Secondary Logo

Trends in Male and Female Genital Warts Among Adolescents in a Safety-Net Health Care System 2004–2013: Correlation With Introduction of Female and Male Human Papillomavirus Vaccination

Perkins, Rebecca B. MD, MSc*; Legler, Aaron MPH; Hanchate, Amresh PhD

doi: 10.1097/OLQ.0000000000000369
Original Study
Free

Background Human papillomavirus (HPV) vaccination remains underused in the United States, and few population-level studies on effectiveness exist.

Methods We examined trends in rates of genital warts diagnoses and HPV vaccination rates (defined as receipt of 1 or more vaccine doses) among low-income and minority adolescents between 2004 and 2013. 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. International Classification of Diseases, Ninth Revision codes were used to determine genital warts diagnoses. We estimated annual rates of genital warts for each period for females and males using an interrupted time-series Poisson regression model.

Results As HPV vaccination rates in low-income, minority adolescents rose from 0% to 59% (females) and 0 to 41% (males) between 2004 and 2013, genital warts rates decreased from 3.5% (females) and 3.6% (males) to 1.5% (females) and 2.9% (males). Rates of genital warts decreased significantly for both females and males from the prevaccination to the postvaccination periods (P < 0.05 for both comparisons). Genital warts rates for males began to decrease after the introduction of female vaccination and continued to decrease after male vaccination was introduced.

Conclusions 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 following the introduction of female vaccination and continued to fall after the introduction of male vaccination, indicating that male vaccination may confer additional benefit to both males and females over herd immunity alone, especially when vaccination rates are suboptimal.

A study of low-income, minority adolescents found that introduction of human papillomavirus vaccination for females correlated with decreased rates of genital warts in females, with additional benefits after male vaccination.

From the *Boston University School of Medicine/Boston Medical Center, Boston MA; †Veterans Affairs Boston Healthcare System, Boston MA; and ‡Veterans Affairs Boston Healthcare System/Boston University School of Medicine, Boston MA

Funding: American Cancer Society Mentored Research Scholar Grant (MRSG-09-151-01). The funders had no role in the design of the intervention, the design of the study, or the writing of the manuscript.

Conflicts of interest: None declared.

Correspondence: Rebecca B. Perkins, MD, MSc, Department of Obstetrics and Gynecology, Boston University School of Medicine/Boston Medical Center, 85 E. Concord St, 6th Floor, Boston, MA 02118. E-mail: rbperkin@bu.edu.

Received for publication February 11, 2015, and accepted September 3, 2015.

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.

Back to Top | Article Outline

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.

Back to Top | Article Outline

RESULTS

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.

TABLE 1

TABLE 1

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.

Figure 1

Figure 1

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).

Back to Top | Article Outline

DISCUSSION

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.

Back to Top | Article Outline

CONCLUSIONS

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.

Back to Top | Article Outline

REFERENCES

1. Ault KA. Epidemiology and natural history of human papillomavirus infections in the female genital tract. Infect Dis Obstet Gynecol 2006; 14: 40470.
2. Flagg EW, Schwartz R, Weinstock H. Prevalence of anogenital warts among participants in private health plans in the United States, 2003–2010: Potential impact of human papillomavirus vaccination. Am J Public Health 2013; 103: 1428–1435.
3. Leval A, Herweijer E, Arnheim-Dahlström L, et al. Incidence of genital warts in Sweden before and after quadrivalent human papillomavirus vaccine availability. J Infect Dis 2012; 206: 860–866.
4. Read TR, Hocking JS, Chen MY, et al. The near disappearance of genital warts in young women 4 years after commencing a national human papillomavirus (HPV) vaccination programme. Sex Transm Infect 2011; 87: 544–547.
5. Nsouli-Maktabi H, Ludwig SL, Yerubandi UD, et al. Incidence of genital warts among U.S. service members before and after the introduction of the quadrivalent human papillomavirus vaccine. MSMR 2013; 20: 17–20.
6. Kahn JA, Lan D, Kahn RS. Sociodemographic factors associated with high-risk human papillomavirus infection. Obstet Gynecol 2007; 110: 87–95.
7. Kahn JA, Brown DR, Ding L, et al. Vaccine-type human papillomavirus and evidence of herd protection after vaccine introduction. Pediatrics 2012; 130: 249–256.
8. Brogly SB, Perkins RB, Zepf D, et al. Human papillomavirus vaccination and cervical cytology in young minority women. Sex Transm Dis 2014; 41: 511–514.
9. Markowitz LE, Dunne EF, Saraiya M, et al. Quadrivalent human papillomavirus vaccine: Recommendations of the Advisory Committee on Immunization Practices. MMWR Morb Mortal Wkly Rep 2007; 56: 1–24.
10. Centers for Disease Control and Prevention (CDC). FDA licensure of quadrivalent human papillomavirus vaccine (HPV4, Gardasil) for use in males and guidance from the Advisory Committee on Immunization Practices (ACIP). MMWR Morb Mortal Wkly Rep 2010; 59: 630–632.
11. Centers for Disease Control and Prevention (CDC). Recommendations on the use of quadrivalent human papillomavirus vaccine in males—Advisory Committee on Immunization Practices (ACIP), 2011. MMWR Morb Mortal Wkly Rep 2011; 60: 1705–1708.
12. Wagner AK, Soumerai SB, Zhang F, et al. Segmented regression analysis of interrupted time series studies in medication use research. J Clin Pharm Ther 2002; 27: 299–309.
13. Bauer HM, Wright G, Chow J. Evidence of human papillomavirus vaccine effectiveness in reducing genital warts: an analysis of California public family planning administrative claims data, 2007–2010. Am J Public Health 2012; 102: 833–835.
14. Kim JJ, Goldie SJ. Cost effectiveness analysis of including boys in a human papillomavirus vaccination programme in the United States. BMJ 2009; 339: b3884.
15. Ali H, Donovan B, Wand H, et al. Genital warts in young Australians five years into national human papillomavirus vaccination programme: National surveillance data. BMJ 2013; 346: f2032.
16. Smith MA, Liu B, McIntyre P, et al. Fall in genital warts diagnoses in the general and indigenous Australian population following implementation of a national human papillomavirus vaccination program: Analysis of routinely collected national hospital data. J Infect Dis 2015; 211: 91–99.
17. Chow EP, Read TR, Wigan R, et al. Ongoing decline in genital warts among young heterosexuals 7 years after the Australian human papillomavirus (HPV) vaccination programme. Sex Transm Infect 2015; 91: 214–219.
18. Gertig DM, Brotherton JM, Budd AC, et al. Impact of a population-based HPV vaccination program on cervical abnormalities: A data linkage study. BMC Med 2013; 11: 227.
19. Palefsky JM, Giuliano AR, Goldstone S, et al. HPV vaccine against anal HPV infection and anal intraepithelial neoplasia. N Engl J Med 2011; 365: 1576–1585.
20. Centers for Disease Control and Prevention (CDC). FDA licensure of bivalent human papillomavirus vaccine (HPV2, Cervarix) for use in females and updated HPV vaccination recommendations from the Advisory Committee on Immunization Practices (ACIP). MMWR Morb Mortal Wkly Rep 2010; 59: 626–629.
21. Drolet M, Brisson M, Maunsell E, et al. The impact of anogenital warts on health-related quality of life: A 6-month prospective study. Sex Transm Dis 2011; 38: 949–956.
22. Senecal M, Brisson M, Maunsell E, et al. Loss of quality of life associated with genital warts: Baseline analyses from a prospective study. Sex Transm Infect 2011; 87: 209–215.
23. Olsen J, Jorgensen TR. Revisiting the cost-effectiveness of universal HPV-vaccination in Denmark accounting for all potentially vaccine preventable HPV-related diseases in males and females. Cost Eff Resour Alloc 2015; 13: 4.
24. Presidents Cancer Panel. President's Cancer Panel Annual Report 2012–2013: Accelerating HPV vaccine uptake: urgency for action to prevent cancer. 2014 Available at: http://deainfo.nci.nih.gov/ADVISORY/pcp/annualReports/HPV/index.htm-sthash.VFWWaxYh.dpbs. Accessed February 24, 2014.
25. Leval A, Herweijer E, Ploner A, et al. Quadrivalent human papillomavirus vaccine effectiveness: A Swedish national cohort study. J Natl Cancer Inst 2013; 105: 469–474.
© Copyright 2015 American Sexually Transmitted Diseases Association