Proteomic studies of VEGFR2 in human placentas reveal protein associations with preeclampsia, diabetes, gravidity, and labor.

VEGFR2 (Vascular endothelial growth factor receptor 2) is a central regulator of placental angiogenesis. The study of the VEGFR2 proteome of chorionic villi at term revealed its partners MDMX (Double minute 4 protein) and PICALM (Phosphatidylinositol-binding clathrin assembly protein). Subsequently, the oxytocin receptor (OT-R) and vasopressin V1aR receptor were detected in MDMX and PICALM immunoprecipitations. Immunogold electron microscopy showed VEGFR2 on endothelial cell (EC) nuclei, mitochondria, and Hofbauer cells (HC), tissue-resident macrophages of the placenta. MDMX, PICALM, and V1aR were located on EC plasma membranes, nuclei, and HC nuclei. Unexpectedly, PICALM and OT-R were detected on EC projections into the fetal lumen and OT-R on 20-150 nm clusters therein, prompting the hypothesis that placental exosomes transport OT-R to the fetus and across the blood-brain barrier. Insights on gestational complications were gained by univariable and multivariable regression analyses associating preeclampsia with lower MDMX protein levels in membrane extracts of chorionic villi, and lower MDMX, PICALM, OT-R, and V1aR with spontaneous vaginal deliveries compared to cesarean deliveries before the onset of labor. We found select associations between higher MDMX, PICALM, OT-R protein levels and either gravidity, diabetes, BMI, maternal age, or neonatal weight, and correlations only between PICALM-OT-R (p < 2.7 × 10-8), PICALM-V1aR (p < 0.006), and OT-R-V1aR (p < 0.001). These results offer for exploration new partnerships in metabolic networks, tissue-resident immunity, and labor, notably for HC that predominantly express MDMX.

Cervical cancer screening among English- and Spanish-speaking Hispanic women in an urban safety net health system, 2015-2020.

BACKGROUND: The Hispanic population is heterogeneous with differences in health behaviors across subgroups by nativity and preferred language. We evaluated cervical cancer screening adherence among English- and Spanish-speaking Hispanic patients receiving care at a safety net health system. METHODS: Electronic health records were used to identify 46,094 women aged 30-65. Up to date (UTD) screening was defined based on date of last Pap test, human papillomavirus (HPV) test, or Pap/HPV co-test. RESULTS: Overall, 81.5% of 31,297 Hispanic women were UTD. English-speaking Hispanic women had a lower prevalence of being UTD when compared to Spanish-speaking Hispanic women (aPR: 0.94, 95% CI: 0.93 - 0.96). Further, those with indigent healthcare plans had a higher prevalence of being UTD when compared to those with private insurance (aPR: 1.10, 95% CI: 1.09 - 1.12), while all other health insurance plans were associated with lower UTD screening when compared to private insurance. CONCLUSIONS: These findings suggest screening differences within the Hispanic population, highlighting the need for disaggregated research assessing heterogeneity within racial/ethnic groups, specifically among Hispanic populations.

Dynamic transcriptome, accessible genome, and PGR cistrome profiles in the human myometrium.

The myometrium undergoes structural and functional remodeling during pregnancy. We hypothesize that myometrial genomic elements alter correspondingly in preparation for parturition. Human myometrial tissues from nonpregnant (NP) and term pregnant (TP) human subjects were examined by RNAseq, ATACseq, and PGR ChIPseq assays to profile transcriptome, assessible genome, and PGR occupancy. NP and TP specimens exhibit 2890 differentially expressed genes, reflecting an increase of metabolic, inflammatory, and PDGF signaling, among others, in adaptation to pregnancy. At the epigenome level, patterns of accessible genome change between NP and TP myometrium, leading to the altered enrichment of binding motifs for hormone and muscle regulators such as the progesterone receptor (PGR), Krüppel-like factors, and MEF2A transcription factors. PGR genome occupancy exhibits a significant difference between the two stages of the myometrium, concomitant with distinct transcriptomic profiles including genes such as ENO1, LHDA, and PLCL1 in the glycolytic and calcium signaling pathways. Over-representation of SRF, MYOD, and STAT binding motifs in PGR occupying sites further suggests interactions between PGR and major muscle regulators for myometrial gene expression. In conclusion, changes in accessible genome and PGR occupancy are part of the myometrial remodeling process and may serve as mechanisms to formulate the state-specific transcriptome profiles.

Trends in ureteral surgery on an academic gynecologic oncology service.

OBJECTIVE: To describe the incidence, complications, and trends associated with ureteral surgeries on a gynecologic oncology service in the context of a fellowship training program over a 24-year period. METHODS: We conducted a retrospective cohort analysis of ureteral surgeries by gynecologic oncologists at either Moffitt Cancer Center or Tampa General Hospital from 1997 to 2020. Patient characteristics, predisposing factors, location and type of injury, repair method, postoperative management and complications were abstracted from the medical record. The recent cohort (2005-2020) was compared to our prior series (1997-2004). RESULTS: Eighty-eight cases were included. The average number of ureteral surgeries per year decreased from 5.75 (1997-2004) to 2.63 (2005-2020). Of 46 iatrogenic injuries, 45 were recognized and repaired intraoperatively. Ureteral transection was the most common type (85% [39 of 46]) and the distal 5 cm was the most common location of injury (63% [29 of 46]). Ureteroneocystostomy was the most common method of repair (83% [73 of 88]). Postoperative management, including stenting and imaging, has not changed significantly. Length of urinary catheter usage decreased in the recent cohort without associated complications. Five patients had major postoperative complications and 4 involved the urinary tract. Of those with follow-up, 96% (66 of 69) of ureteroneocystostomies and 75% (9 of 12) of ureteroureterostomies had radiologically normal urinary tracts. CONCLUSIONS: Ureteral surgery is necessary in the case of injury or involvement with invasive disease. There has been a decrease in number of procedures. Ureteroneocystostomy has remained the most common method of reconstruction for both injury and resection with acceptable postoperative complication rates.

Qualitative assessment of knowledge and attitudes towards cervical cancer screening among male Latino immigrants in Houston, Texas.

BACKGROUND: Male spouses and partners play an important role in determining a woman's willingness to participate in cervical cancer screening. However, the attitudes and behaviors by which they influence a woman's decision to undergo Pap testing remain poorly understood. METHODS: A series of semi-structured, qualitative interviews were conducted in Spanish with 19 recent Latino immigrants in Houston, Texas. The interview format was designed to establish each individual's pattern of engagement with the United States healthcare system, assess baseline knowledge of cervical cancer screening and evaluate attitudes and patterns of communication with their female partners regarding health care. Interview questions were constructed using principles of the Theory of Reasoned Action. All interviews were conducted in Spanish. After translation, responses were coded and scored with the goal of identifying themes and key observations. RESULTS: Most subjects reported few, if any, interactions with the healthcare system since their arrival in the United States. Although most participants reported being aware that women should be seen by their doctors regularly, fewer than half could clearly indicate the purpose of a Pap test or could state with certainty the last time their female partner had undergone screening. Multiple subjects expressed a general distrust of the health care system and concern for its costs. Approximately half of subjects reported that they accompanied their female partner to the health care provider's office and none of the participants reported that they were present in examination rooms at the time their partner underwent screening. Multiple participants endorsed that there may be some concerns within their community regarding women receiving frequent gynecologic care and distrust of the healthcare system. Almost all interviewed subjects stated that while they would allow their female partners to see male physicians, they also expressed the opinion that other men might be uncomfortable with this and that women would likely be more comfortable with female physicians. CONCLUSIONS: Strategies to enhance knowledge of HPV and cancer screening and improve trust in the health care system among male spouses or partners should be explored with the goal of promoting cervical cancer screening among immigrant Latinx populations.

Inversely and adaptively planned interstitial brachytherapy: A single implant approach.

OBJECTIVE: To evaluate the efficacy, feasibility and safety of image-based, inversely and adaptively planned high-dose rate interstitial brachytherapy (HDR-ISBT) to treat advanced primary or recurrent gynecologic malignancy in a single implant, three-consecutive-day regimen. METHODS: Clinical demographics and outcome data were abstracted from all patients with primary and recurrent gynecologic malignancies who received HDR-ISBT boost from 2014 to 2017. Treatment consisted of a single implant (~7 Gy × 4 fractions) of interstitial needles using the Syed-Neblett template over a three-day hospital admission. CT-based (3D) simulation with inverse and adaptive planning was utilized for each fraction. MR prior to and MR immediately after external beam therapy were fused for HDR-ISBT target delineation. RESULTS: Forty women with an overall median follow-up of 18 months (range: 6-54 months) received an HDR-ISBT boost. Of the 30 primary cases (83% cervix, 10% vaginal, 7% uterine), 44% had organ invasion (bladder, rectal or both) on MRI. Median coverage and dose are reported (V100: 98%, HR-CTV EQD2: 85.1 Gy, D90: 92 Gy). A significant association existed between rectal doses exceeding GEC-ESTRO recommendations (D2cc < 75 Gy) and the development of grade 3 gastrointestinal toxicity with a relative risk of 1.4 [1.1-1.8] (p = .046). Actuarial two-year overall survival (OS), local control (LC) and progression-free survival (PFS) were 81%, 81% and 64%, respectively. CONCLUSIONS: A four fraction, inversely and adaptively planned, single-implant approach of image-based HDR-ISBT provides excellent coverage, minimal toxicity and effective local control in patients with advanced and recurrent disease.

Pilot survey of mosquitoes (Diptera: Culicidae) from southeastern Georgia, USA for Wolbachia and Rickettsia felis (Rickettsiales: Rickettsiaceae).

BACKGROUND & OBJECTIVES: Mosquito surveillance is one of the critical functions of local health departments, particularly in the context of outbreaks of severe mosquito-borne viral infections. Unfortunately, some viral and parasitic infections transmitted by mosquitoes, manifests non-specific clinical symptoms which may actually be of rickettsial etiology, including Rickettsia felis infections. This study tested the hypothesis that mosquitoes from southeastern Georgia, USA may be infected with Rickettsia felis and Wolbachia, an endosymbiotic bacterium of the order Rickettsiales. METHODS: Specimens of the five most common mosquito species occurring in the region were collected using gravid and light-traps and identified using morphological keys. Mosquitoes were then pooled by species, sex, trap and collection site and their DNA was extracted. Molecular methods were used to confirm mosquito identification, and presence of Wolbachia and R. felis. RESULTS: Wolbachia DNA was detected in 90.8% of the mosquito pools tested, which included 98% pools of Cx. quinquefasciatus Say (Diptera: Culicidae), 95% pools of Ae. albopictus Skuse (Diptera: Culicidae), and 66.7% of pools of Cx. pipiens complex. Samples of An. punctipennis Say (Diptera: Culicidae) and An. crucians Wiedemann (Diptera: Culicidae) were tested negative for Wolbachia DNA. Three genotypes of Wolbachia sp. belonging to Group A (1 type) and Group B (2 types) were identified. DNA of R. felis was not found in any pool of mosquitoes tested. INTERPRETATION & CONCLUSIONS: This study provides a pilot data on the high presence of Wolbachia in Cx. quinque-fasciatus and Ae. albopictus mosquitoes prevalent in the study region. Whether the high prevalence of Wolbachia and its genetic diversity in mosquitoes affects the mosquitoes' susceptibility to R. felis infection in Georgia will need further evaluation.

Distinct molecular pathways in ovarian endometrioid adenocarcinoma with concurrent endometriosis.

Women with endometriosis, a benign growth of endometrial tissue outside the uterine cavity, are at increased risk of specific histotypes of epithelial ovarian cancer, such as ovarian endometrioid adenocarcinoma (OEA). Women with OEA who have endometriosis at time of surgical staging demonstrate improved clinical prognosis compared to women with OEA without evidence of endometriosis. However, the molecular contributions of the endometriotic tumor microenvironment to these ovarian cancers remain poorly understood. As a starting point, we used a platform for genome-wide transcriptomic profiling to compare specimens of OEA from women with and without concurrent endometriosis and benign reproductive tract tissues, including proliferative endometrium and typical and atypical endometrioma samples (n = 20). Principle component analysis revealed distinct clustering between benign and malignant samples as well as malignant samples with and without concurrent endometriosis. Examination of gene signatures revealed that OEA with concurrent endometriosis contained a unique molecular signature compared to OEA without concurrent endometriosis, distinguished by 682 unique genes differentially expressed (fold change < or >1.5, p < 0.01). Bioinformatic analysis of these differentially expressed gene products using ingenuity pathway analysis revealed activation of NFkB signaling, an inflammatory signaling pathway constitutively active in endometriosis. DAVID functional annotation clustering further revealed enrichment in RAS signaling as both cytoskeleton organization and GTPase regulator activity relied heavily on RAS protein signal transduction. Gene set enrichment analysis highlighted immune and inflammatory nodes involved in OEA with concurrent endometriosis. These observations provide novel resources for understanding molecular subtleties potentially involved in OEA within the context of the endometriotic tumor microenvironment.

An analysis of the association between statin use and risk of endometrial and ovarian cancers in the Women's Health Initiative.

BACKGROUND: Statins have anti proliferative activity in vitro against endometrial and ovarian cancer and can affect levels of reproductive hormones. We analyzed data from the Women's Health Initiative (WHI) to assess whether statins are associated with risk of endometrial and ovarian cancer. METHODS: The WHI study included 161,808 postmenopausal women in which incident cases of endometrial (n = 1377) and ovarian cancer (n = 763) were identified over an average of 10.8 (SD + 3.3) years. Information on statin use and risk factors was collected at baseline and follow-up. Cox proportional hazards regression was used to calculate hazard ratios (HRs) with 95% confidence intervals (CIs) for the association of statin use and risk of endometrial and ovarian cancer. All statistical tests were two-sided. RESULTS: Statins were used at baseline by 7.5% women and by up to 25% at year nine. The multivariable adjusted HR for risk of endometrial cancer for baseline statin use was 0.74, 95% C.I. 0.59-0.94 and for ovarian cancer was 1.15, 95% C.I. 0.89-1.50. In time-dependent models, statins were not associated with endometrial cancer (HR 0.91, 95% C.I. 0.76-1.08) however there was an increased risk of ovarian cancer (HR 1.30, 95% CI 1.04-1.62), largely attributed to the effect of the hydrophilic statin, pravastatin (1.89, 95% CI 1.24-2.88). CONCLUSIONS: There was a reduction in risk of endometrial cancer among statin users at baseline but not in time-dependent models. Pravastatin use was associated with an increased risk of ovarian cancer. Analyses of larger numbers of cases are needed to evaluate these findings.

Prognostic value of endocervical sampling following loop excision of high grade intraepithelial neoplasia.

OBJECTIVE: To assess the role of additional biopsies performed with loop electrosurgical excisional procedure (LEEP) in predicting the likelihood of persistent high grade intraepithelial neoplasia. METHODS: Clinicopathologic data were abstracted from women who underwent excision of high grade intraepithelial lesions between 2001 and 2014. Persistent disease was defined as uninterrupted high grade intraepithelial neoplasia, whereas recurrent disease was defined as disease diagnosed ≥1year after treatment with intervening normal evaluation. Chi-square and Fisher's exact tests were used to examine associations between demographic and histologic parameters and clinical outcomes. RESULTS: A total of 606 women underwent LEEP for high grade intraepithelial neoplasia (HSIL), of whom, 178 (29%) were additionally evaluated by endocervical curettage, 80 (13%), top hat and 99 (16%), both procedures. With mean follow-up of 1.9±1.5years, persistent disease was identified in 87 women (14%) while recurrent disease was diagnosed in 20 (3%). After adjusting for age, HIV status and histologic grade of disease, the presence of disease at the endocervical margin (aOR=2.2, 95% CL 1.8-5.5, p<0.0001), with endocervical curettage (aOR=2.39, 95% CL 1.2-9.9, p=0.025) or on top hat (aOR=4.0, 95% CL 1.1-16.2, p=0.04) correlated with the likelihood of persistent but not recurrent disease. Only endocervical margin status remained predictive (p=0.03) of outcome after controlling for pre-procedure likelihood of endocervical disease. Sensitivity of endocervical margin status for persistent disease was 56.9% with specificity of 72.2%. Positive predictive value (PPV) was 24.9% and negative predictive value (NPV) 90.9%. CONCLUSIONS: Despite frequent use of additional procedures to sample the endocervix, these strategies do not improve the ability of endocervical margin status to predict persistent or recurrent dysplasia.

Assessing the gene regulatory properties of Argonaute-bound small RNAs of diverse genomic origin.

High-throughput sequencing reveals an abundance of microRNA-sized fragments derived from larger non-coding RNAs. Roles for these small RNAs in gene silencing are suggested by their co-precipitation with Argonaute, the microRNA effector protein, though the extent to which they suppress gene expression endogenously remains unclear. To address this, we used luciferase reporters to determine the endogenous functionality of small RNAs from a diverse range of sources. We demonstrate small RNAs derived from snoRNAs have the capacity to act in a microRNA-like manner, though we note the vast majority of these are bound to Argonaute at levels below that required for detectable silencing activity. We show Argonaute exhibits a high degree of selectivity for the small RNAs with which it interacts and note that measuring Argonaute-associated levels is a better indicator of function than measuring total expression. Although binding to Argonaute at sufficient levels is necessary for demonstrating microRNA functionality in our reporter assay, this alone is not enough as some small RNAs derived from other non-coding RNAs (tRNAs, rRNAs, Y-RNAs) are associated with Argonaute at very high levels yet do not serve microRNA-like roles.

The Role of Routine Peritoneal and Omental Biopsies at Risk-Reducing Salpingo-Oophorectomy.

STUDY OBJECTIVE: To assess the potential role of peritoneal and omental biopsies in women undergoing risk-reducing salpingo-oopherectomy (RRSO) for prophylactic management of hereditary breast/ovarian cancer (HBOC) syndromes. DESIGN: A retrospective observational cohort (Canadian Task Force classification II.1). SETTING: An academic gynecology practice. PATIENTS: All women who underwent RRSO for a high-risk BRCA1/2 mutation or deletion at a single institution between January 2003 and June 2016. INTERVENTIONS: After obtaining institutional review board approval, patient demographics, types of surgical intervention, histopathology reports, and outcomes were abstracted. Bilateral fallopian tubes were histologically evaluated using the "sectioning and extensively examining of the fimbriated end" protocol. Descriptive statistics were used to summarize findings. MEASUREMENTS AND MAIN RESULTS: Seventy women underwent RRSO within the study window; 60% (n = 42) carried a high-risk mutation in BRCA1, 37.1% (n = 26) carried a high-risk mutation in BRCA2, and 2.9% (n = 2) had a high-risk BRCA deletion identified by BRAC analysis rearrangement testing (BART). Serous tubal intraepithelial carcinomas were identified in the distal fallopian tube of 3 subjects. In addition to RRSO, subjects underwent pelvic washings (n = 58, 82.9%), omental biopsy (n = 44, 62.9%), peritoneal biopsies of the bilateral paracolic gutters (n = 51, 72.9%), anterior and posterior cul-de-sac (n = 53, 75.7%), and rectosigmoid mesentery (n = 11, 15.7%). Rare atypical cells favoring reactive cells were identified in pelvic washings of 1 subject (1.7%) with histologically normal fallopian tubes. No evidence of atypical mesothelial proliferations or carcinoma was identified in any omental or peritoneal biopsies. The mean duration of follow-up was 32.5 ± 24.7 months. At the last contact, 3 women (4.3%) had died of metastatic breast cancer, whereas another 3 (4.3%) had been diagnosed with a recurrence of their breast cancer. All other subjects were alive and well (n = 64, 91.4%). CONCLUSION: The routine use of peritoneal and omental biopsies for women undergoing RRSO does not appear to improve detection of occult malignancy.

Intimate Partner Violence During Pregnancy and Maternal and Neonatal Health Among Hispanic Women.

OBJECTIVE: To examine the prevalence and the effect of intimate partner violence (IPV) during pregnancy on maternal and neonatal health outcomes among Hispanics. STUDY DESIGN: A cross-sectional survey was conducted among Hispanic women who delivered at a Houston hospital between January 2011 and October 2012; 613 women completed self-administered questionnaires in the postpartum window prior to discharge. Indices of maternal and neonatal health were compared between women with and without reports of IPV during the most recent pregnancy. RESULTS: Approximately 11% of the surveyed population reported having experienced IPV during the most recent pregnancy. Among non-U.S. born participants, women who experienced IPV reported longer U.S. stay (11.4±7.3 years) as compared to women who did not (9.2±6.3 years). They were more likely to be unhappy about their pregnancy and to have evidence of depres-sion. Reported IPV was also associated with later initiation of prenatal care, a greater likelihood of delivery before 34 weeks' gestational age, lower infant birth weight, and lower likelihood of planning to breastfeed beyond 12 months (aOR 0.43, CI 0.21-0.83; p=0.02). CONCLUSION: IPV during pregnancy is associated with adverse maternal and neonatal health outcomes. Prenatal programs should assess Hispanic women for IPV during pregnancy with the goal of mitigating its long-term health consequences.

Assessment of factors impacting cervical cancer screening among low-income women living with HIV-AIDS.

Very little is currently known about factors impacting the prevalence of cervical cancer screening among women living with HIV-AIDS (WLHA). To better understand this issue, we surveyed low-income, medically underserved women receiving subsidized gynecologic care through an integrated HIV clinic. A self-administered questionnaire was completed by 209 women who self-identified as HIV positive. A total of 179 subjects (85.7%) reported having had a Pap test in the last three years. The majority of WLHA (95%) knew that the Pap test screens for cervical cancer. However, overall knowledge of cervical cancer risk factors, such as multiple sexual partners or sex with a man with multiple partners, was low (43% and 35%, respectively). Unscreened women were younger and more likely to be single with multiple current sexual partners. In multivariable analyses, the only factors associated with Pap testing were a woman's perception that her partner wants her to receive regular screening (aOR 4.64; 95% CI: 1.15-23.76; p = .04), number of clinic visits during the past year (aOR 1.36, 95% CI: 1.05-1.94; p = .04) and knowledge that the need for a Pap test does not depend on whether or not a woman is experiencing vaginal bleeding (aOR 6.52, 95% CI: 1.04-49.71; p = .05). We conclude that support from male partners in addition to effective contact with the health system and knowledge of cervical cancer risk factors influence Pap utilization among low-income WLHA. Future measures to improve the care for this population should increase knowledge of cervical cancer risk factors and encourage social support for cervical cancer screening among WLHA.

Pregnancy Increases Relaxation in Human Omental Arteries to the CGRP Family of Peptides.

Calcitonin gene-related peptide (CALCB) and its family members adrenomedullin (ADM) and intermedin (ADM2) play important roles in maintaining vascular adaptations during pregnancy in animal models. The present study was designed to evaluate the responses of omental arteries to CALCB, ADM, and ADM2 in pregnant and nonpregnant women, and to determine the mechanisms involved. By using resistance omental arteries collected from nonpregnant women (n = 15) during laparotomy and from term pregnant women (n = 15) at cesarean delivery, this study shows that the receptor components--calcitonin receptor-like receptor (CALCRL) and receptor activity-modifying proteins (RAMPs) 1, 2 and 3--are localized to endothelial and smooth muscle cells in omental arteries, with increased expressions of both mRNA and protein in pregnant compared with nonpregnant women. The myography study demonstrated that CALCB, ADM, and ADM2 (0.1-100 nM) dose dependently relax U46619 (1 muM) precontracted omental artery segments, and the maximum possible effects to CALCB and ADM2, but not to ADM, are significantly enhanced in pregnant compared with nonpregnant women. Further, the vasodilatory responses to CALCB, ADM, and ADM2 are reduced by inhibitors of nitric oxide (NO) synthase (L-NAME), adenylyl cyclase (SQ22536), voltage-activated potassium channels (4-aminopyrodin and tetrabutylammonium), Ca(2+)-activated potassium channel (charybdotoxin), and cyclooxygenase (indomethacin). In conclusion, the CALCB family of peptides, CALCB and ADM2, increase human omental artery relaxation during pregnancy through diverse mechanisms, including NO, endothelium-derived hyperpolarizing factors (EDHFs) and prostaglandins, and thus could contribute to the vascular adaptations during pregnancy in the human.

Acceptability of self-sample human papillomavirus testing among medically underserved women visiting the emergency department.

OBJECTIVE: Self-sample human papillomavirus (HPV) testing in public emergency departments (EDs) may be a viable strategy to opportunistically screen women who otherwise do not attend for regular Papanicolaou test-based cervical cancer screening. We describe the acceptability of self-sample HPV testing among women presenting to two high-volume, urban EDs that primarily care for the medically underserved. METHODS: In 2014, a total of 210 women 21 years of age and older were recruited from two public ED waiting areas following a two-stage cluster sampling design. Questionnaire items inquired about demographics, healthcare access and utilization, history of cervical cancer screening, and acceptability of self-sample HPV testing. Descriptive analyses were performed. RESULTS: Overall, 34.8% of participants were considered screening non-attendees based on their adherence to the current guidelines for Pap testing every three years. Acceptability of self-sample HPV testing was high, with over 85% of participants reporting that they would be willing to use the test if available. A smaller proportion (58%) was deemed likely to accept self-sample HPV testing in a public ED restroom setting. Primary concerns expressed by women were that the sampling may not be done correctly (64%) and that they may not know how to perform the sampling (39%). CONCLUSIONS: Opportunistic self-sample HPV testing is acceptable to women seeking care at a high-volume, urban emergency care center. The use of this intervention potentially offers a unique strategy to improve cervical cancer screening among high-risk women who otherwise do not attend for regular screening.

Avoidable tragedies: Disparities in healthcare access among medically underserved women diagnosed with cervical cancer.

BACKGROUND: The purpose was to identify barriers including logistical and health belief correlates of late stage presentation of cervical cancer (CxCa) among medically underserved women presenting to a safety net health care system. METHODS: Women presenting with newly diagnosed CxCa were asked to complete a detailed health belief survey that included questions about barriers to care and their knowledge of CxCa. All information was collected prior to initiating cancer treatment. Comparisons were made among women diagnosed at early stages of disease amendable to surgical treatment (≤IB1) and those diagnosed at a stage requiring local-regional or systemic/palliative treatment (≥IB2). RESULTS: Among the 138 women, 21.7% were diagnosed with ≤lB1 disease, while 78.3% were diagnosed with ≥IB2 disease. Late-stage diagnosis was associated with a greater number of emergency room (ER) visits (p<.001) and blood transfusions (p<.001) prior to diagnosis. Compared to 88% with ≤lB1 disease, only 53% of patients with ≥IB2 disease had a car (p=.003). Women with ≥IB2 disease were more likely to be without a primary care provider (75.0% vs. 42.3%, p=.001). CONCLUSION: Access to transportation and lack of a regular primary care provider or a medical home are associated with late-stage of CxCa at diagnosis. Many medically underserved women continue to use the ER as their primary source of health care, and as a result their CxCa is diagnosed in advanced stages, with higher medical costs and lower chances of cure. The lack of Medicaid expansion in Texas may result in a worsening of this situation.

Treatment Compliance and Outcomes for Women With Locoregionally Advanced Cervical Cancer Treated in a Safety Net Health System.

OBJECTIVE: This study aims to assess treatment compliance among women undergoing definitive chemoradiation with weekly cisplatin for cervical cancer within a safety net health system and to quantify the impact of chemotherapy compliance on outcomes. MATERIALS AND METHODS: All women who were treated for International Federation of Gynecology and Obstetrics stage IB2 to stage IVA cervical cancer between April 2008 and May 2014 were identified. Treatment delays were attributed to toxicity, comorbid conditions, or system issues, or categorized as patient-initiated. Disease-free survival and overall survival of women who received fewer than 6 versus 6 or more doses of weekly cisplatin 40 mg/m were compared using Kaplan-Meier analyses. RESULTS: One hundred nineteen women (mean [SD] age, 48.5 [11.8] years) were identified. Most women (n = 112; 94.1%) completed definitive radiotherapy, requiring a mean (SD) of 56.5 (20.1) days. Sixty-four women (57.1%) completed definitive radiotherapy in 56 days or less. Only 44 women (36.4%) received 6 or more cycles of cisplatin. Of 122 delayed cycles, reasons for delay were as follows: grade 2 or higher toxicity (n = 70; 57.4%), medical comorbidity (n = 12; 9.8%), system issues (n = 9; 7.4%), and patient-initiated (n = 14; 11.5%). Multiple issues complicated treatment for 3 doses (2.5%). Reasons for delay were not documented in 14 doses (11.5%). Among patients who received 6 or more cycles, disease-free survival improved by 17.4 months (mean [SD], 61.1 [3.7] vs 43.7 [4.3] months, P = 0.002) and overall survival improved by 8.6 months (mean [SD], 68.7 [2.3] vs 60.1 [3.7] months, P = 0.011). CONCLUSIONS: Higher rates of toxicity and psychosocial barriers to chemotherapy compliance adversely impact survival among women who seek care in low-resource settings. In our population, administration of all 6 cycles of cisplatin was necessary for optimal survival benefit. Future efforts to improve cervical cancer outcomes should address preventable reasons for treatment delays among underinsured or uninsured individuals.

Self-Sampling for Human Papillomavirus Testing: Acceptability in a U.S. Safety Net Health System.

INTRODUCTION: Self-sampling for human papillomavirus testing is increasingly recognized as a strategy to expand cervical cancer screening access and utilization. Acceptability is a key determinant of uptake. This study assesses the acceptability of and experiences with mailed self-sampling kits for human papillomavirus testing among underscreened patients in a safety net health system. METHODS: A nested telephone survey was administered between 2021 and 2023 to a sample (n=272) of the 2,268 participants enrolled in the Prospective Evaluation of Self-Testing to Increase Screening trial. Trial participants include patients of a safety net health system aged 30-65 years who were not up to date on screening. Participants were asked about barriers to provider-performed screening. Kit users and nonusers were asked about their experiences. RESULTS: Prevalent barriers to provider-performed screening included perceived discomfort of pelvic examination (69.4%), being uncomfortable with male providers (65.4%), and embarrassment (57.0%). Among participants who reported using the mailed kit (n=164), most reported good experiences (84.8%). Most reported self-sampling as more/equally convenient (89.0%), less/equally embarrassing (99.4%), and less/equally stressful (95.7%) than provider-performed screening. Among kit nonusers (n=43), reasons for not using the kit included forgetting about it (76.7%), preferring provider-performed screening (76.7%), and fearing cancer (67.4%). CONCLUSIONS: Prospective Evaluation of Self-Testing to Increase Screening trial participants generally had a positive experience with self-sampling for human papillomavirus testing. Increased comfort and reduced embarrassment/anxiety with self-sampling are relevant attributes because these were the most prevalent reported barriers to provider-performed screening. High acceptability suggests potentially high uptake when self-sampling for human papillomavirus testing receives regulatory approval and is available in safety net health systems.

Molecular pathway identification using biological network-regularized logistic models.

BACKGROUND: Selecting genes and pathways indicative of disease is a central problem in computational biology. This problem is especially challenging when parsing multi-dimensional genomic data. A number of tools, such as L1-norm based regularization and its extensions elastic net and fused lasso, have been introduced to deal with this challenge. However, these approaches tend to ignore the vast amount of a priori biological network information curated in the literature. RESULTS: We propose the use of graph Laplacian regularized logistic regression to integrate biological networks into disease classification and pathway association problems. Simulation studies demonstrate that the performance of the proposed algorithm is superior to elastic net and lasso analyses. Utility of this algorithm is also validated by its ability to reliably differentiate breast cancer subtypes using a large breast cancer dataset recently generated by the Cancer Genome Atlas (TCGA) consortium. Many of the protein-protein interaction modules identified by our approach are further supported by evidence published in the literature. Source code of the proposed algorithm is freely available at http://www.github.com/zhandong/Logit-Lapnet. CONCLUSION: Logistic regression with graph Laplacian regularization is an effective algorithm for identifying key pathways and modules associated with disease subtypes. With the rapid expansion of our knowledge of biological regulatory networks, this approach will become more accurate and increasingly useful for mining transcriptomic, epi-genomic, and other types of genome wide association studies.