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Change in Human Papillomavirus Prevalence Among U.S. Women Aged 18–59 Years, 2009–2014

Berenson, Abbey B. MD, PhD; Hirth, Jacqueline M. PhD, MPH; Chang, Mihyun PhD, MPH

doi: 10.1097/AOG.0000000000002193
Contents: Infectious Disease: Original Research
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OBJECTIVE: To examine changes in prevalence of vaginal human papillomavirus (HPV) between 2009–2010 and 2013–2014 among both vaccinated and unvaccinated U.S. women.

METHODS: We evaluated HPV prevalence among women 18–59 years old using cross-sectional survey data from three different cycles of the National Health and Nutrition Examination Survey. Data were stratified into four age groups (18–26, 27–34, 35–44, and 45–49 years) to examine trends over time among women of different ages in the postvaccine era. Multivariable analyses, which controlled for descriptive variables, were used to examine the prevalence of quadrivalent vaccine-type HPV by vaccination status.

RESULTS: We observed a significant decrease in the prevalence of vaccine-type HPV among women 18–59 years of age from 2009–2010 to 2013–2014. This decline was only significant in those 18–26 years old when the sample was stratified into the four age groups. Among vaccinated 18–26 year olds, HPV prevalence remained low from 2009–2010 (3.9%) to 2013–2014 (2.0%; prevalence ratio 0.51, 95% CI 0.18–1.46). Unvaccinated women 18–26 years old also demonstrated a significant decrease over time from 19.5% in 2009–2010 to 9.7% in 2013–2014 (prevalence ratio 0.44, 95% CI 0.22–0.91). Prevalence did not significantly change among unvaccinated women 26 years old or older.

CONCLUSIONS: The decline in HPV infections among unvaccinated 18- to 26-year-old women suggests that young women in the United States are beginning to benefit from herd immunity resulting from the introduction of the HPV vaccine.

The prevalence of vaccine-type human papillomavirus has decreased among unvaccinated 18–26-year-old U.S. women, which may be an early sign of vaccine-driven population-level protection.

Center for Interdisciplinary Research in Women's Health and the Department of Obstetrics & Gynecology, the University of Texas Medical Branch, Galveston, Texas.

Corresponding author: Abbey B. Berenson, MD, PhD, Center for Interdisciplinary Research in Women's Health, Department of Obstetrics & Gynecology, the University of Texas Medical Branch, Galveston, 301 University Boulevard, Galveston, TX 77555-0587; email: abberens@utmb.edu.

Supported by the Center for Interdisciplinary Research in Women's Health at the University of Texas Medical Branch.

Financial Disclosure The authors did not report any potential conflicts of interest.

The authors thank Susan Y. Rojahn, PhD, of UTMB for assistance with manuscript preparation.

Each author has indicated that she has met the journal's requirements for authorship.

Since the introduction of the quadrivalent human papillomavirus (HPV) vaccine in the United States in 2006, vaginal infections caused by vaccine-type strains have fallen among young women. A recent national study by our team demonstrated that the prevalence of HPV-6, -11, -16, and -18 decreased from 15.4% in 2009–2010 to 8.5% in 2011–2012 in women 18–26 years old.1 Another national study by other authors observed declines in vaccine-type HPV among females 14–19 years old from 11.5% in the prevaccine years to 4.3% by 2012 among females 14–19 years old and from 18.5% to 12.1% among women 20–24 years old.2 A third national study that examined data through 2012 reported a decline in quadrivalent vaccine-type HPV among vaccinated women 18–29 years of age, but no decline among their unvaccinated counterparts.3 Thus, this study did not find evidence of herd immunity (indirect protection from HPV infection among unvaccinated individuals resulting from immunity among vaccinated individuals) by 2011–2012.

Using more recent national data collected in 2013–2014, we examined whether further changes have occurred in the United States in HPV prevalence. We stratified by age to more closely examine changes in HPV prevalence among groups with different levels of HPV vaccination. We also stratified by vaccination status to determine whether there was evidence of herd immunity at the national level.

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MATERIALS AND METHODS

The National Health and Nutrition Examination Survey includes a series of nationally representative, cross-sectional surveys conducted in 2-year cycles.4 In addition to being interviewed and examined, women aged 18–59 years were asked to self-collect a vaginal swab for HPV testing. Data on HPV vaccination status were collected by self-report; vaccination was defined as receiving one or more doses of the HPV vaccine. Methods have been previously described.5 To conduct this study, we evaluated the prevalence of HPV for three data collection cycles: 2009–2010, 2011–2012, and 2013–2014. The University of Texas Medical Branch institutional review board deemed this study to be exempt because it was not considered human subject research.

In 2009–2010, 2,290 women aged 18–59 years were interviewed as part of the National Health and Nutrition Examination Survey. Of these, 2,244 (98.0%) participated; 1,970 (87.8%) provided vaginal swabs, and 1,955 samples (85.4%) were adequate for HPV typing based on internal positive controls as previously described.1,5 In 2011–2012, 2,062 women were interviewed. Of these, 1,995 (96.7%) participated; 1,772 (85.9%) provided swabs, and 1,767 samples (88.6%) were adequate. In 2013–2014, 2,230 women were interviewed. Of these, 2,164 (97.0%) participated; 1,995 (92.2%) provided swabs, and 1,985 samples (91.7%) were adequate. In total, 5,707 women were eligible for the final analyses (Fig. 1). To compare changes in HPV prevalence among women with higher vaccination rates with those in groups with lower vaccination rates, we stratified analyses by the following age groups: 18–26, 27–34, 35–44, and 45–59 years. The first age subgroup (18–26 year olds) was selected to allow us to compare these findings with our previous study and because this group has the highest vaccination rate. The second age subgroup (27–34 years) was selected because women up to age 34 years in the 2013–2014 cohort would have been 26 in 2006 and thus represent the oldest possible vaccine-eligible participants. The older age groups were included to allow for comparison of prevalence between those age groups eligible and ineligible for HPV vaccination.

Fig. 1.

Fig. 1.

Bivariate analyses of HPV prevalence, including groups of any tested HPV (37 types), vaccine-type (6, 11, 16, 18), high-risk vaccine-type (16, 18), low-risk vaccine-type (6, 11), and high-risk nonvaccine types (26, 31, 33, 35, 39, 45, 51, 52, 53, 56, 58, 59, 66, 68, 73, 82), were made using Rao-Scott χ2 statistics. Each grouping of HPV types was transformed into a binary variable with 0=no type detected and 1=at least one type in the grouping detected. All data were adjusted for nonresponse and complex survey methods using medical examination weights included in the National Health and Nutrition Examination Survey data set. Generalized linear modeling with log links and binomial distribution was used to estimate unadjusted prevalence ratios and 95% CIs. Unadjusted models were conducted to evaluate the crude associations between each descriptive variable and the prevalence of vaccine-type HPV. Multivariable analyses, which controlled for confounders, were used to examine the association between each National Health and Nutrition Examination Survey cycle and vaccine-type HPV. Multivariable models included only cases with complete data. We also looked at demographic and behavioral characteristics by age group over time in both vaccinated and unvaccinated women to determine whether factors other than vaccination could be responsible for the change in HPV prevalence. Statistical analyses were conducted using SAS.

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RESULTS

Among our total study population, there were no differences in race and ethnicity, marital status, sexual orientation, alcohol use, or marijuana use between cycles (Table 1). Of 14 variables examined, the only differences detected were in the number of vaginal sex partners in the last year and HPV vaccination. No significant difference was observed in the prevalence of gonorrhea or chlamydia (self-reported) nor herpes simplex virus type 2 (self-reported or by blood test) between 2009–2010 and 2013–2014 among this population (Table 1).

Table 1.

Table 1.

Vaccine-type HPV decreased among all women 18–59 years of age between 2009–2010 and 2013–2014 (prevalence ratio 0.68, 95% CI, 0.47–0.99; Table 2). When analyses were stratified by risk status, we observed a significant decline in the prevalence of high-risk vaccine-type HPV (oncogenic vaccine type: HPV-16 and -18) (Appendix 1, available online at http://links.lww.com/AOG/A983). Low-risk vaccine-type HPV did not decline over time, but there was a very low frequency in these types (HPV-6 and -11) in the each observed time period (1.9% in 2009–2010, 1.5% in 2011–2012, and 1.2% in 2013–2014). We also did not observe a significant decline in high-risk nonvaccine-type HPV or in all 37 HPV types.

Table 2.

Table 2.

When the prevalence of HPV between 2009–2010 and 2013–2014 was examined among more precise age subgroups (18–26, 27–34, 35–44, and 45–59 year olds), a significant decline was observed for vaccine-type HPV among 18–26 year olds, but not in the other age subgroups (Table 2). Among 18–26 year olds, high-risk vaccine-type HPV prevalence decreased from 13.1% in 2009–2010 to 5.0% in 2013–2014 (prevalence ratio 0.35, 95% CI 0.18–0.67); no significant change in low-risk vaccine-type HPV prevalence was observed (3.5% in 2009–2010 and 1.1% in 2013–2014; Appendix 2, available online at http://links.lww.com/AOG/A983). Among the other age groups (27–34, 35–44, and 45–59 years of age), no significant declines in HPV prevalence between 2009–2010 and 2013–2014 were observed for any of the HPV groups (Appendices 3–5, available online at http://links.lww.com/AOG/A983).

To examine the effect of vaccination on vaccine-type HPV prevalence and whether there was evidence of herd immunity, we next evaluated vaccine-type HPV prevalence in each vaccine-eligible age group (18–59, 18–26, and 27–34 years old) stratified by vaccination status (Fig. 2). Overall, 11.5% of women 18–59 years old were vaccinated, 44.1% were vaccinated among the 18–26 year olds, and 16.12% were vaccinated in the 27–34 year olds. We observed a significant reduction in vaccine-type HPV between 2009–2010 and 2013–2014 among unvaccinated women 18–26 years old only (prevalence ratio 0.44, 95% CI 0.22–0.91; Table 3). No significant change in vaccine-type HPV prevalence was observed among vaccinated women 18–26 years of age, although this group had a low prevalence of vaccine-type HPV at all time points (3.9% in 2009–2010, 4.4% in 2011–2012, and 2.0% in 2013–2014). Among all other age groups examined (18–59, 27–34, 35–44, and 45–59 years), we found no association between vaccination status and decline in vaccine-type HPV prevalence between 2009–2010 and 2013–2014. High-risk vaccine-type HPV did decline among vaccinated women 18–59 years old during that time (prevalence ratio 0.47, 95% CI 0.24–0.92; Fig. 2).

Fig. 2.

Fig. 2.

Table 3.

Table 3.

To determine whether certain characteristics such as race and ethnicity, drug use, or sexual behaviors were associated with changes in HPV prevalence over time, we then examined prevalence changes by vaccination status within each age group. Among vaccinated women 18–59 years old, only the race and ethnicity variable was significant using bivariable analysis (Appendix 6, available online at http://links.lww.com/AOG/A983). We could not conduct bivariable analyses among vaccinated women by age subgroup as a result of the low frequency of vaccine-type HPV detected in these women.

A number of characteristics was associated with vaccine-type HPV prevalence on bivariable analysis among unvaccinated 18–59 year olds and within each age subgroup (Appendices 7–10, available online at http://links.lww.com/AOG/A983; Table 4). After controlling for confounders, however, only four characteristics remained significant among unvaccinated women. Two or more vaginal sex partners within the last year as compared with zero to one partners was associated with a higher prevalence of HPV in 18- to 59-year-old women and all four subgroups. Among unvaccinated 18- to 59-year-old women, a history of gonorrhea or chlamydia was associated with a higher prevalence of HPV. Having ever been married was associated with a lower vaccine-type HPV prevalence among unvaccinated women 27–34 years old. Among unvaccinated women 18–26 years old (Table 4), women in the 2011–2012 or the 2013–2014 National Health and Nutrition Examination Survey cycle were less likely to test positive for vaccine-type HPV as compared with 2009–2010.

Table 4.

Table 4.

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DISCUSSION

In agreement with other studies,1–3 we found that vaccine-type HPV prevalence is continuing to fall in the United States. In addition, our finding that the prevalence of vaccine-type HPV has declined in unvaccinated 18- to 26-year-old women demonstrates early evidence of herd immunity on a national level. This finding builds on a prior report by Kahn et al,6 which found evidence of herd immunity in Cincinnati, Ohio. We observed almost a 50% decline in vaccine-type HPV among unvaccinated 18- to 26-year-old women between 2009–2010 and 2013–2014 (19.5–9.7%). Because this age group was the only subgroup to demonstrate a significant change in HPV prevalence and this group had the highest vaccination rate, HPV vaccination is likely the cause of the decline. Moreover, no change was observed in the prevalence of gonorrhea or chlamydia, herpes simplex virus type 2, or high-risk nonvaccine-type HPV over this time period, so the change in vaccine-type HPV prevalence cannot be attributed to an overall decrease in sexually transmitted infections.

Among unvaccinated 18- to 26-year-old women, HPV prevalence decreased over time even after controlling for confounders. This is further evidence of emerging herd immunity. Our finding that two or more vaginal sex partners within the last year and a history of gonorrhea or chlamydia were strongly associated with testing positive for vaccine-type HPV among unvaccinated women is congruent with the knowledge that HPV is transmitted sexually and more common among those with risky sexual behaviors. This is further supported by the low prevalence of HPV among those who have ever been married.

We did not find a significant decline in vaccine-type HPV prevalence among vaccinated 18–26 year olds, which is likely the result of the low prevalence in 2009–2010 and 2013–2014. This low prevalence is encouraging, especially because many adolescents in this group were not vaccinated until after the recommended age of 11–12 years.7 We also did not find a significant decline among vaccinated or unvaccinated 27–34 year olds, although this age group was eligible for the vaccine when it was introduced. This is probably the result of the low uptake rates among U.S. women older than 18 years of age.8 Only 16% of 27–34 year olds in this study were vaccinated in 2013–2014. As cohorts with higher HPV vaccination rates grow older, similar reductions to what we observed in the HPV prevalence among 18–26 year olds in this study should be observed among older women.

Our findings are in contrast to a prior study by another group that did not find a significant change in vaccine-type HPV prevalence among unvaccinated young women.3 Differences between studies may be attributed to different time periods examined as well as differences in the age range evaluated. Whereas our study examined prevalence among 18–26 year olds, the prior report examined women 18–29 years of age.3 It is encouraging that we observed a decline in this study among unvaccinated 18- to 26-year-old women when only 44% of that age group had been vaccinated. Because most genital HPV infections among young women are believed to be transmitted by male partners, it is possible that there has been a commensurate reduction in the prevalence of vaccine-type HPV in young males. Future studies should examine the change in HPV prevalence among young males to examine whether herd immunity extends to them.

This study has some limitations, including the possibility that recall bias could have influenced self-reported HPV vaccination rates.9 Its strength is that it includes women from three recent time periods from across the United States and thus may be generalizable to much of the population.

Our finding that the prevalence of vaccine-type HPV is dropping even among unvaccinated young women across the United States is promising. If strengthened, the herd effect could offer protection to individuals who are unable to be vaccinated and help further reduce HPV-associated cancers. To reach this goal, health care providers must continue to recommend the HPV vaccine at every opportunity to every eligible patient. Continued monitoring will allow researchers to observe how vaccination is affecting HPV prevalence and detect groups that continue to be at risk.

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REFERENCES

1. Berenson AB, Laz TH, Rahman M. Reduction in vaccine-type human papillomavirus prevalence among women in the United States, 2009–2012. J Infect Dis 2016;214:1961–4.
2. Markowitz LE, Liu G, Hariri S, Steinau M, Dunne EF, Unger ER. Prevalence of HPV after introduction of the vaccination program in the United States. Pediatrics 2016;137:e20151968.
3. Tarney CM, Klaric J, Beltran T, Pagan M, Han J. Prevalence of human papillomavirus in self-collected cervicovaginal swabs in young women in the United States between 2003 and 2012. Obstet Gynecol 2016;128:1241–1247.
4. Centers for Disease Control and Prevention, National Center for Health Statistics. National Health and Nutrition Examination Survey Data. Available at: https://wwwn.cdc.gov/nchs/nhanes/Default.aspx. Retrieved January 2, 2017.
5. Markowitz LE, Hariri S, Lin C, Dunne EF, Steinau M, McQuillan G, et al. Reduction in human papillomavirus (HPV) prevalence among young women following HPV vaccine introduction in the United States, National Health and Nutrition Examination Surveys, 2003–2010. J Infect Dis 2013;208:385–93.
6. Kahn JA, Brown DR, Ding L, Widdice LE, Shew ML, Glynn S, et al. Vaccine-type human papillomavirus and evidence of herd protection after vaccine introduction. Pediatrics 2012;130:e249–56.
7. Rahman M, McGrath CJ, Hirth JM, Berenson AB. Age at HPV vaccine initiation and completion among US adolescent girls: trend from 2008 to 2012. Vaccine 2015;33:585–7.
8. Centers for Disease Control and Prevention (CDC). Noninfluenza vaccination coverage among adults—United States, 2011. MMWR Morb Mortal Wkly Rep 2013;62:66–72.
9. Hirth J, Kuo YF, Laz TH, Starkey JM, Rupp RE, Rahman M, et al. Concordance of adolescent human papillomavirus vaccination parental report with provider report in the National Immunization Survey-Teen (2008–2013). Vaccine 2016;34:4415–21.
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