Search

Objective: To evaluate the sensitivity of human papillomavirus (HPV) tested urine to detect high‐grade cervical precancer (cervical intraepithelial neoplasia grade 2+ [CIN2+]) using two urine collection devices. Design: Randomised controlled trial. Setting: St Mary's Hospital, Manchester, UK. Population: Colposcopy attendees with abnormal cervical screening; a total of 480 participants were randomised. Matched urine and cervical samples were available for 235 and 230 participants using a first‐void urine (FVU)‐collection device and standard pot, respectively. Methods: Urine was self‐collected and mixed with preservative – randomised 1:1 to FVU‐collection device (Novosanis Colli‐pee® 10 mL with urine conservation medium [UCM]) or standard pot. Matched clinician‐collected cervical samples were taken before colposcopy. HPV testing used Roche cobas® 8800. A questionnaire evaluated urine self‐sampling acceptability. Main outcome measures: The primary outcome measured sensitivity of HPV‐tested urine (FVU‐collection device and standard pot) for CIN2+ detection. Secondary outcomes compared HPV‐tested cervical and urine samples for CIN2+ and evaluated the acceptability of urine self‐sampling. Results: Urine HPV test sensitivity for CIN2+ was higher with the FVU‐collection device (90.3%, 95% CI 83.7%–94.9%, 112/124) than the standard pot (73.4%, 95% CI 64.7%–80.9%, 91/124, p = 0.0005). The relative sensitivity of FVU‐device‐collected urine was 0.92 (95% CI 0.87–0.97, pMcN = 0.004) compared with cervical, considering that all women were referred after a positive cervical HPV test. Urine‐based sampling was acceptable to colposcopy attendees. Conclusions: Testing of FVU‐device‐collected urine for HPV was superior to standard‐pot‐collected urine in colposcopy attendees and has promising sensitivity for CIN2+ detection. General population HPV testing of FVU‐device‐collected urine will establish its clinical performance and acceptability as an alternative to routine cervical screening. [ABSTRACT FROM AUTHOR]

Objectives: Develop an endometrial cancer risk prediction model and externally validate it for UK primary care use. Design: Cohort study. Setting: The UK Biobank was used for model development and a linked primary (Clinical Practice Research Datalink, CPRD) and secondary care (HES), mortality (ONS) and cancer register (NRCAS) dataset was used for external validation. Population: Women aged 45–60 years with no history of endometrial cancer or hysterectomy. Methods: Model development was performed using a flexible parametric survival model and stepwise backward selection aiming to minimise the Akaike information criterion. Model performance on external validation was assessed through flexible calibration plots, calculation of the expected to observed ratio and C‐statistic and decision curve analysis. Main outcome measures: Endometrial cancer diagnosis within 1–10 years of the index date. Results: Model development included 222 031 women (902 incident endometrial cancer cases) and external validation 3 094 371 women (8585 endometrial cancer cases). The final model (with equation provided) incorporated age, body mass index, waist circumference, age at menarche, menopause and last birth, hormone replacement, tamoxifen and oral contraceptive pill use, type 2 diabetes, smoking and family history of bowel cancer. It was well calibrated on external validation (calibration slope 1.14, 95% confidence interval [CI] 1.11–1.17, E/O 1.03, 95% CI 1.01–1.05), with moderate/good discrimination (C‐statistic 0.70, 95% CI 0.69–0.70) and had improved net benefit compared with previously developed models. Conclusions: The Predicting risk of endometrial cancer in asymptomatic women model (PRECISION), using easily measurable anthropometric, reproductive, personal and family history, accurately quantifies a woman's 10‐year risk of endometrial cancer. Its use could determine eligibility for primary endometrial cancer prevention trials and for targeted resource allocation in UK general practices. [ABSTRACT FROM AUTHOR]

Objective: To understand whether self‐sampling can reduce carbon emissions (CO2e) from the NHS cervical screening programme (NHSCSP) by comparing the carbon footprint of three sampling strategies: routine cervical sampling, vaginal self‐sampling and first‐void (FV) urine collection. Design: Descriptive study. Setting: National Health Service (NHS), United Kingdom (UK). Population or Sample: Patients aged 25–64 years eligible for cervical screening in the UK. Methods: A carbon footprint analysis was undertaken for three cervical screening sampling approaches, from point of invitation to screening through to preparation for transport to the laboratory for HPV testing. A combination of primary and secondary data were used, with a bottom‐up approach applied to collection of primary data. Main Outcome Measures: We report CO2e per sampling approach, which is the unit used to express carbon footprint and harmonise the contributions of greenhouse gases with different global warming potentials. Results: The total carbon footprint of routine cervical sampling is 3670 g CO2e. By comparison, vaginal self‐sampling had a total carbon footprint of 423 g CO2e, and FV urine sampling 570 g CO2e. The largest share of emissions for routine sampling was attributable to the carbon footprint associated with an appointment in a primary care setting, which totalled 2768 g CO2e. Conclusions: Routine cervical sampling is up to 8.7‐fold more carbon‐intensive than self‐sampling approaches with equivalent effectiveness. We found negligible differences in the carbon footprint of alternative self‐sampling methods, supporting the need for an informed choice of screening options for participants, which includes sharing information on their environmental impacts. [ABSTRACT FROM AUTHOR]

Women at high inherited risk of ovarian cancer are offered risk‐reducing salpingo‐oophorectomy (RRSO) from age 35 to 45 years. Although potentially life‐saving, RRSO may induce symptoms that negatively affect quality of life and impair long‐term health. Clinical care following RRSO is often suboptimal. This scoping review describes how RRSO affects short‐ and long‐term health and provides evidence‐based international consensus recommendations for care from preoperative counselling to long‐term disease prevention. This includes the efficacy and safety of hormonal and non‐hormonal treatments for vasomotor symptoms, sleep disturbance and sexual dysfunction and effective approaches to prevent bone and cardiovascular disease. [ABSTRACT FROM AUTHOR]

The article discusses the importance of a life course approach in addressing the unmet health needs of women. It emphasizes the need for collaboration among various stakeholders, including men, to achieve maximum impact. The article highlights several studies published in BJOG that explore different aspects of women's health, such as fetal health indicators, prevention of preterm preeclampsia, interventions to reduce neurodisability in preterm infants, prevention of maternal and neonatal sepsis, management of post-partum hemorrhage, and the impact of vulval lichen sclerosis on pregnancy and postpartum. The article also covers topics like uterine transplantation, medical management of missed miscarriage, cost-effectiveness of treatments for pelvic organ prolapse, triage alternatives for cervical cancer screening, the association between paracetamol use and ovarian cancer risk, and the use of artificial intelligence in medical education. The author emphasizes the importance of prioritizing women's health and involving all stakeholders in research and healthcare services. [Extracted from the article]

Objective: To investigate serum human epididymis‐4 (HE4) as a predictive biomarker of intrauterine progestin response in endometrial cancer and atypical endometrial hyperplasia (AEH). Design: Prospective prognostic factor study. Setting Consecutive sample of women attending a tertiary gynaecological oncology centre in northwest England. Population Women with AEH or early‐stage, low‐grade endometrial cancer who were unfit for or declined primary surgical management. Methods: A total of 76 women, 32 with AEH and 44 with endometrial cancer, were treated with a levonorgestrel intrauterine system (LNG‐IUS) for 12 months. Endometrial biopsies and imaging were performed to assess treatment response. Pretreatment serum HE4 was analysed by chemiluminescence immunoassay and diagnostic accuracy and logistic regression analyses were performed. Main Outcome Measures: Progestin response at 12 months defined by histology and imaging. Results: The median age and body mass index (BMI) of the final cohort were 52 years (interquartile range [IQR] 33–62 years) and 46 kg/m2 (IQR 38–54 kg/m2), respectively. Baseline serum HE4 was significantly higher in non‐responders than responders (119.2 pmol/L, IQR 94.0–208.4 pmol/L versus 71.8 pmol/L, IQR 56.1–84.2 pmol/L, p < 0.001). Older age (odds ratio [OR] 0.96, 95% CI 0.93–0.99, p = 0.02), baseline serum HE4 (OR 0.97, 95% CI 0.96–0.99, p = 0.001) and endometrial cancer histology (OR 0.22, 95% CI 0.72–0.68, p = 0.009) were associated with a lower likelihood of progestin treatment response. Serum HE4 remained independently associated with progestin treatment failure when adjusted for age and histology (adjusted hazard ratio 0.97, 95% CI 0.96–0.99, p = 0.008). Conclusion: Serum HE4 shows promise as a predictive biomarker of progestin treatment response in endometrial cancer and AEH. [ABSTRACT FROM AUTHOR]

The incidence of endometrial cancer is rising. Measures to identify women at risk and to detect endometrial cancer earlier are required to reduce the morbidity triggered by the aggressive treatment required for advanced endometrial cancer. We developed the WID‐EC (Women's cancer risk IDentification‐Endometrial Cancer) test, which is based on DNA methylation at 500 CpG sites, in a discovery set of cervical liquid‐based cytology samples from 1086 women with and without an endometrial cancer (217 cancer cases and 869 healthy controls) with a worse prognosis (grade 3 or ≥stage IB). We validated the WID‐EC test in an independent external validation set of 64 endometrial cancer cases and 225 controls. We further validated the test in 150 healthy women (prospective set) who provided a cervical sample as part of the routine Swedish cervical screening programme, 54 of whom developed endometrial cancer within 3 years of sample collection. The WID‐EC test identified women with endometrial cancer with a receiver operator characteristic area under the curve (AUC) of 0.92 (95% CI: 0.88‐0.97) in the external set and of 0.82 (95% CI: 0.74‐0.89) in the prospective validation set. Using an optimal cutoff, cancer cases were detected with a sensitivity of 86% and a specificity of 90% in the external validation set, and a sensitivity and specificity of 52% and 98% respectively in the prospective validation set. The WID‐EC test can identify women with or at risk of endometrial cancer. [ABSTRACT FROM AUTHOR]

The article discusses various topics related to obstetrics and gynecology, emphasizing the importance of the principle "first do no harm." It explores controversies surrounding procedures for urinary incontinence and pelvic organ prolapse, as well as the escalating rates of caesarean deliveries globally. The long-term impacts of interventions, such as caesarean deliveries and bariatric surgery, are also examined. Additionally, the article addresses the risks and outcomes associated with the COVID-19 pandemic in relation to pregnancy. The importance of patient-centered care, education, and innovation in improving healthcare outcomes is highlighted. The article concludes by emphasizing the need for evidence-based medicine and research to guide healthcare practices. [Extracted from the article]

Ovarian cancer (OC) is the least survivable gynecological malignancy and presents late. Five‐year survival for OC is around 45% increasing the need for innovative treatments. Checkpoint inhibitors have shown significant clinical efficacy in mismatch repair deficient (MMRd) cancers and could be a powerful treatment in OC. However, their application in OC is limited due to the lack of data on the prevalence of MMRd. The aim of our study was to conduct a systematic review of the literature and meta‐analysis to provide an accurate estimate of the prevalence of MMRd in OC. We followed PRISMA guidelines throughout. Studies were identified by electronic searches of Medline, Embase, Cochrane CENTRAL and Web of Science followed by citation searching. Studies not written in English were excluded. All studies were reviewed by at least two independent reviewers. Proportions of test positivity were calculated by random and fixed‐effects meta‐analysis models. I2 score was used to assess heterogeneity across studies. In total 54 studies were included with 17 532 analyzed for MMRd. The overall proportions of MMRd by immunohistochemistry and microsatellite instability analysis were 6.7% and 10.4%, respectively. MMRd was reported in all histotypes of epithelial OC but was most common in endometrioid OC. We estimate that on average 46.7% (95% CI: 28.8‐65.4) of ovarian carcinomas showing MMRd by IHC had a germline path_MMR variant identified. OC in those with Lynch syndrome seems to present at an earlier age and stage. Studies however were generally of low quality and there was a high degree of heterogeneity. A significant minority (up to 16%) of OC displays MMRd and, therefore, could be amenable to checkpoint inhibition therapy. However, the current literature base is of limited quality and therefore high‐quality prospective studies exploring MMRd in OC with the use of multimodal testing are required. In addition, trials researching efficacy of checkpoint inhibition in MMRd OC are needed. [ABSTRACT FROM AUTHOR]

Defective DNA mismatch repair (dMMR) causes elevated tumour mutational burden (TMB) and microsatellite instability (MSI) in multiple cancer types. dMMR/MSI colorectal cancers (CRCs) have enhanced T‐cell infiltrate and favourable outcome; however, this association has not been reliably detected in other tumour types, including endometrial cancer (EC). We sought to confirm this and explore the underpinning mechanisms. We first meta‐analysed CRC and EC trials that have examined the prognostic value of dMMR/MSI and confirmed that dMMR/MSI predicts better prognosis in CRC, but not EC, with statistically significant variation between cancers (hazard ratio [HR] = 0.63, 95% confidence interval [CI] = 0.54–0.73 versus HR = 1.15, 95% CI = 0.72–1.58; PINT = 0.02). Next, we studied intratumoural immune infiltrate in CRCs and ECs of defined MMR status and found that while dMMR was associated with increased density of tumour‐infiltrating CD3+ and CD8+ T‐cells in both cancer types, the increases were substantially greater in CRC and significant only in this group (PINT = 4.3e‐04 and 7.3e‐03, respectively). Analysis of CRC and EC from the independent Cancer Genome Atlas (TCGA) series revealed similar variation and significant interactions in proportions of tumour‐infiltrating lymphocytes, CD8+, CD4+, NK cells and immune checkpoint expression, confirming a more vigorous immune response to dMMR/MSI in CRC than EC. Agnostic analysis identified the IFNγ pathway activity as strongly upregulated by dMMR/MSI in CRC, but downregulated in EC by frequent JAK1 mutations, the impact of which on IFNγ response was confirmed by functional analyses. Collectively, our results confirm the discordant prognosis of dMMR/MSI in CRC and EC and suggest that this relates to differences in intratumoural immune infiltrate and tumour genome. Our study underscores the need for tissue‐specific analysis of cancer biomarkers and may help inform immunotherapy use. © 2022 The Authors. The Journal of Pathology published by John Wiley & Sons Ltd on behalf of The Pathological Society of Great Britain and Ireland. [ABSTRACT FROM AUTHOR]

BRIP1 is a moderate susceptibility epithelial ovarian cancer (EOC) gene. Having identified the BRIP1 c.1045G>C missense variant in a number of families with EOC, we aimed to investigate the frequency of this and BRIP1.2392C>T pathogenic variant in patients with breast cancer (BC) and/or EOC. A case‐control study of 3767 cases and 2043 controls was undertaken investigating the presence of these variants using Sanger sequencing and gene panel data. Individuals with BC and/or EOC were grouped by family history. BRIP1 c.1045G>C was associated with increased risk of BC/EOC (OR = 37.7; 95% CI 5.3–444.2; P = 0.0001). The risk was highest for women with EOC (OR = 140.8; 95% CI 23.5–1723.0; P < 0.0001) and lower for BC (OR = 11.1; 95% CI 1.2–106.5; P = 0.1588). BRIP1 c.2392C>T was associated with smaller risks for BC/EOC (OR = 5.4; 95%CI 2.4–12.7; P = 0.0003), EOC (OR = 5.9; 95% CI 1.3–23.0; p = 0.0550) and BC (OR = 5.3; 95%CI 2.3–12.9; P = 0.0009). Our study highlights the importance of BRIP1 as an EOC susceptibility gene, especially in familial EOC. The variant BRIP1 c.1045G>C, rs149364097, is of particular interest as its dominant‐negative effect may confer a higher risk of EOC than that of the previously reported BRIP1 c.2392C>T nonsense variant. Dominant‐negative missense variants may confer higher risks than their loss‐of‐function counterparts. [ABSTRACT FROM AUTHOR]

Prediction models have clinical utility to identify those at higher risk of a particular adverse health outcome, allowing us to direct limited resources towards these individuals, whilst minimising unnecessary morbidity to those at negligible risk. I "Of all the forms of inequality, injustice in health is the most shocking and inhumane." i I Martin Luther King Jr i Health inequities are 'systematic differences in the opportunities groups have to achieve optimal health, leading to unfair and avoidable differences in health outcomes' ([1]). [Extracted from the article]

Key content: Endometrial cancer (EC) is the most common gynaecological cancer in the UK.Ninety percent of women with EC present with postmenopausal bleeding (PMB), but less than 10% of women with PMB have a sinister underlying cause.National Institute for Health and Care Excellence guidance advises that symptomatic postmenopausal women undergo urgent investigation; however, guidance is unclear for premenopausal women.Current investigations for PMB, including transvaginal ultrasound scan, endometrial biopsy and/or outpatient hysteroscopy, have advantages and disadvantages.Novel detection tools are in development, which combine minimally invasive sampling with genomic, proteomic and single cell technologies. Learning objectives: To understand who is at risk of EC and who should be referred for urgent investigations.To understand the evidence underpinning the current diagnostic pathway for EC.To highlight unique and promising perspectives for EC detection and their potential to transform clinical care. Ethical issues: Current diagnostics for EC are invasive and often painful. There is an urgent need for high‐quality randomised controlled trials to inform effective pain relief options.Premenopausal women with suspected EC do not fit criteria for urgent investigations. How can we identify those at highest risk to ensure they are fast‐tracked appropriately?Novel diagnostic tools hold promise, but they must be robustly validated before being introduced into clinical practice. [ABSTRACT FROM AUTHOR]

Risk‐reducing bilateral salpingo‐oophorectomy (RRBSO) is highly effective for the prevention of high‐grade serous ovarian cancer (HGSOC) in BRCA1/2 pathogenic variant carriers (PVCs), but does not completely eliminate future risk of primary peritoneal cancer (PPC). The requirement to completely remove fallopian tubes at RRBSO and carefully exclude occult cancer/serous tubal intraepithelial carcinoma (STIC) lesions may not have been appreciated historically. We calculated rates of HGSOC and PPC in confirmed BRCA1/2 PVCs registered on the regional database in those who did (cases) and did not (controls) undergo RRBSO after genetic testing. Expected annual rates of ovarian/peritoneal cancer were 1% for BRCA1 ≥ 35 years and 0.5% for BRCA2 ≥ 45 years. Follow‐up before 35/45 years was "risk free" and lead time excluded RRBSO <35 years and <45 years for BRCA1 and BRCA2, respectively. Women were followed from personal mutation report (controls) or RRBSO (cases) to death, ovarian/peritoneal cancer or last follow‐up, whichever was sooner. In total, 891 cases (BRCA1 = 468, BRCA2 = 423) and 1302 controls had follow‐up ≥35 years (BRCA1 = 736) and ≥45 years (BRCA2 = 566), respectively, over a total of 7261.1 risk eligible years (mean = 8.15 years). Twenty‐one occult ovarian cancers were found at RRBSO (2.4%), 16 at stage 1. Post RRBSO, 56.97 ovarian/peritoneal cancers were expected but only 3 were observed (HR = 0.053; 95% CI = 0.013‐0.14), with combined Kaplan‐Meier analysis HR = 0.029 (95% CI = 0.009‐0.100, P <.001). Risk reduction was greater in specialist (HR = 0.03; 95% CI = 0.001‐0.13) compared to non‐specialist centres (HR = 0.11; 95% CI = 0.02‐0.37) (P =.07). In controls, 23.35 ovarian/peritoneal cancers were expected with 32 observed (HR = 1.37; 95% CI = 0.95‐1.91). RRBSO <35/<45 years reduces the risk of ovarian/peritoneal cancer by 95% in BRCA1/2 PVCs and may be greater in specialist centres. What's new? Women who carry genetic variants in BRCA1/2 that are linked to high‐grade serous ovarian cancer are advised to undergo risk‐reducing prophylactic bilateral salpingo‐oophorectomy (RRBSO). RRBSO, however, is associated with a significant residual risk of primary peritoneal cancer (PPC). Here, the rate of PPC following prophylactic surgery for high‐grade serous ovarian cancer was investigated among 2,193 BRCA1/2 mutation carriers who had undergone RRBSO. Estimates indicate that prophylactic surgery reduced the overall risk of PPC by 95 percent, a far greater reduction than previously described. Residual risk was lowest when RRBSO was carried out at specialist centers compared to non‐specialist centers. [ABSTRACT FROM AUTHOR]

Key content: Lynch syndrome is an autosomal dominant condition closely associated with colorectal, endometrial and ovarian cancer.Women with Lynch syndrome are at increased risk of both endometrial and ovarian cancer and should be offered personalised counselling regarding family planning, red flag symptoms and risk‐reducing strategies.Surveillance for gynaecological cancer in women with Lynch syndrome remains controversial; more robust data are needed to determine its effectiveness.Universal testing for Lynch syndrome in endometrial cancer is being adopted by centres across Europe and is now recommended by the National Institute for Health and Care Excellence; thus, gynaecologists must become familiar with testing strategies and their results.Testing strategies involve risk stratification of cancers based on phenotypical features and definitive germline testing. Learning objectives: To define the pathogenesis of Lynch syndrome and its associated gynaecological cancers.To understand the testing strategies for Lynch syndrome in women with gynaecological cancer.To learn how best to counsel women with Lynch syndrome regarding gynaecological cancer and risk‐reducing strategies to enable informed decision‐making. Ethical issues: Offering gynaecological surveillance despite a lack of robust evidence for its clinical effectiveness may falsely reassure women and delay risk‐reducing hysterectomy.Genetic testing may yield variants of unknown significance with ill‐defined clinical implications, which can lead to confusion and anxiety.Genetic testing has implications not only for the individual, but also for the whole family, so expert counselling is crucial. [ABSTRACT FROM AUTHOR]

Ovarian cancer is the fourth most common cause of cancer‐related death in women in the developed world, and one of the most heritable cancers. One of the most significant risk factors for epithelial ovarian cancer (EOC) is a family history of breast and/or ovarian cancer. Combined risk factors can be used in models to stratify risk of EOC, and aid in decisions regarding risk‐reduction strategies. Germline pathogenic variants in EOC susceptibility genes including those involved in homologous recombination and mismatch repair pathways are present in approximately 22% to 25% of EOC. These genes are associated with an estimated lifetime risk of EOC of 13% to 60% for BRCA1 variants and 10% to 25% for BRCA2 variants, with lower risks associated with remaining genes. Genome‐wide association studies have identified single nucleotide polymorphisms (SNPs) thought to explain an additional 6.4% of the familial risk of ovarian cancer, with 34 susceptibility loci identified to date. However, an unknown proportion of the genetic component of EOC risk remains unexplained. This review comprises an overview of individual genes and SNPs suspected to contribute to risk of EOC, and discusses use of a polygenic risk score to predict individual cancer risk more accurately. [ABSTRACT FROM AUTHOR]

Aims: Lynch syndrome (LS) is associated with an increased risk of developing endometrial carcinoma (EC) and ovarian carcinoma (OC). There is considerable variability in current practices and opinions related to screening of newly diagnosed patients with EC/OC for LS. An online survey was undertaken to explore the extent of these differences. Methods and results: An online questionnaire was developed by a panel of experts and sent to all members of the British Association of Gynaecological Pathologists (BAGP) and the International Society of Gynecological Pathologists (ISGyP). Anonymised results were received and analysed. Thirty‐six BAGP and 44 ISGyP members completed the survey. More than 90% of respondents were aware of the association of LS with both EC and OC, but 34% were not aware of specific guidelines for LS screening. Seventy‐one per cent of respondents agreed that universal screening for LS should be carried out in all newly diagnosed EC cases, with immunohistochemistry (IHC) alone as the preferred approach. Only 36% of respondents currently performed IHC or microsatellite instability testing on all newly diagnosed EC cases, with most of the remaining respondents practising selective screening, based on clinical or pathological features or both. A significant minority of respondents (35%) believed that patient consent was required before performance of mismatch repair (MMR) protein IHC. Almost all respondents favoured the use of standardised terminology for reporting MMR protein staining results, and this is proposed herein. Conclusion: There is wide support for universal LS screening in patients with EC, but this survey highlights areas of considerable variation in practice. [ABSTRACT FROM AUTHOR]

Key content: Of the 20 most common tumour types, endometrial cancer has the strongest association with obesity.Endometrial cancer should be considered in young, obese women with irregular or heavy menstrual bleeding.To reduce the risk of postoperative complications, surgery for endometrial cancer should be performed using minimal access techniques whenever possible.For women who are unfit for, or who decline, surgery, alternative treatments include progestins or radiotherapy, but these have lower efficacy and are associated with a higher risk of disease relapse.Obesity is associated with reduced overall survival following endometrial cancer because of increased cardiovascular mortality; it may also affect disease‐specific survival. Learning objectives: To further understanding of the mechanisms through which obesity drives endometrial carcinogenesis.To improve understanding of the potential difficulties associated with the management of endometrial cancer in obese women.To increase knowledge of alternative treatment options for women who are unfit for, or who decline, standard endometrial cancer management. Ethical issues: The number of young, premenopausal women with endometrial cancer is increasing – how should these women be managed?Should super‐obese women with endometrial cancer only be treated in cancer centres?After treating a woman's endometrial cancer, how should she be counselled her about her weight and cardiovascular disease risk? [ABSTRACT FROM AUTHOR]

Obesity is the strongest risk factor for endometrial cancer (EC). To inform targeted screening and prevention strategies, we assessed the impact of obesity and subsequent bariatric surgery‐induced weight loss on endometrial morphology and molecular pathways implicated in endometrial carcinogenesis. Blood and endometrial tissue were obtained from women with class III–IV obesity (body mass index ≥40 and ≥50 kg/m2, respectively) immediately prior to gastric bypass or sleeve gastrectomy, and at two and 12 months' follow up. The endometrium underwent pathological examination and immunohistochemistry was used to quantify proliferation (Ki‐67), oncogenic signaling (PTEN, pAKT, pERK) and hormone receptor (ER, PR) expression status. Circulating biomarkers of insulin resistance, reproductive function and inflammation were also measured at each time point. Seventy‐two women underwent bariatric surgery. At 12 months, the mean change in total and excess body weight was −32.7 and −62.8%, respectively. Baseline endometrial biopsies revealed neoplastic change in 10 women (14%): four had EC, six had atypical hyperplasia (AH). After bariatric surgery, most cases of AH resolved (5/6) without intervention (3/6) or with intrauterine progestin (2/6). Biomarkers of endometrial proliferation (Ki‐67), oncogenic signaling (pAKT) and hormone receptor status (ER, PR) were significantly reduced, with restoration of glandular PTEN expression, at 2 and 12 months. There were reductions in circulating biomarkers of insulin resistance (HbA1c, HOMA‐IR) and inflammation (hsCRP, IL‐6), and increases in reproductive biomarkers (LH, FSH, SHBG). We found an unexpectedly high prevalence of occult neoplastic changes in the endometrium of women undergoing bariatric surgery. Their spontaneous reversal and accompanying down‐regulation of PI3K‐AKT–mTOR signaling with weight loss may have implications for screening, prevention and treatment of this disease. What's new? Obesity is a major risk factor for endometrial cancer (EC). In this study, the authors found that, in obese women, bariatric surgery‐induced weight loss resulted in significant, beneficial changes in circulating biomarkers of insulin resistance, inflammation, and reproductive hormones, in endometrial morphology, and in molecular pathways that are implicated in endometrial carcinogenesis. The latter included changes in Ki‐67 expression and activation of the PI3K‐AKT‐mTOR oncogenic signaling pathway, including PTEN and pAKT. These results may have important implications for screening, prevention and treatment of EC. [ABSTRACT FROM AUTHOR]

Objective Women with a prior history of polycystic ovary syndrome ( PCOS) have an increased risk of endometrial cancer ( EC). Aim To investigate whether the endometrium of women with PCOS possesses gene expression changes similar to those found in EC. Design and Methods Patients with EC, PCOS and control women unaffected by either PCOS or EC were recruited into a cross-sectional study at the Nottingham University Hospital, UK. For RNA sequencing, representative individual endometrial biopsies were obtained from women with EC, PCOS and a woman unaffected by PCOS or EC. Expression of a subset of differentially expressed genes identified by RNA sequencing, including NAD(P)H quinone dehydrogenase 1 ( NQO1), was validated by quantitative reverse transcriptase PCR validation (n = 76) and in the cancer genome atlas UCEC (uterine corpus endometrioid carcinoma) RNA sequencing data set (n = 381). The expression of NQO1 was validated by immunohistochemistry in EC samples from a separate cohort (n = 91) comprised of consecutive patients who underwent hysterectomy at St Mary's Hospital, Manchester, between 2011 and 2013. A further 6 postmenopausal women with histologically normal endometrium who underwent hysterectomy for genital prolapse were also included. Informed consent and local ethics approval were obtained for the study. Results We show for the first that NQO1 expression is significantly increased in the endometrium of women with PCOS and EC. Immunohistochemistry confirms significantly increased NQO1 protein expression in EC relative to nonmalignant endometrial tissue ( P < .0001). Conclusions The results obtained here support a previously unrecognized molecular link between PCOS and EC involving NQO1. [ABSTRACT FROM AUTHOR]

Urocortin ( UCN1) peptide shares structural and functional homology with corticotropin-releasing factor ( CRF). UCN1 is significantly reduced in endometrial adenocarcinoma compared to healthy controls. However, there are no data which evaluate the effects of UCN1 in the endometrium, or how it is modulated. We used proliferation and transwell assays to determine the effect of UCN1 on the proliferation and migration of Ishikawa and HEC1A cells. We also determined the expression levels of UCN1 and its receptors produced by estrogen receptor agonists, and the effect of UCN1 on estrogen receptor expression, using quantitative polymerase chain reaction. UCN1 suppressed migration of endometrial cancer cells in vitro. This effect appears to be specific to CRF receptor 2 ( CRFR2), as selective antagonism of CRFR2 but not CRFR1 completely eliminated suppression of migration. Activation of ERA reduced UCN1 expression, but only had a small effect on the expression of CRFR1. However, expression of CRFR2 was more notably reduced at both the m RNA and protein levels by activation of ERB. UCN1 in turn reduced both ERA and ERB expression, as assessed by real-time quantitative PCR. We demonstrate that UCN1 significantly suppresses the migration of endometrial cancer cells but has no effect on their proliferation. Thus, loss of UCN1 in endometrial cancer may promote invasion and metastatic spread. There is a complex relationship between the UCN1 system and estrogen receptors, which may provide insights into endometrial carcinogenesis, a disease known to be driven by estrogen excess. [ABSTRACT FROM AUTHOR]

Endometrial cancer (EC) is the most common gynaecological malignancy in the developed world, and obesity is its strongest risk factor. Thus, by delivering high intrauterine but low systemic progestin levels, Mirena is the ideal drug delivery system for obese women with early-stage EC whose medical fitness or fertility requirements prohibit safe surgery. [Extracted from the article]

A correction is presented to the article "Expression of NAD(P)H quinone dehydrogenase 1 (NQO1) is increased in the endometrium of women with endometrial cancer and women with polycystic ovary syndrome" which appeared in the November 2017 issue.

The article focuses on the regulation in Great Britain which states that refusal of surgery for mild conditions to morbidly and super obese (MORSO) women is morally and legally wrong. Topics discussed include the effects of several medical conditions to the patients quality of life including heavy menstrual bleeding, chronic pelvic pain, and stress urinary incontinence, the surgery management, and the effects of gynaecological diseases such as psychological distress and social isolation.

This article discusses a pilot clinical study that explores the use of measuring human epididymis protein 4 (HE4) alongside CA125 for the diagnosis of ovarian cancer. The study found that elevated levels of HE4 were present in cases of ovarian cancer and other conditions such as hepatic cirrhosis. The authors suggest that further research is needed to determine if measuring both markers can improve the diagnostic performance of the standard pathway for ovarian cancer detection. The study was funded by various organizations and approved by the Cambridge East Research Ethics Committee. [Extracted from the article]

Objective: To evaluate the sensitivity of human papillomavirus (HPV) tested urine to detect high-grade cervical precancer (cervical intraepithelial neoplasia grade 2+ [CIN2+]) using two urine collection devices., Design: Randomised controlled trial., Setting: St Mary's Hospital, Manchester, UK., Population: Colposcopy attendees with abnormal cervical screening; a total of 480 participants were randomised. Matched urine and cervical samples were available for 235 and 230 participants using a first-void urine (FVU)-collection device and standard pot, respectively., Methods: Urine was self-collected and mixed with preservative - randomised 1:1 to FVU-collection device (Novosanis Colli-pee® 10 mL with urine conservation medium [UCM]) or standard pot. Matched clinician-collected cervical samples were taken before colposcopy. HPV testing used Roche cobas® 8800. A questionnaire evaluated urine self-sampling acceptability., Main Outcome Measures: The primary outcome measured sensitivity of HPV-tested urine (FVU-collection device and standard pot) for CIN2+ detection. Secondary outcomes compared HPV-tested cervical and urine samples for CIN2+ and evaluated the acceptability of urine self-sampling., Results: Urine HPV test sensitivity for CIN2+ was higher with the FVU-collection device (90.3%, 95% CI 83.7%-94.9%, 112/124) than the standard pot (73.4%, 95% CI 64.7%-80.9%, 91/124, p = 0.0005). The relative sensitivity of FVU-device-collected urine was 0.92 (95% CI 0.87-0.97, p McN  = 0.004) compared with cervical, considering that all women were referred after a positive cervical HPV test. Urine-based sampling was acceptable to colposcopy attendees., Conclusions: Testing of FVU-device-collected urine for HPV was superior to standard-pot-collected urine in colposcopy attendees and has promising sensitivity for CIN2+ detection. General population HPV testing of FVU-device-collected urine will establish its clinical performance and acceptability as an alternative to routine cervical screening., (© 2024 The Authors. BJOG: An International Journal of Obstetrics and Gynaecology published by John Wiley & Sons Ltd.)

Objective: To understand whether self-sampling can reduce carbon emissions (CO 2 e) from the NHS cervical screening programme (NHSCSP) by comparing the carbon footprint of three sampling strategies: routine cervical sampling, vaginal self-sampling and first-void (FV) urine collection., Design: Descriptive study., Setting: National Health Service (NHS), United Kingdom (UK)., Population or Sample: Patients aged 25-64 years eligible for cervical screening in the UK., Methods: A carbon footprint analysis was undertaken for three cervical screening sampling approaches, from point of invitation to screening through to preparation for transport to the laboratory for HPV testing. A combination of primary and secondary data were used, with a bottom-up approach applied to collection of primary data., Main Outcome Measures: We report CO 2 e per sampling approach, which is the unit used to express carbon footprint and harmonise the contributions of greenhouse gases with different global warming potentials., Results: The total carbon footprint of routine cervical sampling is 3670 g CO 2 e. By comparison, vaginal self-sampling had a total carbon footprint of 423 g CO 2 e, and FV urine sampling 570 g CO 2 e. The largest share of emissions for routine sampling was attributable to the carbon footprint associated with an appointment in a primary care setting, which totalled 2768 g CO 2 e., Conclusions: Routine cervical sampling is up to 8.7-fold more carbon-intensive than self-sampling approaches with equivalent effectiveness. We found negligible differences in the carbon footprint of alternative self-sampling methods, supporting the need for an informed choice of screening options for participants, which includes sharing information on their environmental impacts., (© 2023 The Authors. BJOG: An International Journal of Obstetrics and Gynaecology published by John Wiley & Sons Ltd.)

Women at high inherited risk of ovarian cancer are offered risk-reducing salpingo-oophorectomy (RRSO) from age 35 to 45 years. Although potentially life-saving, RRSO may induce symptoms that negatively affect quality of life and impair long-term health. Clinical care following RRSO is often suboptimal. This scoping review describes how RRSO affects short- and long-term health and provides evidence-based international consensus recommendations for care from preoperative counselling to long-term disease prevention. This includes the efficacy and safety of hormonal and non-hormonal treatments for vasomotor symptoms, sleep disturbance and sexual dysfunction and effective approaches to prevent bone and cardiovascular disease., (© 2023 The Authors. BJOG: An International Journal of Obstetrics and Gynaecology published by John Wiley & Sons Ltd.)

Objective: To investigate serum human epididymis-4 (HE4) as a predictive biomarker of intrauterine progestin response in endometrial cancer and atypical endometrial hyperplasia (AEH)., Design: Prospective prognostic factor study., Setting: Consecutive sample of women attending a tertiary gynaecological oncology centre in northwest England., Population: Women with AEH or early-stage, low-grade endometrial cancer who were unfit for or declined primary surgical management., Methods: A total of 76 women, 32 with AEH and 44 with endometrial cancer, were treated with a levonorgestrel intrauterine system (LNG-IUS) for 12 months. Endometrial biopsies and imaging were performed to assess treatment response. Pretreatment serum HE4 was analysed by chemiluminescence immunoassay and diagnostic accuracy and logistic regression analyses were performed., Main Outcome Measures: Progestin response at 12 months defined by histology and imaging., Results: The median age and body mass index (BMI) of the final cohort were 52 years (interquartile range [IQR] 33-62 years) and 46 kg/m 2 (IQR 38-54 kg/m 2 ), respectively. Baseline serum HE4 was significantly higher in non-responders than responders (119.2 pmol/L, IQR 94.0-208.4 pmol/L versus 71.8 pmol/L, IQR 56.1-84.2 pmol/L, p < 0.001). Older age (odds ratio [OR] 0.96, 95% CI 0.93-0.99, p = 0.02), baseline serum HE4 (OR 0.97, 95% CI 0.96-0.99, p = 0.001) and endometrial cancer histology (OR 0.22, 95% CI 0.72-0.68, p = 0.009) were associated with a lower likelihood of progestin treatment response. Serum HE4 remained independently associated with progestin treatment failure when adjusted for age and histology (adjusted hazard ratio 0.97, 95% CI 0.96-0.99, p = 0.008)., Conclusion: Serum HE4 shows promise as a predictive biomarker of progestin treatment response in endometrial cancer and AEH., (© 2023 The Authors. BJOG: An International Journal of Obstetrics and Gynaecology published by John Wiley & Sons Ltd.)