Acceptability of human papillomavirus self-collection and the role of telehealth: a prospective, randomized study stratified by menopausal status.

OBJECTIVE: We investigated the utility of telehealth instruction versus mail-based written instruction in facilitating high-risk human papillomavirus (hrHPV) self-collection among post-menopausal patients compared with pre-menopausal patients, as well as the impact on acceptability and feasibility. METHODS: We conducted a prospective, randomized study of people eligible for cervical cancer screening, stratified by menopausal status, to undergo standard written or telehealth-based instructions for hrHPV self-collection. English speaking individuals residing in Oregon, with a cervix, eligible for primary hrHPV testing, and with access to a video-capable device were included. Patients with prior hysterectomy, trachelectomy, diagnosis of cervical cancer, or pelvic radiation for gynecologic cancer were excluded. We compared preference for and opinions about self-collection and hrHPV test results, by randomization group and stratified by menopausal status using descriptive statistics. RESULTS: Among 123 patients enrolled, 61 identified as post-menopausal with a median age of 57 years. While the majority of post-menopausal participants who received telehealth instructions found it helpful, only 6.1% considered telehealth instructions necessary to complete self-testing. There was no difference in opinion of telehealth by menopausal status. Overall, 88.5% of post-menopausal participants preferred self-collection to provider-collection. There were no significant differences between pre- and post-menopausal participants in terms of test preference, discomfort, ease of use, or perceptions of self-collection. CONCLUSION: Telehealth instruction did not add significant value to patients participating in hrHPV self-collection, nor did it alter the acceptability of hrHPV-self collection among an English-speaking cohort. Compared with prior experiences with provider-collected screening, hrHPV self-collection was preferred by both pre- and post-menopausal participants. There were no significant differences in preference for provider- versus self-collection when stratified by menopausal status.

Intratumoral expression analysis reveals that OX40 and TIM-3 are prominently expressed and have variable associations with clinical outcomes in high grade serous ovarian cancer.

Patients with ovarian cancer exhibit low response rates to anti-programmed cell death protein-1 (PD-1) based therapies, despite ovarian tumors demonstrating measurable immune responses. Therefore, the aim of the present study was to comparatively examine expression of notable immune co-stimulatory and co-inhibitory receptors in order identify the most abundant receptors that could potentially serve as therapeutic targets to enhance immunotherapy response in high grade serous ovarian cancer (HGSOC). The Cancer Genome Atlas (TCGA) was employed to compare levels of various HGSOC and pan-cancer cohorts. To confirm these findings at the protein level, immunofluorescence of select receptors was performed in 29 HGSOC patient tissue samples. TCGA and Kaplan Meier analysis was employed to determine the association of highly expressed immune receptors with clinical outcomes. TIM-3 and OX40 exhibited the highest expression in HGSOC at both the gene and protein level, with TIM-3 demonstrating highest levels on both CD8+ and CD4+ T cell subsets. Pan-cancer analysis determined that TIM-3 and OX40 levels were similar to those in immunotherapy-responsive cancers, while PD-1 exhibited much lower expression in HGSOC. Finally, OX40 was most strongly associated with improved patient survival. Overall, the current study suggested that TIM-3 and OX40 are frequently expressed intratumoral immune receptors in HGSOC and thus represent promising immune targets. Furthermore, the present analysis strongly suggested that OX40 was significantly associated with a longer survival and could potentially be utilized as a prognostic factor for improved patient outcomes in HGSOC.

Outpatient Opioid Use After Cesarean Delivery.

OBJECTIVES: With a goal of informing opioid prescribing after cesarean delivery, we compared inpatient, prescribed, and outpatient Morphine Equivalent Doses (MED) and patient characteristics. METHODS: Patients were enrolled after cesarean delivery and followed for 2-5 weeks with demographic, opioid use, and clinical characteristics collected from participants and the medical record. T-test, ANOVA, linear regression, and Pearson correlation coefficients were used in analyses. RESULTS: Among 76 women, 21% used all opioids prescribed and 20% used none. History of psychiatric comorbidities was associated with higher outpatient opiate use (172 MED vs 103 MED; p = 0.046). There was no difference in opiates consumed inpatient and amount prescribed at discharge (p = 0.502). However, low, medium, and high inpatient consumers used 53 (SD 76), 111 (SD 96), and 195 (SD 132) MEDs outpatient, respectively (p < 0.001). CONCLUSIONS: Outpatient opioid prescribing based on inpatient needs may facilitate judicious opioid use after cesarean delivery. Significance What Is Already Known: Opioid abuse is a growing problem in this country, and excess prescribing contributes to the availability of opioids. Limited data exist regarding the amount of opioids patients need after cesarean delivery, or what factors are predictive of an individual patient's opioid needs. WHAT THIS STUDY ADDS: This study further supports the growing literature demonstrating that providers frequently over-prescribe opioids following cesarean delivery. It uniquely adds associations of patient-specific factors and outpatient opioid needs.

The biomarker HE4 (WFDC2) promotes a pro-angiogenic and immunosuppressive tumor microenvironment via regulation of STAT3 target genes.

Epithelial ovarian cancer (EOC) is a highly lethal gynecologic malignancy arising from the fallopian tubes that has a high rate of chemoresistant recurrence and low five-year survival rate. The ovarian cancer biomarker HE4 is known to promote proliferation, metastasis, chemoresistance, and suppression of cytotoxic lymphocytes. In this study, we sought to examine the effects of HE4 on signaling within diverse cell types that compose the tumor microenvironment. HE4 was found to activate STAT3 signaling and promote upregulation of the pro-angiogenic STAT3 target genes IL8 and HIF1A in immune cells, ovarian cancer cells, and endothelial cells. Moreover, HE4 promoted increases in tube formation in an in vitro model of angiogenesis, which was also dependent upon STAT3 signaling. Clinically, HE4 and IL8 levels positively correlated in ovarian cancer patient tissue. Furthermore, HE4 serum levels correlated with microvascular density in EOC tissue and inversely correlated with cytotoxic T cell infiltration, suggesting that HE4 may cause deregulated blood vessel formation and suppress proper T cell trafficking in tumors. Collectively, this study shows for the first time that HE4 has the ability to affect signaling events and gene expression in multiple cell types of the tumor microenvironment, which could contribute to angiogenesis and altered immunogenic responses in ovarian cancer.

Inhibition of DUSP6 sensitizes ovarian cancer cells to chemotherapeutic agents via regulation of ERK signaling response genes.

Dual specificity phosphatase 6 (DUSP6) is a protein phosphatase that deactivates extracellular-signal-regulated kinase (ERK). Since the ovarian cancer biomarker human epididymis protein 4 (HE4) interacts with the ERK pathway, we sought to determine the relationship between DUSP6 and HE4 and elucidate DUSP6's role in epithelial ovarian cancer (EOC). Viability assays revealed a significant decrease in cell viability with pharmacological inhibition of DUSP6 using (E/Z)-BCI hydrochloride in ovarian cancer cells treated with carboplatin or paclitaxel, compared to treatment with either agent alone. Quantitative PCR was used to evaluate levels of ERK pathway response genes to BCI in combination with recombinant HE4 (rHE4), carboplatin, and paclitaxel. Expression of EGR1, a promoter of apoptosis, was higher in cells co-treated with BCI and paclitaxel or carboplatin than in cells treated with chemotherapeutic agents alone, while expression of the proto-oncogene c-JUN was decreased with co-treatment. The effect of BCI on the expression of these two genes opposed that of rHE4. Pathway focused quantitative PCR also revealed suppression of ERBB3 in cells co-treated with BCI plus carboplatin or paclitaxel. Finally, expression levels of DUSP6 in EOC tissue were evaluated by immunohistochemistry, revealing significantly increased levels of DUSP6 in serous EOC tissue compared to adjacent normal tissue. A positive correlation between HE4 and DUSP6 levels was determined by Spearman Rank correlation. In conclusion, DUSP6 inhibition sensitizes ovarian cancer cells to chemotherapeutic agents and alters gene expression of ERK response genes, suggesting that DUSP6 could plausibly function as a novel therapeutic target to reduce chemoresistance in EOC.

Less Is More: Minimally Invasive and Quality Surgical Management of Gynecologic Cancer.

Surgery is a cornerstone of gynecologic oncology. Minimally invasive techniques have been adopted rapidly, in lieu of open approaches, in cervical and endometrial cancer staging. In addition, nodal assessment has undergone significant changes with the introduction of SLN biopsies. The movement toward less is more has also been seen with perioperative and postoperative care and the advent of ERAS protocols, which attempt to maintain normal physiology with the goal of improving functional recovery. It is imperative that new technology be critically evaluated to ensure that oncologic outcomes are not compromised.

Opioid Knowledge and Prescribing Practices Among Obstetrician-Gynecologists.

OBJECTIVE: To describe obstetrician-gynecologists' (ob-gyns) knowledge and prescribing practices regarding opioid analgesics. METHODS: We conducted a cross-sectional survey of a national sample of American College of Obstetricians and Gynecologists Fellows and Junior Fellows who are part of the Collaborative Ambulatory Research Network. We used a sequential mixed-method approach. We collected data on opioid knowledge and typical prescribing practices, including number, type, and indication for prescriptions. We determined adherence to four recommended practices: 1) screening for dependence, 2) prescribing the smallest amount required, 3) tailoring prescriptions, and 4) counseling on proper disposal. We also explored variables associated with prescribing practices. RESULTS: Sixty percent (179/300) of sampled members responded. Respondents reported prescribing a median of 26 (5-80) pills per patient across all indications combined. Ninety-eight percent prescribed opioids after surgery and a smaller proportion for nonsurgical indications: vaginal birth (22%), ovarian cysts (30%), endometriosis (24%), and chronic pelvic pain of unknown cause (18%). The number prescribed varied only by indication for the prescription. Nineteen percent reported adherence to three or more (of four) recommended practices. There was no significant difference in the median number of pills prescribed between those who reported adherence to at least one compared with those who did not adhere to any recommended practices (25 [interquartile range 25-30] vs 28 [interquartile range 20-30], P=.58). Regarding knowledge, 81% incorrectly identified the main source of misused opioids, which is through diversion from a friend or family member, and 44% did not know how to properly dispose of unused prescription opioids. CONCLUSION: Obstetrician-gynecologists reported prescribing a median of 26 opioid pills across all indications combined. Amount prescribed varied widely by indication but not by reported adherence to recommended prescribing practices. This study highlights an urgent need for increased efforts to improve ob-gyns' knowledge of opioid use, misuse, disposal, and best prescribing practices.

Gender Differences in Scholarly Productivity Within Academic Gynecologic Oncology Departments.

OBJECTIVE: To estimate whether there is a gender difference in scholarly productivity among academic gynecologic oncologists. METHODS: In this cross-sectional study, the academic rank and gender of gynecologic oncology faculty in the United States were determined from online residency and fellowship directories and departmental web sites. Each individual's h-index and years of publication were determined from Scopus (a citation database of peer-reviewed literature). The h-index is a quantification of an author's scholarly productivity that combines the number of publications with the number of times the publications have been cited. We generated descriptive statistics and compared rank, gender, and productivity scores. RESULTS: Five hundred seven academic faculty within 137 U.S. teaching programs were identified. Of these, 215 (42%) were female and 292 (58%) were male. Men had significantly higher median h-indices than women, 16 compared with 8, respectively (P<.001). Women were more likely to be of junior academic rank with 63% of assistant professors being female compared with 20% of full professors. When stratifying h-indices by gender and academic rank, men had significantly higher h-indices at the assistant professor level (7 compared with 5, P<.001); however, this difference disappeared at the higher ranks. Stratifying by the years of active publication, there was no significant difference between genders. CONCLUSION: Female gynecologic oncologists at the assistant professor level had lower scholarly productivity than men; however, at higher academic ranks, they equaled their male counterparts. Women were more junior in rank, had published for fewer years, and were underrepresented in leadership positions. LEVEL OF EVIDENCE: III.

Third-Trimester Prenatal Syphilis Screening: A Cost-Effectiveness Analysis.

OBJECTIVE: To estimate the cost to prevent one case of congenital syphilis or fetal or neonatal death with universal third-trimester syphilis rescreening in the United States and to estimate the incidence of syphilis seroconversion at which rescreening becomes cost-effective. METHODS: We created a decision model comparing universal third-trimester syphilis rescreening in women who screened negative in the first trimester with no rescreening. The assumed base case incidence of seroconversion was 0.012%. The primary outcome was the cost to prevent one case of congenital syphilis. Secondary outcomes included the cost to prevent one fetal or neonatal death and the number needed to rescreen to prevent one adverse outcome. A strategy was considered cost-effective if it cost less than $285,000 to prevent one case of congenital syphilis (the estimated long-term care cost). RESULTS: Under our assumptions, universal third-trimester rescreening would cost an additional $419,842 for each case of congenital syphilis prevented and $3,621,144 and $6,052,534, respectively, for each fetal and neonatal death prevented. Rescreening 4,000,000 women would prevent 60 cases of congenital syphilis and seven fetal and four neonatal deaths. Prevention of one case of congenital syphilis would require 65,790 women be rescreened. Seroconversion incidence of 0.017% would make third-trimester rescreening cost-effective. CONCLUSION: Universal third-trimester syphilis rescreening requires a large number of women be rescreened at a high health care cost to prevent one adverse outcome from maternal syphilis. Seroconversion incidence must be 19-fold higher than the national average of primary and secondary syphilis in women for universal third-trimester rescreening to be cost-effective.