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Figure 1.  Comparison of Dual and Concordant Infection Prevalence
Comparison of Dual and Concordant Infection Prevalence

Dual infection is defined as an infection of any human papillomavirus serotype in both the oral and vaginal regions. Concordant infection is defined as infection of matching serotype in both locations.

Figure 2.  Prevalence of Dual and Concordant Human Papillomavirus Infection by Age
Prevalence of Dual and Concordant Human Papillomavirus Infection by Age

Dual infection has a bimodal distribution pattern, with a higher incidence in the 20- to 29-year and 50- to 60-year age groups. The 30- to 39-year and 40- to 49-year age groups are negatively associated with dual infection compared with the group younger than 20 years on multivariate analysis. Concordant infection does not have a bimodal distribution pattern. For the definitions for dual and concordant infections, see the legend to Figure 1.

Table 1.  Results of Bivariate Analysis for Dual and Concordant HPV Infection Prevalence by Demographic Characteristics, NHANES 2009-2012
Results of Bivariate Analysis for Dual and Concordant HPV Infection Prevalence by Demographic Characteristics, NHANES 2009-2012
Table 2.  Results of Bivariate Analysis for Dual and Concordant HPV Infection Prevalence by Sexual Behavior Characteristics, NHANES 2009-2012
Results of Bivariate Analysis for Dual and Concordant HPV Infection Prevalence by Sexual Behavior Characteristics, NHANES 2009-2012
Table 3.  Results of Multivariate Analysis for Predictors of Dual and Concordant HPV Infection, NHANES 2009-2012
Results of Multivariate Analysis for Predictors of Dual and Concordant HPV Infection, NHANES 2009-2012
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Muñoz  N, Bosch  FX, de Sanjosé  S,  et al; International Agency for Research on Cancer Multicenter Cervical Cancer Study Group.  Epidemiologic classification of human papillomavirus types associated with cervical cancer.  N Engl J Med. 2003;348(6):518-527.PubMedGoogle ScholarCrossref
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Walboomers  JM, Jacobs  MV, Manos  MM,  et al.  Human papillomavirus is a necessary cause of invasive cervical cancer worldwide.  J Pathol. 1999;189(1):12-19.PubMedGoogle ScholarCrossref
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Berrington de González  A, Green  J; International Collaboration of Epidemiological Studies of Cervical Cancer.  Comparison of risk factors for invasive squamous cell carcinoma and adenocarcinoma of the cervix: collaborative reanalysis of individual data on 8,097 women with squamous cell carcinoma and 1,374 women with adenocarcinoma from 12 epidemiological studies [correction published in Int J Cancer. 2007;120(11):2525].  Int J Cancer. 2007;120(4):885-891.PubMedGoogle ScholarCrossref
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Gillison  ML, D’Souza  G, Westra  W,  et al.  Distinct risk factor profiles for human papillomavirus type 16-positive and human papillomavirus type 16-negative head and neck cancers.  J Natl Cancer Inst. 2008;100(6):407-420.PubMedGoogle ScholarCrossref
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Heck  JE, Berthiller  J, Vaccarella  S,  et al.  Sexual behaviours and the risk of head and neck cancers: a pooled analysis in the International Head and Neck Cancer Epidemiology (INHANCE) consortium.  Int J Epidemiol. 2010;39(1):166-181.PubMedGoogle ScholarCrossref
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Smith  EM, Ritchie  JM, Summersgill  KF,  et al.  Age, sexual behavior and human papillomavirus infection in oral cavity and oropharyngeal cancers.  Int J Cancer. 2004;108(5):766-772.PubMedGoogle ScholarCrossref
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Gillison  ML, Broutian  T, Pickard  RKL,  et al.  Prevalence of oral HPV infection in the United States, 2009-2010.  JAMA. 2012;307(7):693-703.PubMedGoogle ScholarCrossref
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Smith  JS, Gilbert  PA, Melendy  A, Rana  RK, Pimenta  JM.  Age-specific prevalence of human papillomavirus infection in males: a global review.  J Adolesc Health. 2011;48(6):540-552.PubMedGoogle ScholarCrossref
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Jaisamrarn  U, Castellsagué  X, Garland  SM,  et al; HPV PATRICIA Study Group.  Natural history of progression of HPV infection to cervical lesion or clearance: analysis of the control arm of the large, randomised PATRICIA study.  PLoS One. 2013;8(11):e79260.PubMedGoogle ScholarCrossref
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Kreimer  AR, Pierce Campbell  CM, Lin  H-Y,  et al.  Incidence and clearance of oral human papillomavirus infection in men: the HIM cohort study.  Lancet. 2013;382(9895):877-887.PubMedGoogle ScholarCrossref
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Gillison  ML, Castellsagué  X, Chaturvedi  A,  et al.  Eurogin Roadmap: comparative epidemiology of HPV infection and associated cancers of the head and neck and cervix.  Int J Cancer. 2014;134(3):497-507.PubMedGoogle ScholarCrossref
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Termine  N, Giovannelli  L, Matranga  D,  et al.  Oral human papillomavirus infection in women with cervical HPV infection: new data from an Italian cohort and a meta-analysis of the literature.  Oral Oncol. 2011;47(4):244-250.PubMedGoogle ScholarCrossref
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Menezes  LJ, Poongulali  S, Tommasino  M,  et al.  Prevalence and concordance of human papillomavirus infection at multiple anatomic sites among HIV-infected women from Chennai, India.  [published online May 22, 2015].  Int J STD AIDS. 2015;0956462415587226. doi:10.1177/0956462415587226.PubMedGoogle Scholar
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Du  J, Nordfors  C, Ahrlund-Richter  A,  et al.  Prevalence of oral human papillomavirus infection among youth, Sweden.  Emerg Infect Dis. 2012;18(9):1468-1471.PubMedGoogle ScholarCrossref
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Meyer  MF, Huebbers  CU, Siefer  OG,  et al.  Prevalence and risk factors for oral human papillomavirus infection in 129 women screened for cervical HPV infection.  Oral Oncol. 2014;50(1):27-31.PubMedGoogle ScholarCrossref
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Smith  EM, Ritchie  JM, Yankowitz  J, Wang  D, Turek  LP, Haugen  TH.  HPV prevalence and concordance in the cervix and oral cavity of pregnant women.  Infect Dis Obstet Gynecol. 2004;12(2):45-56.PubMedGoogle ScholarCrossref
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Original Investigation
May 2016

Concordant Oral and Vaginal Human Papillomavirus Infection in the United States

Author Affiliations
  • 1School of Medicine, University of California, San Diego
  • 2Division of Head and Neck Surgery, Department of Surgery, University of California, San Diego
  • 3Department of Surgery, University of California, San Diego
JAMA Otolaryngol Head Neck Surg. 2016;142(5):457-465. doi:10.1001/jamaoto.2016.0064
Abstract

Importance  Human papillomavirus (HPV) is a common infection in adults, with tropism for sites in the head and neck and the genital tracts. To date, few studies have addressed concurrent infection in these sites.

Objective  To understand the prevalence, characteristics, and concordance of HPV infections in the oral and vaginal regions.

Design, Setting, and Participants  This study was a retrospective analysis of cross-sectional survey data from the National Health and Nutrition Examination Survey, 2009-2012. The database was reviewed for all women aged 18 to 69 years with available oral and vaginal HPV DNA screening data. The study was performed from August 1, 2014, to November 1, 2014. Data analysis was performed from November 1, 2014, to June 30, 2015.

Main Outcomes and Measures  Logistic regression models were constructed to identify factors associated with infection. Covariates for multivariate analysis included age, income to poverty ratio, number of prior sexual partners, number of prior oral sex partners, and having recent oral sex partners. Dual infection was defined as having an infection of any serotype in both the oral and vaginal HPV regions. Concordant infection was defined as an infection of matching serotype in both locations.

Results  A total of 3463 women were identified (mean [SD] age, 37.5 [12.1] years). Racial distribution was 1341 white (38.7%), 786 black (22.7%), 554 Mexican American (16.0%), 378 other Hispanic (10.9%), and 404 self-identified as other (11.7%). Vaginal HPV infection was present in 1586 (45.2%) and oral HPV infection in 141 (4.1%). Dual infection was identified in 107 (3.0%) of all patients, and concordant infection was observed in 41 (1.1%). The prevalence of dual infection was 75.9% in those with oral infection and 6.8% in those with vaginal infection. On multivariate analysis, age (30-50 years) and higher income to poverty ratios had negative associations with dual and concordant infections. A new sexual partner within the last year was positively associated with dual infection (odds ratio, 2.28; 95% CI, 1.03-5.02; P = .04). More than 2 oral sex partners in the past year was positively associated with concordant infection (odds ratio, 3.43; 95% CI, 1.06-11.06; P = .04).

Conclusions and Relevance  This analysis reveals the importance of several demographic factors (age and socioeconomic status) and behavioral factors (oral sex practices) in the development of dual and concordant HPV infection in women. Notably, other sexual behaviors, other sexually transmitted infections, sexual orientation, and number of lifetime sexual partners did not demonstrate any significant associations. Women with multiple oral sex partners and oral HPV infection have a high likelihood of having concurrent vaginal HPV infection.

Introduction

Human papillomavirus (HPV) is one of the most common sexually transmitted infections and may result in the development of benign neoplasms, such as condyloma or papilloma, or malignant tumors, such as squamous cell carcinoma. More than 150 serotypes of the virus exist, and these serotypes may be classified into high- and low-risk categories based on their oncogenic potential.1

Mucosal HPV is associated with genital and oral disease and is the primary cause of carcinoma of the uterine cervix,2 whereby high-risk serotypes, such as HPV-16 and HPV-18, induce malignant transformation of normal squamous epithelial cells. Human papillomavirus testing has gained an increasingly prominent role in cervical cancer screening and prevention efforts.3,4

Human papillomavirus has long been known to cause benign lesions of the upper aerodigestive tract, such as recurrent papillomatosis.5 The virus was more recently recognized to induce malignant transformation within the mucosa of the oropharynx. Whereas oropharyngeal squamous cell carcinoma (OPSCC) was once primarily attributable to tobacco and alcohol exposure, OPSCC in the United States and elsewhere is now more frequently the result of HPV infection.6 Known risk factors for HPV-positive OPSCC are distinct from HPV-negative OPSCC and most notably include sexual exposure history.6-9

Longitudinal studies1,10,11 have outlined the prevalence and natural history of cervical and oral HPV infection. Data reveal similarities and differences in the epidemiology and natural history of HPV in these 2 sites. Quiz Ref IDBoth infections are highly associated with sexual behaviors, with HPV-16 being the most common serotype associated with tumors at each site. In the adult population, cervical HPV infection is highly prevalent (40%), whereas oral HPV infection has a relatively lower prevalence (7%).11 In addition, both indicate bimodal age distribution, with peaks in the third and sixth decades suggesting reinfection.11,12Quiz Ref ID Furthermore, oral and cervical infections seem to exhibit similar clearance characteristics, with most clearing within 1.5 to 2 years.13-15

Although the infections are well understood independently, little is known about correlations between oral and cervical HPV infections. Relatively few studies examine concordance. There is some evidence of increased oral HPV prevalence in people with cervical infection, although studies16-19 report wide prevalence estimates, ranging from 2% to 50%. Other studies20,21 fail to find a correlation. Many of these studies are not representative of the general population because of the small sample size or limited patient selection.

We sought to understand the prevalence and characteristics of HPV infection in the oral and vaginal regions. Associations for dual infection (infection of any serotype in both locations) and concordant infection (infection of matching serotype in both locations) were examined.

Methods

We performed a retrospective analysis of cross-sectional survey data from August 1, 2014, to November 1, 2014. Data analysis was performed from November 1, 2014, to June 30, 2015. This database is publicly available by the National Health and Nutrition Examination Survey (NHANES) (through the Centers for Disease Control and Prevention) and does not require institutional review board approval. Data from these public datasets have been approved by the CDC's Research Ethics Review Board (ERB) for research applications. The data were already deidentified when provided to us.

The NHANES is conducted by the Centers for Disease Control and Prevention and assesses the health and nutrition status of adults and children in the United States through interviews and physical examinations. The design of NHANES includes self-reported questionnaires, household interviews, physical examinations, and laboratory testing performed at a mobile examination center (MEC). The NHANES population is representative of the US population. The NHANES laboratory methods are described in detail elsewhere.19 In brief, oral samples were collected by a swish and gargle with alcohol-based or saline mouthwash to identify oral and oropharyngeal HPV infection. The samples were processed at the Ohio State University Gillison Laboratory for HPV DNA by polymerase chain reaction. Self-collected vaginal swab samples, representative of vaginal and cervical infection, were collected at the MEC and processed at the Centers for Disease Control and Prevention by a digene hc2 DNA test (Qiagen) and a Roche Linear Array (Roche Molecular Diagnostics). All samples were tested for the presence of 37 known strains of HPV. Eighteen HPV DNA types were classified as high-risk infection (16, 18, 26, 31, 33, 35, 39, 45, 51, 52, 53, 56, 58, 59, 66, 68, 73, and 82), and 19 were classified as low-risk infection (6, 11, 40, 42, 54, 55, 61, 62, 64, 67, 69, 70, 71, 72, 81, 83, 84, 89, and IS39).

Quiz Ref IDThe NHANES 2009-2010 and 2011-2012 data sets were used to identify women aged 18 to 69 years who were examined in the MEC and were screened for vaginal and oral HPV infection. The women were healthy volunteers, and data regarding oropharyngeal and cervical diseases were not captured. Bivariate analyses with demographic and behavioral characteristics were computed using logistic regression models. Associations were reported as odds ratios (ORs). For multivariate analysis, additional logistic regression models were constructed to identify factors independently associated with dual and concordant HPV infection. Covariates for multivariate analysis were selected based on bivariate analyses and included age, income to poverty (IP) ratio, number of prior sexual partners, number of prior oral sex partners, and having a recent oral sex partner. The IP ratio is defined as a ratio of family income to federal poverty level, such that an IP ratio less than 1 is below poverty level and greater than 3 is more than 3 times the poverty level.

Analyses were performed using STATA SE software, version 11.1 (StataCorp). Statistical significance was defined as P < .05. All analyses were computed using NHANES 2009-2010 and 2011-2012 MEC sample weights to account for sample variability between the 2 survey cycles and to provide unbiased estimates of the prevalence of and associations with dual and concordant infection.

Results
Prevalence

A total of 3463 women were identified who had been tested for oral and vaginal HPV (mean [SD] age, 37.5 [12.1] years). Racial distribution was 1341 white (38.7%), 786 black (22.7%), 554 Mexican American (16.0%), 378 other Hispanic (10.9%), and 404 self-identified as other (11.7%). Most women were married or living with their partner (1845 [53.3%]), whereas 1385 (40.0%) were single (never married, divorced, or widowed). The median household income was $35 000 to $45 000, and the mean IP ratio was 2.3.

Of the women who answered the sexual history questionnaire, 2814 (91.1%) described themselves as heterosexual, 181 (5.9%) as homosexual or bisexual, and 91 (2.9%) as other; 2621 (88.9%) reported no history of sexually transmitted infection, whereas 327 (11.1%) reported having previously been diagnosed as having genital herpes, gonorrhea, chlamydia, or genital warts. Of those who responded, 2966 (95.3%) reported having had a prior sexual encounter, and 2422 (78.0%) reported having oral sex. The median number of lifetime sexual partners and oral sex partners were 4 and 2, respectively. The mean age of sexual debut was 17.4 years. Eleven patients (0.3%) tested human immunodeficiency virus (HIV) positive, all of whom tested negative for oral HPV. Other demographic and behavioral data are included in Table 1 and Table 2.

Vaginal HPV infection was present in 1568 women (45.2%), and oral HPV infection was observed in 141 women (4.1%) (Figure 1). Vaginal infection without oral infection occurred in 1461 women (42.2%), and oral infection without vaginal infection occurred in 34 women (1.0%). Dual infection was identified in 107 (3.1%), and concordant infection occurred in 41 (1.1%). Thus, although only 107 (6.8%) of those with vaginal infection had dual infection, 107 (75.9%) of those with oral infection had dual infection.

The most common low-risk vaginal serotypes identified included 61 and 62, which were observed in 223 (14.2%) and 215 (13.7%) cases, respectively. The most common high-risk vaginal serotypes included 53 and 16, which occurred in 196 (12.5%) and 141 (9.0%) cases, respectively. The most common low-risk oral serotypes included 55 and 62, observed in 26 (18.4% of oral infections) and 11 (7.8%) cases. The most common high-risk serotypes included 16 and 59, observed 12 (8.5%) and 10 (7.1%) times. Among those with concordant infection, the most common matching serotypes were 83 and 16, with 5 (12.2%) and 4 (9.8%) occurrences, respectively.

Bivariate Analysis

A few demographic factors were associated with dual and concordant infections (Table 1). Increasing age, higher educational level, being married or living with a partner, and higher IP ratios had negative associations with dual infection. Cigarette use had a positive association with dual infection. On the other hand, age, marital status, and IP ratio had negative associations with concordant infection. Ethnicity, alcohol use, birth control, and HPV vaccination status were not associated with dual or concordant infection.

A number of behavioral variables were also associated with dual and concordant infection on bivariate analysis (Table 2). Ever having any type of sex, increased number of sexual partners (vaginal and oral), younger age of sexual debut, ever having oral sex, and having a recent new oral sex partner revealed positive associations with dual infection. Increased number of sexual partners (vaginal and oral), younger age of sexual debut, and having a recent new oral sex partner revealed a positive association with concordant infection. Sexual orientation, history of sexually transmitted infection, or having ever performed anal sex failed to reveal associations with dual or concordant infection.

Multivariate Analysis

The results of the multivariate logistic regression are provided in Table 3. Initially, all covariates that were significant in bivariate analysis were tested in multivariate models. Among the demographic variables, marital status, educational level, and cigarette use were no longer significant, whereas age and IP ratio were significant. Among behavioral characteristics, only variables related to oral sexual history were significantly associated with rates of dual or concordant infection. Number of sexual partners and age of sexual debut were not significant factors.

Dual Infection

Quiz Ref IDSignificant covariates for dual infection included age, IP ratio, and having a recent new oral sex partner. The age groups 30 to 39 years and 40 to 49 years revealed a negative association with dual infection compared with the group younger than 20 years (OR, 0.3; 95% CI, 0.11-0.83; P = .02, and OR, 0.37; 95% CI, 0.15-0.89; P = .30, respectively). Higher IP ratios demonstrated a negative association with dual infection compared with an IP ratio less than 1 (IP ratio 2-3: OR, 0.29; 95% CI, 0.12-0.69; P = .01; IP ratio >3: OR, 0.25; 95% CI, 0.10-0.59; P = .002). Having performed oral sex on a new partner in the past year revealed a positive association with dual infection (OR, 2.28; 95% CI, 1.03-5.02; P = .04). In contrast, women who had a new oral sex partner more than a year ago did not have a higher association of dual infection. In addition, age of sexual debut and number of lifetime sexual partners were not determined to be associated with dual infection.

Concordant Infection

Quiz Ref IDSignificant covariates for concordant infection included age, IP ratio, and number of oral sex partners in the past year. The age groups 20 to 29, 30 to 39, and 40 to 49 years were negatively associated with concordant infection compared with the reference group of younger than 20 years (OR, 0.24; 95% CI, 0.10-0.56; P = .002; OR, 0.07; 95% CI, 0.2-0.30; P < .001; and OR, 0.28; 95% CI, 0.08-0.94; P = .04, respectively). Higher IP ratios revealed a negative association with concordant infection (IP ratio >3: OR, 0.19; 95% CI, 0.05-0.71; P = .02). Two or more oral sex partners in the past year had a positive association with concordant infection compared with those who had no oral sex partners in the past year (OR, 3.43; 95% CI, 1.06-11.06; P = .04). The number of sexual partners, age of sexual debut, and having a recent new oral sex partner were not significantly associated with concordant infection.

Discussion

Prior examination of dual HPV infections of separate mucosal sites has been limited. Gillison et al11 determined that a pooled prevalence of oral HPV infection in those already known to have cervical HPV was 18.1%, which is higher than the prevalence of oral infection in the general population. This group also observed a positive association for dual infection with HIV infection and age of sexual debut. Du et al19 found a higher prevalence in youth and, similar to our findings, noted that having an infection at 1 body site increases the risk of infection at the other.

Although dual infection has been more commonly studied, less is known about type-specific concordance in multiple sites. Termine et al16 found concordant infection in 27% of women, whereas analysis by Meyer et al20 revealed no type-specific correlation between the 2 locations. Prior work by Smith et al21 suggested that self-inoculation is an unlikely cause of transmission, although the study group was limited to pregnant women. One behavioral risk factor for concordant infection may include a younger age of sexual debut, but the association with other factors, such as those related to oral sexual practices, has not yet been determined.22 One weakness of prior studies is sample size because the largest of the existing studies includes fewer than 600 participants. Because oral infection has a relatively low prevalence compared with vaginal infection, a larger sample size improves evaluation of the association between these sites. To our knowledge, this study is the largest to examine risk factors of dual and concordant HPV infection.

This analysis observed that the prevalence of dual infection in US women aged 18 to 69 years is 3%, with a concordant infection rate of 1.1%. Of interest, the prevalence of dual infection in individuals with oral HPV is 75.8%, substantially higher than previous observations. On the other hand, the prevalence of dual infection in the population with cervical infection is 6.8%, lower than the 18.1% reported by Termine et al.16 The higher prevalence of HPV infection at 1 site in the setting of infection at the other site suggests potential clinical utility for selective screening. Specifically, this finding points to a potential role for OPSCC screening in patients with proven high-risk vaginal infection or positive Papanicolaou smear results because no screening protocol for OPSCC currently exists. Similarly, these findings suggest that women with HPV-positive OPSCC may merit closer screening for cervical infection or cancer because most of the oral HPV-positive women in this study also had vaginal HPV. However, because this is an observational study in people whose cancer history is unknown, data are inadequate to establish a causative association between HPV infection and malignant tumors. Certainly, the individuals with a higher prevalence of HPV in this study may clear the infection over time and not develop HPV-related neoplasms at all.

This investigation also identifies several demographic characteristics and sexual behaviors as associations with dual and concordant infection. The prevalence of dual infection is highest for women younger than 20 years, with a second peak after 50 years of age (Figure 2). This bimodal distribution is similar to that observed for vaginal and oral infection independently and may be indicative of reinfection or a change in immune response with increasing age.

An increasing IP ratio reveals a negative association with dual and concordant infections. It has been previously observed that lower socioeconomic status is an independent risk factor for HIV.23 Moreover, decreased access to health care, less sexual health education, and resource distribution inequalities have been attributed to increased sexually transmitted disease rates in certain communities with low socioeconomic status.24 These factors may play a role in HPV infection as well.

Our data also indicate that having performed oral sex on a new partner within the past year is associated with dual infection. Furthermore, there is no association with the women whose last new partner was more than 1 year ago. Thus, recent new oral sexual exposure may result in transient infection via genital-oral transmission. Lower observed prevalence when last new oral sex exposure was more than 1 year ago may be a result of clearance of the infection or development of an immune response. These data also indicate that an increased number of oral sex partners has a positive association with concordant infection. This finding also supports the genital-oral transmission theory, especially because the number of vaginal sex partners is not associated in the same manner.

Other demographic factors significant on bivariate analysis, such as educational level and marital status, were not significant on multivariate analysis. It is likely that the factors such as age, IP ratio, and sexual behaviors are more important and independent of these other demographic factors. Prior groups have found that HIV status has a positive association with dual infection.17,18,25,26 We did not observe this association, but the scarcity of HIV-positive women in this study limits the ability to draw any conclusions regarding HIV status and HPV infection. The HPV vaccination status was also not associated with dual infection. Because vaccination efforts have been limited to the last decade only in young individuals, the lack of observed effect in this NHANES population is not surprising.

Notably, sexual behaviors other than oral sex, sexually transmitted infections, sexual orientation, and number of lifetime sexual partners did not reveal significant associations with dual infection, although these are independent risk factors for infection at either anatomical site. The only behavioral risk factors identified in this study relate to oral sex, which may be considered when counseling patients concerned about HPV transmission. The lack of statistical significance with some of these behavioral factors may be attributed to the relatively low number of women with dual and concordant infection in this study.

Although the findings in this study highlight certain characteristics of individuals who may be at higher risk for HPV infection, the potential utility of this knowledge is not straightforward. Not all of these HPV infection serotypes are considered malignant. In addition, because the data set does not provide a history of malignant tumors or follow-up data, it is impossible to link the infection to HPV-associated neoplasms. However, the study sheds light on infection patterns and spread. This information could be of use to counsel high-risk individuals or their partners about certain behaviors linked to increased HPV prevalence. Whether these individuals may benefit from vaccination or increased surveillance to prevent OPSCC is unclear.

The NHANES data allow for in-depth analysis using a large population representative of the US population. However, limitations of such a data set include the lack of longitudinal data. In particular, HPV infection is highly associated with clearance and reinfection. Thus, follow-up data would provide important insight about the persistence of dual and concordant infection. Because only a subset of all the participating individuals opt to answer the sexual history questionnaire and to be tested for HPV, the reduced population may be subject to selection bias. Furthermore, additional information regarding sexual partners of included individuals would help complete the picture of HPV transmission. This data set also fails to reflect information regarding the presence or risk of HPV-associated neoplasms, which is an important consideration in the public health effect of HPV. Prospective studies may address some of these shortcomings.

Conclusions

To our knowledge, this is the largest cross-sectional study evaluating dual and concordant HPV infection. As previously reported, sexual behavior has been associated with oral and vaginal HPV infection. The novelty of this analysis is the demonstration of the relative importance of several demographic (age and socioeconomic status) and behavioral (oral sex practices) factors. Furthermore, the increased prevalence of dual infection in patients who are already infected with 1 infection may have implications for selective screening. Women with vaginal HPV infection who have multiple oral sex partners, regardless of other risk factors, may have a concurrent oral infection. However, these findings do not elucidate a definitive association with OPSCC. Future investigation with longitudinal studies could further elucidate these associations.

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Article Information

Accepted for Publication: January 5, 2016.

Corresponding Author: Ryan K. Orosco, MD, Division of Head and Neck Surgery, Department of Surgery, University of California, San Diego, 200 W Arbor Dr, Ste 8895, San Diego, CA 92103-8895 (ryanorosco@gmail.com).

Published Online: March 24, 2016. doi:10.1001/jamaoto.2016.0064.

Author Contributions: Mr Kedarisetty and Dr Orosco had full access to all the data in the study and take responsibility for the integrity of the data and the accuracy of the data analysis.

Study concept and design: All authors.

Acquisition, analysis, or interpretation of data: All authors.

Drafting of the manuscript: Kedarisetty, Orosco, Hecht.

Critical revision of the manuscript for important intellectual content: All authors.

Statistical analysis: Kedarisetty, Orosco, Hecht.

Administrative, technical, or material support: Kedarisetty, Hecht, Chang, Weissbrod.

Study supervision: Chang, Weissbrod, Coffey.

Conflict of Interest Disclosures: None reported.

Previous Presentation: This study was presented as a poster at the American Head and Neck Society Annual Meeting at the Combined Otolaryngology Spring Meetings; April 23, 2015; Boston, Massachusetts.

References
1.
Muñoz  N, Bosch  FX, de Sanjosé  S,  et al; International Agency for Research on Cancer Multicenter Cervical Cancer Study Group.  Epidemiologic classification of human papillomavirus types associated with cervical cancer.  N Engl J Med. 2003;348(6):518-527.PubMedGoogle ScholarCrossref
2.
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