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Background: Uterine rupture of an unscarred uterus is a rare complication in a quadruplet pregnancy.Case: A 30-year-old woman, gravida 4 para 0030, with a quadruplet pregnancy and no previous uterine surgeries presented with moderate vaginal bleeding at 32 4/7 weeks of gestation. Fetal testing was reassuring, and the cervix showed no signs of preterm labor. A decision was made to proceed with cesarean delivery because of the amount of vaginal bleeding, with surgical findings of uterine rupture superior to the lower uterine segment.Conclusion: High-order gestations may be an independent risk factor for uterine rupture. [ABSTRACT FROM AUTHOR]

Background: Black women are at an increased risk of developing uterine leiomyomas and experiencing worse disease prognosis than White women. Epidemiologic and molecular factors have been identified as underlying these disparities, but there remains a paucity of deep, multiomic analysis investigating molecular differences in uterine leiomyomas from Black and White patients., Objective: To identify molecular alterations within uterine leiomyoma tissues correlating with patient race by multiomic analyses of uterine leiomyomas collected from cohorts of Black and White women., Study Design: We performed multiomic analysis of uterine leiomyomas from Black (42) and White (47) women undergoing hysterectomy for symptomatic uterine leiomyomata. In addition, our analysis included the application of orthogonal methods to evaluate fibroid biomechanical properties, such as second harmonic generation microscopy, uniaxial compression testing, and shear-wave ultrasonography analyses., Results: We found a greater proportion of MED12 mutant uterine leiomyomas from Black women (>35% increase; Mann-Whitney U, P<.001). MED12 mutant tumors exhibited an elevated abundance of extracellular matrix proteins, including several collagen isoforms, involved in the regulation of the core matrisome. Histologic analysis of tissue fibrosis using trichrome staining and secondary harmonic generation microscopy confirmed that MED12 mutant tumors are more fibrotic than MED12 wild-type tumors. Using shear-wave ultrasonography in a prospectively collected cohort, Black patients had fibroids that were firmer than White patients, even when similar in size. In addition, these analyses uncovered ancestry-linked expression quantitative trait loci with altered allele frequencies in African and European populations correlating with differential abundance of several proteins in uterine leiomyomas independently of MED12 mutation status, including tetratricopeptide repeat protein 38., Conclusion: Our study shows that Black women have a higher prevalence of uterine leiomyomas harboring mutations in MED12 and that this mutational status correlates with increased tissue fibrosis compared with wild-type uterine leiomyomas. Our study provides insights into molecular alterations correlating with racial disparities in uterine leiomyomas and improves our understanding of the molecular etiology underlying uterine leiomyoma development within these populations., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Purpose: We investigated racial disparities in survival by histology in cervical cancer and examined the factors contributing to these disparities., Methods: Non-Hispanic Black and non-Hispanic White (hereafter known as Black and White) patients with stage I-IV cervical carcinoma diagnosed between 2004 and 2017 in the National Cancer Database were studied. Survival differences were compared using Cox modeling to estimate hazard ratio (HR) or adjusted HR (AHR) and 95% confidence interval (CI). The contribution of demographic, socioeconomic and clinical factors to the Black vs White differences in survival was estimated after applying propensity score weighting in patients with squamous cell carcinoma (SCC) or adenocarcinoma (AC)., Results: This study included 10,111 Black and 43,252 White patients with cervical cancer. Black patients had worse survival than White cervical cancer patients (HR = 1.40, 95% CI = 1.35-1.45). Survival disparities between Black and White patients varied significantly by histology (HR = 1.20, 95% CI = 1.15-1.24 for SCC; HR = 2.32, 95% CI = 2.12-2.54 for AC, interaction p < 0.0001). After balancing the selected demographic, socioeconomic and clinical factors, survival in Black vs. White patients was no longer different in those with SCC (AHR = 1.01, 95% CI 0.97-1.06) or AC (AHR = 1.09, 95% CI = 0.96-1.24). In SCC, the largest contributors to survival disparities were neighborhood income and insurance. In AC, age was the most significant contributor followed by neighborhood income, insurance, and stage. Diagnosis of AC (but not SCC) at ≥65 years old was more common in Black vs. White patients (26% vs. 13%, respectively)., Conclusions: Histology matters in survival disparities and diagnosis at ≥65 years old between Black and White cervical cancer patients. These disparities were largely explained by modifiable factors., Competing Interests: Declaration of competing interest Chad A. Hamilton reported personal fees from GlaxoSmithKline outside the submitted work. Yovanni Casablanca cited personal fees from AstraZeneca outside the submitted work. John K. Chan reported personal fees from Agenus, AstraZeneca, Eisai, Genmab, GlaxoSmithKline, Immunogen, Mersana, Molecular Targeting Technologies, Myriad, Roche, and Seagen outside the submitted work. Thomas P. Conrads is a ThermoFisher Scientific, Inc. SAB member and receives research funding from AbbVie outside the submitted work. Charles A. Leath, III received funding from the NIH UG1 CA23330 and P50 CA098252, contracted research with Agenus and Seattle Genetics, and served on a scientific advisory board for Seattle Genetics, all outside of the submitted work. The other authors have no conflicts of interest to disclose., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Objective: This study investigated the risk of an aggressive endometrial cancer (EC) diagnosis by race, ethnicity, and country of origin to further elucidate histologic disparities in non-Hispanic Black (NHB), Hispanic, Asian/Pacific Islander (API), American Indian/Alaskan Native (AIAN) vs. non-Hispanic White (NHW) patients, particularly in Hispanic or API subgroups., Methods: Patient diagnosed between 2004 and 2020 with low grade (LG)-endometrioid endometrial cancer (ECC) or an aggressive EC including grade 3 EEC, serous carcinoma, clear cell carcinoma, mixed epithelial carcinoma, or carcinosarcoma in the National Cancer Database were studied. The odds ratio (OR) and 95% confidence interval (CI) for diagnosis of an aggressive EC histology was estimated using logistic modeling., Results: There were 343,868 NHW, 48,897 NHB, 30,013 Hispanic, 15,015 API and 1646 AIAN patients. The OR (95% CI) for an aggressive EC diagnosis was 3.07 (3.01-3.13) for NHB, 1.08 (1.06-1.11) for Hispanic, 1.17 (1.13-1.21) for API and 1.07 (0.96-1.19) for AIAN, relative to NHW patients. Subset analyses by country of origin illustrated the diversity in the OR for an aggressive EC diagnosis among Hispanic (1.18 for Mexican to 1.87 for Dominican), Asian (1.14 Asian Indian-Pakistani to 1.48 Korean) and Pacific Islander (1.00 for Hawaiian to 1.33 for Samoan) descendants. Hispanic, API and AIAN patients were diagnosed 5-years younger that NHW patients, and the risk for an aggressive EC histology were all significantly higher than NHW patients after correcting for age. Insurance status was another independent risk factor for aggressive histology., Conclusions: Risk of an aggressive EC diagnosis varied by race, ethnicity, and country of origin. NHB patients had the highest risk, followed by Dominican, South/Central American, Cuban, Korean, Thai, Vietnamese, and Filipino descendants., Competing Interests: Declaration of competing interest Stuart S. Winkler, Chunqiao Tian, Nicholas W. Bateman, Suzanne Jokajtys, Calen W. Kucera, Christopher M. Tarney, Michael T. Richardson, Daniel Kapp, Cheng-I Liao, Megan Reddy, Michele L Cote, Timothy D. O'Connor, Nathaniel L. Jones, Matthew A. Powell, John Farley, Craig D. Shriver, Neil T. Phippen, G. Larry Maxwell and Kathleen M Darcy do not have any potential conflicts to disclose. Chad A. Hamilton reported personal fees from GlaxoSmithKline outside the submitted work. Yovanni Casablanca cited personal fees from AstraZeneca outside the submitted work. John K. Chan reported personal fees from Agenus, AstraZeneca, Eisai, Genmab, GlaxoSmithKline, Immunogen, Mersana, Molecular Targeting Technologies, Myriad, Roche, and Seagen outside the submitted work. Thomas P. Conrads is a ThermoFisher Scientific, Inc. SAB member and receives research funding from AbbVie outside the submitted work. Charles A. Leath, III received funding from the NIH UG1 CA23330 and P50 CA098252, contracted research with Agenus and Seattle Genetics, and served on a scientific advisory board for Seattle Genetics, all outside of the submitted work., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Objective: Investigate racial disparities in outcomes and molecular features in Black and White patients with endometrioid endometrial carcinoma (EEC)., Methods: Black and White patients diagnosed with EEC who underwent hysterectomy ± adjuvant treatment in SEER, National Cancer Database (NCDB), the Genomics Evidence Neoplasia Information Exchange (GENIE) project (v.13.0), and eight NCI-sponsored randomized phase III clinical trials (RCTs) were studied. Hazard ratio (HR) and 95% confidence interval (CI) were estimated for cancer-related death (CRD), non-cancer death (NCD), and all-cause death., Results: Black (n = 4397) vs. White (n = 47,959) patients in SEER had a HR (95% CI) of 2.04 (1.87-2.23) for CRD and 1.22 (1.09-1.36) for NCD. In NCDB, the HR (95% CI) for death in Black (n = 13,468) vs. White (n = 155,706) patients was 1.52 (1.46-1.58) dropping to 1.29 (1.23-1.36) after propensity-score matching for age, comorbidity, income, insurance, grade, stage, LVSI, and treatment. In GENIE, Black (n = 109) vs. White (n = 1780) patients had fewer PTEN, PIK3R1, FBXW7, NF1, mTOR, CCND1, and PI3K-pathway-related gene mutations. In contrast, TP53 and DNA-repair-related gene mutation frequency as well as tumor mutational burden-high status were similar in Black and White patients. In RCTs, Black (n = 187) vs. White (n = 2877) patients were more likely to have advanced or recurrent disease, higher grade, worse performance status and progressive disease. Risk of death in Black vs. White patients in RCTs was 2.19 (1.77-2.71) persisting to 1.32 (1.09-1.61) after matching for grade, stage, and treatment arm while balancing age and performance status., Conclusions: Differences exist in clinical presentation, outcomes, and molecular features in Black vs. White patients with EEC in real-world registries and RCTs. Targeted-drug development, strategies to modify social determinants, and diverse inclusion in RCTs are approaches to reduce disparities., Competing Interests: Declaration of interests Zachary A. Kopelman, Chunqiao Tian, Jordyn Tumas, Neil T. Phippen, Christopher M. Tarney, Erica R. Hope, Stuart S. Winkler, Suzanne Jokajtys, Calen W. Kucera, Michael T. Richardson, Daniel S. Kapp, Nathaniel L. Jones, Rodney P. Rocconi, John H. Farley, Angeles Alvarez Secord, Casey M. Cosgrove, Matthew A. Powell, Ann Klopp, Joan L Walker, Gini F. Fleming, Nicholas W. Bateman, G. Larry Maxwell, and Kathleen M. Darcy do not have any conflicts to report. John K. Chan reported personal fees from Agenus, AstraZeneca, Eisai, Genmab, GlaxoSmithKline, Immunogen, Mersana, Molecular Targeting Technologies, Myriad, Roche, and Seagen outside the submitted work. Chad A. Hamilton reported personal fees from GlaxoSmithKline outside the submitted work. Charles A. Leath, III received funding from the NIH UG1 CA23330 and P50 CA098252, contracted research with GSK and Merck, and served on a scientific advisory board for GSK and Merck, all outside of the submitted work. Thomas P. Conrads is a ThermoFisher Scientific, Inc. SAB member and receives research funding from AbbVie outside the submitted work., (Copyright © 2024 Elsevier Inc. All rights reserved.)

We performed a deep proteogenomic analysis of bulk tumor and laser microdissection enriched tumor cell populations from high-grade serous ovarian cancer (HGSOC) tissue specimens spanning a broad spectrum of purity. We identified patients with longer progression-free survival had increased immune-related signatures and validated proteins correlating with tumor-infiltrating lymphocytes in 65 tumors from an independent cohort of HGSOC patients, as well as with overall survival in an additional 126 HGSOC patient cohort. We identified that homologous recombination deficient (HRD) tumors are enriched in pathways associated with metabolism and oxidative phosphorylation that we validated in independent patient cohorts. We further identified that polycomb complex protein BMI-1 is elevated in HR proficient (HRP) tumors, that elevated BMI-1 correlates with poor overall survival in HRP but not HRD HGSOC patients, and that HRP HGSOC cells are uniquely sensitive to BMI-1 inhibition., (© 2024. The Author(s).)

Purpose: To investigate IMT use and survival in real-world stage IVB cervical cancer patients outside randomized clinical trials., Methods: Patients diagnosed with stage IVB cervical cancer during 2013-2019 in the National Cancer Database and treated with chemotherapy (CT) ± external beam radiation (EBRT) ± intracavitary brachytherapy (ICBT) ± IMT were studied. The adjusted hazard ratio (AHR) and 95% confidence interval (CI) for risk of death were estimated in patients treated with vs. without IMT after applying propensity score analysis to balance the clinical covariates., Results: There were 3164 evaluable patients, including 969 (31%) who were treated with IMT. The use of IMT increased from 11% in 2013 to 46% in 2019. Age, insurance, facility type, sites of distant metastasis, and type of first-line treatment were independently associated with using IMT. In propensity-score-balanced patients, the median survival was 18.6 vs. 13.1 months for with vs. without IMT ( p < 0.001). The AHR was 0.72 (95% CI = 0.64-0.80) for adding IMT overall, 0.72 for IMT + CT, 0.66 for IMT + CT + EBRT, and 0.69 for IMT + CT + EBRT + ICBT. IMT-associated survival improvements were suggested in all subgroups by age, race/ethnicity, comorbidity score, facility type, tumor grade, tumor size, and site of metastasis., Conclusions: IMT was associated with a consistent survival benefit in real-world patients with stage IVB cervical cancer.

Numerous multi-omic investigations of cancer tissue have documented varying and poor pairwise transcript:protein quantitative correlations, and most deconvolution tools aiming to predict cell type proportions (cell admixture) have been developed and credentialed using transcript-level data alone. To estimate cell admixture using protein abundance data, we analyzed proteome and transcriptome data generated from contrived admixtures of tumor, stroma, and immune cell models or those selectively harvested from the tissue microenvironment by laser microdissection from high grade serous ovarian cancer (HGSOC) tumors. Co-quantified transcripts and proteins performed similarly to estimate stroma and immune cell admixture (r ≥ 0.63) in two commonly used deconvolution algorithms, ESTIMATE or Consensus TME . We further developed and optimized protein-based signatures estimating cell admixture proportions and benchmarked these using bulk tumor proteomic data from over 150 patients with HGSOC. The optimized protein signatures supporting cell type proportion estimates from bulk tissue proteomic data are available at https://lmdomics.org/ProteoMixture/., Competing Interests: T.P.C. is a Thermo Fisher Scientific, Inc. SAB member and receives research funding from AbbVie., (© 2024 The Author(s).)

Objective: ATR kinase inhibitors promote cell killing by inducing replication stress and through potentiation of genotoxic agents in gynecologic cancer cells. To explore mechanisms of acquired resistance to ATRi in ovarian cancer, we characterized ATRi-resistant ovarian cancer cells generated by metronomic dosing with the clinical ATR inhibitor AZD6738., Methods: ATRi-resistant ovarian cancer cells (OVCAR3 and OV90) were generated by dosing with AZD6738 and assessed for sensitivity to Chk1i (LY2603618), PARPi (Olaparib) and combination with cisplatin or a CDK4/6 inhibitor (Palbociclib). Models were characterized by diverse methods including silencing CDC25A in OV90 cells and assessing impact on ATRi response. Serum proteomic analysis of ATRi-resistant OV90 xenografts was performed to identify circulating biomarker candidates of ATRi-resistance., Results: AZD6738-resistant cell lines are refractory to LY2603618, but not to Olaparib or combinations with cisplatin. Cell cycle analyses showed ATRi-resistant cells exhibit G1/S arrest following AZD6738 treatment. Accordingly, combination with Palbociclib confers resistance to AZD6738. AZD6738-resistant cells exhibit altered abundances of G1/S phase regulatory proteins, including loss of CDC25A in AZD6738-resistant OV90 cells. Silencing of CDC25A in OV90 cells confers resistance to AZD6738. Serum proteomics from AZD6738-resistant OV90 xenografts identified Vitamin D-Binding Protein (GC), Apolipoprotein E (APOE) and A1 (APOA1) as significantly elevated in AZD6738-resistant backgrounds., Conclusions: We show that metronomic dosing of ovarian cancer cells with AZD6738 results in resistance to ATR/ Chk1 inhibitors, that loss of CDC25A expression represents a mechanism of resistance to ATRi treatment in ovarian cancer cells and identify several circulating biomarker candidates of CDC25A low, AZD6738-resistant ovarian cancer cells., Competing Interests: Declaration of Competing Interest Nothing to declare., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Importance: Disparities in survival exist between non-Hispanic Black (hereafter, Black) and non-Hispanic White (hereafter, White) patients with uterine cancer., Objective: To investigate factors associated with racial disparities in survival between Black and White patients with uterine cancer., Design, Setting, and Patients: This cohort study used data from the National Cancer Database on 274 838 Black and White patients who received a diagnosis of uterine cancer from January 1, 2004, to December 31, 2017, with follow-up through December 2020. Statistical analysis was performed in July 2022., Main Outcomes and Measures: Overall survival by self-reported race and evaluation of explanatory study factors associated with hazard ratio (HR) reduction for Black vs White patients. A propensity scoring approach was applied sequentially to balance racial differences in demographic characteristics, comorbidity score, neighborhood income, insurance status, histologic subtype, disease stage, and treatment., Results: The study included 32 230 Black female patients (mean [SD] age at diagnosis, 63.8 [10.0] years) and 242 608 White female patients (mean [SD] age at diagnosis, 63.5 [10.5] years) and had a median follow-up of 74.0 months (range, 43.5-113.8 months). Black patients were more likely than White patients to have low income (44.1% vs 14.0%), be uninsured (5.7% vs 2.6%), present with nonendometrioid histologic characteristics (46.1% vs 21.6%), have an advanced disease stage (34.1% vs 19.8%), receive first-line chemotherapy (33.8% vs 18.2%), and have worse 5-year survival (58.6% vs 78.5%). Among patients who received a diagnosis at younger than 65 years of age, the HR for death for Black vs White patients was 2.43 (95% CI, 2.34-2.52) in a baseline demographic-adjusted model and 1.29 (95% CI, 1.23-1.35) after balancing other factors. Comorbidity score, neighborhood income, insurance status, histologic subtype, disease stage, treatment, and unexplained factors accounted for 0.8%, 7.2%, 11.5%, 53.1%, 5.8%, 1.2%, and 20.4%, respectively, of the excess relative risk (ERR) among the younger Black vs White patients. Among patients 65 years or older, the HR for death for Black vs White patients was 1.87 (95% CI, 1.81-1.93) in the baseline model and 1.14 (95% CI, 1.09-1.19) after balancing other factors. Comorbidity score, neighborhood income, insurance status, histologic subtype, disease stage, treatment, and unexplained factors accounted for 3.0%, 7.5%, 0.0%, 56.2%, 10.6%, 6.9%, and 15.8%, respectively, of the ERR among Black vs White patients aged 65 years or older., Conclusions and Relevance: This study suggests that histologic subtype was the dominant factor associated with racial survival disparity among patients with uterine cancer, while insurance status represented the main modifiable factor for women younger than 65 years. Additional studies of interactions between biology and social determinants of health are merited.

Characterization of ancestry-linked peptide variants in disease-relevant patient tissues represents a foundational step to connect patient ancestry with disease pathogenesis. Nonsynonymous single-nucleotide polymorphisms encoding missense substitutions within tryptic peptides exhibiting high allele frequencies in European, African, and East Asian populations, termed peptide ancestry informative markers (pAIMs), were prioritized from 1000 genomes. In silico analysis identified that as few as 20 pAIMs can determine ancestry proportions similarly to >260K SNPs (R 2  = 0.99). Multiplexed proteomic analysis of >100 human endometrial cancer cell lines and uterine leiomyoma tissues combined resulted in the quantitation of 62 pAIMs that correlate with patient race and genotype-confirmed ancestry. Candidates include a D451E substitution in GC vitamin D-binding protein previously associated with altered vitamin D levels in African and European populations. pAIMs will support generalized proteoancestry assessment as well as efforts investigating the impact of ancestry on the human proteome and how this relates to the pathogenesis of uterine neoplasms., Competing Interests: G.L.M. is a consultant for Kiyatec, GSK, and Merck. T.P.C. is a ThermoFisher Scientific, Inc SAB member and receives research funding from AbbVie. G.J.P. has received a patent based on concepts presented in this study (US 8,877,455 B2, Australian Patent 2011229918, Canadian Patent CA 2794248, and European Patent EP11759843.3)., (© 2021 The Author(s).)

Pathogenic mutations in fumarate hydratase (FH) drive hereditary leiomyomatosis and renal cell cancer (HLRCC) and increase the risk of developing uterine leiomyomas (ULMs). An integrated proteogenomic analysis of ULMs from HLRCC (n = 16; FH-mutation confirmed) and non-syndromic (NS) patients (n = 12) identified a significantly higher protein:transcript correlation in HLRCC (R = 0.35) vs. NS ULMs (R = 0.242, MWU p = 0.0015). Co-altered proteins and transcripts (228) included antioxidant response element (ARE) target genes, such as thioredoxin reductase 1 (TXNRD1), and correlated with activation of NRF2-mediated oxidative stress response signaling in HLRCC ULMs. We confirm 185 transcripts previously described as altered between HLRCC and NS ULMs, 51 co-altered at the protein level and several elevated in HLRCC ULMs are involved in regulating cellular metabolism and glycolysis signaling. Furthermore, 367 S-(2-succino)cysteine peptides were identified in HLRCC ULMs, of which sixty were significantly elevated in HLRCC vs. NS ULMs (LogFC = 1.86, MWU p < 0.0001). These results confirm and define novel proteogenomic alterations in uterine leiomyoma tissues collected from HLRCC patients and underscore conserved molecular alterations correlating with inactivation of the FH tumor suppressor gene.

Background: Endometrial cancer is the most common gynecological cancer in the United States. However, no early detection test exists for asymptomatic women at average risk for endometrial cancer., Objective: We sought to identify early detection biomarkers for endometrial cancer using prediagnostic serum., Study Design: We performed a nested case-control study of postmenopausal women in the Prostate, Lung, Colorectal, and Ovarian cancer screening trial (n = 78,216), including 112 incident endometrial cancer cases and 112 controls. Prediagnostic serum was immunodepleted of high-abundance proteins and digested with sequencing grade porcine trypsin via pressure cycling technology. Quantitative proteomics and phosphoproteomics was performed using high-resolution liquid chromatography-tandem mass spectrometry and highly multiplexed isobaric mass tag combined with basic reversed-phase liquid chromatography. A set of proteins able to predict cancer status was identified with an integrated score assessed by receiver-operator curve analysis., Results: Mean time from blood draw to endometrial cancer diagnosis was 3.5 years (SD, 1.9 years). There were 47 differentially abundant proteins between cases and controls (P < .05). Protein alterations with high predictive potential were selected by regression analysis and compiled into an aggregate score to determine the ability to predict endometrial cancer. An integrated risk score of 6 proteins was directly related to disease incidence in cases with blood draw ≤2 years, >2 years to ≤5 years or >5 years prior to cancer diagnosis. The integrated score distinguished cases from controls with an area under the curve of 0.80 (95% confidence interval, 0.72-0.88)., Conclusion: An integrated score of 6 proteins using prediagnostic serum from the Prostate, Lung, Colorectal, and Ovarian cancer screening trial distinguishes postmenopausal endometrial cancer cases from controls. Validation is needed to evaluate whether this test can improve prediction or detection of endometrial cancer among postmenopausal women., (Copyright © 2019. Published by Elsevier Inc.)

Objective: To evaluate relationships between an objective biomarker of current tobacco exposure and high-risk genital human papillomavirus (HPV) prevalence among adult women in the United States., Methods: We performed a retrospective analysis of adult women (aged 18-59 years) using three consecutive 2-year cycles (2009-2014) from the cross-sectional National Health and Nutrition Examination Surveys. Women who provided self-collected cervicovaginal swabs and serum were included. Human papillomavirus genotyping was conducted on cervicovaginal samples with a Linear Array HPV assay. Cotinine, a major metabolite of nicotine, was assayed from serum to provide a biomarker of recent tobacco exposure. Participants were stratified into three levels of tobacco exposure (nonsmokers, secondhand smoke exposure, and smokers) based on serum cotinine concentration levels using previously published ethnic-specific cut points. Weighted percentages are provided to account for unequal selection probabilities among participants and adjustments for nonresponse., Results: Among the 5,158 women analyzed, 2,778 were classified as nonsmokers (57.1%, 95% CI 54.5-59.6%), 1,109 classified as having secondhand smoke exposure (18.4%, 95% CI 16.5-20.3%), and 1,271 classified as smokers (24.6%, 95% CI 22.8-26.5%) using serum cotinine concentration levels. Prevalence of HPV infection differed between nicotine exposure groups (P<.001): 441 smokers (32.1%, 95% CI 29.6-34.7%), 322 women with secondhand smoke exposure (26.1%, 95% CI 22.7-29.7%), and 451 nonsmokers (15.1%, 95% CI 13.3-17.1%) had a high-risk genital HPV infection. Controlling for demographics and number of lifetime sexual partners, the risks compared with nonsmokers for infection with a high-risk HPV genotype for smokers (adjusted odds ratio [OR] 1.7, 95% CI 1.4-22) and secondhand smokers (adjusted OR 1.4, 95% CI 1.1-1.8) are similarly increased (P<.001)., Conclusion: In this large cross-sectional, population-based study, we show a relationship between an objective biomarker of current tobacco use and genital HPV infection. Cigarette smoking and exposure to secondhand smoke are associated with increased odds of infection with high-risk genital HPV independent of lifetime number of sexual partners.

Introduction: Although black patients with endometrial cancer (EC) have worse survival compared with white patients, the interaction between age/race has not been examined. The primary objective was to evaluate the impact of age at diagnosis on racial disparities in disease presentation and outcome in EC., Methods: We evaluated women diagnosed with EC between 1991 and 2010 from the Surveillance, Epidemiology, and End Results. Mutation status for TP53 or PTEN, or with the aggressive integrative, transcript-based, or somatic copy number alteration-based molecular subtype were acquired from the Cancer Genome Atlas. Logistic regression model was used to estimate the interaction between age and race on histology. Cox regression model was used to estimate the interaction between age and race on survival., Results: 78,184 white and 8518 black patients with EC were analyzed. Median age at diagnosis was 3-years younger for black vs. white patients with serous cancer and carcinosarcoma (P<0.0001). The increased presentation of non-endometrioid histology with age was larger in black vs. white patients (P<0.0001). The racial disparity in survival and cancer-related mortality was more prevalent in black vs. white patients, and in younger vs. older patients (P<0.0001). Mutations in TP53, PTEN and the three aggressive molecular subtypes each varied by race, age and histology., Conclusions: Aggressive histology and molecular features were more common in black patients and older age, with greater impact of age on poor tumor characteristics in black vs. white patients. Racial disparities in outcome were larger in younger patients. Intervention at early ages may mitigate racial disparities in EC., (Copyright © 2017 Elsevier Inc. All rights reserved.)

Objectives: Racial differences in the molecular subtypes of endometrial cancer and associations with progression-free survival (PFS) were evaluated., Methods: Molecular, clinical and PFS data were acquired from the Cancer Genome Atlas (TCGA) including classification into the integrative, somatic copy number alteration and transcript-based subtypes. The prevalence and prognostic value of the aggressive molecular subtypes (copy number variant [CNV]-high, cluster 4 or mitotic) were evaluated in Black and White patients., Results: There were 337 patients including 14% self-designated as Black, 27% with advanced stage, and 82% with endometrioid histology. The CNV-high subtype was more common in Black than White patients (61.9% vs. 23.5%, P=0.0005) and suggested worse PFS in Black patients (hazard ratio [HR]=3.4, P=0.189). The cluster 4 subtype was more prevalent in Black patients (56.8% vs. 20.9%, P<0.0001) and associated with worse PFS in Black patients (HR=3.4, P=0.049). The mitotic subtype was more abundant in Black patients (64.1% vs. 33.7%, P=0.002), indicated worse PFS in Black patients (HR=4.1, P=0.044) including the endometrioid histology (HR=6.1, P=0.024) and exhibited race-associated enrichment in cell cycle signaling and pathways in cancer including PLK1 and BIRC7. All of these aggressive molecular subtypes also indicated worse PFS in White patients, with unique enrichments in mitotic signaling different from Black patients., Conclusions: The aggressive molecular subtypes from TCGA were more common in Black endometrial cancer patients and indicated worse PFS in both Black and White patients. The mitotic subtypes also indicated worse PFS in Black patients with endometrioid histology. Enrichment patterns in mitotic signaling may represent therapeutic opportunities., (Copyright © 2017. Published by Elsevier Inc.)

Objective: Gestational choriocarcinoma is a malignant form of gestational trophoblastic disease that usually arises after a molar pregnancy, but may follow any antecedent pregnancy. Investigations in this rare cancer are limited. We evaluated the prognostic effects of age, race, and stage in choriocarcinomas diagnosed for 4 decades., Methods: Patients diagnosed as having gestational choriocarcinoma between 1973 and 2014 from the Surveillance, Epidemiology, and End Results program were eligible. Relationships with overall survival and cancer-specific survival were evaluated using log-rank testing and Cox modeling. Multivariate analyses included adjustments for age, race, and stage., Results: There were 947 patients with choriocarcinoma including 403 non-Hispanic white (NHW) patients, 473 with distant stage, and 142 who died. Median age at diagnosis was 25 years for non-Hispanic black (NHB) patients and 35 years for Asian/Pacific Islanders (API) compared with 29 years for NHW patients (P = 0.0001). Five-year overall survival varied between 82% and 92% when diagnosed at the age of at least 40 years compared with less than 20 years (P < 0.0001), and from 85% to 95% in patients with distant vs local disease (P < 0.0001), respectively. Multivariate analysis demonstrated that age, race, and stage were independent predictors of mortality. Risk of death increased incrementally in patients diagnosed at 20 to 39 years of age (adjusted hazard ratio [aHR], 3.87; 95% confidence interval [CI], 1.69-8.86; P = 0.001) and at least 40 years of age (aHR, 7.18; 95% CI, 2.95-17.49; P < 0.0001) compared with 20 years or younger. Non-Hispanic black patients were the only racial group at higher risk of death compared with NHW patients (aHR, 1.86; 95% CI, 1.22-2.82; P < 0.004). Distant vs local disease added an additional risk of death (aHR, 2.43; 95% CI, 1.57-3.75; P < 0.0001) over that attributable to age at diagnosis and NHB race. Similar relationships to cancer-specific survival were also observed (P < 0.05)., Conclusions: Most patients with choriocarcinoma have excellent prognosis. However, NHB patients and patients who are diagnosed at the age of at least 20 years or have distant stage have significantly worse mortality.

Human papillomavirus (HPV) is the most common sexually transmitted infection that causes majority of anogenital and oropharyngeal cancers. Prophylactic HPV vaccine is available for the primary prevention of cancer and HPV transmission. Here, we are going to discuss the variation of HPV prevalence, HPV vaccination coverage and potential risk factors of men and women, retrieved from the cross-sectional study of the National Health Nutrition Examination Survey, a representative sample of noninstitutionalized, civilian residents in the USA. The overall penile HPV prevalence in men was 45.2% and the high risk oncogenic HPV prevalence defined by DNA testing was 25.1% that appeared to be widespread among all the age groups, which contrasts the vaginal HPV prevalence of 26.8% in women.

Objective: To evaluate whether there was a change in prevalence of human papillomavirus (HPV) in the United States correlated with the introduction of HPV vaccines in both vaccinated and unvaccinated women., Methods: We performed a retrospective review of prevalence data for women aged 18-29 years living in the United States using the National Health and Nutrition Examination Surveys, which is an ongoing series of cross-sectional surveys. Participants provided responses to standardized questions and self-collected cervicovaginal swabs in which a Linear Array HPV Assay was used to determine HPV prevalence. A total of 783 women from the prevaccine era (2003-2004) and 1,526 from the postvaccine era (2007-2012) were analyzed., Results: Among women aged 18-29 years, the prevalence of vaccine-type HPV declined among women receiving one or more doses of vaccine (P=.003): 10.1% (95% confidence interval [CI] 7.1-13.8%) in the prevaccine era to 4.2% (95% CI 3.3-10.9%) in the postvaccine era. There was no change in prevalence of nonvaccine-type HPV among women receiving one or more doses of vaccine (P>.05). There was also no change in prevalence of vaccine-type HPV among unvaccinated women from the prevaccine era 10.1% (95% CI 7.1-13.8%) to 8.8% (95% CI 5.6-12.9%) in the postvaccine era (P=.4). Vaccine coverage increased to 31.5% of eligible women aged 18-29 years as of 2011-2012., Conclusion: Six years after introduction of HPV vaccination in the United States, there has been a decrease in the prevalence of vaccine-type HPV among women correlated with receiving one or more vaccine doses with no change in nonvaccine-type HPV. Furthermore, there has been no change in prevalence of vaccine-type HPV among unvaccinated women.

Objective: To evaluate the association of spousal deployment during the antenatal period on maternal and neonatal outcomes and to estimate whether group prenatal care may be beneficial in reducing adverse outcomes when spouses are deployed., Methods: Primigravid women who delivered at Womack Army Medical Center, Fort Bragg, North Carolina, were prospectively enrolled and selected for participation on a random basis between January 2013 and January 2014. Women whose spouses were deployed to a combat zone during the entire pregnancy (deployed group) were compared with women whose spouses were not deployed during the pregnancy (nondeployed group). Pregnancy and neonatal outcomes were compared between groups., Results: Three hundred ninety-seven women were enrolled with 183 (46.1%) in the deployed group and 214 (53.9%) in the nondeployed group. Spouse deployment was associated with increased risk of preterm delivery (38 [20.8%] compared with 16 [7.5%], P<.001) and postpartum depression (30 [16.4%] compared with 13 [6.1%], P=.001) when compared with women in the nondeployed group. There were no differences in the incidence of preterm delivery and postpartum depression for women in the deployed group who participated in group prenatal care when compared with women participating in traditional care (preterm delivery 6 [14.6%] compared with 32 [22.5%], P=.38; postpartum depression 4 [9.8%] compared with 26 [18.3%], P=.24)., Conclusion: Women who have a spouse deployed during their pregnancy are at increased risk for preterm birth and postpartum depression. Larger studies are needed to evaluate whether spouse deployment during pregnancy has other perinatal effects and whether group prenatal care may have a positive effect on adverse perinatal outcomes in this population., Level of Evidence: II.

Background: Cogan syndrome is a rare, multisystem, autoimmune disorder of unknown etiology. Little is known about whether it affects pregnancy or whether pregnancy affects the disease., Case: A 24-year-old primigravid woman with Cogan syndrome diagnosed 3 years before her pregnancy presented to our clinic for prenatal care. During pregnancy she experienced no worsening of symptoms of her disease but reported subjective improvement in vision and hearing. Cesarean delivery was performed at term because of nonreassuring fetal status. There were no obstetric or postpartum complications., Conclusion: Cogan syndrome requires close monitoring. If it worsens, then the disease process can be similar to both physiologic and pathologic changes of pregnancy. However, unlike the former, worsening Cogan syndrome can have irreversible maternal consequences.

Postcoital bleeding refers to spotting or bleeding that occurs after intercourse and is not related to menstruation. The prevalence of postcoital bleeding ranges from 0.7 to 9.0 percent of menstruating women. There are multiple etiologies for this common complaint in which most are benign such as cervicitis or cervical polyps. However, the most serious cause of postcoital bleeding is cervical cancer. There are currently no recommendations from governing bodies such as the American College of Obstetricians and Gynecologists on evaluating and treating women with postcoital bleeding. The purpose of this paper is to discuss the common causes of postcoital bleeding, the etiologies of postcoital bleeding, and the likelihood that malignancy is the underlying cause. After an extensive literature review, we compiled a paper illustrating the key concepts a practitioner should know when it comes to postcoital bleeding. Finally, this review will conclude with treatment options for women who are found to have an identifiable source for their bleeding and a discussion on the natural history of postcoital bleeding in women who are found to have no identifiable etiology on evaluation.

Objective: To evaluate the natural history of vaginal intraepithelial neoplasia (VAIN) and to identify risk factors for invasive vaginal carcinoma., Methods: The records of all women with VAIN diagnosed at military treatment facilities over a 10-year period with minimum follow-up of 12 months were reviewed. Patient demographics and clinical information related to the diagnosis and treatment of VAIN were recorded., Results: One hundred twenty-seven women with VAIN met inclusion criteria. The mean age was 47.4 years, and median surveillance was 34 months (range 12-169 months). Seventy-five patients had low-grade vaginal dysplasia as their initial diagnosis, and 15 (20%) of these patients underwent treatment. Fifty-two patients had high-grade vaginal dysplasia, of which 38 (73%) underwent treatment. Overall, 113 patients (89%) demonstrated normalization of disease, 11 patients (9%) demonstrated persistence of disease, and three patients (2%) experienced recurrence of disease. No patients experienced development of invasive vaginal carcinoma. However, median time to normalization was 6 months longer in patients with low-grade dysplasia compared with those with high-grade dysplasia (15.9 months compared with 10.0 months; hazard ratio 1.5; 95% confidence interval 1.004-2.1; P=.045). Patients with high-grade dysplasia had more biopsies performed during their surveillance than patients with low-grade dysplasia (3.3 compared with 2.5; P=.045)., Conclusion: Overall, 89% of patients demonstrated normalization of VAIN, and none had progression to invasive cancer. Normalization, persistence, and recurrence rates did not significantly differ by grade of dysplasia or treatment status. Based on our findings regarding the time to normalization, annual surveillance with combined cytology and colposcopy is likely adequate. Because 11% of patients with VAIN either will experience recurrence or will have persistent disease, lifetime surveillance is recommended., Level of Evidence: : III.

Cesarean section is the most common surgery performed in the United States with over 30% of deliveries occurring via this route. This number is likely to increase given decreasing rates of vaginal birth after cesarean section (VBAC) and primary cesarean delivery on maternal request, which carries the inherent risk for intraoperative complications. Urologic injury is the most common injury at the time of either obstetric or gynecologic surgery, with the bladder being the most frequent organ damaged. Risk factors for bladder injury during cesarean section include previous cesarean delivery, adhesions, emergent cesarean delivery, and cesarean section performed at the time of the second stage of labor. Fortunately, most bladder injuries are recognized at the time of surgery, which is important, as quick recognition and repair are associated with a significant reduction in patient mortality. Although cesarean delivery is a cornerstone of obstetrics, there is a paucity of data in the literature either supporting or refuting specific techniques that are performed today. There is evidence to support double-layer closure of the hysterotomy, the routine use of adhesive barriers, and performing a Pfannenstiel skin incision versus a vertical midline subumbilical incision to decrease the risk for bladder injury during cesarean section. There is also no evidence that supports the creation of a bladder flap, although routinely performed during cesarean section, as a method to reduce the risk of bladder injury. Finally, more research is needed to determine if indwelling catheterization, exteriorization of the uterus, and methods to extend hysterotomy incision lead to bladder injury.