In this study, we examined the rate of completion of the 3-dose HPV4 vaccine series and adherence to the recommended intervals between doses among female patients who initiated the vaccine series in academic clinical settings. We also examined factors associated with successful completion of the vaccine series.
In this population, we found a completion rate among those who initiated vaccination of 14.3% by 7 months. This is similar to the 13% completion rate by 6 months reported among those who initiated vaccination in a longitudinal study of women 13 to 26 years old recruited from the same adolescent base clinic shortly after HPV4 licensure.19
However, our finding of a completion rate of 27.7% by 12 months is substantially lower than previously reported HPV4 vaccine-completion rates. In a managed health care organization, there was a 42.8% completion rate within 12 months among 9- to 26-year-old women who received their first HPV4 dose between October 2006 and March 2007.20
The rate of HPV4 vaccine series completion in our population was also lower than most reports of completion rates among those who initiated vaccination for other adolescent vaccines. Reported completion rates for the 3-dose hepatitis B vaccine have ranged from 11% to 73% in health maintenance organizations21–23
and from 72% to 87% in academic health centers using reminder-recall and patient incentives for vaccination.24,25
Examining more than half a million patient records from 7 managed-care organizations participating in the Vaccine Safety Datalink project between 1997 and 2004, Nelson et al23
found that rates of hepatitis B vaccine completion within 1 year of the first dose among adolescents aged 9 to 12 years and 13 to 17 years were 63.4% and 45.1%, respectively. Completion rates of the 2-dose hepatitis A vaccine in the same age groups were 48.4% and 40.3%, respectively. Completion of the 2-dose varicella vaccine was 35.9% among 13- to 17-year-olds. Additional research is needed to understand reasons for nonadherence to adolescent vaccination recommendations and to test interventions to improve adherence.
Few women in our population received doses at intervals earlier than recommended, but most received the second and third doses at intervals that were substantially longer than recommended. Despite a provisional change in recommended intervals (dose 2 to be given 1–2 months after dose 1) in late 200926
that occurred after the completion of our analyses, our definitions of adherence were not compromised. Therefore, our reported rates reflect adherence to the current and previous recommendations.
In comparison to HPV4 clinical trials, mean completion rates in this population were lower and mean intervals between doses were longer (mean time between first and second dose was 6 months and between first and third dose was 11 months). Clinical improvement efforts should focus on timing of the second dose as well as completion of 3 doses. Little is known about the impact of incomplete vaccination and prolonged intervals on the immunogenicity and efficacy of HPV4 vaccine. Studies of hepatitis B vaccination reveal that a longer interval between doses 1 and 2 is associated with decreased antibody response.27,28
However, longer intervals between doses 2 and 3 have been associated with increased antibody response.27,29,30
This raises the concern, especially when dose 2 is delayed, that female patients may have lower immune responses than expected from published clinical trials. Lower immune responses could adversely impact vaccine efficacy or the duration of protection. Studies to examine immunogenicity at various dosing intervals are ongoing. However, given the robust immune response to each HPV4 dose and the importance of having immune protection before exposure to HPV, there is no current evidence to support withholding or delaying initiation of the HPV4 vaccine even if the clinician or patient is concerned that subsequent doses may be late. Current recommendations are to give dose 2 and 3 with no need to restart the series even if doses are substantially late.9,26
Identification of variables associated with adherence to immunization schedules in adolescents may help to explain reasons underlying poor adherence. Although 11- to 12-year-olds had the lowest rate of completion in unadjusted analyses, differences in completion rates according to age were not statistically significant in multivariable models. In addition, despite the fact that 19- to 26-year-olds were not eligible for the Vaccines for Children program, completion was higher in this age group compared with 9- to 18-year-olds in unadjusted analyses. The majority of older female patients used private insurance. Both public and private insurance coverage were independently associated with completion, implying that insurance coverage is a key driver of vaccination completion.
An increased rate of completion was seen among patients who received DMPA. DMPA is an injectable form of birth control requiring clinic visits every 3 months, presumably increasing opportunities for vaccine delivery. Also, many women who use DMPA are or intend to be sexually active; thus, these women and/or their clinicians may perceive more need for vaccination against an infection transmitted through sexual contact. In addition, these women may be more accepting of intramuscular injections. This finding supports evidence showing the importance of decreasing missed opportunities for vaccination.7
Because adolescents have a relatively low number of visits for preventive health care compared with visits for nonpreventive health care and visits to subspecialists,31,32
the importance of decreasing missed opportunities for vaccination, including extending immunization programs beyond the medical home, is magnified.33–35
Within our organization, these findings have strengthened efforts to improve established practices and introduce interventions to increase immunization rates.7
Female patients who self-identified as black, compared with those who self-identified as white, were less likely to complete vaccination within 7 and 12 months. This is consistent with previous reports of HPV4 vaccine completion8,20,36,37
as well as hepatitis B vaccine completion in adolescents.25,30,38
This disparity is concerning given that the incidence of and mortality from cervical cancer is higher among black women than white women in our community and nationally.39–41
The reasons underlying racial disparities in completion are unclear, but beliefs and attitudes may play a role42
as may access to health care. Findings from studies in which knowledge, beliefs, and attitudes about initiation of HPV vaccination are examined reveal that differences according to race exist.43,44
Factors associated with initiating versus completing immunization may differ19,45
: in future studies, factors that underlie the association between race and completion of the HVP4 series should be examined. Regardless, the health care community must be vigilant in providing education and access to all patients.
Clinic location was not associated with completion when controlling for patient-related factors. In the unadjusted analysis, differences in completion between clinic locations, including differences between the adolescent and pediatric clinics, were most likely caused by variations in the patient populations served, clinic policies, and clinician practice patterns that were immeasurable with accessible data sources. Given the limitations of the available data, we were unable to reliably measure additional factors that may influence completion, such as patient refusal of vaccination, for reasons such as adverse events after previous doses; other patient visits during the study period; and patient, parent, or provider vaccination attitudes and beliefs. In future studies, immunization status for HPV and other adolescent vaccines should be compared. Given this study involved only 1 medical center, and the participants were predominantly black, the findings may not be generalizable to other populations.
Limitations of the data set prevented reliable calculation of rate of initiation among all female patients who seek care at Cincinnati Children's Hospital Medical Center. To optimize HPV4 vaccine coverage, researchers who conduct future studies should aim to understand rates of and reasons for not initiating vaccination. After the study period ended, HPV4 vaccine received a permissive recommendation for use in male patients. It will be important to assess factors related to HPV4 vaccine adherence in male patients as they could differ from female patients. In addition, it is possible that subjects in this study received HPV4 doses at clinics outside of our medical center. Overall, this was unlikely to have had a large impact on our results because the pediatric and adolescent clinics in this study are the largest Medicaid providers in the area and have stable patient populations.