Completion of the human papillomavirus (HPV) vaccine in a large percentage of young females is an important goal to prevent anogenital cancers associated with HPV. The current study examined whether the percentage of insured women who complete the vaccine series has changed across time, and how provider type and age at initiation affects rates of completion.
This retrospective cohort study used administrative data from a private insurance company. The study included 271,976 females in whom the HPV vaccine series was initiated and who had been continuously enrolled in their respective insurance plan for 365 days after vaccine initiation. Multivariate logistic regression was used to determine the odds of completing the vaccine series within 365 days after initiation.
Females aged 13 years to 18 years, 19 years to 26 years, and ≥ 27 years were found to be less likely than those ages 9 years to 12 years to complete their HPV vaccine series. Obstetricians/gynecologists were more likely to administer vaccines to completers than pediatricians, whereas clinics, nurses, family care practitioners, and specialists were less likely to administer initial vaccines to completers compared with pediatricians. The results of the current study also found that females aged 9 years to 12 years and 13 years to 18 years had lower odds of completing the HPV vaccine series for each subsequent year compared with those aged 19 years to 26 years and ≥ 27 years.
Human papillomavirus (HPV) is a highly prevalent sexually transmitted disease that has been linked to genital warts as well as oropharyngeal and anogenital cancers.1, 2 A vaccine that is effective in preventing HPV type 6-, type 11-, type 16-, and type 18-related premalignant genital or anal lesions and genital warts in women3-6 was licensed by the US Food and Drug Administration (FDA) for females aged 9 years to 26 years in June 2006. The quadrivalent vaccine is given as a series of 3 injections, with the recommendation that the second vaccination be administered 1 to 2 months after the first, and the third vaccination be administered 6 months after the initial injection. It is important that the 3-dose series is completed within the recommended time frame because the efficacy and duration of protection are not well established for incomplete immunizations.7, 8
Recommendations that are based on age and various policies concerning the requirement for HPV vaccination from state to state may affect completion rates. In 2006, the Advisory Committee on Immunization Practices (ACIP) recommended the vaccine for females aged 11 years to 12 years, although it can be administered to girls as young as 9 years. The ACIP also recommends catch-up vaccinations for females aged 13 years to 26 years who have not been vaccinated or have not received the full series. The HPV vaccination is not required to enroll in the majority of public schools, with the exception of Washington, DC and Virginia, which passed legislation in 2007 requiring vaccination for sixth grade girls with an option for parents to opt out. Because in most states the HPV vaccine is not required to be enrolled in schools, uptake and completion rates may be lower than those for other vaccines that are required.
Various characteristics may affect whether the HPV vaccine series is completed. For example, areas with a higher concentration of pediatricians have been shown to have a higher percentage of children who are up to date on all of their vaccinations.9 Pediatricians may be an important advocate for HPV vaccinations among females aged 11 years to 12 years, who are presumably receiving the bulk of the vaccinations, and may be more likely to encourage completion of the series than other types of physicians. However, it is important to know whether there are differences in completion rates between pediatricians and other types of physicians who initiate the HPV vaccine series because this could affect older adolescents, who may be more likely to visit family physicians or gynecologists to receive their vaccinations. Furthermore, a study of claims data in Maryland found that publicly insured HPV vaccine initiators are more likely to complete the series than privately insured initiators.10 Therefore, it is important to determine what factors may be related to completing the vaccine series among privately insured females, and how completion among the privately insured has changed since the vaccine was licensed by the FDA.
The purpose of the current study was to estimate the percentage of insured women who complete the HPV vaccine series over time. In addition, the effects of age and type of health provider on completion among enrollees of a private insurance program that is available in all 50 states were examined. This study also explored the off-label administration of the HPV quadrivalent vaccine among women aged >26 years when the initial dose was administered.
MATERIALS AND METHODS
Participants and Procedure
This retrospective cohort study used administrative health data from a large health insurance company. Enrollees in this private health insurance plan were located in the United States, with a higher concentration residing in the Southern states. During the study period, which encompassed 2006 to 2010, a total of 20,492,526 individuals were included in the data set. Records for 277,725 individual subjects were obtained that 1) contained a Current Procedural Terminology (CPT) code for HPV quadrivalent vaccine (90649), 2) included only patients who had been enrolled continuously for 365 days from the initiation of the vaccine series, and 3) were from patients who were at least 9 years of age. Males (n = 987), cases that included claims for the bivalent HPV vaccine (n = 53), subjects from an unknown region (n = 1033) of the United States, and subjects who received their first vaccine from an unknown provider type (n = 3676) were excluded due to low frequencies and a lack of information regarding focal variables. The final number of vaccine initiators included in the current study was 271,976. Informed consent was not obtained because this study was an analysis of deidentified secondary data. The current study was exempted from full review by the institutional review board of the University of Texas Medical Branch in Galveston.
Subjects who had at least 3 claims for the quadrivalent HPV vaccine on 3 different dates (that were at least 10 days apart) within 365 days were considered completers. For data analysis, completed vaccination series were dichotomized as 1 versus 0 for those with completed versus noncompleted vaccination series, respectively. Enrollees who received only 1 or 2 doses of the vaccine were also examined in this study. Initiating enrollees were counted as only 1 case across time, and were not included in the data set more than once regardless of the date of subsequent vaccine claims. For an enrollee to be classified as receiving 2 vaccines, they must have had claims for 2 HPV vaccine injections during the study period on 2 different dates.
Enrollees were categorized into 4 groups based on their age at the time of first vaccination: aged 9 years to 12 years, aged 13 years to 18 years, aged 19 years to 26 years, and aged >26 years. Females aged 9 years to 10 years were included with those aged 11 years to 12 years in the comparison group because of the small number of females aged 9 years to 10 years who received the vaccine. Females aged 13 years to 18years are included in the catch-up recommendations issued by the ACIP, but are still likely to have substantial parental involvement in their decision to return for additional doses of vaccines. Women aged 19 years to 26 years are also included in the catch-up group, but may not have as much parental involvement in their decision to return for additional doses as the younger groups. The group of individuals aged ≥27 years are the adults who received the vaccination on an off-label basis.
There were 346 insurance codes for the type of providers who filed a claim for a HPV vaccination; these were grouped into 8 categories. “Allied health” included nonphysician providers such as chiropractors and nutritionists. “Clinic, hospital, and other facilities” included hospitals, clinics, and other facilities, such as extended care or outpatient facilities. Although a nurse or physician may have provided the vaccine in these facilities, that information was not available; hence, their inclusion in a separate category. The “nurse” category included nurses, such as nurse midwives, nurse practitioners, or nurses with training in a medical specialty. “Obstetrician/gynecologist” included obstetricians or gynecologists. The “pediatrician” category included pediatricians and specialists in adolescent medicine. The “family care practitioner, internist” category included family practitioners, general practitioners, or internal medicine physicians. The “specialist” category included physicians not already included who specialized in a specific area of medicine, such as allergists or cardiovascular disease specialists.
The United States was divided into 6 regions: Northeast, Mid-Atlantic, South, Midwest, Southwest, and West. The Northeast included Connecticut, Maine, Massachusetts, New Hampshire, Rhode Island, and Vermont. The Mid-Atlantic included Delaware, Maryland, New Jersey, New York, Pennsylvania, and Washington, DC. The South included Alabama, Arkansas, Florida, Georgia, Kentucky, Louisiana, Mississippi, North Carolina, South Carolina, Tennessee, Virginia, and West Virginia. The Midwest included Illinois, Indiana, Iowa, Kansas, Michigan, Minnesota, Missouri, Nebraska, North Dakota, Ohio, South Dakota, and Wisconsin. The Southwest included Arizona, New Mexico, Oklahoma, and Texas. The West included Alaska, Colorado, California, Hawaii, Idaho, Montana, Nevada, Oregon, Utah, Washington, and Wyoming. The South was the comparison category because it represented the largest proportion of enrollees.
Year at first vaccination
The year at first vaccination included 2006 through 2009. The year 2010 was not included because of the requirement that subjects be enrolled continuously for 365 days in their respective insurance plan from the time of vaccination to be included in the current study. Therefore, any subject in whom vaccination was initiated after January 1, 2010 would not have been enrolled for 365 days from the date of initiation because the data did not extend past December 31, 2010. For analyses that examined trends across time for each age group, year at first vaccination was included as a continuous variable.
Subjects were classified into 4 age groups. For each age group, the percentage completion for year of initiation was graphed. Subjects were then stratified by the number of vaccinations that they received, and the percentages that received 1, 2, or 3 vaccinations were graphed by year of initiation. Student t tests and chi-square tests were used for bivariate associations for continuous and categorical variables, respectively. Logistic regression analysis was used to evaluate factors associated with vaccine completion. Because the trend of completion across time appeared to vary by age groups, we also examined the age and time interaction in the logistic regression model. The data analysis for this study was performed using SAS statistical software (version 9.2; SAS Institute Inc, Cary, NC).
Descriptive characteristics were divided by vaccination completion (Table 1). In this sample, 168,170 females received ≥1 vaccinations and did not complete the series within 365 days, whereas 103,806 enrollees (38.2%) received 3 vaccinations within 365 days and were considered completers. It should be noted that 286 enrollees had claims for at least 3 doses, but these were not received within 365 days and therefore were not considered complete. In addition, 1153 females received >3 doses of the HPV vaccine. Of those women, 876 were considered completers because 2 of those doses were received within 365 days of a previous dose. The majority of subjects (98.0%) were aged ≤ 26 years at the time of vaccine initiation. Pediatricians administered a high percentage of initial vaccines (47.4%), and 29.2% of subjects lived in Southern states. Females who received their first 3 vaccinations within 365 days received the first 2 vaccines on average 73.9 days (standard deviation [SD], 26.4 days) apart and the second and third vaccinations 136.4 days (SD, 35.5 days) apart. Subjects had been enrolled in their insurance plan for an average of 1731 days (SD, 950 days; range, 365 days-3896 days) from the first day of enrollment until the time that the insurance was dropped or the end of the study period (December 31, 2010). Total vaccination initiation peaked in 2007, with a total of 115,193 subjects having at least 1 claim for a HPV vaccine that year.
Table 1. Descriptive Characteristics of Females with ≥1 quadrivalent HPV Vaccinations (n=271,976)
Across the time period that was assessed for vaccine series completion, the percentage of females who completed the series dropped for those aged 9 years to 12 year, 13 years to 18 years, and 19 years to 26 years (Fig. 1). In those females aged 9 years to 12 years, the percentage of initiators who completed the vaccination series dropped from 57.45% in 2006 to 21.15% in 2009. In the group aged 13 years to 18 years, the completion rate dropped from 54.91% in 2006 to 20.77% in 2009; the same rate dropped from 44.31% in 2006 to 22.61% in 2009 among females aged 19 years to 26 years. In contrast, among the women aged ≥ 27 years, there was an increase in the rate of completion from 15% in 2006 to 26% in 2007 and 26.63% in 2008. However, in 2009, there was a slight decline to 24.47%.
Some females received only 1 or 2 quadrivalent HPV vaccines after vaccine initiation. The percentage of females receiving only 1 vaccine within 365 days increased between 2006 and 2009, from 22.4% of initiators in 2006 to 48.9% of initiators in 2009, crossing over the downward trajectory of patients who completed the series within 365 days between 2006 (50.6% of initiators) and 2009 (21.4%) (Fig. 2). The percentage of initiators who received 2 vaccines only during the 365 days after vaccine initiation, however, remained relatively stable between 2006, with 26.8% of initiators receiving 2 HPV vaccinations compared with 29.7% of initiators in 2009 receiving 2 vaccinations.
After controlling for provider type, geographic region, year at first vaccination, and total length of continuous enrollment, enrollees who were aged 13 years to 18 years at the time of initial vaccination had no significant difference in their odds ratio (OR) of completing the HPV vaccination series than enrollees who were aged 9 years to 12 years at the time of initiation (Table 2). Females aged 19 years to 26 years had 0.76 (95% confidence interval [95% CI], 0.73-0.78) lower odds of completing the vaccine series, and those aged ≥ 27 years had 0.44 (95% CI, 0.41-0.47) lower odds of completing the HPV vaccination series compared with females aged years 9 to 12 years. If the first vaccine was administered by a “clinic, hospital, or other facilities,” a specialist, or by a nurse, the subjects were less likely to complete the series than those who received the vaccination from a pediatrician. Subjects who went to a gynecologist or obstetrician for their first vaccine were more likely to complete the series than those who received their first vaccination from a pediatrician. In contrast, subjects who had a claim from a family care practitioner had slightly lower odds of completing the vaccine series than subjects who received their first vaccination from a pediatrician.
Table 2. Binary Logistic Regression Analysis Estimating ORs of Completing HPV 3-Vaccine Series in 365 Days (n=271,976)
Figure 1 indicates that the groups of females aged 9 years to 12 years and 13 years to 18 years appeared to have a more pronounced decline in the percentage of completers across time compared with those aged 19 years to 26 years and aged ≥ 27 years. This was tested, and it was found that the ORs of completion for each subsequent year of initiation in the group aged 9 years to 12 years (OR, 0.669 [95% CI, 0.664-0.675]) and the group aged 13 years to 18 years (OR, 0.835 [95% CI, 0.832-0.838]) were smaller than those for females aged 19 years to 26 years (OR, 0.922 [95% CI, 0.920-0.923]) and those aged ≥ 27 years (OR, 0.917 [95% CI, 0.915-0.918]) after controlling for provider type and geographic region. This indicates that the decrease in the OR of vaccine series completion by year is more pronounced among the younger vaccine initiators than among the older vaccine initiators.
Among females aged 9 years to 26 years with private insurance, we observed a decrease in the percentage of initiators who completed the quadrivalent HPV vaccine series between 2006 and 2009. Two other studies from state-level data had similar results. One of these previous studies found comparable percentages of completion among initiators, whereas the other also demonstrated a declining trend in HPV vaccine completion between 2006 and 2008, which is similar to our observations.11, 12 Furthermore, the results of the current study found that females aged 9 years to 12 years and 13 years to 18 years had the steepest declines in completion compared with the other 2 age groups. This is concerning because the average age of sexual debut in the United States is 17.4 years and may be lower than 14 years in 5% of females.13 Thus, most women need to complete the series before age 18 years to obtain maximum efficacy from the vaccine.
Although completion decreased over time, it is important to note that the percentage of females who received only 1 injection during the study period increased over the study interval. These trends may indicate that physicians are focusing more on initiating the vaccine series as time passes, but may not be following up with their patients for subsequent doses of the vaccine. It is also possible that adverse socioeconomic conditions discouraged patients from completion because the copay or deductible for the vaccination became burdensome for them as the economic recession progressed. To improve completion for the HPV vaccine series, physicians of all types should be encouraged to use various methods to remind parents and patients to return to the clinic to receive the remaining doses. Calling patients has been shown to be an effective method of reminding them to return for immunizations of all types, although it was not found to be effective in one study of adolescents in which there were problems with telephone number discontinuity.14 Recently, texting has been shown to improve rates of return for a subsequent HPV vaccine dose.15 This may offer a less expensive alternative to telephone calls to remind patients to return for vaccinations.
In the current study sample, there were differences in the ORs of administering the first vaccine to completers by physician specialties. “Clinics, hospitals, and other facilities,” nurses, specialists, and family practitioners were found to be less likely to administer a first vaccination to completers than pediatricians. However, it was observed that obstetricians/gynecologists were more likely to administer the first dose of the vaccine to completers than pediatricians. Similar to the results in the current study, vaccine initiators in North Carolina who received their injections from family providers or hospitals were less likely to complete the vaccine series than those who received them from pediatricians.12 This indicates that physicians who initiate the HPV vaccination, but may not be as familiar with the recommendations of the series or may not be the primary care provider of the patient, need to stress the importance of completing the series and follow up with their patients. This is particularly important in clinics, hospitals, and other facilities in which patients may not seek continuous care. If the patient returns to these providers, the opportunity should be taken to administer remaining vaccinations because it has been shown that when patients do return to the same clinic facilities, they often do not receive additional vaccinations, even if their visit coincides with the time the vaccinations are due.16 Providing the facilities with the means to flag the records of patients who have received the first vaccine may improve completion rates for those patients who do return. The increasing use of electronic medical records may make it easier for facilities to do this.
This study also included data on those women aged > 26 years who received HPV vaccinations on an off-label basis. Older women who initiate this vaccine series may view themselves as having a higher risk of contracting HPV, which may account for the demand we observed among this age group. Although the vaccine is currently not recommended for women aged > 26 years, research indicates that it is safe and effective in the development of immunogenicity to HPV infections in women up to aged 45 years.17 Future research should investigate the benefits of extending current vaccine recommendations to include older women so that physicians can adequately counsel those who express interest.
The insurance records we examined also indicated that some males initiated the HPV vaccine before it was licensed or recommended for use in this population. They were excluded from the current study because the FDA did not license the quadrivalent vaccine for routine use in males until October 2009. Its use in males was not recommended by the ACIP until October 2011, at which time they changed their recommendations to include initial vaccinations for boys aged 11 years to 12 years with a catch-up vaccination for those aged 13 years to 21 years who had not already been vaccinated. They also stated that males as young as 9 years and up to 26 years of age could receive the vaccine. The males in this database who received the vaccine must have been very motivated, considering the difficulties they likely would have encountered in finding a physician who would administer the vaccine outside of FDA licensure. Economic research has indicated that if an adequate percentage of women are not vaccinated, then vaccinating males is a cost-effective method of preventing genital warts and precancerous conditions related to HPV types 6/11/16/18 among women.18, 19 The low prevalence of females who have initiated and completed the HPV vaccine series in the United States20 thus far indicates that vaccination of males would not only decrease their risk of genital warts and several cancers, but also help to reduce the burden of cervical cancer in the United States.
The current study was not able to capture those enrollees who dropped the insurance plan they had when they received the first vaccine dose but completed the series later, which may have led to a loss of enrollees who completed the series of vaccinations. However, it is likely that the percentage who completed is higher among enrollees who were continuously enrolled in their insurance plan, because it indicates more stability in their financial situation. Therefore, the results of the current study are likely to be conservative estimates of HPV vaccination completion rates among insured females. In addition, sociodemographic characteristics were not available, which may have introduced some bias into the study that cannot be addressed.
The current study only assessed the percentage of females who completed the quadrivalent HPV vaccine, and did not assess the percentage who completed the bivalent HPV vaccine. However, the bivalent vaccine is not commonly used in the United States, and there were very few cases in which the vaccine was initiated or that included a code for the bivalent HPV vaccine in the claims data set. Therefore, it is unlikely that including these cases would have changed the analyses. Furthermore, completion was defined as 3 vaccinations within 365 days, which means that 286 subjects did receive at least 3 doses but not in 1 year's time. Although these patients may gain adequate immunity from 3 vaccinations that were administered outside of 1 year's time, the format that was chosen for this study follows more closely the guidelines of the ACIP.
Among insured females in the current study, younger females had a noted decrease in the ORs of completing each year compared with older females. This decrease could reduce the effectiveness of the vaccine in preventing HPV that is associated with anogenital malignancies. However, more females received 1 vaccine, indicating a shift in emphasis from completion to simple initiation among providers of insured females. Thus, it is important that all providers who initiate the HPV vaccine series make an effort to follow up with and stress the importance of completing the vaccine series to their patients. Calling or texting patients or their parents may be important methods of increasing HPV vaccine series completion among this population.
Federal support for this study was provided by the Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD) as follows: to Dr. Hirth as a National Research Service Award (NRSA) postdoctoral fellow under an institutional training grant (T32HD055163; Principal Investigator: A. Berenson) and to Dr. Berenson, under a midcareer investigator award in patient-oriented research (K24HD043659; Principal Investigator: A. Berenson).The content is solely the responsibility of the authors and does not necessarily represent the official views of the NICHD or the National Institutes of Health.