Abstract
To estimate changes in oral human papillomavirus (HPV) prevalence attributable to vaccination vs herd immunity, this national survey study uses National Health and Nutrition Examination Survey data to compare oral HPV prevalence for 4 types targeted by HPV vaccine and 33 nonvaccine types in unvaccinated US adults aged 18 to 59 years from 2009 to 2016.
Prophylactic human papillomavirus (HPV) vaccination has been recommended for routine use in US females since 2006 and males since 2011 for the prevention of anogenital HPV infections.1 Although studies have demonstrated high vaccine efficacy in reducing prevalence of oral HPV infection,2 prevention of oral HPV infections and oropharyngeal cancers is not a vaccine indication because of lack of randomized trials. Also lacking are surveillance studies for herd protection against oral HPV infections.3
We investigated evidence for herd protection against oral HPV infections in unvaccinated US men and women aged 18 to 59 years via temporal (2009-2016) comparisons of oral HPV prevalence for 4 vaccine types (HPV-16/-18/-6/-11) and 33 nonvaccine types.
Methods
This study was conducted across 4 cycles of the National Health and Nutrition Examination Survey (NHANES), a cross-sectional, stratified, multistage probability sample of the civilian US population. Response rates for the examination component were in 68.5% in 2009-2010, 69.5% in 2011-2012, 68.5% in 2013-2014, and 58.7% in 2015-2016. Procedures for data collection and HPV testing have been described.4 DNA from oral rinses was evaluated for presence of HPV using PGMY09/11 polymerase chain reaction and linear array genotyping for 37 types.4
Sex-stratified analyses were conducted in unvaccinated individuals. All analyses accounted for the complex sample design, including the use of NHANES sample weights adjusted for unit nonresponse and the combination of 4 NHANES cycles. Weights were further poststratified to the age × sex × race distribution of the cycle-specific US population to account for nonparticipation in the sexual behavioral questionnaire or oral HPV components. Prevalence comparisons across cycles were conducted through multivariable logistic regression, with adjustment for age, self-reported race/ethnicity, education level, marital status, smoking, and lifetime number of same- and opposite-sex oral sex partners. Heterogeneity across age subgroups was evaluated through cycle × age interaction.
Analyses were conducted in SAS-callable SUDAAN version 11.0.1 (RTI International). A 2-sided P < .05 was considered statistically significant. Participants provided written informed consent. The study was approved by ethics committees of NHANES and The Ohio State University.
Results
During 2009-2016 (n = 13 676, representing 174 333 402 individuals in the US population aged 18-59 years), HPV vaccination rates increased from 0% to 5.8% in men and from 7.3% to 15.1% in women. Demographic and behavioral characteristics were unchanged in men and women (Table).
Table. Characteristics of the US Population Aged 18-59 Years, NHANES, 2009-2016a.
| Characteristic | Men, % | Women, % | ||||||||
|---|---|---|---|---|---|---|---|---|---|---|
| 2009-2010 | 2011-2012 | 2013-2014 | 2015-2016 | P Valueb | 2009-2010 | 2011-2012 | 2013-2014 | 2015-2016 | P Valueb | |
| ≥1 Dose of HPV vaccinec | ||||||||||
| No | 100 | 98.0 | 95.9 | 94.2 | <.001 | 92.7 | 89.8 | 85.8 | 84.9 | <.001 |
| Yes | 0 | 2.0 | 4.1 | 5.8 | 7.3 | 10.2 | 14.2 | 15.1 | ||
| Age, mean (SD), yd | 38.5 (12.0) | 38.4 (12.4) | 38.3 (12.3) | 38.6 (12.1) | .93 | 38.7 (12.0) | 38.8 (12.2) | 38.5 (12.2) | 38.9 (12.0) | .92 |
| Race/ethnicity | ||||||||||
| White, non-Hispanic | 65.0 | 63.0 | 61.8 | 59.7 | .87 | 64.5 | 61.1 | 60.9 | 58.6 | .89 |
| Black, non-Hispanic | 11.5 | 11.5 | 11.3 | 11.5 | 13.2 | 13.7 | 13.2 | 17.8 | ||
| Hispanic | 16.7 | 17.3 | 17.8 | 18.7 | 14.8 | 16.5 | 17.0 | 13.4 | ||
| Other | 6.8 | 8.2 | 9.1 | 10.1 | 7.5 | 8.7 | 8.9 | 10.2 | ||
| Smokinge | ||||||||||
| Never | 53.5 | 55.1 | 56.2 | 54.7 | .63 | 59.8 | 64.1 | 66.3 | 66.0 | .10 |
| Former | 21.9 | 20.0 | 20.6 | 24.0 | 17.7 | 18.1 | 13.7 | 15.9 | ||
| Current | 24.6 | 24.9 | 23.2 | 21.3 | 22.4 | 17.8 | 19.9 | 18.1 | ||
| Lifetime oral sex partnerse,f | ||||||||||
| 0-1 | 31.5 | 31.0 | 30.2 | 31.8 | .98 | 38.1 | 36.2 | 37.0 | 38.2 | .61 |
| 2-5 | 36.8 | 36.4 | 39.0 | 38.0 | 45.2 | 46.6 | 44.6 | 41.1 | ||
| 6-10 | 15.0 | 14.8 | 14.3 | 14.3 | 10.9 | 10.4 | 10.9 | 12.4 | ||
| ≥11 | 16.7 | 17.8 | 16.5 | 15.9 | 5.7 | 6.8 | 7.5 | 8.3 | ||
| Recent oral sex partnerse,g | ||||||||||
| 0 | 32.9 | 33.6 | 32.7 | 32.1 | .25 | 37.0 | 37.6 | 36.9 | 34.9 | .83 |
| 1 | 54.0 | 53.8 | 54.1 | 56.9 | 53.6 | 54.4 | 54.1 | 56.7 | ||
| ≥2 | 13.1 | 12.6 | 13.2 | 11.0 | 9.4 | 8.0 | 9.0 | 8.4 | ||
Abbreviations: HPV, human papillomavirus; NHANES, National Health and Nutrition Examination Survey.
All analyses accounted for the complex sample design, including the use of NHANES sample weights adjusted for unit nonresponse and the combination of 4 NHANES cycles. Weights were further poststratified to the age × sex × race distribution of the cycle-specific US population to account for nonparticipation in the sexual behavioral questionnaire or oral HPV components.
From χ2 test for heterogeneity across the 4 NHANES cycles.
Individuals who did not report receipt of at least 1 vaccine dose were considered unvaccinated.
Age at NHANES participation.
Individuals with missing covariate values for smoking (n = 895) were imputed the sex-specific modal value. Individuals with missing lifetime (n = 1606) or recent (n = 1592) number of oral sex partners were imputed the sex-specific mean.
Lifetime number of oral sex partners represents the sum of same- and opposite-sex partners.
Number of oral sex partners over the past 12 months.
Vaccine-type oral HPV prevalence declined from 2.7% during 2009-2010 to 1.6% during 2015-2016 in unvaccinated men aged 18 to 59 years (Figure) (adjusted prevalence ratio [PR], 0.63 [95% CI, 0.44-0.90]; P= .009 for trend). This decline was not heterogeneous by age (P = .41 for interaction). Prevalence of nonvaccine-type oral HPV infections remained unchanged in unvaccinated men aged 18 to 59 years (8.6% in 2009-2010 vs 8.4% in 2015-2016; adjusted PR, 1.02 [95% CI, 0.79-1.33]; P = .66 for trend).
Figure. Prevalence Estimates and Ratios for Vaccine-Type and Nonvaccine-Type Oral HPV Infections Among Unvaccinated Men and Women Aged 18-59 Years, NHANES, 2009-2016.
Human papillomavirus (HPV) prevalence data shown across 4 National Health and Nutrition Examination Survey (NHANES) cycles (2009-2010, 2011-2012, 2013-2014, and 2015-2016). HPV-16/-18/-6/-11 were considered vaccine types. Prevalence ratios were adjusted for age, race/ethnicity, education-level, marital status, smoking, and lifetime number of same- and opposite-sex oral sex partners. Prevalence trends across cycles were assessed using integer scores and quantified through odds ratios and 95% confidence intervals (CIs). Individuals with missing covariate values for education (n = 8), marital status (n = 5), or smoking (n = 895) were imputed the modal value. Individuals with missing lifetime (n = 1606) number of oral sex partners were imputed the sex-specific mean. All analyses accounted for the complex sample design, including the use of sample weights adjusted for unit nonresponse and the combination of 4 cycles. Weights were further poststratified to the age × sex × race distribution of the cycle-specific US population to account for nonparticipation in the sexual behavioral questionnaire or oral HPV components. Error bars indicate 95% CIs.
In unvaccinated women aged 18 to 59 years, oral HPV prevalence remained unchanged for vaccine types (0.6% in 2009-2010 vs 0.5% in 2015-2016; adjusted PR, 0.96 [95% CI, 0.23-3.98]; P = .79 for trend) and for nonvaccine types (2.6% in 2009-2010 vs 3.3% in 2015-2016; adjusted PR, 1.29 [95% CI, 0.71-2.35]; P = .58 for trend) (Figure).
Discussion
Vaccine-type oral HPV prevalence declined by 37% between 2009-2010 and 2015-2016 in a sample of unvaccinated US men aged 18 to 59 years, suggesting herd protection against oral HPV infections. Nonvaccine-type oral HPV prevalence remained unchanged. Herd protection likely arises from increased levels of female HPV vaccination in the US population. These results are consistent with modeling and surveillance studies of herd protection against genital HPV infections in unvaccinated US females during 2004-2014.5,6 The lack of herd protection toward oral HPV infections in unvaccinated women could reflect low statistical power due to low prevalence in women.
A limitation of this study is the use of self-reported HPV vaccination status. Also, there was low statistical power to investigate herd protection stratified by age subgroups.
The estimated herd protection should be incorporated into evaluations of the cost-effectiveness of HPV vaccination of men older than 26 years. Vaccine trials of oral HPV incidence and persistence in men should inflate sample sizes to account for herd protection.
Section Editor: Jody W. Zylke, MD, Deputy Editor.
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