Endometrial cancer is the sixth commonest cancer in women worldwide, with over 417,000 diagnoses in 2020. The disease incidence has increased by 132% over the last 30 years and is set to continue to rise in response to an ageing population and increasing global rates of obesity and diabetes. A greater understanding of the mechanisms driving endometrial carcinogenesis has led to the identification of potential strategies for primary disease prevention, although prospective evaluation of their efficacy within clinical trials is still awaited. The early diagnosis of endometrial cancer is associated with improved survival, but has historically relied on invasive endometrial sampling. New, minimally invasive tests using protein and DNA biomarkers and cytology have the potential to transform diagnostic pathways and to allow for the surveillance of high-risk populations. The molecular classification of endometrial cancers has been shown to not only have a prognostic impact, but also to have therapeutic value and is increasingly used to guide adjuvant treatment decisions. Advanced and recurrent disease management has also been revolutionised by increasing the use of debulking surgery and targeted treatments, particularly immunotherapy. This review summarises the recent advances in the prevention, diagnosis and treatment of endometrial cancer and seeks to identify areas for future research.

Objectives: United Kingdom (UK) guidelines recommend delaying cervical screening due during pregnancy to 12 weeks postnatal, despite a lack of supporting evidence. This questionnaire-based study aimed to determine the feasibility of a clinical study of cervical screening and urine self-sampling for human papillomavirus (HPV) at 6 weeks postnatal, as pilot work suggested this would improve uptake, if offered at the routine postnatal check-up. Methods: Females who were pregnant/recently pregnant were invited to participate in a web-based questionnaire. Questions assessed acceptability of postnatal cervical screening at 6 weeks postnatal, analysed with chi-square, Fisher's exact and Mann–Whitney tests. Free-text responses were coded using the Theoretical Framework of Acceptability (TFA) to conduct a qualitative content analysis. Results: Among the 454 participants, 266 (58.6%) would be more likely to undergo cervical screening if offered at 6 weeks postnatal, and an even higher proportion expressed increased willingness if urine self-sampling were offered ( n = 338; 74.4%). Two-thirds (308/454; 67.8%) would be willing to be screened at 6 weeks postnatal for a research study and 356/454 (78.4%) if it would be limited only to urine self-sampling. When considering screening modality, over half (245/454; 54%) would prefer urine self-sampling to cervical screening, although a fifth (93/454; 21%) preferred conventional sampling. Free-text responses were provided by 279 participants, and these highlighted that affective attitude and burden TFA constructs underpinned prospective acceptability of having screening at 6 weeks postnatal. Conclusions: Offering cervical screening at the 6-week postnatal check-up has potential to increase cervical screening participation. Most participants would be interested in taking part in the research. The feasibility of screening at 6 weeks postnatal and concurrent acceptability should be tested in pilot clinical studies.

Despite curative treatment, an endometrial cancer (EC) diagnosis is associated with an elevated risk of death compared with age-matched women in the general population. This study aimed to quantify their risk of death from EC, cardiovascular disease, and other causes. A systematic review of Medline, Embase, and CENTRAL databases was performed to February 2024. Studies reporting cause of death after a diagnosis of EC were included. Mortality rates and 95% CIs were calculated using a random-effects model. Heterogeneity was assessed through visual inspection of forest plots and the I² statistic. Risk of bias and evidence quality were appraised using the Newcastle-Ottawa scale and Grading of Recommendations Assessment, Development and Evaluation (GRADE), respectively. The effect of ethnicity, stage, grade, and time from diagnosis was examined. In total, 22 studies including 323,551 participants were analyzed and 102,711 (31.7%) died within 20 years of diagnosis, 62.6% (n = 64,155) from non-EC causes. In the 12 studies that reported cardiovascular death, 24.6% of participants (n = 24,309) died from cardiovascular disease. Those with local disease at presentation were more likely to die from non-EC causes than those with advanced disease at presentation (48.9% vs 13.5%). A total of 2 studies reported cause of death by ethnicity; overall, Black individuals were more likely to die than individuals of White or Other ethnicities (40.8% vs 27.9% vs 18.9%). Deaths related to non-EC causes, including cardiovascular disease, overtook EC-specific deaths >5 years after diagnosis. Significant heterogeneity was noted, despite sub-group analyses, and the findings were based on very low certainty evidence. Individuals with a history of EC are at increased risk of death from other causes. Oncology follow-up appointments provide the ideal opportunity to optimize cardiovascular risk factors to reduce preventable deaths. Future research needs to reflect the global majority.

Key content: Borderline ovarian tumours (BOTs) are a diverse and heterogeneous set of diseases, which are encountered by all obstetricians and gynaecologists. They occur on average around 10 years earlier than malignant ovarian cancers and are associated with a significantly better prognosis. Preoperative diagnosis of BOTs is challenging as radiological features overlap with benign and malignant disease. There are no blood tumour markers that can delineate between benign, malignant and BOTs. Oncological safety should be maintained in surgical management. Fertility‐sparing management is acceptable but should include full surgical staging. There is no role for adjuvant treatment in the management of BOTs. Recurrence rates vary between 2 and 24% and invasive recurrence rates are low. Recurrences can occur late; therefore, follow‐up is recommended beyond 5 years of initial diagnosis. Learning objectives: To gain knowledge of the epidemiology, pathology, and biology of BOTs. To understand the radiological challenges associated with BOTs and the effect this has on planning surgical management. To understand the principles of surgical management, including fertility‐sparing surgery and the importance of a personalised approach. To appreciate the role of surveillance for BOTs including the role of ultrasound scans and tumour markers.

Introduction Cervical screening rates in the UK are falling, limiting our ability to prevent cervical cancer. Peak incidence of cervical cancer coincides with average age of childbirth, and women with young children are less likely to be screened. Current UK guidelines advise waiting 12 weeks after delivery to perform cervical screening, but this recommendation is not based on evidence from the era of liquid-based cytology or high-risk human papillomavirus (HPV) testing. New mums suggested offering cervical screening at 6 weeks postdelivery, in conjunction with the postnatal check-up with the general practice team in primary care. This study aims to assess the feasibility and acceptability of a paired-sample study design for cervical screening at 6 weeks and 12 weeks postnatal. Methods and analysis A study of 100 participants will be performed to assess feasibility and acceptability of cervical screening at both 6 weeks and 12 weeks postnatal, with urine self-sampling using a Colli-pee collection device at each time point. This will inform whether women are prepared to undergo cervical screening at 6 weeks postnatal and the feasibility of a future pair-wise diagnostic test accuracy (of HPV and abnormal cervical cytology) study or whether alternative study designs are needed. Participants must be aged 24.5–64 years old and eligible for the National Health Service Cervical Screening Programme (NHS CSP). At each appointment, participants will complete a questionnaire about their experience and thoughts regarding screening. Substudies ask participants who withdraw or decline to participate their reasons, to identify barriers. The study will be closed for recruitment once 100 participants have completed the 6-week screen in Postnatal Instead of Normally-Timed Cervical Screening (PINCS-1) or if recruitment is poor and 50% not recruited by 6 months, indicating that a paired-sample design is not feasible. Ethics and dissemination Ethical approval for PINCS-1 was given by the Stanmore Research Ethics Committee. The results, including participant feedback at each stage, built into the trial design, will inform the design of large studies to determine accuracy and clinical impact of cervical screening at 6 weeks postnatal, identifying whether giving choice (eg, from timing of appointments and/or offering self-sampling) will improve screening uptake. Data will inform the sample size needed for future studies to have adequate power. Results will also inform future NHS CSP management. Results will be shared via scientific publication and via conventional and social media channels accessed by young women. Trial registration number ISRCTN10071810.

Background: Obesity may increase endometrial cancer risk through pathways involving chronic inflammation, insulin resistance, and altered sex hormone levels. Methods: Within the European Prospective Investigation into Cancer and Nutrition cohort, we investigated these mediating pathways using prediagnostic circulating biomarkers measured in 337 matched case-control pairs with postmenopausal measurements and 196 pairs with premenopausal measurements. We estimated the natural indirect effect (NIE) of obesity (body mass index ≥30 kg/m2 vs <25 kg/m2) on endometrial cancer risk: (1) for each biomarker separately, (2) for all biomarkers jointly, and (3) sequentially, accounting for upstream biomarkers based on an assumed causal sequence specified a priori. Results: The adjusted odds ratio (OR) between obesity and endometrial cancer risk was 3.34 (95% confidence interval [CI] = 1.97 to 5.65) in the postmenopausal analysis and 3.24 (95% CI = 1.43 to 7.36) in the premenopausal analysis. Jointly, the ORNIE through all biomarkers was 1.82 (95% CI = 1.21 to 2.74; proportion mediated [PM] = 50%) in the postmenopausal analysis and 1.79 (0.97 to 3.29; 49%) in the premenopausal analysis. In sequential mediation analysis, estrone (ORNIE = 1.20, 95% CI = 1.02 to 1.41; PM = 15%) remained a key mediator beyond upstream biomarkers in the postmenopausal analysis and interleukin-6 (1.35, 1.03 to 1.78; 24%) remained a key mediator in the premenopausal analysis. Conclusions: Circulating biomarkers for inflammation, insulin resistance, and sex hormones may mediate the effect of obesity on endometrial cancer risk, with some overlaps in mediating pathways. Sex hormones were the most prominent mediators in postmenopausal obesity, whereas biomarkers for inflammation may play an important role in premenopausal obesity.