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"Nucci-Sack, Anne"
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molBV reveals immune landscape of bacterial vaginosis and predicts human papillomavirus infection natural history
2022
Bacterial vaginosis (BV) is a highly prevalent condition that is associated with adverse health outcomes. It has been proposed that BV’s role as a pathogenic condition is mediated via bacteria-induced inflammation. However, the complex interplay between vaginal microbes and host immune factors has yet to be clearly elucidated. Here, we develop
molBV
, a 16 S rRNA gene amplicon-based classification pipeline that generates a molecular score and diagnoses BV with the same accuracy as the current gold standard method (i.e., Nugent score). Using 3 confirmatory cohorts we show that
molBV
is independent of the 16 S rRNA region and generalizable across populations. We use the score in a cohort without clinical BV states, but with measures of HPV infection history and immune markers, to reveal that BV-associated increases in the IL-1β/IP-10 cytokine ratio directly predicts clearance of incident high-risk HPV infection (HR = 1.86, 95% CI: 1.19-2.9). Furthermore, we identify an alternate inflammatory BV signature characterized by elevated TNF-α/MIP-1β ratio that is prospectively associated with progression of incident infections to CIN2 + (OR = 2.81, 95% CI: 1.62-5.42). Thus, BV is a heterogeneous condition that activates different arms of the immune response, which in turn are independent risk factors for HR-HPV clearance and progression. Clinical Trial registration number: The CVT trial has been registered under: NCT00128661.
Here, Burk et al. develop an algorithm to diagnose bacterial vaginosis (BV) using the 16S rRNA gene, called
molBV
, which they use to profile the inflammatory landscape of BV and predict progression of human papillomavirus infection to cervical pre-cancer.
Journal Article
Using School-Based Health Programs to Prevent Human Trafficking: The Mount Sinai Experience
by
Diaz, Angela
,
Steever, John
,
Arden, Martha
in
Adolescents
,
Behavior modification
,
Birth control
2021
This article describes how school-based health centers can serve as human trafficking prevention sites.Setting: School-based health centers are available to all students attending a school and are often located in schools whose students have risk factors associated with human trafficking: those with a history of running away from home; unstable housing or homelessness; a history of childhood maltreatment or substance use; LGBTQidentification; physical or developmental disabilities, including students who have Individualized Education Programs and need special education; gang involvement; and/or a history of involvement in child welfare or the juvenile justice system. The Mount Sinai Adolescent Health Center provides a model of the types of service school clinics can offer, including integrated medical, sexual, and reproductive health, health education, and behavioral and mental health.Activities: Identifying young people with risk factors and addressing those factors in our clinics in a timely way can disrupt the progression to human trafficking. In addition, if young people who are trafficked are attending schools that have a clinic, their health needs, such as care for sexually transmitted infections and mental health issues, can be addressed on-site. Lastly, some people go to school to recruit students for human trafficking. By raising awareness and addressing human trafficking in the school, students can become aware of this issue and perhaps gain the ability to ask for help if they are approached or know of other students being recruited by a trafficker.Implications: The location of easily-accessible, adolescent-friendly, trafficking-aware services in schools can prevent, identify and intervene in human trafficking.
Journal Article
Anti-HPV16 Antibody Titers Prior to an Incident Cervical HPV16/31 Infection
2021
The goal of this study was to investigate the serological titers of circulating antibodies against human papillomavirus (HPV) type 16 (anti-HPV16) prior to the detection of an incident HPV16 or HPV31 infection amongst vaccinated participants. Patients were selected from a prospective post-HPV vaccine longitudinal cohort at Mount Sinai Adolescent Health Center in Manhattan, NY. We performed a nested case–control study of 43 cases with incident detection of cervical HPV16 (n = 26) or HPV31 (n = 17) DNA who had completed the full set of immunizations of the quadrivalent HPV vaccine (4vHPV). Two control individuals whom had received three doses of the vaccine (HPV16/31-negative) were selected per case, matched on age at the first dose of vaccination and follow-up time in the study: a random control, and a high-risk control that was in the upper quartile of a sexual risk behavior score. We conducted an enzyme-linked immunosorbent assay (ELISA) for the detection of immunoglobulin G (IgG) antibodies specific to anti-HPV16 virus-like particles (VLPs). The results suggest that the average log antibody titers were higher among high-risk controls than the HPV16/31 incident cases and the randomly selected controls. We show a prospective association between anti-HPV16 VLP titers and the acquisition of an HPV16/31 incident infection post-receiving three doses of 4vHPV vaccine.
Journal Article
Cervical, Anal and Oral HPV in an Adolescent Inner-City Health Clinic Providing Free Vaccinations
by
Strickler, Howard D.
,
Diaz, Angela
,
Burk, Robert D.
in
Adolescent
,
Adolescents
,
Ambulatory care facilities
2012
Published human papillomavirus (HPV) vaccine trials indicate efficacy is strongest for those naive to the vaccine-types. However, few high-risk young women have been followed and cervical HPV has been the predominant outcome measure.
We collected cervical and anal swabs, as well as oral rinse specimens from 645 sexually active inner-city young females attending a large adolescent health-clinic in New York City that offers free care and HPV vaccination. Specimens were tested for HPV-DNA using a MY09/MY11-PCR system. Type-specific prevalence of HPV at each anatomic site was compared for individuals by vaccination dose using generalized estimating equation logistic regression models.
The majority of subjects reported being of non-Caucasian (92%) and/or Hispanic ethnicity (61%). Median age was 18 years (range:14-20). All had practiced vaginal sex, a third (33%) practiced anal sex, and most (77%) had also engaged in oral sex. At enrollment, 21% had not received the vaccine and 51% had received three doses. Prevalent HPV infection at enrollment was detected in 54% of cervical, 42% of anal and 20% of oral specimens, with vaccine types present in 7%, 6% and 1% of specimens, respectively. Comparing prevalence for vaccine types, the detection of HPV in the cervix of vaccinated compared to unvaccinated adolescents was significantly reduced: HPV6/11 (odds ratio [OR] = 0.19, 95%CI:0.06-0.75), HPV16 (OR = 0.31, 95%CI:0.11-0.88) and HPV18 (OR = 0.14, 95%CI:0.03-0.75). For anal HPV, the risk of detecting vaccine types HPV6/11 (OR = 0.27, 95%CI:0.10-0.72) and HPV18(OR = 0.12, 95%CI:0.01-1.16) were significantly reduced for vaccinated adolescents however, the risk for HPV16 was not significantly decreased (OR = 0.63, 95%CI:0.18-2.20).
HPV Prevalence is extremely high in inner-city female adolescents. Administration of the HPV vaccine reduced the risk for cervical HPV; however continued follow-up is required to assess the protection for HPV at all sites in young women with high exposure.
Journal Article
TRiCit: A High-Throughput Approach to Detect ITrichomonas vaginalis/I from ITS1 Amplicon Sequencing
by
Diaz, Angela
,
Sollecito, Christopher C
,
Schlecht, Nicolas F
in
Chlamydia infections
,
Disease transmission
,
Epidemiology
2023
Trichomoniasis, caused by Trichomonas vaginalis (TV), is the most common non-viral sexually transmitted infection (STI) worldwide, affecting over 174 million people annually and is frequently associated with reproductive co-morbidities. However, its detection can be time-consuming, subjective, and expensive for large cohort studies. This case–control study, conducted at the Mount Sinai Adolescent Health Center in New York City, involved 36 women with prevalent TV infections and 36 controls. The objective was to examine Internal Transcribed Spacer region-1 (ITS1) amplicon-derived communities for the detection of prevalent TV infections with the same precision as clinical microscopy and the independent amplification of the TV-specific TVK3/7 gene. DNA was isolated from clinician-collected cervicovaginal samples and amplified using ITS1 primers in a research laboratory. Results were compared to microscopic wet-mount TV detection of concurrently collected cervicovaginal samples and confirmed against TV-specific TVK3/7 gene PCR. The area under the receiver operating characteristics curve (AUC) for diagnosing TV using ITS1 communities was 0.92. ITS1 amplicons displayed an intra-class correlation coefficient (ICC) of 0.96 (95% CI: 0.93–0.98) compared to TVK3/7 PCR fragment testing. TV cases showed an increased risk of bacterial vaginosis (BV) compared to the TV-negative controls (OR = 8.67, 95% CI: 2.24–48.54, p-value = 0.0011), with no significant differences regarding genital yeast or chlamydia infections. This study presents a bioinformatics approach to ITS1 amplicon next-generation sequencing that is capable of detecting prevalent TV infections. This approach enables high-throughput testing for TV in stored DNA from large-scale epidemiological studies.
Journal Article
TRiCit: A High-Throughput Approach to Detect Trichomonas vaginalis from ITS1 Amplicon Sequencing
by
Diaz, Angela
,
Burk, Robert D.
,
Sollecito, Christopher C.
in
Bioinformatics
,
Chlamydia
,
Condoms
2023
Trichomoniasis, caused by Trichomonas vaginalis (TV), is the most common non-viral sexually transmitted infection (STI) worldwide, affecting over 174 million people annually and is frequently associated with reproductive co-morbidities. However, its detection can be time-consuming, subjective, and expensive for large cohort studies. This case–control study, conducted at the Mount Sinai Adolescent Health Center in New York City, involved 36 women with prevalent TV infections and 36 controls. The objective was to examine Internal Transcribed Spacer region-1 (ITS1) amplicon-derived communities for the detection of prevalent TV infections with the same precision as clinical microscopy and the independent amplification of the TV-specific TVK3/7 gene. DNA was isolated from clinician-collected cervicovaginal samples and amplified using ITS1 primers in a research laboratory. Results were compared to microscopic wet-mount TV detection of concurrently collected cervicovaginal samples and confirmed against TV-specific TVK3/7 gene PCR. The area under the receiver operating characteristics curve (AUC) for diagnosing TV using ITS1 communities was 0.92. ITS1 amplicons displayed an intra-class correlation coefficient (ICC) of 0.96 (95% CI: 0.93–0.98) compared to TVK3/7 PCR fragment testing. TV cases showed an increased risk of bacterial vaginosis (BV) compared to the TV-negative controls (OR = 8.67, 95% CI: 2.24–48.54, p-value = 0.0011), with no significant differences regarding genital yeast or chlamydia infections. This study presents a bioinformatics approach to ITS1 amplicon next-generation sequencing that is capable of detecting prevalent TV infections. This approach enables high-throughput testing for TV in stored DNA from large-scale epidemiological studies.
Journal Article
Psychosocial Effects of Frequent Cannabis Smoking in Adolescent Women of Color: Results from a Prospective Cohort of Inner-City Youth
by
Diaz, Angela
,
Burk, Robert D.
,
Niu, Li
in
Community and Environmental Psychology
,
Females
,
Health Psychology
2024
Frequent or chronic cannabis use can have negative effects on the adolescent and young adult (AYA) brain and psychosocial development. This study investigated the psychosocial impact of frequent cannabis use in a prospective study of sexually active female AYA patients. Participants completed questionnaires at three separate visits over a period of one year. A total of 545 AYA women were included in our analysis. Most (94%) identified as individuals of color, including 37% as non-Black Hispanic, 16% as Hispanic Black, and 41% as non-Hispanic Black. Multivariable regression analyses showed that using cannabis 20 or more times in the prior month was significantly associated with a higher likelihood of being suspended (OR = 2.71, 95%CI:1.48, 4.57; p < .001), as well as with increased number of depressive symptoms (β = 0.48, 95%CI:0.23, 0.75; p < .001) and delinquent behaviors (β = 0.81, 95%CI:0.56–1.06; p < .001). Cross-lagged models showed that frequent cannabis use was associated with increased depressive symptoms six months later (β = 0.09, p < .05), and higher levels of delinquency six months (β = 0.20, p < .001) and 12 months later (β = 0.12, p < .05). This study demonstrated that frequent cannabis use was prospectively associated with negative psychosocial outcomes for AYA women of color, including depression and delinquency.
Journal Article
Incidence and Types of Human Papillomavirus Infections in Adolescent Girls and Young Women Immunized With the Human Papillomavirus Vaccine
2021
Rates of human papillomavirus (HPV) infection have decreased since the introduction of HPV vaccines in populations with high vaccine uptake. Data are limited for adolescent and young adult populations in US metropolitan centers.
To determine HPV infection rates in adolescent girls and young women aged 13 to 21 years in New York City following HPV vaccination.
This cohort study of type-specific cervical HPV detection was conducted at a large adolescent-specific integrated health center in New York City between October 2007 and September 2019. Participants included an open cohort of adolescent girls and young adult women who received the HPV vaccine (Gardasil; Merck & Co) over a 12-year period following HPV vaccination introduction. Data analysis was concluded September 2019.
Calendar date and time since receipt of first vaccine dose.
Temporal associations in age-adjusted postvaccine HPV rates.
A total of 1453 participants, with a mean (SD) age at baseline of 18.2 (1.4) years, were included in the cohort (African American with no Hispanic ethnicity, 515 [35.4%] participants; African American with Hispanic ethnicity, 218 [15.0%] participants; Hispanic with no reported race, 637 [43.8%] participants). Approximately half (694 [47.8%] participants) were vaccinated prior to coitarche. Age-adjusted detection rates for quadrivalent vaccine types (HPV-6, HPV-11, HPV-16, and HPV-18) and related types (HPV-31, and HPV-45) decreased year over year, with the largest effect sizes observed among individuals who had been vaccinated before coitarche (adjusted odds ratio [aOR], 0.81; 95% CI, 0.67-0.98). By contrast, detection was higher year over year for nonvaccine high-risk cervical HPV types (aOR, 1.08; 95% CI, 1.04-1.13) and anal HPV types (aOR, 1.11; 95% CI, 1.05-1.17). The largest effect sizes were observed with nonvaccine types HPV-56 and HPV-68.
Whereas lower detection rates of vaccine-related HPV types were observed since introduction of vaccines in female youth in New York City, rates of some nonvaccine high-risk HPV types were higher. Continued monitoring of high-risk HPV prevalence is warranted.
Journal Article
Risk of Delayed Human Papillomavirus Vaccination in Inner-City Adolescent Women
by
Diaz, Angela
,
Strickler, Howard D.
,
Szporn, Arnold H.
in
Adolescent
,
Anal Canal - virology
,
Cervix Uteri - virology
2016
Background. Uptake of human papillomavirus (HPV) vaccine in the United States is slow, and the effectiveness of the vaccine has not been assessed in high-risk adolescent populations. Methods. We conducted a longitudinal study of 1139 sexually active, inner-city adolescent women receiving the 3-dose quadrivalent (4vHPV) vaccine. Cervical and anal specimens collected semiannually were tested using an L1-specific polymerase chain reaction assay. Postvaccination incidence of 4vHPV vaccine and nonvaccine HPV types, and risk of cervical cytological abnormalities, were assessed in relation to time to completion of all 3 vaccine doses. Results. Compared to vaccine naive women at enrollment, vaccinated women had significantly lower incidence rate ratios of cervical infection with HPV6/11/16/18 (0.2; 95% confidence interval [CI], .1–.4) and the related types HPV31 and HPV45 (0.4 [95% CI, .2–1.0] and 0.3 [95% CI, .1–.6], respectively), as well as significantly lower incidence rate ratios of anal infection with HPV6/11/16/18 (0.4; 95% CI, .2–.7). Notably, we observed higher risks of cervical HPV6/11/16/18 infection (hazards ratio [HR], 2.9; 95% CI, 1.0–8.0) and associated cytological abnormalities (HR, 4.5; 95% CI, .7–26.0) among women immunized at ≥15 years of age who took ≥12 months (vs <12 months) to complete the 3-dose regimen. Conclusions. Among adolescents immunized at ≥15 years of age, a longer time to complete the 3-dose schedule was associated with an increased risk of anogenital HPV6/11/16/18 infection and an increased incidence of associated cervical cytological abnormalities.
Journal Article
Risk of Oral Human Papillomavirus Infection Among Sexually Active Female Adolescents Receiving the Quadrivalent Vaccine
2019
Human papillomavirus (HPV) is the most common sexually transmitted infection in the United States, and oral HPV infection is associated with increased risk of oropharyngeal cancer.
To describe the risk factors for oral HPV in sexually active female adolescents receiving the quadrivalent vaccine.
Longitudinal cohort study involving repeated collection of oral rinse specimens from sexually active female adolescents conducted between October 19, 2007, and March 9, 2017, at a large adolescent health center in New York, New York, that provides free health care, including HPV vaccination.
Human papillomavirus vaccination and self-reported history of sexual behavior.
Prevalence of HPV in the oral cavity.
Among the 1259 participants who were included in this study, median age at entry into the study was 18 (range, 13-21) years; 638 (50.7%) were of African American descent, 569 (45.2%) were of Hispanic descent, 43 (3.4%) reported another race/ethnicity, and race/ethnicity was unspecified for 9 (0.7%). The median (mode) age at first sexual activity was 14.8 (14) years, and 1161 (92.2%) reported having had oral sex. Human papillomavirus DNA was detected in baseline oral rinse samples of 78 of the 1259 participants (6.2%; 95% CI, 4.9%-7.6%). There was a significant decrease in oral HPV detection with time (in years) since first engaging in sexual activities, independent of age and concurrent detection of cervical HPV; comparing 4 or more years with 1 year or less, the odds ratio was 0.45 (95% CI, 0.21-0.96). Detection of vaccine types (HPV-6, HPV-11, HPV-16, and HPV-18) was significantly lower among participants who had received at least 1 dose of the quadrivalent HPV vaccine at the time of enrollment compared with those who were unvaccinated (odds ratio, 0.20; 95% CI, 0.04-0.998).
This study's findings suggest that detection of HPV in the oral cavity is not uncommon in sexually active female adolescents. In addition, HPV vaccination is associated with a significant decrease in detection of HPV vaccine types in the oral cavity.
Journal Article