Prevalence of Sexually Transmitted Infections and Bacterial Vaginosis among Female Adolescents in the United States: Data from the National Health and Nutrition Examination Survey (NHANES) 2003-2004 Sara E. Forhan, MD, MPH Division of STD Prevention Centers for Disease Control and Prevention Good morning.

Adolescents & sexually transmitted infections (STIs) Adolescent females vulnerable to STIs and sequelae Community-level studies & surveillance data suggest high STI prevalence No U.S. population-based studies of overall STI burden among female adolescents Adolescent females are especially vulnerable to sexually transmitted infections (STIs) and STI-associated sequelae for both biological and behavioral reasons. Several community-level studies and national surveillance data suggest a high STI prevalence among young women in their teens, but these data are subject to selection and reporting biases. There have been no U.S. population-based studies of the overall STI burden among female adolescents.

Most common STIs in adolescents and their sequelae Human papillomavirus (HPV) Can lead to cervical cancer and genital warts Chlamydia trachomatis (chlamydia) Can lead to pelvic inflammatory disease (PID) --> infertility, ectopic pregnancy Trichomonas vaginalis (trichomonas) Herpes simplex virus, type 2 (HSV-2) Bacterial vaginosis (BV) ↑ HIV risk Prior studies have suggested that the STIs listed here are the most common STIs in adolescents: The human papillomavirus (or HPV). High-risk types can lead to cervical cancer and low-risk types can cause genital warts. Chlamydia trachomatis, can lead to pelvic inflammatory disease which, in turn, can cause infertility and ectopic pregnancy. Other STIs include Trichomonas vaginalis (trichomonas) and herpes simplex virus, type 2, or HSV-2 . Bacterial vaginosis (or BV), while not an STI, has several adverse outcomes, including preterm labor and possible increased HIV risk. Several of these, including chlamydia, trichamonas, HSV-2 , and BV have been linked to increased risk of HIV infection.

Objective To estimate prevalence of the most common STIs and of BV among a nationally representative sample of 14–19 year-old females We undertook this analysis to estimate the prevalence of the most common STIs, and also of BV, among a nationally representative sample of 14–19 year-old females in the U.S.

Methods National Health and Nutrition Examination Surveys (NHANES) 2003–2004 Female adolescents, aged 14–19 years Prevalence of 4 most common STIs: chlamydia, HSV-2, HPV, trichomonas, and of BV HPV evaluation limited to 23 high-risk types & types 6 or 11 = HR/6/11 HPV We analyzed data from the National Health and Nutrition Examination Surveys (NHANES) 2003-2004, for female adolescents, aged 14–19 years to determine the individual and overall prevalence estimates of the 4 most common STIs: Chlamydia, HSV-2, HPV, and trichomonas AND of BV Our HPV evaluation was limited to the 23 oncogenic, or high-risk, HPV types responsible for cervical cancer, and low-risk types 6 and 11, which are responsible for almost all genital warts. I will refer to this variable as HIGH-RISK OR 6 OR 11 HPV (HR/6/11 HPV). This NHANES cycle was the first to measure HPV in women and in female adolescents.

Primary outcome: Overall STI burden “Any STI” = chlamydia or HSV-2 or HR/6/11 HPV or trichomonas Our primary outcome, overall STI burden, was measured by a composite STI variable, called “any STI”, defined as a positive test for chlamydia or HSV-2 or HR/6/11 HPV or trichomonas. Not included were gonorrhoea , syphilis, or HIV for the reasons listed on the slide. gonorrhea (GC): data not released syphilis & HIV: no cases in 18–19-year-olds (only 18–49-year-olds tested) Not included:

NHANES 2003–2004 laboratory methods Specimen Infection Analytic method Urine Chlamydia Polymerase chain reaction (PCR) Serum HSV-2 Immunodot Vaginal swab (self-collected) HPV PCR Trichomonas BV Gram stain Nugent’s score ≥7 I’ll now go over the laboratory methods used to test for each STI. 14–19 year-old female participants provided urine, sera, and self-collected vaginal swab specimens for STI and BV analysis.

NHANES 2003–2004 laboratory methods Specimen Infection Analytic method Urine Chlamydia Polymerase chain reaction (PCR) Serum HSV-2 Immunodot Vaginal swab (self-collected) HPV PCR Trichomonas BV Gram stain Nugent’s score ≥7 Urine specimens were tested for chlamydia using a polymerase chain reaction (PCR) by BD Amplified Assay.

NHANES 2003–2004 laboratory methods Specimen Infection Analytic method Urine Chlamydia PCR Serum HSV-2 Immunodot Vaginal swab (self-collected) HPV Trichomonas BV Gram stain Nugent’s score ≥7 Sera were evaluated for HSV-2 antibodies using Immunodot Assay.

NHANES 2003–2004 laboratory methods Specimen Infection Analytic method Urine Chlamydia PCR Serum HSV-2 Immunodot Vaginal swab (self-collected) HPV Trichomonas BV Gram stain Nugent’s score ≥7 Vaginal swabs specimens were used for: detection of, 23 high-risk and 20 low-risk HPV types, and of trichomonas using PCR methods, and for BV using gram stain, with Nugent score ≥7 as the criterion for diagnosis.

NHANES analytic considerations and definitions Complex probability sample to represent the U.S. civilian population Race/ethnicity: non-Hispanic (NH) white, NH black, & Mexican American Adolescents, NH blacks, & Mexican Americans oversampled Sex = oral, vaginal, or anal All prevalence estimates weighted NHANES are annual cross-sectional surveys which use a complex, probability sample design to represent the U.S. civilian, non-institutionalized population. Race/ethnicity categories in NHANES were self-reported as non-Hispanic (NH) white, NH black, and Mexican American. Adolescents, non-Hispanic blacks, and Mexican Americans were over-sampled. Sex was defined as vaginal, oral, or anal sex. We defined “sexually experienced” as those who answered “yes” to the question “Have you ever had sex?” All prevalence estimates were weighted to account for the complex survey design.

Study participants 838 female adolescents interviewed 96% had lab results for at least 1 STI or BV 612 (76%)—evaluated for “any STI” 750 answered “Have you ever had sex?” 404 sexually experienced Our study included 838 female adolescents who were interviewed. 96% of whom had lab results for at least 1 STI or BV. .These were included in the overall analysis. 612, or 76%, of these could be evaluated for “any STI” . We had information on sexual experience for 750 participants who answered the question “ Have you ever had sex?” Of these,, 404 answered “yes”. This is the population included as “sexually experienced”.

Prevalence of STIs among 14–19 year-old U. S Prevalence of STIs among 14–19 year-old U.S. females (n=838), NHANES 2003–2004   n Prevalence % (95% CI) HR/6/11 HPV 652 18.3 (13.5–24.8) chlamydia 793 3.9 (2.2–6.9) trichomonas 695 2.5 (1.3–5.1)* HSV-2 729 1.9 (1.0–3.5) “Any STI” 612 25.7 (20.1–32.9) The weighted prevalence estimates for the 4 individual STIs and for “any STI” are shown here. The prevalence of “any STI”, was 25.7%. HPV was the most prevalent individual STI. 18% of all females adolescents were infected with HR/6/11 HPV. Chlamydia was the next most common STI, at 3.9%, followed by trichomonas and HSV-2. *Relative Standard Error > 30%

Prevalence of STIs among sexually experienced 14–19 year-old U. S Prevalence of STIs among sexually experienced 14–19 year-old U.S. females (n=404), NHANES 2003–2004   n Prevalence % (95% CI) HR/6/11 HPV 357 29.5 (22.6–38.4) chlamydia 396 7.1 (4.1–12.2) trichomonas 371 3.6 (1.6–8.1)* HSV-2 370 3.4 (1.7–6.6) “Any STI” 347 39.5 (31.1–50.3) This table gives the prevalence estimates for the same STIs among sexually experienced females. Among those who reported ever having had sex, the prevalence of “any STI”, was nearly 40%. Again, HPV was the most prevalent STI, with almost 30% of sexually experienced teens infected with HR/6/11 HPV types. 7% had chlamydia. *Relative Standard Error > 30%

Prevalence of BV Overall prevalence of 24.1% (19.9–29.2) Did not vary by sexual experience In this study, the overall prevalence of BV was 24.1% . The prevalence did not vary by sexual experience.

Multiple STIs Of those with an STI, 15% had more than 1 82% of those with more than 1 STI had HR/6/11 HPV as 1 of their infections Of female adolescents with an STI, 15% had more than 1. 82% of those adolescent young women with more than 1 STI had HR/6/11 HPV as one of their infections.

“Any STI” prevalence by race/ethnicity Adjusted OR† (95% CI) NH white 184 20.3 1 Mexican American 182 19.7 1.1 (0.5–2.4) NH black 221 47.7 3.5 (1.8–6.9) This slide shows “any STI” by race/ethnicity. Almost half (47.7%) of non-Hispanic black females adolescents had at least 1 STI. Even after controlling for the other demographic characteristics and for # of lifetime sex partners, non-Hispanic blacks had over 3 times the odds of having an STI compared with non-Hispanic whites. * Positive test for CT, HSV-2, HR/6/11 HPV, or TV † Adjusted for demographic variables, # of lifetime sexual partners, and BV

“Any STI” prevalence by duration of sexual experience Current age minus age at sexual debut* n Prevalence “any STI”† % Adjusted OR‡ (95% CI) Never had sex 233 7.5¶ 0.4 (0.1–1.5) Same age 62 20.6 1 1 year older 82 32.6 2.2 (0.6–8.1) 2 years older 75 50.3 4.4 (1.2–16.1) ≥3 years older 128 51.6 4.0 (0.8–18.8) This slide shows overall STI prevalence by duration of sexual experience, which we defined as current age minus the age at sexual debut. For those who were the same age as their age at sexual debut, that is those with less than 1 year of sexual experience, the prevalence of “any STI” was already 20.6%. The prevalence increased to 50% among those who were 2 years older than their age at sexual debut. *Current age minus age at first sex † Positive test for CT, HSV-2, HR/6/11 HPV, or TV ‡ Adjusted for age , race/ethnicity, poverty index, and BV ¶ RSE > 30%

“Any STI” prevalence by number of lifetime sexual partners Adjusted OR† (95% CI) 233 7.5‡ 0.4 ( 0.1–1.4) 1 125 20.4 2 62 43.1 2.9 (0.7–11.5) ≥3 159 54.7 5.4 (2.3–12.8) This slide shows overall STI prevalence by # of lifetime sexual partners. STI prevalence was 20% among those who reported having had 1 lifetime partner. By the time people had 3 lifetime partners, 55% among those who reported having had ≥3 lifetime partners. Positive test for CT, HSV-2, HR/6/11 HPV, or TV † Adjusted for age, race/ethnicity, poverty index, and BV ‡RSE > 30%

Limitations STI burden probably slightly underestimated GC, syphilis, HIV not in composite STI variable Self-reported behavioral data STIs among who reported never having had sex This analysis has limittions that need to be considered. First, the STI burden is slightly underestimated because gonorrhea, syphilis, and HIV were not included the composite STI variable. Other studies have shown the prevalence of these 3 STIs as low in female adolescents Nevertheless, our estimate is a conservative one. Second, self-reported behavioral data could lead to misclassification and might have accounted for the few STIs we encountered among those who reported never having had sex; however false positive test results had contributed to this finding.

Summary High STI burden in female adolescents: 1 in 4 infected Estimated 3.2 million young women with STIs Substantial racial disparity High STI prevalence soon after sexual debut, even with few partners Predominant HPV In summary, we found: A high STI burden in U.S. female adolescents. 1 in 4 is infected This translates into an estimated 3.2 million young women with STIs There is substantial racial disparity,. The prevalence his highest among non-Hispanic blacks. High STI prevalence appears soon after sexual debut, even among those with few partners. Study findings highlight the predominant contribution f HPV to the overall STI prevalence.

Discussion Important public health priority Sequelae = infertility, cervical cancer, HIV infection Comprehensive approach to address the problem Increased awareness and education Steps to narrow racial disparities HPV vaccine Recommended routinely all 11- and 12-year-old girls Chlamydia screening Recommended for all sexually active women, aged ≤ 25 Given the magnitude of this STI burden, prevention of STIs and their complications in female adolescents remains an important public health priority. While not all of these infections will lead to sequelae, for example, most HPV infections clear on their own, a proportion of these will lead to serious sequelae including infertility, cervical cancer and an increased risk of HIV infection. We need a comprehensive approach to address the problem squarely. Such an approach should include increased awareness and education and steps to narrow racial disparities The approach would also include the full adoption of several existing prevention strategies. would decrease STIs, especially the most common STI, HPV, in female adolescents. An HPV vaccine is now recommended routinely for 11 and 12 year-old girls. Its uptake is critical to prevent against HPV types 16 and 18, which are responsible for 70% of cervical cancer, and types 6, and 11, which are responsible for nearly all genital warts. For more than a decade, CDC has recommended chlamydia screening of all sexually active women younger than 25 years. Chlamydia, the most common, treatable STI, and that clearly linked to long-term consequences with its risk of The most common, treatable STI, CT ___% would be picked up if 100% CT screening and then treated

Acknowledgements Sami Gottlieb Maya Sternberg Lauri Markowitz Fujie Xu Eileen Dunne Stuart Berman Deblina Datta I would like to thank and acknowledge the following people that made this analysis possible. "The findings and conclusions in this presentation are those of the author(s) and do not necessarily represent the views of the CDC/ATSDR."