Detection of high-grade cervical neoplasia using extended genotyping: Performance data from the longitudinal phase of the Onclarity trial.

OBJECTIVES: The Onclarity cervical cancer screening trial was designed to establish the clinical validity of the Onclarity HPV assay for extended genotyping (xGT) during detection of high-grade cervical neoplasia grades 2 or 3 (≥CIN2 or ≥CIN3). Here, three-year follow up data is presented to evaluate the overall efficacy of these screening strategies, compared to the baseline data. METHODS: At baseline 29,513 women, ≥25 years, had evaluable cytology and valid high-risk HPV results. Women with atypical squamous cells-undetermined significance or worse cytology or a positive HPV test were referred for colposcopy/biopsy. Participants that did not reach the study end point (treatment for ≥CIN2) continued into the longitudinal phase that included the same protocol as baseline. RESULTS: The three-year cumulative incident risk (CIR) for ≥CIN3 in HPV-negative women was 0.15% [95%CI: 0.06, 0.26] and for HPV- and cytology-negative women was 0.12% [95% CI: 0.03,0.23]. HPV16 carried the highest baseline and three-year ≥CIN3 CIR, followed by HPV31 and HPV18. At least one year of genotype-specific persistence increased ≥CIN3 risk for xGT results compared to genotype non-persistence, HPV clearance, or new infection over the same time period. Risk-based screening with immediate colposcopy for HPV16/18/31 and further xGT triage resulted in better ≥CIN3 sensitivity (79.2% versus 72.3%; relative difference of 6.9 [95%CI: 3.3, 10.4]) and a lower colposcopy/≥CIN3 ratio (9.2 versus 11.2; relative difference of -1.9 [95%CI: -2.6, -1.3]) when compared to primary HPV16/18-based screening. CONCLUSIONS: An HPV-negative result offers the same assurance of no disease over three years of follow up as that offered by a negative co-testing result. xGT facilitates risk-based screening and persistence tracking and can help optimize disease detection during screening without excessive colposcopic procedures.

A pragmatic approach for dynamically incorporating predicate device data in prospective diagnostic test studies.

Clinical studies are generally required to characterize the accuracy of new diagnostic tests. In some cases, historical data are available from a predicate device, which is directly relevant to the new test. If this data can be appropriately incorporated into the new test study design, there is an opportunity to reduce the sample size and trial duration for the new test. One approach to achieve this is the Bayesian power prior method, which allows for the historical information to be down-weighted via a power parameter. We propose a dynamic method to calculate the power parameter based on first comparing the data between the historical and new data sources using a one-sided comparison, and second mapping the comparison probability through a scaled-Weibull discount function to tune the effective sample size borrowed. This pragmatic and conservative approach is embedded in an adaptive trial framework allowing for the trial to stop early for success. An example is presented for a new test developed to detect Methicillin-resistant Staphylococcus aureus present in the nasal carriage.

Antigen-Based Testing but Not Real-Time Polymerase Chain Reaction Correlates With Severe Acute Respiratory Syndrome Coronavirus 2 Viral Culture.

BACKGROUND: Individuals can test positive for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) by molecular assays following the resolution of their clinical disease. Recent studies indicate that SARS-CoV-2 antigen-based tests are likely to be positive early in the disease course, when there is an increased likelihood of high levels of infectious virus. METHODS: Upper respiratory specimens from 251 participants with coronavirus disease 2019 symptoms (≤7 days from symptom onset) were prospectively collected and tested with a lateral flow antigen test and a real-time polymerase chain reaction (rt-PCR) assay for detection of SARS-CoV-2. Specimens from a subset of the study specimens were utilized to determine the presence of infectious virus in the VeroE6TMPRSS2 cell culture model. RESULTS: The antigen test demonstrated a higher positive predictive value (90%) than rt-PCR (70%) when compared to culture-positive results. The positive percentage agreement for detection of infectious virus for the antigen test was similar to rt-PCR when compared to culture results. CONCLUSIONS: The correlation between SARS-CoV-2 antigen and SARS-CoV-2 culture positivity represents a significant advancement in determining the risk for potential transmissibility beyond that which can be achieved by detection of SARS-CoV-2 genomic RNA. SARS-CoV-2 antigen testing can facilitate low-cost, scalable, and rapid time-to-result, while providing good risk determination of those who are likely harboring infectious virus, compared to rt-PCR.

Performance Evaluation of the BD SARS-CoV-2 Reagents for the BD MAX System.

Nucleic acid amplification testing (NAAT) for SARS-CoV-2 is the standard approach for confirming COVID-19 cases. This study compared results between two emergency use authorization (EUA) NAATs, with two additional EUA NAATs utilized for discrepant testing. The limits of detection (LOD) for the BD SARS-CoV-2 reagents for the BD MAX system (MAX SARS-CoV-2 assay), the bioMérieux BioFire respiratory panel 2.1 (BioFire SARS-CoV-2 assay), the Roche cobas SARS-CoV-2 assay (cobas SARS-CoV-2 assay), and the Hologic Aptima SARS-CoV-2 assay Panther (Aptima SARS-CoV-2 assay) NAAT systems were determined using a total of 84 contrived nasopharyngeal specimens with 7 target levels for each comparator. The positive and negative percent agreement (PPA and NPA, respectively) of the MAX SARS-CoV-2 assay, compared to the Aptima SARS-CoV-2 assay, was evaluated in a postmarket clinical study utilizing 708 nasopharyngeal specimens collected from suspected COVID-19 cases. Discordant testing was achieved using the cobas and BioFire SARS-CoV-2 NAATs. In this study, the measured LOD for the MAX SARS-CoV-2 assay (251 copies/ml; 95% confidence interval [CI], 186 to 427) was comparable to the cobas SARS-CoV-2 assay (298 copies/ml; 95% CI, 225 to 509) and the BioFire SARS-CoV-2 assay (302 copies/ml; 95% CI, 219 to 565); the Aptima SARS-CoV-2 assay had an LOD of 612 copies/ml (95% CI, 474 to 918). The MAX SARS-CoV-2 assay had a PPA of 100% (95% CI, 97.3% to 100.0%) and an NPA of 96.7% (95% CI, 94.9% to 97.9%) compared to the Aptima SARS-CoV-2 assay. The clinical performance of the MAX SARS-CoV-2 assay agreed with another sensitive EUA assay.

Clinical Performance of the BD CTGCTV2 Assay for the BD MAX System for Detection of Chlamydia trachomatis, Neisseria gonorrhoeae, and Trichomonas vaginalis Infections.

BACKGROUND: Diagnostic options to combat the increasing rates of sexually transmitted infections recorded throughout the world increasingly include multiplex assays. Here we describe the estimated sensitivity and specificity of a triplex molecular assay that simultaneously detects Chlamydia trachomatis (CT), Neisseria gonorrhoeae (or gonococci [GC]), and Trichomonas vaginalis (TV). METHODS: Participants (2547 women and 1159 men) were recruited from 12 clinics in the United States. BD CTGCTV2 for BD MAX System assay (CTGCTV2) results were obtained from vaginal and endocervical swabs, endocervical samples in cytology medium, and female and male urine. Results were compared with infection standards that were sample type and pathogen dependent. RESULTS: Female specimen sensitivity estimates ranged from 92.7% to 98.4%, 92.9% to 100%, and 86.6% to 100% for CT, GC and TV, respectively. Male urine sensitivity estimates were 96.7%, 99.2%, and 97.9% for CT, GC, and TV, respectively. Specificity estimates were >98.7% for all sample types. CONCLUSIONS: BD CTGCTV2 performed well using a variety of sample types. As a true triplex assay, performed using a benchtop instrument, BD CTGCTV2 may be useful in settings where no testing is currently performed and in settings, such as reference laboratories, where testing turnaround time may be several days. Use of this assay at local laboratories may result in greater access to testing and a shorter time to result, which are important steps for improving our ability to combat sexually transmitted infections.

Multicenter Study of the Accuracy of the BD MAX Multidrug-resistant Tuberculosis Assay for Detection of Mycobacterium tuberculosis Complex and Mutations Associated With Resistance to Rifampin and Isoniazid.

BACKGROUND: Tuberculosis (TB) control is hindered by absence of rapid tests to identify Mycobacterium tuberculosis (MTB) and detect isoniazid (INH) and rifampin (RIF) resistance. We evaluated the accuracy of the BD MAX multidrug-resistant (MDR)-TB assay (BD MAX) in South Africa, Uganda, India, and Peru. METHODS: Outpatient adults with signs/symptoms of pulmonary TB were prospectively enrolled. Sputum smear microscopy and BD MAX were performed on a single raw sputum, which was then processed for culture and phenotypic drug susceptibility testing (DST), BD MAX, and Xpert MTB/RIF (Xpert). RESULTS: 1053 participants with presumptive TB were enrolled (47% female; 32% with human immunodeficiency virus). In patients with confirmed TB, BD MAX sensitivity was 93% (262/282 [95% CI, 89-95%]); specificity was 97% (593/610 [96-98%]) among participants with negative cultures on raw sputa. BD MAX sensitivity was 100% (175/175 [98-100%]) for smear-positive samples (fluorescence microscopy), and 81% (87/107 [73-88%]) in smear-negative samples. Among participants with both BD MAX and Xpert, sensitivity was 91% (249/274 [87-94%]) for BD MAX and 90% (246/274 [86-93%]) for Xpert on processed sputa. Sensitivity and specificity for RIF resistance compared with phenotypic DST were 90% (9/10 [60-98%]) and 95% (211/222 [91-97%]), respectively. Sensitivity and specificity for detection of INH resistance were 82% (22/27 [63-92%]) and 100% (205/205 [98-100%]), respectively. CONCLUSIONS: The BD MAX MDR-TB assay had high sensitivity and specificity for detection of MTB and RIF and INH drug resistance and may be an important tool for rapid detection of TB and MDR-TB globally.

Multicenter Evaluation of the BD Phoenix CPO Detect Test for Detection and Classification of Carbapenemase-Producing Organisms in Clinical Isolates.

Limited treatment options contribute to high morbidity/mortality rates with carbapenem-resistant, Gram-negative bacterial infections. New approaches for carbapenemase-producing organism (CPO) detection may help inform clinician decision-making on patient treatment and infection control. BD Phoenix CPO detect (CPO detect) detects and classifies carbapenemases in Enterobacterales, Acinetobacter baumannii, and Pseudomonas aeruginosa during susceptibility testing. The clinical performance of CPO detect is reported here. Enterobacterales, Acinetobacter baumannii, and Pseudomonas aeruginosa isolates were evaluated across three sites using CPO detect and a composite reference method (RM); the latter was comprised of the modified carbapenem inactivation method and a MIC screen for ertapenem, imipenem, and meropenem. Multiplex PCR testing was also utilized for Ambler class determination. Positive and negative percentages of agreement (PPA and NPA, respectively) between CPO detect and the RM were determined. The PPA and NPA for Enterobacterales were 98.5% (confidence intervals, 96.6%, 99.4%) and 97.2% (95.8%, 98.2%), respectively. The A. baumannii PPA and NPA, respectively, were 97.1% (90.2%, 99.2%) and 97.1% (89.9%, 99.2%). The P. aeruginosa PPA and NPA, respectively, were 95.9% (88.6%, 98.6%) and 92.3% (86.7%, 95.6%). The PPA values for carbapenemase class designations for all organisms combined and Enterobacterales alone, respectively, were 95.3% (90.2%, 97.8%) and 94.6% (88.8%, 97.5%) for class A, 94.0% (88.7%, 96.6%) and 96.4% (90.0%, 98.8%) for class B, and 95.0% (90.1%, 97.6%) and 99.0% (94.4%, 99.8%) for class D carbapenemases. NPA values for all organisms and Enterobacterales alone ranged from 98.5% to 100%. CPO detect provided accurate detection and classification of CPOs for the majority of isolates of Enterobacterales, Acinetobacter baumannii, and Pseudomonas aeruginosa tested.

Clinical Evaluation of BD Veritor SARS-CoV-2 Point-of-Care Test Performance Compared to PCR-Based Testing and versus the Sofia 2 SARS Antigen Point-of-Care Test.

The clinical performance of the BD Veritor System for Rapid Detection of SARS-CoV-2 nucleocapsid antigen (Veritor), a chromatographic immunoassay used for SARS-CoV-2 point-of-care testing, was evaluated using nasal specimens from individuals with COVID-19 symptoms. Two studies were completed to determine clinical performance. In the first study, nasal specimens and either nasopharyngeal or oropharyngeal specimens from 251 participants with COVID-19 symptoms (≤7 days from symptom onset [DSO], ≥18 years of age) were utilized to compare Veritor with the Lyra SARS-CoV-2 PCR assay (Lyra). In the second study, nasal specimens from 361 participants with COVID-19 symptoms (≤5 DSO, ≥18 years of age) were utilized to compare performance of Veritor to that of the Sofia 2 SARS Antigen FIA test (Sofia 2). The positive, negative, and overall percent agreement (PPA, NPA, and OPA, respectively) were the primary outcomes. In study 1, the PPA for Veritor, compared to Lyra, ranged from 81.8 to 87.5% across the 0 to 1 and 0 to 6 DSO ranges. In study 2, Veritor had PPA, NPA, and OPA values of 97.4, 98.1, and 98.1%, respectively, with Sofia 2. Discordant analysis showed one Lyra positive missed by Veritor and five Lyra positives missed by Sofia 2; one Veritor positive result was negative by Lyra. Veritor met FDA emergency use authorization (EUA) acceptance criteria for SARS-CoV-2 antigen testing for the 0 to 5 and 0 to 6 DSO ranges (PPA values of 83.9% and 82.4%, respectively). Veritor and Sofia 2 showed a high degree of agreement for SARS-CoV-2 detection. The Veritor test allows for more rapid COVID-19 testing utilizing easy-to-collect nasal swabs but demonstrated <100% PPA compared to PCR.

Analytical and Clinical Sample Performance Characteristics of the Onclarity Assay for the Detection of Human Papillomavirus.

The objective of this study was to determine the result reproducibility and performance of the BD Onclarity human papillomavirus (HPV) assay (Onclarity) on the BD Viper LT platform using both contrived and clinical specimens. Reproducibility was assessed in BD SurePath liquid-based cytology (LBC) medium (SurePath) using contrived panels (HPV genotype 16 [HPV16] positive, HPV18 positive, or HPV45 positive) or clinical specimens (HPV16, -18, -31, -33/58, -45, or -52 positive or HPV negative). In addition, specimens from 3,879 individuals from the Onclarity trial were aliquoted prior to or following cytology processing and tested for HPV. Finally, specimens were collected using either the Cervex-Brush or Cytobrush (or Cytobrush/spatula) for comparison of HPV results. Contrived specimens showed >95% concordance with the expected results, and pooled clinical specimens had standard deviations and coefficients of variation ranging from 0.87 to 1.86 and 2.9% to 5.6%, respectively. For precytology and postcytology aliquot analyses, specimens showed >98.0% overall agreement and mean differences in cycle threshold (CT ) scores for HPV ranging from -0.07 to 0.31. Positivity rates were close between the Cervex-Brush and Cytobrush/spatula for all age groups tested. Onclarity results are reproducible and reliable, regardless of sample collection before or after cytology aliquoting. Onclarity performs well regardless of the method of specimen collection (Cervex-Brush or Cytobrush/spatula) for cervical cancer screening.

Molecular-based Testing for Sexually Transmitted Infections Using Samples Previously Collected for Vaginitis Diagnosis.

Background: Vaginal symptoms are a leading cause of primary care visits for women. Individuals exhibiting symptoms often receive laboratory testing based on clinic-specific standards of care. Thus, women seen at a family practice clinic might only receive a vaginitis workup, whereas those seen at a sexually transmitted diseases clinic could be more likely to receive only sexually transmitted infection (STI) testing. Methods: The likelihood of STIs was assessed in women from whom samples were tested for vaginitis using a molecular diagnostic assay. Positivity rates for Chlamydia trachomatis, Neisseria gonorrhoeae, and Trichomonas vaginalis DNA, detected using the BD MAX CT/GC/TV assay, were calculated. Concordance between the BD MAX Vaginal Panel and the BD MAX CT/GC/TV assay for detection of T. vaginalis was determined. Results: Women with bacterial vaginosis alone or with concurrent Candida spp infections had high rates of coinfection with sexually transmitted infections (24.4%-25.7%); samples from women who were negative for vaginitis had significantly lower positivity rates (7.9%; P < .001). Trichomonas vaginalis results were concordant between the BD MAX Vaginal Panel and the BD MAX CT/GC/TV assay in 559 of 560 samples tested. Conclusions: These data suggest, as have other studies, that women with vaginitis symptoms may be at risk for an STI. Molecular testing could provide broad diagnostic coverage for symptomatic women and improve patient management, regardless of the type of clinic in which patients are treated.

New GJA8 variants and phenotypes highlight its critical role in a broad spectrum of eye anomalies.

GJA8 encodes connexin 50 (Cx50), a transmembrane protein involved in the formation of lens gap junctions. GJA8 mutations have been linked to early onset cataracts in humans and animal models. In mice, missense mutations and homozygous Gja8 deletions lead to smaller lenses and microphthalmia in addition to cataract, suggesting that Gja8 may play a role in both lens development and ocular growth. Following screening of GJA8 in a cohort of 426 individuals with severe congenital eye anomalies, primarily anophthalmia, microphthalmia and coloboma, we identified four known [p.(Thr39Arg), p.(Trp45Leu), p.(Asp51Asn), and p.(Gly94Arg)] and two novel [p.(Phe70Leu) and p.(Val97Gly)] likely pathogenic variants in seven families. Five of these co-segregated with cataracts and microphthalmia, whereas the variant p.(Gly94Arg) was identified in an individual with congenital aphakia, sclerocornea, microphthalmia and coloboma. Four missense variants of unknown or unlikely clinical significance were also identified. Furthermore, the screening of GJA8 structural variants in a subgroup of 188 individuals identified heterozygous 1q21 microdeletions in five families with coloboma and other ocular and/or extraocular findings. However, the exact genotype-phenotype correlation of these structural variants remains to be established. Our data expand the spectrum of GJA8 variants and associated phenotypes, confirming the importance of this gene in early eye development.

Stratified risk of high-grade cervical disease using onclarity HPV extended genotyping in women, ≥25 years of age, with NILM cytology.

OBJECTIVES: Increasing evidence suggests that extended human papillomavirus (HPV) genotyping (beyond 16/18) is effective for risk stratification in women with normal cytology. This report provides extended genotyping results, using the BD Onclarity HPV Assay, for individual genotypes HPV16, 18, 31, 45, 51, and 52 ̶ and three pooled genotype results for HPV33/58, 35/39/68, and 56/59/66. METHODS: 27,037 women with normal cytology, ≥25 years, were enrolled into the Onclarity HPV trial during routine screening. Women positive for any HPV genotype were referred to colposcopy/biopsy. Hierarchical-ranked prevalence and risk values, associated with cervical intraepithelial neoplasia, grade 2 or worse (≥CIN2) or ≥CIN3, were calculated based on extended genotyping results. RESULTS: HPV 16 and 31 carried the highest risk for ≥CIN2 (11.6% and 12.1%, respectively) and ≥CIN3 (8.1% and 7.5%, respectively); these genotypes were the most prevalent in both ≥CIN2 (29.6% and 19.3%, respectively) and ≥CIN3 (43.7% and 22.5%, respectively). Of the other 12 genotypes, HPV 18, 33/58, and 52 comprised an intermediate risk band (≥CIN2 risk range: 4.9-6.8%; ≥CIN3 risk range: 3.9-5.0%). Genotypes 45, 51, 35/39/68, and 56/59/66 constituted the lowest risk band for both disease grades (≥CIN2 value risk range: 1.7-3.0%; ≥CIN3 value risk range: 1.2-3.6%). CONCLUSIONS: Extended genotyping stratifies risk for ≥CIN2/3 in the ≥25 year-old, normal cytology population. While baseline HPV 16/31 values exceeded the risk threshold for colposcopy referral, the management of women with normal cytology who were positive for the intermediate- or lower-risk genotypes may evolve based on refined risk estimates as well as clinical factors.

Risk detection for high-grade cervical disease using Onclarity HPV extended genotyping in women, ≥21 years of age, with ASC-US or LSIL cytology.

OBJECTIVES: There is growing interest in using human papillomavirus (HPV) genotyping as a risk-based triage approach for women with atypical squamous cells-undetermined significance (ASC-US) and low-grade squamous intraepithelial lesions (LSIL) cytology. METHODS: This analysis includes 2807 subjects with ASC-US or LSIL cytology, ≥21 years, from the baseline phase of the Onclarity HPV trial. All women were referred to colposcopy/biopsy. Hierarchical-ranked prevalence and risk values, associated with high-grade cervical disease, were calculated based on extended genotyping. RESULTS: HPV 16 carried the highest risk for cervical intraepithelial neoplasia grade 2 or worse (≥CIN2) in both the ASC-US and LSIL populations. Risk of ≥CIN3 and ≥CIN2 associated with the other 13 genotypes varied somewhat for women with ASC-US and LSIL, however, HPV 31, 18, 33/58, 51 and 52 appear to comprise an intermediate risk band. Risk associated with HPV 35/39/68, 45, and 56/59/66, in either cytology population, was relatively low and beneath the benchmark threshold risk for immediate colposcopy. Restricting the analysis to women 21-24 years, ≥25 years, or ≥30 years produced similar results. CONCLUSIONS: HPV genotyping identified multiple risk bands for ≥CIN3 and ≥CIN2 in the ≥21 year-old ASC-US and LSIL populations. These results support a 1-year follow-up period to preclude immediate colposcopy for ASC-US or LSIL women positive for the lowest-risk HPV genotypes.

HPV infections and cytologic abnormalities in vaccinated women 21-34 years of age: Results from the baseline phase of the Onclarity trial.

OBJECTIVES: Countries with school-based human papillomavirus (HPV) vaccination have seen significant reductions in vaccine-targeted HPV infections, cytologic abnormalities, and high-grade cervical intraepithelial neoplasia (≥CIN2). However, the impact of HPV vaccination in the United States (where vaccination is largely opportunistic) may be less due to lower coverage rates and vaccination in patients at ages beyond the recommended routine vaccination age. METHODS: The Onclarity trial enrolled 33,858 subjects ≥21 years who were screened with cytology and the BD Onclarity HPV Assay. HPV positive women or those with cytologic abnormalities underwent colposcopy and biopsy. The prevalence of HPV, cytologic abnormalities, and ≥CIN2 was compared in a subset of 14,153, vaccinated and unvaccinated women, 21-34 years. Results were compared by vaccination status; Mantel-Haenszel analysis was performed to determine the association between vaccination status and prevalence, adjusting for age. RESULTS: The prevalence of overall HPV, HPV16, 18, 31, and 33/58 were all lower in vaccinated women for each age group; a significant difference (p < 0.001) was observed in vaccinated women for all ages combined. Cytologic low-grade squamous intraepithelial lesion (LSIL) or worse was lower in vaccinated women (p = 0.021), as was ≥CIN2 prevalence associated with HPV 16 or 18 (p = 0.011). CONCLUSIONS: Women with a prior history of HPV vaccination have a lower prevalence of any high-risk HPV, HPV 16, 18, 31, and 33/58; a cytology result of ≥LSIL, and ≥CIN2 associated with HPV 16/18 compared to unvaccinated women. A lower HPV prevalence in older, vaccinated women suggests that "catch-up" vaccination provides benefit.

Diagnostic Performance of a Molecular Test versus Clinician Assessment of Vaginitis.

Vaginitis is a common complaint, diagnosed either empirically or using Amsel's criteria and wet mount microscopy. This study sought to determine characteristics of an investigational test (a molecular test for vaginitis), compared to reference, for detection of bacterial vaginosis, Candida spp., and Trichomonas vaginalis Vaginal specimens from a cross-sectional study were obtained from 1,740 women (≥18 years old), with vaginitis symptoms, during routine clinic visits (across 10 sites in the United States). Specimens were analyzed using a commercial PCR/fluorogenic probe-based investigational test that detects bacterial vaginosis, Candida spp., and Trichomonas vaginalis Clinician diagnosis and in-clinic testing (Amsel's test, potassium hydroxide preparation, and wet mount) were also employed to detect the three vaginitis causes. All testing methods were compared to the respective reference methods (Nugent Gram stain for bacterial vaginosis, detection of the Candida gene its2, and Trichomonas vaginalis culture). The investigational test, clinician diagnosis, and in-clinic testing were compared to reference methods for bacterial vaginosis, Candida spp., and Trichomonas vaginalis The investigational test resulted in significantly higher sensitivity and negative predictive value than clinician diagnosis or in-clinic testing. In addition, the investigational test showed a statistically higher overall percent agreement with each of the three reference methods than did clinician diagnosis or in-clinic testing. The investigational test showed significantly higher sensitivity for detecting vaginitis, involving more than one cause, than did clinician diagnosis. Taken together, these results suggest that a molecular investigational test can facilitate accurate detection of vaginitis.

The Onclarity Human Papillomavirus Trial: Design, methods, and baseline results.

OBJECTIVES: The baseline phase of the Onclarity trial was conducted to determine the screening performance of the Onclarity human papillomavirus (HPV) assay for detecting cervical cancer and precancer (≥CIN2) during triage of women ≥21 years with ASC-US cytology, as an adjunct test in women ≥30 years with normal cytology and for primary screening (HPV alone) in women ≥25 years. METHODS: 33,858 women ≥21 years were enrolled during routine clinic visits. All women with abnormal cytology, women ≥25 years that were high-risk HPV positive, and a random subset of women ≥25 years, negative by cytology and for HPV, were referred for colposcopy and cervical biopsy. Verification bias adjustment with 95% confidence intervals was applied. RESULTS: ASC-US prevalence was 5.8%. The overall HPV prevalence was 14.7%; for HPV 16, 18, and the 12 other HPV types it was 2.7%, 0.8%, and 11.2%, respectively. The prevalence of ASC-US and HPV was inversely proportional with age. The verification bias adjusted prevalence of ≥CIN2 and ≥CIN3 was 1.8% and 0.8%, respectively. Overall, five cases of cervical cancer were identified (all were HPV positive). The odds ratios associated with any HPV positive genotype, or with individual genotypes HPV 16, HPV 18, and HPV 31, for ≥CIN3, were statistically significant when compared to negative histology (p < 0.0001 for all). CONCLUSIONS: This report provides demographic information, cytology findings, HPV genotype information, and histopathology for participants in the baseline phase of this trial and offers further evidence to support genotype-specific screening for cervical cancer and precancer. Clinical Trial Registry URL:https://clinicaltrials.gov/ct2/show/NCT01944722.

Cardiovascular Disease Risk Factors in Hispanic Adolescents in South Texas.

OBJECTIVES: Despite a national crisis of increased prevalence of obesity and type 2 diabetes mellitus in adolescents, especially among Hispanics, there is a paucity of data on health indicators among farmworker adolescents and their peers. The main aim of this study was to estimate the prevalence of cardiovascular disease risk factors in a population of Hispanic adolescent students in south Texas. The study also aimed to compare the prevalence of these risk factors between students enrolled in the Migrant Education Program (MEP) and other students, and between boys and girls. METHODS: In partnership with the Weslaco (Texas) Independent School District and the Migrant Education Department, a cohort study was conducted from 2007 to 2010 to estimate the prevalence of overall obesity (body mass index ≥85th percentile for age and sex), abdominal obesity (waist circumference ≥75th percentile for age, sex, and ethnicity), acanthosis nigricans (AN), and high blood pressure (HBP; ≥90th percentile for age, height, and sex or systolic/diastolic BP ≥120/80 mm Hg) among MEP students compared with other students from two south Texas high schools. Multilevel logistic regression was used to assess the relation between sex and our main outcomes of interest while accounting for within-school nesting of participants. RESULTS: Among 628 sampled students, 508 (80.9%) completed the consent procedure and participated in the study. Of these, 257 were MEP students and 251 were non-MEP peers. Approximately 96.7% of participants were Hispanic and 50.0% were boys. Analyses of data across the years comparing MEP students and non-MEP students show an average prevalence of 44.8% versus 47.7% for overall obesity, 43.2% versus 43.7% for abdominal obesity, 24.7% versus 24.7% for AN, and 29.2% versus 32.8% for HBP. Across recruitment and follow-up years, the prevalence of overall obesity, abdominal obesity, and HBP was 1.3 to 1.5, 1.2 to 1.8, and 2.9 to 4.6 times higher in boys than in girls, respectively. In contrast, the prevalence of AN varied little by sex. CONCLUSIONS: The high prevalence of cardiovascular risk factors in both groups suggests a compelling need for comprehensive, culturally targeted interventions to prevent future cardiovascular diseases in these high-risk Hispanic adolescents, especially among boys. There were not, however, substantial differences between MEP students and other students. These findings also support the feasibility of conducting future epidemiologic studies among adolescent farmworkers and their families, as well as culturally appropriate school or community-based interventions.