MAJOR ARTICLE
Human Papillomavirus (HPV) 6, 11, 16, and 18
Prevalence Among Females in the United
States—National Health and Nutrition
Examination Survey, 2003–2006: Opportunity to
Measure HPV Vaccine Impact?
Eileen F. Dunne,1 Maya Sternberg,1 Lauri E. Markowitz,1 Geraldine McQuillan,2 David Swan,3 Sonya Patel,3 and
Elizabeth R. Unger3
1Division of STD Prevention, National Center for HIV, Viral Hepatitis, STD, and TB Prevention, 2National Center for Health Statistics, and 3Division of
High-Consequence Pathogens and Pathology, National Center for Emerging and Zoonotic Infectious Diseases, Centers for Disease Control and
Prevention, Atlanta, Georgia
The 2003–2006 National Health and Nutrition Examination Surveys were used to assess human papillomavirus
(HPV) types 6, 11, 16, and 18 DNA detection from females aged 14–59 years who self-collected cervicovaginal
swab specimens. Prevalence was 8.8% (95% confidence interval [CI], 7.8%–10.0%) and was highest among
women aged 20–24 years (18.5%; 95% CI, 14.9%–22.8%). Age group, education, marital status, and sexual
behavior were associated with detection. These data provide baseline information before HPV vaccine
introduction. Early impact of vaccine in the United States may be determined by a reduction in the prevalence
of HPV 6, 11, 16, and 18 infection among young women.
Since 2006, routine human papillomavirus (HPV) vaccination of females aged 11 or 12 year and catch-up
vaccination through age 26 years has been recommended
in the United States; the quadrivalent HPV vaccine was
licensed in June 2006, and the bivalent vaccine was licensed in October 2009. [1, 2]. Both vaccines prevent
HPV 16 and 18 infection and 70% of cervical cancers
(and a large proportion of cervical precancers); the
quadrivalent vaccine also prevents HPV 6 and 11 infection and 90% of genital warts [1–3]. The quadrivalent
HPV vaccine may be given to male individuals aged 9–26
years, but vaccination for male individuals is not included
in the routine immunization schedule [3]. The National
Health and Nutrition Examination Surveys (NHANES)
Received 28 January 2011; accepted 29 March 2011.
Potential conflicts of interest: none reported.
Correspondence: Eileen F. Dunne, MD, MPH, Centers for Disease Control and
Prevention, 1600 Clifton Rd, MS E-02, Atlanta, GA 30333 ([email protected]).
The Journal of Infectious Diseases 2011;204:562–5
Published by Oxford University Press on behalf of the Infectious Diseases Society of
America 2011.
0022-1899 (print)/1537-6613 (online)/2011/2044-0012$14.00
DOI: 10.1093/infdis/jir342
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are nationally representative surveys of adults and children in the US noninstitutionalized population. Since
2002, girls and women aged 14–59 years participating in
these surveys have self-collected cervicovaginal swab
specimens for HPV DNA testing. We previously published data on the prevalence of any HPV infection
among females aged 14–59 years from NHANES during
2003–2004 with use of samples tested with a prototype
HPV assay [4]. In this article, we describe the prevalence
of HPV 6, 11, 16, and 18 infection from NHANES during
2003–2006 with use of samples tested using the Roche
Linear Array Assay. These data provide information on
baseline DNA detection of 2 high-risk HPV types targeted
by both the bivalent and the quadrivalent HPV vaccine
and 2 low-risk HPV types additionally targeted by the
quadrivalent HPV vaccine before vaccine introduction.
METHODS
Study Population and Study Design
NHANES is conducted by the National Center for
Health Statistics (NCHS), Centers for Disease Control
Demographic and behavioral characteristics of participants
were evaluated. The multivariate model was limited to sexually
active women aged 18–59 years, because all questions were asked
of this group for both cycles. The multivariate logistic regression
model was developed using backwards elimination. For a variable to remain in the model, the Satterthwaite adjusted F-test
P value had to be #.05. Confounding was assessed at each stage of
elimination to ensure that no parameter estimate of a significant
variable changed by .30% from one step to the next. After all
the variables in the model were statistically significant at .05 level,
all pairwise interactions in the main effects model were explored.
and Prevention (CDC), and uses a representative sample of the
US noninstitutionalized civilian population. Of the 5178 female
participants aged 14–59 years who were interviewed at home for
the 2003–2004 and 2005–2006 cycles, 4990 (96.4%) were examined in the mobile examination center. Females aged 14–59
years were asked to self-collect a cervicovaginal sample in the
mobile examination center. In brief, each female participant was
given a collection device, which was a small foam swab on
a plastic handle packaged in an individual reclosable plastic sleeve
(Catch-All Sample Collection Swabs Epicentre). HPV detection
and typing was performed using the Research Use Only Roche
Linear Array HPV Genotyping Test (Roche Diagnostics). Details
of the population and the sampling and the laboratory methods
for HPV detection are presented elsewhere [5]. This human
subjects research was approved by the CDC, NCHS Research
Ethics Review Board.
RESULTS
The overall prevalence of HPV 6, 11, 16, or 18 infection was
8.8% (95% CI, 7.8%–10.0%). Of the female particpants with
HPV 6, 11, 16, or 18 detected, 90.2% had 1 type, 9.8% had 2
types, 0.05% had 3 types, and none had all 4 types. Overall
prevalence of specific types was 2.8% (95% CI, 2.2%–3.6%) for
HPV 6, 0.3% (relative standard error, 35%; 95% CI, 0.2%-0.7%)
for HPV 11, 4.7% (95% CI, 4.0%–5.5%) for HPV 16, and 1.9%
(95% CI, 1.4%–2.5%) for HPV 18. [Table 1].
Prevalence of HPV 6, 11, 16, or 18 infection was highest
(18.5%) among women aged 20–24 years (Table 1, Figure 1).
Peak prevalence of HPV 16 (12.5%) and HPV 18 infections
(3.6%) was among women aged 20–24 years. In contrast, peak
prevalence of HPV 6 (5.4%) and HPV 11 (1.0%) infections was
among female participants aged 14–19 years. Of note, agespecific prevalence estimates for HPV 11 had relative standard
errors of $30%.
Age-related trends differed for the 2 high-risk types (HPV 16
or 18), compared with the 2 low-risk types (HPV 6 or 11)
(Figure 1). For prevalence of HPV 16 or 18 infection, there was
a statistically significant increase from female participants aged
14–19 years to female participants aged 20–24 years (P , .001)
and a statistically significant decrease from female participants
aged 20–24 years to women aged 25–29 years (P , .01).
Statistical Analysis
Female participants who submitted an adequate swab sample for
HPV evaluation were included in the final analysis (n 5 4150).
Statistical analyses were conducted using SAS, version 9.1 (SAS
Institute) [6] and SAS callable SUDAAN, version 10 (RTI)
[7]. Variance estimates were calculated using a Taylor series
linearization [8]. All estimates were weighted using both 2-year
weights constructed from the mobile examination center
examination weights provided by NCHS to account for the
unequal probabilities of selection and adjustments for nonresponse. Prevalence estimates with a relative standard error
(RSE) of $30% were considered to be unstable and are noted in
this article. Confidence intervals (CIs) for the estimated prevalences were based on a logit transformation. Tests of association
between HPV and the demographic or behavioral characteristics
were based on the Wald v2 statistic. Specific contrasts were
constructed in SUDAAN to compare the prevalence of HPV
infection among certain age groups with use of PROC DESCRIPT. No adjustments were made to the P values for multiple
comparisons.
Table 1. Weighted Prevalence of HPV 6, 11, 16, and 18 Infection, by Age Group, NHANES, 2003–2006
Prevalence, % (95% CI)
Age group,
years
HPV 6, 11, 16, or 18
HPV 6
HPV 11
HPV 16
HPV 18
Overall
8.8 (7.8–10.0)
2.8 (2.2–3.6)
0.3 (0.2–0.7)a
4.7 (4.0–5.5)
1.9 (1.4–2.5)
14–19
11.5 (9.1–14.5)
5.4 (3.8–7.6)
1.0 (0.5–2.2)a
6.0 (4.6–7.9)
1.6 (1.1–2.5)
20–24
18.5 (14.9–22.8)
3.7 (2.4–5.8)
0.4 (0.1–3.3)a
12.5 (9.0–17.0)
3.6 (2.1–6.1)
25–29
11.8 (8.8–15.6)
4.0 (2.4–6.6)
0.0 (0.0–0.7)a
6.8 (4.8–9.6)
1.9 (0.6–6.0)a
a
30–39
9.2 (7.0–12.0)
3.1 (1.9–4.9)
0.2 (0.0–0.7)
4.3 (2.5–7.2)
2.9 (1.9–4.3)
40–49
5.2 (3.4–7.8)
1.4 (0.6–3.1)a
0.4 (0.1–2.1)a
2.2 (1.2–4.1)a
1.2 (0.5–2.8)a
50–59
P
4.7 (3.1–7.1)
,.0001
1.7 (0.8–3.6)a
,.001
0.2 (0.0–1.3)a
.06
2.2 (1.3–3.8)
,.001
0.8 (0.2–2.4)a
,.05
NOTE. a RSE $ 30%.
P values are based on the F-statistic computed from the Wald v2 statistic.
HPV 6, 11, 16, and 18 Prevalence Among Females in the US
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Figure 1. Weighted prevalence of HPV 6, 11, 16, or 18 infection; HPV 6 or
11 infection; and HPV 16 or 18 infection, by age group, NHANES, 2003–2006.
However, for prevalence of HPV 6 or 11 infection there was no
statistically significant increase between female participants aged
14–19 years and women aged 20–24 years (P 5 .97), nor a statistically significant decrease between women aged 20–24 years
and women aged 25–29 years (P 5 .45).
Several demographic and behavioral variables were found to be
associated with HPV 6, 11, 16, or 18 detection. These factors were
further evaluated in a logistic regression model among sexually
active females aged $18 years (n 5 2761). Factors independently
associated with HPV 6, 11, 16, and 18 included age group (18–19
years vs 50–59 years: adjusted OR [aOR], 2.8; 95% CI, 1.3–5.8),
education (less than high school or high school vs greater than
high school: aOR, 1.6; 95% CI, 1.2–2.3), marital status (living with
partner vs married: aOR, 2.9; 95% CI, 1.6–5.1), sexual behavior
($6 lifetime partners vs 1 partner: aOR, 2.9; 95% CI, 1.4–5.9; $3
recent partners vs 1 partner: aOR, 1.8; 95% CI, 1.1–2.8), and ever
had genital warts (aOR, 1.7; 95% CI, 1.0–2.8).
DISCUSSION
In this representative sample of females aged 14–59 years in the
US noninstitutionalized population, prevalence of HPV 6, 11, 16,
or 18 infection was 8.8%, and the highest prevalence (18.5%) was
among women aged 20–24 years; the peak prevalence among
women aged 20–24 years is similar to findings of any HPV [5].
The prevalence of HPV 6, 11, 16, or 18 infection was higher than
the previously reported prevalence in NHANES during 2003–
2004 with use of a different HPV test (3.4%) [4]. Of note, the
prevalence of HPV 6, 11, 16, or 18 DNA detection in a crosssectional assessment represents infection at 1 time point and does
not represent the proportion of women at risk for disease or
cancer related to these types. Instead, persistent infections, which
are less common in young women, are the most important
predictor of development of disease or cancer [9, 10].
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Other studies have found a similar prevalence of HPV 6, 11,
16, or 18 infection, and prevalence of HPV infection depends on
the methods used and the population studied. A study evaluating North American females aged 16–25 years in the quadrivalent HPV vaccine clinical trials found that 13.8% had HPV 6,
11, 16, or 18 infection, similar to our findings of 18.5% among
women aged 20–24 years [11]. In an evaluation of urine specimens from women aged 18–25 years in the United States; HPV 6
and 11 were found in 2.2%, and types 16 or 18 were present in
7.8% [12]. A study of sexually experienced urban females aged
13–26 years (n 5 409) found a higher prevalence; 33.1% were
positive for HPV 6, 11, 16, or 18, and 3.5% were positive for both
HPV 16 and HPV 18 [13]. One prospective study found that, by
24 months, 10.4% (95% CI, 7.8–13.8) of sexually experienced
young women with no baseline HPV infection had evidence of
HPV type 16 infection by DNA detection [14]. These studies,
although using different methods and populations, found that few
or no females had concurrent infection with all 4 types [11–13].
Our study found differences in trends by age group for
detection of HPV 6 and 11, compared with HPV 16 and 18.
Prevalence of HPV 6 and 11 infection was highest in the
youngest age group (14–19 years), whereas HPV 16 and 18
peaked among women aged 20–24 years. Studies of genital
warts may also suggest higher prevalence of HPV types 6 and
11 in the late teens and early 20s, because the peak age of
genital warts among females is in their early 20s, and infection
precedes development of disease by months to years [14–17].
The reasons for the differences in age-related trends between
HPV 6 and 11 and HPV 16 and 18 are unclear but could
suggest differences in type tropism or transmission dynamics.
Limited data are available on prevalence of HPV 6 or 11 infection from other studies to further explore type-specific
differences in age-related trends.
Our study found that young age, education, marital status,
and sexual behavior were independent predictors of HPV 6, 11,
16, or 18 infection. Age, marital status, and sexual behavior
(increasing lifetime and increasing recent sex partners) have
been found to be predictors of any HPV infection in populationbased studies [4, 5, 12]. Clinic-based studies have also found
these predictors of HPV 6, 11, 16, or 18 infection [13], but few
population-based studies have described risk factors for HPV 6,
11, 16, or 18 infection [12].
Our study is subject to some limitations. The self-collected
cervicovaginal swab sample may not accurately assess the
prevalence of cervical HPV 6, 11, 16, or 18 infection because
these swabs do not sample the cervix only. Some prevalence
estimates, especially for certain types, or for age groups, had
relative standard error $30%; these prevalence estimates are
indicated. The assessment of HPV DNA prevalence does not
assess cumulative incidence.
Reduction in prevalent HPV 6, 11, 16, and 18 infections,
especially in the young women, will likely be one of the earliest
biologic markers of HPV vaccine impact. Among females aged
14–19 years, we found a prevalence of HPV 6, 11, 16, or 18
infection of 11.5% and, among women aged 20–24 years,
a prevalence of 18.5%. With the anticipated NHANES 4-year
sample size of females aged 14–19 years and a design effect of 2,
we would have 80% power to detect at least a 40% reduction in
HPV 6, 11 16, or 18 infection (significance level, .025) in future
analyses of NHANES data. Vaccine coverage in the United States
will determine when impact would be able to be detected. In
2009, completion of all 3 doses of HPV vaccine was only 26.7%
in 13–17-year-old females in the United States [18]. Studies
measuring vaccine impact will depend on high overall vaccine
coverage or, in the setting of suboptimal coverage, a reliable
measure of individual level vaccination.
In conclusion, prevalent HPV 6, 11, 16, and 18 infection is
most common in women 20–24 years of age; evaluating reductions in prevalent HPV 6, 11, 16, and 18 infection among females
,24 years of age could be an important early measure of HPV
vaccine impact in the US population. We intend to explore this
possibility with use of these methods in future cycles of NHANES.
Funding
This study was supported by the National Center for HIV, Viral
Hepatitis, STD, and TB Prevention, and the National Center for Health
Statistics, Centers for Disease Control and Prevention.
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