Human papillomavirus (HPV)-associated diseases result in substantial morbidity worldwide. In addition to cervical cancer, HPV has been linked to vulvar, vaginal, and anal cancer; preinvasive disease of the lower genital tract; and genital warts.1–5 In women, HPV-associated diseases are often accompanied by substantial anxiety and result in significant health care expenditures.6–8
Given the burden of HPV-related diseases, the development of strategies to prevent HPV is a major public health concern. The first commercially available HPV vaccine that provides protection against four HPV viral types was approved by the U.S. Food and Drug Administration in 2006.9–13 Subsequently, a bivalent vaccine received U.S. Food and Drug Administration clearance in 2009. Although initially approved for females 9–26 years of age, the quadrivalent vaccine later received approval for males as well.14,15 Both vaccines are highly efficacious in preventing subsequent HPV infection with the relevant viral types.9–15
Despite the efficacy of HPV vaccination, uptake of the vaccines has been modest.16–18 Data from the 2010 National Health Interview Survey noted that among adolescent girls aged 11–17 years, only 29% had received at least one dose of an HPV vaccine, whereas just 14% had completed the series of three doses.16 Data from the 2008 National Health Interview Survey found that just over one-fourth of girls aged 13–17 years had initiated the vaccine series.17 These data suggest not only that the overall use of the HPV vaccine is relatively low, but also that uptake of the vaccine is increasing slowly.
Given the slow uptake of HPV vaccination, strategies to promote vaccination are warranted. One of the difficulties in promoting HPV vaccination stems from the fact that adolescent girls and young women frequently have little interaction with physicians and the medical system. We developed a targeted intervention of HPV vaccination during the postpartum period when women are actively engaged with the health care system. Specifically, we tested the acceptance and compliance of women with a program of HPV vaccination at three time points during the postpartum period: during hospitalization immediately after delivery (first dose), at the 6-week postpartum visit (second dose), and at a subsequent visit for vaccination (third dose).
MATERIALS AND METHODS
We estimated the acceptability of HPV vaccination in postpartum women aged 18–26 years. Women with singleton or multiple gestations who delivered (vaginal, operative vaginal, or by cesarean) between 32 and 44 weeks of gestation were eligible for participation. Patients were enrolled from August 2009 to April 2011. The study sample was drawn from a tertiary, university hospital. The catchment area of our facility captures a large number of minority patients. Study approval was obtained from the institutional review board of Columbia University.
All women were asked to participate in the study on postpartum day 1 or 2. Potential patients were initially asked about their interest in a study to receive the HPV vaccine. If patients were willing to consider the study, they were approached by a research coordinator and completed a questionnaire regarding their knowledge and attitudes toward HPV and HPV-related disease. The HPV questionnaire consisted of 39 items and was administered before obtaining written informed consent so patient responses were unbiased. After completion of the questionnaire, the study was described in detail and informed consent obtained from women interested in participating. Those women who signed informed consent make up the study cohort. After study enrollment, patients also completed a validated 16-item questionnaire to measure decisional conflict with HPV vaccination.19 Decisional conflict is the uncertainty about the correct decision to make when competing choices involving risk and benefit are present.19 Prior work has shown that decisional conflict plays an important role in a number of medical decisions.20,21 All questionnaires were available in both English and Spanish.
The first dose of the HPV vaccine was administered before discharge after delivery. The date and time of each patient's postpartum visit was recorded and the patient instructed that the second dose of vaccine would be administered at the 6-week postpartum visit. Two weeks before the postpartum visit, patients were either called or a letter sent to remind them of the visit. We attempted to contact patients who did not attend the postpartum visit by both telephone and by mail. Patients were encouraged to follow-up for the second dose of vaccine. To comply with the study patients must have received the second dose of vaccine between 42 and 70 days after the first dose. After receipt of the second dose, a date and time for follow-up for the third dose was given to each patient. Patients who did not receive the second vaccination by 70 days after the first dose were removed from study. The vaccine was provided to all participants as part of the study.
The third dose of vaccine was administered in the outpatient setting in a vaccine-specific visit as close to 120 days after the second dose of vaccine as possible. Patients again were given a reminder letter or phone call 2 weeks before their vaccine visit. We attempted to contact noncompliant patients by both telephone and mail and encouraged them to follow-up for vaccination. Patients who did not receive the third vaccine dose by 160 days after the second dose were removed from the study.
After each vaccine dose, a short seven-item questionnaire was administered to determine the patient's satisfaction with the study protocol. The quadrivalent HPV vaccine was used for all vaccinations. The vaccine was administered as an intramuscular injection as previously described.
The primary end point of the study was to estimate compliance in receiving three doses of vaccine when the vaccine was administered in the postpartum setting. With an enrollment of 150 patients, we estimated that we could determine compliance with three doses with a 95% confidence interval (CI) of ±8%. Secondary objectives were to examine the influence of knowledge and decisional conflict on compliance with the vaccine series and to estimate patient satisfaction with postpartum vaccination. The association among demographic characteristics, knowledge and attitudes, and decisional conflict with receipt of three doses of vaccine was estimated using χ2 tests. Multivariable logistic regression models were developed to examine predictors of completion of vaccination. A series of models were developed that included the clinical and demographic characteristics along with individual questions from the HPV knowledge and decisional conflict questionnaires. A P value of <.05 was considered statistically significant. All analyses were conducted using SAS 9.2.
A total of 150 women were enrolled in the study. The clinical and demographic characteristics of the study cohort are displayed in Table 1. The majority of the women were of Hispanic descent (73.3%) and unmarried (77.3%). Most women enrolled in the study had Medicaid coverage (90.0%). Overall, the highest level of education was high school in 36.7%, whereas 42.0% had received some college education. Seventy percent of the women had a vaginal delivery, 27.3% a cesarean delivery, and 2.0% underwent an operative vaginal delivery. Most women (96.0%) delivered between 37 and 41 weeks of gestation and 98.7% had received some prenatal care.
Table 2 displays the baseline knowledge and attitudes about HPV and HPV-related disease. Overall, 80.0% of women had heard of HPV, 44.0% knew HPV was a sexually transmitted disease, 64.0% knew HPV caused cervical cancer, 44.0% knew that HPV caused genital warts, and 45.3% believed that HPV was common. However, misconceptions about HPV were also common; 28.0% of women believed that HPV caused ovarian cancer, 35.3% believed only women could become infected with HPV, and 30.0% thought there was a cure for HPV. Among participants, 65.3% had heard of the HPV vaccine, 43.3% thought the vaccine was safe, and 90.7% believed that it was important to vaccinate to prevent HPV. Within the cohort, 83.3% reported that they would vaccinate their daughter, whereas 80.7% responded that they would vaccinate their son.
When asked whether the decision to receive the HPV vaccine was hard, 12.0% of women strongly agreed and 15.3% agreed (Table 3). Similarly, 24.0% reported that they were unsure whether to undergo vaccination. However, 93.3% agreed or strongly agreed with the statement that they were clear as to the best choice regarding vaccination. Overall, 94.0% of patients felt they knew the benefits of receiving the HPV vaccination and 80% felt that they knew the risks. The majority of women, 97.3%, were satisfied with the choice to undergo HPV vaccination in the postpartum period.
Among the 150 women in the cohort, seven (4.7%, 95% CI 1.9–9.4%) did not receive any doses of the vaccine as a result of patient refusal after enrollment, 62 (41.3%, 95% CI 33.4–49.7%) received one dose, 35 (23.3%, 95% CI 16.8–30.9%) received two doses, and 46 (30.7%, 95% CI 23.4–38.7%) completed the series and received all three doses of the vaccine (Fig. 1). The only individual HPV knowledge and attitudes question that correlated with receipt of three doses of vaccine was whether the respondent thought that the vaccine protected against all types of HPV that cause genital warts and cancer; 31.0% of those who believed this was true completed the vaccine series compared with 61.9% of those who believed that this was false and 24.0% of those who did not know (P=.003) (Table 2). None of the questions on the decisional conflict scale correlated with completion of three doses of the vaccine (Table 3). In a series of multivariable logistic regression models examining knowledge, attitudes, and decisional conflict, none of the individual responses were associated with completion of vaccine series (P>.05).
Table 4 displays patient satisfaction after vaccination. After the first dose of vaccine, 97.2% of women felt it was worthwhile to receive the vaccine, whereas 98.6% said that administration was convenient. When asked, 50.4% of participants said they would not have asked to be vaccinated if they were not part of the study. Among those vaccinated, 99.3% were happy they participated in the study and 97.9% would have recommended the vaccine to a friend. After the first dose, only 17.5% of respondents would rather have made a separate trip for vaccination. These trends were similar when the questionnaire was administered after the second and third doses of vaccine.
Our findings suggest that postpartum administration of the HPV vaccine is feasible and is associated with a high degree of satisfaction among women. Despite the acceptability of this strategy, only 30.7% of enrolled patients completed the three-vaccine series. Baseline knowledge and attitudes about HPV-related disease appeared to have little influence on completion of vaccination among postpartum women.
The United States currently lags far behind other developed countries in HPV vaccination rates. The latest national statistics suggest that fewer than one-third of adolescents have initiated the vaccine series and only 14% have completed all three doses.16 Countries such as Australia and the United Kingdom, which have school-based vaccination programs, have vaccination rates at or over 80%.22 Providing the HPV vaccine free of charge also appears to increase uptake; reported vaccination rates in Italy and Denmark, countries where the vaccine is provided, are 56% and 58%, respectively.22 Because neither school-based vaccination nor providing vaccines without charge appear likely in the United States, novel strategies to promote vaccination are needed.
A number of factors including race, age, area of residence, educational level, income, insurance, attitudes, and knowledge influence HPV vaccination.22–30 Although many of these factors are nonmodifiable, access to the health care system, a modifiable factor, also plays an important role in vaccination.22,25,27 In a cross-sectional survey of females aged 13–26 years, those patients who reported a health care visit within the 6 months before survey had an adjusted odds ratio of 7.31 (95% CI 2.00–26.80) for receiving the HPV vaccine compared with women who had not had a health care visit.25 Given that pregnant women are actively engaged participants in the health care system, we hypothesized that administration of the HPV vaccine during the postpartum hospitalization and at the 6-week postpartum visit would overcome the limited access to the health care system. Our results suggest that this strategy was well accepted by women and most participants reported that they preferred to receive the vaccine while they were already hospitalized or at a clinic appointment as opposed to making a separate visit for vaccination.
Completion of the series of three HPV vaccine injections remains a major challenge.26,30,31 Most studies have suggested that a large percentage of women who initiate vaccination do not complete the recommended three-dose course.16,17,22,31 Widdice and colleagues30 reported that only 28% of women aged 9–26 years completed all three vaccinations within a 12-month timeframe. These investigators noted that black women, users of injectable contraception, and patients with private insurance were more likely to complete the series. The Centers for Disease Control and Prevention reported that completion of three doses was lower among black (23%) and Hispanic populations (23%).18 Given that our cohort was composed of predominantly lower-income, Hispanic patients, our completion rate of 31% compares favorably with prior data.
Knowledge of HPV and HPV-related disease had a relatively minor influence on completion of vaccination in our cohort. Prior studies have suggested that knowledge of HPV, both in young women and their parents, correlates with vaccination.22–24,28,29 In our cohort, knowledge of HPV varied considerably and many women lacked basic knowledge about HPV and the burden of disease associated with HPV. In our series, we were also unable to discern an association between decisional conflict and completion of vaccination. Decisional conflict is defined as the uncertainty about the correct decision to make when competing choices involve risks and benefits. Prior studies have shown that decisional conflict has an important influence in a number of medical decision-making scenarios.19–21 Perhaps the fact that most patients felt relatively confident about the benefits of HPV vaccination explains why decisional conflict exerted only a mild influence on decision-making.
We recognize a number of important limitations in our study. Perhaps most importantly, our study cohort represents a relatively selective population. The majority of women enrolled in the study were Medicaid recipients and from minority ethnic groups. Given that both race and insurance status are important determinants of receipt and completion of HPV vaccination, we believe that further studies of postpartum vaccination in other populations are warranted and that higher completion rates may be achieved. Similarly, we approached women after they had already delivered. Further studies in which women are approached antenatally and by their primary obstetrician may bolster enrollment as well as vaccine completion. Before being approached by the research team, patients were asked if they would be willing to consider a research study. We lack data on why women declined and are unable to estimate the number who had previously been vaccinated. A priori our study was powered to examine rates of vaccine completion and not differences in HPV knowledge or decisional conflict. We cannot exclude the possibility that differences in HPV knowledge and decisional conflict may have become evident if a larger sample of patients were included. Finally, although the efficacy of the quadrivalent HPV vaccine has been described in a number of randomized controlled trials, we did not specifically evaluate the efficacy of the vaccine in the prevention of lower genital tract disease.9,10
In conclusion, we found that a strategy of postpartum HPV vaccination is highly acceptable to women. This paradigm allows for vaccination after delivery and at the 6-week postpartum follow-up visit when women are actively engaged with the health care system. Compared with prior work in high-risk populations, our rate of vaccine completion compares favorably. Further studies to encourage follow-up and vaccine completion are needed, but postpartum vaccination may be one strategy to improve vaccination rates against HPV.
1. Machalek DA, Poynten M, Jin F, Fairley CK, Farnsworth A, Garland SM, et al.. Anal human papillomavirus infection and associated neoplastic lesions in men who have sex with men: a systematic review and meta-analysis. Lancet Oncol 2012;13:487–500.
2. Tota JE, Chevarie-Davis M, Richardson LA, Devries M, Franco EL. Epidemiology and burden of HPV infection and related diseases: implications for prevention strategies. Prev Med 2011;53:S12–21.
3. Carter JR, Ding Z, Rose BR. HPV infection and cervical disease: a review. Aust N Z J Obstet Gynaecol 2011;51:103–8.
4. D'Souza G, Dempsey A. The role of HPV in head and neck cancer and review of the HPV vaccine. Prev Med 2011;53:S5–11.
5. Schiffman M, Castle PE, Jeronimo J, Rodriguez AC, Wacholder S. Human papillomavirus and cervical cancer. Lancet 2007;370:890–907.
6. Drolet M, Brisson M, Maunsell E, Franco EL, Coutlée F, Ferenczy A, et al.. The impact of anogenital warts on health-related quality of life: a 6-month prospective study. Sex Transm Dis 2011;38:949–56.
7. Kwan TT, Cheung AN, Lo SS, Lee PW, Tam KF, Chan KK, et al.. Psychological burden of testing positive for high-risk human papillomavirus on women with atypical cervical cytology: a prospective study. Acta Obstet Gynecol Scand 2011;90:445–51.
8. Insinga RP, Dasbach EJ, Elbasha EH. Assessing the annual economic burden of preventing and treating anogenital human papillomavirus-related disease in the US: analytic framework and review of the literature. Pharmacoeconomics 2005;23:1107–22.
9. FUTURE II Study Group. Quadrivalent vaccine against human papillomavirus to prevent high-grade cervical lesions. N Engl J Med 2007;356:1915–27.
10. Garland SM, Hernandez-Avila M, Wheeler CM, Perez G, Harper DM, Leodolter S, et al.. Quadrivalent vaccine against human papillomavirus to prevent anogenital diseases. N Engl J Med 2007;356:1928–43.
11. Giuliano AR, Palefsky JM, Goldstone S, Moreira ED Jr, Penny ME, Aranda C, et al.. Efficacy of quadrivalent HPV vaccine against HPV Infection and disease in males. N Engl J Med 2011;364:401–11.
12. Kenter GG, Welters MJ, Valentijn AR, Lowik MJ, Berends-van der Meer DM, Vloon AP, et al.. Vaccination against HPV-16 oncoproteins for vulvar intraepithelial neoplasia. N Engl J Med 2009;361:1838–47.
13. Palefsky JM, Giuliano AR, Goldstone S, Moreira ED Jr, Aranda C, Jessen H, et al.. HPV vaccine against anal HPV infection and anal intraepithelial neoplasia. N Engl J Med 2011;365:1576–85.
14. Lehtinen M, Paavonen J, Wheeler CM, Jaisamrarn U, Garland SM, Castellsagué X, et al.. Overall efficacy of HPV-16/18 AS04-adjuvanted vaccine against grade 3 or greater cervical intraepithelial neoplasia: 4-year end-of-study analysis of the randomised, double-blind PATRICIA trial. Lancet Oncol 2012;13:89–99.
15. GlaxoSmithKline Vaccine HPV-007 Study Group; Romanowski B, de Borba PC, Naud PS, Roteli-Martins CM, De Carvalho NS, Texeira JC, et al.. Sustained efficacy and immunogenicity of the human papillomavirus (HPV)-16/18 AS04-adjuvanted vaccine: analysis of a randomised placebo-controlled trial up to 6.4 years. Lancet 2009;374:1975–85.
16. Laz TH, Rahman M, Berenson AB. An update on human papillomavirus vaccine uptake among 11–17 year old girls in the United States: National Health Interview Survey, 2010. Vaccine 2012;30:3534–40.
17. Wong CA, Berkowitz Z, Dorell CG, Anhang Price R, Lee J, Saraiya M. Human papillomavirus vaccine uptake among 9- to 17-year-old girls: National Health Interview Survey, 2008. Cancer 2011;117:5612–20.
18. Centers for Disease Control and Prevention (CDC). National, state, and local area vaccination coverage among adolescents aged 13–17 years—United States, 2009. MMWR Morb Mortal Wkly Rep 2010;59:1018–23.
19. O'Connor AM. Validation of a decisional conflict scale. Med Decis Making 1995;15:25–30.
20. Goh AC, Kowalkowski MA, Bailey DE Jr, Kazer MW, Knight SJ, Latini DM. Perception of cancer and inconsistency in medical information are associated with decisional conflict: a pilot study of men with prostate cancer who undergo active surveillance. BJU Int 2012;110:E50–6.
21. Miller SM, Hudson SV, Egleston BL, Manne S, Buzaglo JS, Devarajan K, et al.. The relationships among knowledge, self-efficacy, preparedness, decisional conflict, and decisions to participate in a cancer clinical trial. Psychooncology [Epub ahead of print]. DOI: 10.1002/pon.3043.
22. Kessels SJ, Marshall HS, Watson M, Braunack-Mayer AJ, Reuzel R, Tooher RL. Factors associated with HPV vaccine uptake in teenage girls: a systematic review. Vaccine 2012;30:3546–56.
23. Agius PA, Pitts MK, Smith AM, Mitchell A. Human papillomavirus and cervical cancer: Gardasil vaccination status and knowledge amongst a nationally representative sample of Australian secondary school students. Vaccine 2010;28:4416–22.
24. Allen JD, Othus MK, Shelton RC, Li Y, Norman N, Tom L, et al.. Parental decision making about the HPV vaccine. Cancer Epidemiol Biomarkers Prev 2010;19:2187–98.
25. Caskey R, Lindau ST, Alexander GC. Knowledge and early adoption of the HPV vaccine among girls and young women: results of a national survey. J Adolesc Health 2009;45:453–62.
26. Chou B, Krill LS, Horton BB, Barat CE, Trimble CL. Disparities in human papillomavirus vaccine completion among vaccine initiators. Obstet Gynecol 2011;118:14–20.
27. Dempsey A, Cohn L, Dalton V, Ruffin M. Patient and clinic factors associated with adolescent human papillomavirus vaccine utilization within a university-based health system. Vaccine 2010;28:989–95.
28. Gerend MA, Weibley E, Bland H. Parental response to human papillomavirus vaccine availability: uptake and intentions. J Adolesc Health 2009;45:528–31.
29. Mathur MB, Mathur VS, Reichling DB. Participation in the decision to become vaccinated against human papillomavirus by California high school girls and the predictors of vaccine status. J Pediatr Health Care 2010;24:14–24.
30. Widdice LE, Bernstein DI, Leonard AC, Marsolo KA, Kahn JA. Adherence to the HPV vaccine dosing intervals and factors associated with completion of 3 doses. Pediatrics 2011;127:77–84.
31. Hirth JM, Tan A, Wilkinson GS, Berenson AB. Completion of the human papillomavirus vaccine series among insured females between 2006 and 2009. Cancer 2012 [Epub ahead of print]. DOI: 10.1002/cncr.27598.