Human papillomavirus (HPV) vaccination is intended to decrease rates of genital warts and precancerous lesions and cancers of the cervix, vagina, vulva, and anus and may also decrease HPV-related oropharyngeal and penile cancers. Precancerous lesions and cancers grow over decades, but genital warts often develop within months of HPV infection, so reductions in genital warts are often the first evidence of vaccine effectiveness.1 Studies of primarily white and insured populations in the United States and abroad indicate reductions in genital warts after the introduction of HPV vaccines into the population.2–52–52–52–5 Low-income and minority populations have higher rates of infection with HPV and thus stand to benefit greatly from vaccination.6 Some studies in low-income and minority populations indicate reductions in HPV infection rates7 and cytologic abnormalities8 after vaccine introduction. No study has specifically examined the effects of HPV vaccination on genital warts in low-income and minority adolescent populations. We examined changes in rates of HPV vaccination and genital wart diagnoses in low-income and minority adolescents seeking care in a safety-net health system between 2004 and 2013.
MATERIALS AND METHODS
Data were obtained from a database containing de-identified medical record information including all outpatient visits to an urban medical center and 6 affiliated community health centers. The Boston Medical Center institutional review board considered this research exempt from human subjects review. We obtained counts of unique patients between the ages of 16 and 26 years seen in family medicine, pediatrics, or adolescent medicine clinics between 2004 and 2013. These clinics were chosen because most 16- to 26-year-old patients in this health care system receive care at these locations. Human papillomavirus vaccination was determined by the presence of an administrative billing code for vaccine administration in the electronic medical record. The quadrivalent formulation was the only HPV vaccine available in this health care system during the study period. International Classification of Diseases, Ninth Revision diagnosis codes were used to determine cases of genital warts as done in prior studies using administrative data.2 An examination of the data revealed 3 distinct periods in the database that corresponded to changes in HPV vaccine policy: period 1 (prevaccination) included the years 2004–2006; period 2 (female vaccination) included the years 2007–2010; and period 3 (universal vaccination) included the years 2011–2013. In period 1 (2004–2006), vaccination was not available at study sites. Although the Food and Drug Administration–approved HPV vaccination for females in 2006,9 HPV vaccination of females at study sites did not begin until 2007 when public funding became available. In period 2 (2007–2010), only 2% of males were vaccinated although the Advisory Committee on Immunization Practices permissively approved HPV vaccine for males in 2009 and Vaccines For Children funds were available.10 In period 3 2011–2013, both males and females were routinely vaccinated following the stronger Advisory Committee on Immunization Practices recommendation for males.11 The percentages (defined as rate per 100 unique patients per year and per period) were calculated for receipt of a diagnosis of genital warts and receipt of at least one dose of HPV vaccine. We estimated annual rates of genital warts for each period for females and males using an interrupted time-series Poisson regression model. This method is designed to quantify changes in rates of genital warts after vaccination while accounting for underlying annual trends and is well suited to examining time trends of relatively rare discrete outcomes, such as genital warts.12 Tests of temporal trends were evaluated at the 5% level of significance.
A total of 45,787 female and male patients aged 16 to 26 years received at least 1 health care visit between January 1, 2004, and December 31, 2013. The demographics of the study population are detailed in Table 1 and change slightly over time. In each period, the adolescents' mean age ranged from 17 to 19 years, and they were approximately 18% white, 53% black, 10% Hispanic, and 14% other. Most (80%) had public insurance (primarily Medicaid) and nearly 20% did not speak English as their primary language.
Six patients received HPV vaccination before 2007 (period 1). Between 2007 and 2010 (period 2), annual HPV vaccination rates rose for females, from 22.2% in 2007 to 56.2% in 2010 (Fig. 1). Rates for females were stable in period 3, approximately 60%. Less than 2% of males seen in each year had received HPV vaccines each year before 2011. Annual HPV vaccination rates for males rose during period 3, from 10.6% in 2011 to 41.3% in 2013.
Rates of genital warts for males and females rose each year during period 1 (prevaccination) from 3.6% (males) and 3.5% (females) in 2004 to 4.1% (males) and 3.9% (females) in 2006 (Fig. 1). After the introduction of female vaccination in 2007, rates of genital warts declined significantly among both females and males, reaching 2.9% for males and 1.5% for females in 2013. Declines were similar for males and females of all races/ethnicities (Table 1). Although the overall incidence of genital warts per period did not decrease until period 3, annual rates of genital warts were increasing by 9.1% and 7.7% per year for females and males, respectively, during period 1. That trend was arrested and reversed during period 2, when females began receiving vaccination, with a significant decrease of 9.8% per year for females (P < 0.001) and a nonsignificant decrease of 0.4% per year for males (P = 0.854). Additional decreases of 22.1% for females and 13.5% for males were noted in period 3 when both males and females were vaccinated (P < 0.001 for both comparisons).
Similar to other studies,2,132,13 this study demonstrates that rates of genital warts were increasing for both males and females in the period before vaccination. In our study population, these trends were arrested for both males and females after the introduction of HPV vaccination for females, with females showing a statistically significant reduction immediately after vaccine introduction, with rates continuing to decrease after the introduction of male vaccination. The rates of genital warts in males began to decrease after the introduction of female vaccination, but did not reach statistical significance until males began receiving vaccination themselves. This may indicate that at current low levels of vaccination in the United States, males are benefiting directly from vaccination and females may receive additional protection from vaccination of males. Previous studies in populations with more modest vaccination rates demonstrate reductions in females only, indicating that a threshold may exist for herd immunity.2,3,52,3,52,3,5 Modeling studies indicate increased benefits to male vaccination when female vaccination rates are low, as noted in this study.14
Human papillomavirus vaccination coverage in the United States lags behind other industrialized countries, and US national data have not yet noted substantial reductions in HPV-related disease or evidence of herd immunity. In contrast, Australia, which vaccinates more than 70% of school-aged females, reported a greater than 90% decrease in genital warts among young women and an 80% decrease among young men before the introduction of male vaccination.15–1715–1715–17 In addition, Australia has noted a substantial population-wide reduction in cervical dysplasia.18 The most important benefit of HPV vaccination is the reduction in precancerous lesions of the cervix and anus,18,1918,19 and ultimately, the intended reduction in cervical, anal, vaginal, vulvar, and oropharyngeal cancers.9,11,209,11,209,11,20 Although genital warts are rarely life threatening, they cause significant morbidity and decreased quality of life, due to pain, depression, and a negative impact on patients' feelings about sexuality and intimacy.21,2221,22 In addition, when genital warts and other HPV-related diseases of males are considered, HPV vaccination of both males and females may be cost-effective.23 At current vaccination coverage, a substantial proportion of US youth are failing to reap benefits of vaccination seen in other countries, and ongoing national programs are dedicated to improving vaccination coverage and monitoring its effects.24
This study is limited because it describes a cohort of adolescents from a single geographic area. Results should be interpreted with caution because this temporal association cannot determine causation. However, the results are similar to trends described in other nationwide, international studies.4,16,254,16,254,16,25 Because of unrelated secular changes at our institution during the study period, we were not able to find a suitable control group against which to compare changes in rates of genital warts in adolescents that would have made a stronger case for a causal association. In addition, we did not link individual receipt of vaccination or the number of vaccine doses to personal risk of disease, and further studies on this are warranted.
Introduction of HPV vaccination correlated with lower rates of genital warts among a cohort of low-income and minority adolescents. Rates of genital warts began to decrease in females and males after the introduction of female vaccination and continued to fall after the introduction of male vaccination, indicating that male vaccination may confer additional benefit over herd immunity alone, especially when vaccination rates are suboptimal.
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