all age groups. Completion rates as defined by having receiving at least two dose injections in the youngest age group (through age 14 years) were also evaluated as per the updated 2016 CDC recommendations for a two-dose series for this age group.21 The follow-up duration for this study was defined as 1 year from the index vaccination dose, ensuring equal follow-up time among all ages and racial and ethnic group subsets.
A power calculation was performed based on the 2010 National Health Interview Survey in which 15% of non-Hispanic white females and 10% of Hispanic females were estimated to complete the vaccine series.22 We performed a two-group continuity-corrected χ2 test with a 0.05 two-sided significance level comparing the chances of completing the series. Our calculations indicated that a difference in completion rates between the two groups (odds ratio of 0.63) could be detected at 80% power with sample sizes of 1,340 and 515 for non-Hispanic and Hispanic females, respectively. Our final cohort was significantly larger than this sample size.
The prevalence of vaccine completion was determined for each race and ethnicity and predetermined age categories: younger adolescents (11–14 years), teens (15–17 years), and young adults (18–26 years). Among Hispanic females, vaccine series completion was also determined by the degree of Hispanic acculturation. Bivariate analyses were conducted to compare the proportion that completed the vaccine series by race and ethnicity, age, and category of acculturation using χ2 tests. Mean age at vaccine initiation was compared among different groups using analysis of variance. For prevalence of HPV vaccine series completion, point estimates and 95% CIs were generated. Logistic regression modeling was used to compare odd ratios for HPV vaccine series completion among racial and ethnic groups and degree of acculturation after adjusting for age at vaccine initiation. A two-sided α level of 0.05 was considered statistically significant.
All analyses were conducted using SAS 9.3. The Kaiser Foundation Research Institute's institutional review board approved this study with waiver of consent. Funding was through Kaiser Permanente Northern California Graduate Medical Education Residency Research, funded by Kaiser Foundation Hospitals.
A total of 102,186 female members initiated the HPV vaccine series in the Kaiser Permanente Northern California system during the 4-year study period (Fig. 1). Among these, 134 were excluded because of a concurrent diagnosis of cervical malignancy (n=1), cervical carcinoma in situ (n=36), or cervical intraepithelial neoplasia (n=97). The final cohort consisted of 102,052 females. Of these, 27.5% (n=28,084) were Hispanic and the remaining 72.5% (n=73,968) were non-Hispanic (Fig. 1). The study cohort was representative of the overall female Kaiser Permanente Northern California community with no statistical difference in race between the cohort and general Kaiser Permanente Northern California membership in the same age group from 2008 through 2012 (cohort vs Kaiser Permanente Northern California membership: white, 39.1% vs 42.5%; black, 10.5% vs 10.1%; Asian or Pacific Islander, 20.1% vs 18.9%; Hispanic 27.5% vs 27.7%; Native American, 0.8% for both, data not shown). The mean age of vaccine initiation was 14.5 years (SD 3.4). The majority of females who initiated vaccination were younger adolescents (n=60,032 [58.8%]) followed by teens (n=27,668 [27.1%]) and young adults (n=14,349 [14.1%]). Demographics are shown in Table 1.
A total of 41.0% of the cohort (41,847/102,052) who initiated the HPV-4 vaccine during the study period completed the series. Prevalence point estimates and 95% CIs are shown in Table 2. The highest prevalence for vaccine series completion was seen among Asian and Pacific Islander patients (49.5%) and the lowest among black patients (28.7%) (P<.001). Among Hispanic patients, 38.9% completed the vaccine series and the prevalence of vaccine completion varied by degree of acculturation. We found an inverse relationship between acculturation and vaccine completion rates: the lowest acculturated group had the highest rate of vaccine completion (44.2%) compared with the moderate acculturation group (40.6%) and the high acculturation group (37.2%) as shown in Table 2 (P<.001).
Logistic regression modeling was used to examine the association between vaccine series completion and racial and ethnic groups for the full cohort (Table 3) and the degree of acculturation among Hispanic patients only (Table 4). After adjusting for age at vaccine initiation, black and Hispanic patients were less likely to complete the series compared with white patients. The odds of vaccine completion were 47% and 18% lower among black patients and Hispanic patients, respectively, compared with white patients (P<.001). In contrast, Asian or Pacific Islander patients were more likely to complete the vaccine series. The odds of vaccine completion was 1.3 times higher among Asian or Pacific Islander patients compared with white patients (P<.001; Table 3). Among the Hispanic group, the odds of series completion was 23% and 13% higher for the low and moderately acculturated groups, respectively, compared with the highest level of acculturation (P<.01; Table 4).
Among younger adolescents, HPV vaccine completion rates were also determined as defined by completion of two or more doses given the updated 2016 CDC recommendations after the study period. Among 60,032 girls who initiated vaccination at ages 14 years and younger, a total of 69.7% (95% CI 69.3–70.1%) completed at least two vaccine doses. Logistic regression modeling with this definition of vaccine completion maintained our findings of statistically significant decreased age-adjusted odds of vaccine completion among Hispanic and black patients as well as Hispanic acculturation: age-adjusted odds of vaccine completion defined as at least two vaccine doses among low compared with highly acculturated Hispanic patients in this age group was 1.29 (95% CI 1.29–1.38; data not shown).
Human papillomavirus vaccine coverage across all racial and ethnic groups has the opportunity to not only decrease the overall burden of HPV-related cancer; this strategy might also reduce cancer disparities that exist in the United States.7 Human papillomavirus vaccination, however, remains suboptimal with an estimated 43% of adolescents completing their recommended series in 2016.23 Our retrospective analysis of females in an integrated health care system showed similarly low vaccine completion rates that varied by race and ethnicity despite having the same health care coverage.
Our findings are consistent with previous investigations showing decreased HPV vaccine uptake among minority ethnic young women in high-income countries.24–28 Other barriers associated with low HPV vaccine rates include socioeconomic status, health care insurance, mistrust of vaccination programs, health care provider recommendation, lack of receiving other adolescent vaccinations, and education level of parents.10–13,25,27,29–31 Previous studies have shown that non-Hispanic black women compared with white women are not only less likely to receive an initial vaccine recommendation from health care providers, but also more likely to miss a clinical opportunity for subsequent vaccination.24,32 Identifying these disparities and barriers to HPV vaccination is needed to implement effective population-level cancer prevention.4,33
Within the Hispanic population specifically, acculturation may affect health outcomes including HPV vaccination.15,17 In our study, the degree of Hispanic acculturation was inversely associated with vaccine completion. This “epidemiologic paradox,” in which low acculturation confers health benefits, has been demonstrated in prior studies showing improved rates of infant morbidity and mortality among low acculturated Hispanics.34–36 Low acculturated groups might exhibit higher adherence to medical recommendations or have social networks that encourage healthy behaviors.37–39 A recent investigation among Latina college women highlighted the preference of this group to receive an HPV vaccine recommendation from a Latin health care provider.31 Increasing the diversity and cultural awareness of health care providers may decrease medical mistrust and increase HPV vaccination adherence.31
National guidelines recommend routine HPV vaccination among girls ages 11–12 years with a recent CDC recommendation for a two-dose rather than three-dose series for immunocompetent females who initiate vaccination before their 15th birthday.8,9,21 The majority (58.8%) of girls who initiated HPV vaccination in our cohort were in this youngest age category and exhibited the highest completion rates compared with their older counterparts. We showed that completion rates in this age group increased to 69.7% when defined as having received at least two doses. This new practice recommendation will likely result in better overall vaccination coverage.
Focusing implementation efforts on routine vaccination at annual pediatric visits at ages 11–12 years may be an effective targeted strategy. One method is to recommend the three adolescent vaccinations of meningitis, tetanus, diphtheria, and acellular pertussis, and HPV as a bundle.40 Various strategies for practice and community-level interventions to improve HPV vaccination have been suggested, including physician-focused education, school-based programs, social marketing efforts, and patient reminders.41 Within the Kaiser Permanente Northern California pediatrics departments, electronic medical record prompts to health care providers for patients who are due for initial and subsequent vaccinations are being used to encourage same-day services. Dedicated nursing staff also provide patient outreach through email and phone reminders to improve follow-up. Although a systematic approach in a large health care system with support services may be effective, scaling up vaccination delivery strategies in primary care practices is challenging.40–43 In addition to sociocultural factors of the patient population, financial and technical considerations should be addressed for choice of an implementation strategy in different clinical settings.41
The strengths of this analysis include the large, diverse cohort of females in an integrated health system in which all vaccination visits are captured electronically. Because this group does not represent the extremes of wealth and is a universally insured population, the observed differences in vaccination uptake by ethnic groups likely reflect cultural rather than economic factors. Limitations include its retrospective design, a limited definition of Hispanic acculturation, lack of acculturation data among other groups, and completion rates among boys. We lack data on the number of females who were eligible for but did not receive vaccination. There may be limited generalizability of our study to other uninsured populations or primary care settings.
Opportunities to prevent HPV-associated cancers are being missed. Despite national recommendations for routine vaccination, administration of this safe and effective vaccine remains far below the Healthy People's goal of 80% HPV vaccine coverage by 2020.44 Recognition of cancer health disparities and improved HPV vaccine administration across all groups is urgently needed.
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