Human papillomavirus (HPV) infection is one of the most
common sexually transmitted infections in the United States. Cervical infection
with certain types of HPV is a major risk factor for cervical cancer in women.
The “high-risk” types of HPV (e.g., HPV 16, 18) are associated with cervical
cancer as well as other anogenital cancers, and the “low-risk” types of HPV
(e.g., HPV 6, 11) are associated with genital warts. No national surveillance
system exists to measure the full burden of HPV infection, and no reliable
national population estimate of HPV exists. NHANES offers a unique opportunity
to assess the prevalence of HPV infection in the general population.
Reducing the prevalence of HPV infection is a
Developmental Healthy People 2010 objective: “Reducing the number of new HPV
cases can help minimize the overall number of cases of high risk subtypes
associated with cervical cancer in females...” Detection and typing of HPV DNA
in vaginal swabs will allow evaluation of trends in prevalence of type-specific
HPV infection by age, sexual behavior, and race/ethnicity. Three HPV vaccines
(Gardasil, Gardasil 9, and Cervarix) are licensed and recommended for use in females.
Two vaccines are licensed and recommended for use in males (Gardasil and
Gardasil 9). In mid-2006, the Advisory Committee on Immunizations (ACIP)
recommended routine vaccination of females aged 11 or 12 years and for those
13-26 years not previously vaccinated. In December 2011, ACIP recommended
routine vaccination of males aged 11 or 12 years and for those aged 13 through
21 years not previously vaccinated. As a vaccine becomes more widely used, the
national prevalence of HPV infection will be critical for evaluating
vaccination strategies in the United States.
Examined female participants aged 14-59 years were
eligible. This restricted data file includes data for examined participants
aged 14 to 17 years. Please see Analytic
Notes about the release of data for adults aged 18-59 years.
Description of Laboratory Methodology
This assay used Roche Linear Array HPV Genotyping test
that is based on HPV L1 consensus polymerase chain reaction (PCR) with
biotinylated PGMY09/11 primer sets. It also includes biotinylated β-globin
primers as an internal control for sample amplification. The primer mix
amplified essentially all HPV types found in the genital tract along with the
human β-globin gene. After amplification, the samples were typed by
hybridization to the typing strips followed by colorimetric detection. The
strip is a linear array of probes specific for 37 HPV types (6, 11, 16, 18, 26,
31, 33, 35, 39, 40, 42, 45, 51, 52, 53, 54, 55, 56, 58, 59, 61, 62, 64, 66, 67,
68, 69, 70, 71, 72, 73, 81, 82, 83, 84, 89, and IS39) and for the positive
β-globin control as well. Types were read by comparing the reaction pattern to
the typing template. Samples that were negative for HPV and the β-globin
control indicated lack of a suitable sample and are considered inadequate for
interpretation (Linear Array HPV Genotyping Test Application manual,
2008). Refer to the Laboratory Method Files section for a
detailed description of the laboratory methods used.
Laboratory Method Files
HPV Vaginal Swab Linear Array Laboratory Procedure Manual
Laboratory Quality Assurance and Monitoring
Vaginal swab samples were processed, stored, and shipped
to the Chronic Viral Diseases Branch, Division of High-Consequence Pathogens
and Pathology, National Center for Emerging and Zoonotic Infectious Diseases,
Centers for Disease Control and Prevention, Atlanta, GA for analysis.
Detailed instructions on specimen collection and
processing are discussed in the NHANES
Laboratory Procedures Manual (LPM). Swabs were stored at room
temperature until they were shipped to the National Center for Emerging and
Zoonotic Infectious Diseases for testing.
Detailed QA/QC instructions are discussed in the NHANES LPM.
Mobile Examination Centers (MECs)
Laboratory team performance is monitored using several
techniques. NCHS and contract consultants use a structured competency
assessment evaluation during visits to evaluate both the quality of the
laboratory work and the quality-control procedures. Each laboratory staff
member is observed for equipment operation, specimen collection and
preparation; testing procedures and constructive feedback are given to each
staff member. Formal retraining sessions are conducted annually to ensure that
required skill levels were maintained.
NHANES uses several methods to monitor the quality of the
analyses performed by the contract laboratories. In the MEC, these methods
include performing blind split samples collected on “dry run” sessions. In
addition, contract laboratories randomly perform repeat testing on 2% of all
Progress reports containing any problems encountered
during shipping or receipt of specimens, summary statistics for each control
pool, QC graphs, instrument calibration, reagents, and any special
considerations are submitted to NCHS quarterly. The reports are reviewed for trends
or shifts in the data. The laboratories are required to explain any identified
areas of concern.
Data Processing and Editing
The data were reviewed. Incomplete data or improbable
values were sent to the performing laboratory for confirmation.
Note: In the 2015-2016 cycle, Cobas HPV Swab High-Risk
results (LBXHP2C) are being released separately in two new datasets: HPVSWC_I
and HPVC_I_R. In the 2013-2014 cycle, LBXHP2C results were released with the
Roche Linear Array results in datasets HPVSWR_H and HPVS_H_R.
Refer to the 2015-2016
Laboratory Data Overview for general information on NHANES
MEC exam sample weights should be used for analyses.
Demographic and Other Related Variables
The analysis of NHANES laboratory data must be conducted
using the appropriate survey design and demographic variables. The NHANES 2015-2016
Demographics File contains demographic data, health indicators, and
other related information collected during household interviews as well as the
sample design variables. The recommended procedure for variance estimation
requires use of stratum and PSU variables (SDMVSTRA and SDMVPSU, respectively)
in the demographic data file.
This laboratory data file can be linked to the other
NHANES data files using the unique survey participant identifier (i.e., SEQN).
The Questionnaire data files contain socio-economic data,
health indicators, and other related information collected during household
interviews. Certain sensitive data on participants under 18 years of age (e.g.,
HPV typing results, sexual behavior variables) are not included in the public
use files. These data may be requested as described in the NHANES guidelines.
The public release data file includes HPV vaginal swab
data for participants aged 18-59. HPV vaginal swab data for youth aged 14-17
years are available through the NCHS Research Data Center (RDC).
HPV Summary Variable
The HPV PCR Summary variable (LBDRPCR) indicates if at
least one type is positive (LBDRPCR=1); the sample is negative (LBDRPCR=2); the
sample is inadequate (LBDRPCR=3); or the sample is missing (LBDRPCR=.).
If beta-globin is not present, both LBDRHP and LBDRLP are
negative in the sample and no HPV type is detected, the sample is coded as “Inadequate”.
If any of the types on the strips (LBDR06-LBDRPI) are
positive, the sample is coded as positive. If all of the types on the strip are
coded as negative, and beta-globin is detected (either LBDRHP or LBDRLP is
positive) the sample is coded as negative.
Variables LBDRHP through LBDRPI are from the RUO Roche
Linear Array HPV typing assay, however LBDR52 also includes information from a
type-specific assay for HPV 52. The Linear Array typing strip includes an XR
probe that hybridizes with HPV 52 as well as HPV types 33, 35 and 58. Samples
positive for the XR probe and 33, 35, or 58 require specific testing to confirm
the presence of HPV 52 (Onyekwuluje et al., 2012).
If data is
qualitative, the use of lower limits of detection (LLODs) is not applicable.
Please refer to the NHANES Analytic
Guidelines and the on-line NHANES Tutorial for further
details on the use of sample weights and other analytic issues.