BJOG: An International Journal of Obstetrics & Gynaecology

Cervical cancer prevention in transgender men: a review

There is increased awareness of transgender physical and mental health widely and in academic research. A significant proportion of transgender men will retain their cervix with an increased risk of cervical cancer. In this review of cervical cancer screening among transgender men, we try to estimate how many transgender men still have a cervix, understand to identify challenges and barriers to cervical screening and propose possible solutions. Organised cervical screening programmes need to consider the needs of this population, in particular the provision of HPV self‐sampling.Tweetable abstractTransgender men need access to cervical screening.

Assessment of prognostic and reproductive outcomes of omentectomy for patients with clinically apparent early‐stage (I, II) malignant ovarian germ cell tumours: A multicentre retrospective study

AbstractObjectiveThis study assessed the effect of omentectomy on the prognosis and fertility in patients with clinically early‐stage (I, II) malignant ovarian germ cell tumours (MOGCT).DesignA retrospective multicentre study.SettingFour university teaching hospitals in China.PopulationA total of 268 patients with clinically apparent early‐stage (I, II) MOGCT.MethodsData were obtained from the medical records. Additionally, the propensity score matching (PSM) algorithm was adopted.Main outcome measuresPrognostic outcomes were disease‐free survival (DFS) and overall survival (OS). Fertility outcomes were pregnancy and live birth rates.ResultsA total of 187 (69.8%) patients underwent omentectomy. Kaplan–Meier analysis showed no significant differences in DFS and OS between the omentectomy and non‐omentectomy groups before and after PSM (p > 0.05). Additionally, subgroup analysis stratified by age (<18 and ≥18 years) showed similar results. International Federation of Gynecology and Obstetrics (FIGO) stage was the only risk factor associated with DFS (hazard ratio [HR] 14.71, 95% confidence interval [CI] 4.47–48.38, p < 0.001) and OS (HR 37.36, 95% CI 3.87–361.16, p = 0.002). Pregnancy and live birth rates in the total population were 80.3% and 66.7%, respectively. There were no significant differences between the two groups before and after PSM.ConclusionsOmentectomy did not improve survival or affect fertility in patients with clinically apparent early‐stage (I, II) MOGCT, regardless of the age. The clinical FIGO stage was an independent risk factor for recurrence and death.

Genomic Scar Score: A robust model predicting homologous recombination deficiency based on genomic instability

AbstractObjectiveTo develop a novel machine learning‐based algorithm called the Genomic Scar Score (GSS) for predicting homologous recombination deficiency (HRD) events.DesignMethod development study.SettingAmoyDx Medical Laboratory and Jiangsu Cancer Hospital.Population or sampleA cohort of individuals with ovarian or breast cancer (n = 377) were collected from the AmoyDx Medical Laboratory. Another cohort of patients with ovarian cancer treated with PARP inhibitors (n = 58) was enrolled in the Jiangsu Cancer Hospital.MethodsWe used linear support vector machines to build a Genomic Scar (GS) model to predict HRD events, and Kaplan–Meier analyses were performed by comparing the progression‐free survival (PFS) of patients in different groups using a two‐sided log‐rank test.Main outcome measuresThe performance of the GS model and the result of clinical validation.ResultsThe GS model displayed more than 97.0% sensitivity to detect BRCA‐deficient events, and the GS model identified patients that could benefit from poly(ADP‐ribose) polymerase inhibitors (PARPi), as the GS score (GSS)‐positive group had a longer progression‐free survival (PFS) (9.4 versus 4.4 months; hazard ratio [HR] = 0.54, P < 0.001) than the GSS‐negative group after PARPi treatment. Meanwhile, the GSS showed high concordance among different NGS panels, which implied the robustness of the GS model.ConclusionsThe GS was a robust model to predict HRD and had broad clinical applications in predicting which patients will respond favourably to PARPi treatment.

Neoadjuvant chemotherapy for ovarian cancer: Avoiding ‘needless hurt’?

Linked article: This is a mini commentary on C. Marchetti et al., pp.1579–1588 in this issue. To view this article visit https://doi.org/10.1111/1471‐0528.17558.

Risk Factors of Complications After Uterine Artery Embolisation for Symptomatic Fibroids: A Case–Control Study

ABSTRACTObjectiveWe aim to clarify potential risk factors of complications after uterine artery embolisation (UAE).SettingComplications after uterine artery embolisation (UAE) for symptomatic fibroids are rare, but failure of treatment occurs for approximately 13%–24% of patients at 10 years.DesignWe conducted a case–control study including all complications post UAE over 15 years in our specialised unit.PopulationAll Grade 2 complications (or worse) for the Society of Interventional Radiology Standards of Practice Committee complications post UAE were considered. One thousand one hundred seventy‐two UAE were performed.MethodsComplications were divided into two groups: early (< 1 month) or late (≥ 1 month) to differentiate complications from failure of procedure. Multinomial analysis was conducted to assess links between complications and potential risk factors.ResultsSixty‐nine (0.06%) complications were found: 24.6% hospitalisation for pain (n = 17/69), 30.4% for infection (n = 21/69) and 2.9% expulsion of fibroid (n = 2/69). Overall, 31 patients underwent a second procedure (45%).Main Outcome MeasuresIntra‐uterine device and multiple fibroids were strongly related to early complications (ORearly = 4.44, IC 95%: 1.5–13.3 and ORearly = 3.7, IC 95%: 1.2–11.3, respectively). The only factor that appeared to be associated with risk of early and late complications was the major fibroid's diameter (for an increased size of 25 mm, ORearly = 1.7, IC 95%: 1.1–2.6; ORlate = 1.5, IC 95%: 1.04–2.2).ConclusionOur study enlightens about the potential risk factors of UAE's complications and differentiate their impact between early and late complications.

Clinical performance of primary HPV screening cut‐off for colposcopy referrals in HPV‐vaccinated cohort: Observational study

AbstractObjectiveTo understand the effect of changing from cytology‐based to primary HPV screening on the positive predictive value (PPV) of colposcopy referrals for cervical intraepithelial neoplasia (CIN) in a cohort offered HPV vaccination.DesignRetrospective pre/post observational cohort study.SettingScotland.Population or sample2193 women referred to colposcopy between September 2019 and February 2020 from cytology‐based screening and between September 2020 and February 2021 from primary high‐risk HPV (hrHPV) screening.MethodsCalculating positive predictive values (PPVs) for two cohorts of women; one having liquid‐based cytology screening and the other, the subsequent hrHPV cervical screening as a pre/post observational study.Main outcome measuresPositive predictive values of LBC and hrHPV cut‐offs for colposcopy referral for CIN at colposcopy.ResultsThree papers fitted our criteria; these reported results only for cytology‐based screening. The PPV was lower for women in HPV‐vaccinated cohorts indicating a lower prevalence of disease. Vaccination under the age of 17 had the lowest PPV reported. Scottish colposcopy data concerning hrHPV and cytology showed a non‐significant difference between PPV (17.5%, 95% CI 14.3–20.7, and 20.6, 95% CI 16.7–24.5, respectively) for referrals with a cut‐off of low grade dyskaryosis (LGD); both met the standard set of 8–25%. The hrHPV PPV (66.7, 95% CI 56.8–76.6) was comparable to cytology (64.1, 95% CI 55.8–72.4) for referrals with a cut‐off of high grade dyskaryosis (HGD) but neither met the standard set of 77–92%.ConclusionsCurrent literature only provides PPVs for LBC and, overall, the vaccinated cohort had lower PPVs. Only LG dyskaryosis met PHE criteria. The PPV for HPV‐vaccinated women undergoing either LBC or HR‐HPV screening were not statistically different. However, similar to papers in the current literature, HG dyskaryosis (HGD) PPVs of both techniques did not meet the PHE threshold of 76.6–91.6% outlined in the cervical standards data report.

Urine high‐risk human papillomavirus testing as an alternative to routine cervical screening: A comparative diagnostic accuracy study of two urine collection devices using a randomised study design trial

AbstractObjectiveTo 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.DesignRandomised controlled trial.SettingSt Mary's Hospital, Manchester, UK.PopulationColposcopy 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.MethodsUrine 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 measuresThe 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.ResultsUrine 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.ConclusionsTesting 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.

Topical imiquimod treatment of residual or recurrent cervical intraepithelial neoplasia lesions (TOPIC‐2): A randomised controlled trial

AbstractObjectiveTo investigate the efficacy of imiquimod in women with residual or recurrent cervical intraepithelial neoplasia (rrCIN), compared with large loop excision of the transformation zone (LLETZ).DesignRandomised controlled non‐inferiority trial.SettingOne academic and one regional hospital in the Netherlands.PopulationThirty‐five women with rrCIN were included in the study between May 2016 and May 2021.MethodsWomen were randomised to receive treatment with 5% imiquimod cream (12.5 mg) intravaginally (three times a week for a duration of 16 weeks) or a LLETZ procedure (standard treatment).Main outcome measuresThe primary outcome was reduction to normal cytology at 6 months after starting treatment. Secondary outcomes were clearance of high‐risk human papilloma virus (hr‐HPV) in both groups and reduction to ≤CIN1 in the imiquimod group. Side effects were monitored.ResultsTreatment success was 33% (6/18) in the imiquimod group versus 100% (16/16) in the LLETZ group (P < 0.001), whereas HPV clearance was 22% (4/18) in the imiquimod group versus 88% (14/16) in the LLETZ group (P < 0.001). After the randomisation of 35 women, the futility of treatment with imiquimod was proven and the trial was prematurely finished. In the follow‐up period, three patients remained without additional treatment, whereas all other patients underwent LLETZ, conisation or hysterectomy. In the LLETZ group none of the patients received additional treatment during 2 years of follow‐up.ConclusionsThis is the first randomised controlled trial to show that topical imiquimod has a significantly lower success rate in terms of reduction to normal cytology and hr‐HPV clearance, compared with LLETZ, in women with rrCIN. Additionally, imiquimod has numerous side effects and after using imiquimod most women with rrCIN still required additional surgical treatment.

Introducing human papillomavirus (HPV) primary testing in the age of HPV vaccination: projected impact on colposcopy services in Wales

ObjectiveTo determine the demand for colposcopy in the Cervical Screening Wales programme after the introduction of human papillomavirus (HPV) cervical screening, which coincided with the start of screening of women vaccinated against HPV types 16/18.DesignThe study used a computational model that assigns screening and screening‐related colposcopy events to birth cohorts in individual calendar years.SettingCervical Screening Wales.PopulationWomen aged 25–64 years from birth cohorts 1953–2007.Methods and main outcome measuresWe estimated the numbers of colposcopies and high‐grade cervical intraepithelial lesions (CIN2+) within Cervical Screening Wales in 2018–32, using official population projections for Wales and published estimates of the effects of HPV screening and vaccination.ResultsVaccination will reduce the number of colposcopies by 10% within the first 3–4 years after the national roll‐out of HPV screening, and by about 20% thereafter. The number of screening colposcopies is estimated to increase from 6100 in 2018 and peak at 8000 (+31%) in 2021, assuming current screening intervals are maintained. The numbers of CIN2+ lesions follow similar patterns, stabilising at around 1000 diagnoses per year by 2026, approximately 60% lower than at present. Extending the screening intervals to 5 years for all women shows similar trends but introduces peaks and troughs over the years.ConclusionsVaccination will not fully prevent an increase in colposcopies and detected CIN2+ lesions during the first 2–3 years of HPV‐based screening but the numbers are expected to decrease substantially after 5–6 years.Tweetable abstractHPV‐based cervical screening will initially increase colposcopy referral. In 6 years, this increase will be reversed, partly by HPV vaccination.

SIP 7: Progress in Cervical Cancer Prevention in the UK (2025 Second Edition)

Plain Language SummaryCervical cancer remains a preventable yet significant healthcare problem for women globally. The World Health Organization (WHO) announced a call to eliminate cervical cancer in 2018, with recommendations for screening, vaccination, and treatment of precancerous cervical lesions.Screening uptake is on the decline in the UK, particularly for younger women, where the rate has now dropped below 70%. Primary screening is now performed with high‐risk human papillomavirus (hrHPV) testing. This test is sensitive, but not specific, meaning it is good at not missing cancers or precancer, but most people who test hrHPV positive will not have cervical cancer or precancer, and therefore testing positive can lead to unnecessary worry. Any samples that test positive for the virus undergo ‘reflex’ cytology (the process by which cells suspended in liquid are stained and examined under the microscope by those trained to perform this assessment). This means only virus‐positive samples are tested to select patients for colposcopy (visualisation of the cervix with special lenses, in a specialist gynaecology clinic). Other possibilities for this triage test, which may improve the accuracy of screening, are currently under investigation and include methylation (a chemical change in DNA that can be measured) testing, and testing for specific markers. HPV type 16 is the most common high‐risk strain found globally, including in the UK.The UK national vaccination programme was started in 2008, and uptake in the UK is currently around 80%. Since 2021, Gardasil9 (offering protection against seven hrHPV types and two HPV types that cause genital warts) has been offered to both boys and girls, at school, aged 12–13. In 2023, new guidance from the Joint Committee on Vaccination and Immunisation (JCVI) recommended a single dose as sufficient. HPV vaccination has almost eliminated cervical cancer in those born in or after 1995.Future directions for the screening programme in the UK include self‐sampling, adaptations in the post‐vaccine era, and increasing the upper age limit of screening. Self‐sampling has been shown to be similarly accurate to clinician‐taken samples, and may be a good option for those who do not attend for screening, who have been shown to have increased risk of cervical cancer and worse outcomes. One in ten women with cervical cancer in the UK is diagnosed over the age of 75.Globally, recommendations for cervical screening exist in 139/202 countries. Of these, 48 currently recommend hrHPV testing. Efforts must be made to encourage uptake of both screening and vaccination in order to continue to reduce rates of cervical cancer in the UK.

Re: Mirena Coil is a suitable treatment of early stage endometrial cancer in obese women: FOR or AGAINST?

The Mirena coil is a suitable treatment of early‐stage endometrial cancer in obese women

Is there any move to use metformin for endometrial hyperplasia in routine clinical practice?

Efficacy of Maintenance Therapy With Adjuvant Chemotherapy of Three Steps in Patients Newly Diagnosed With Advanced Ovarian Cancer: A Phase II Randomised Clinical Trial

ABSTRACTObjectiveTo evaluate the efficacy and safety of adjuvant chemotherapy of three steps (ACTS) in patients newly diagnosed with advanced ovarian cancer.DesignRandomised clinical trial.SettingThe study was conducted at a single centre.PopulationNewly diagnosed patients with advanced ovarian cancer who showed a complete response to standard chemotherapy (paclitaxel plus carboplatin) were included in this study.MethodsIn this open‐label phase II trial, patients were randomised 1:1 to receive either ACTS therapy or no maintenance treatment. The ACTS group received step‐2 chemotherapy with cyclophosphamide and etoposide (six cycles) and step‐3 chemotherapy with cyclophosphamide and carboplatin (six cycles). Key endpoints were overall survival (OS), progression‐free survival (PFS) and adverse events.Main Outcome MeasuresThe main outcome measures were OS, PFS and adverse events.ResultsOf the 130 enrolled patients, 65 were assigned to the ACTS group and 65 to the control group. The median OS in the ACTS group was 61.2 months, and patients in the ACTS group had a significantly longer PFS than those in the control group (22.2 vs. 9.73 months). The most common grade ≥ 3 adverse events were thrombocytopenia and neutropenia. No treatment‐related deaths occurred during the study period.ConclusionsThe Maintenance ACTS Regimen Improved PFS but Not OS and Showed a Tolerable Safety Profile in Patients Newly Diagnosed With Advanced Ovarian cancer.Trial RegistrationClinicalTrials.org NCT02562365

Implications for women testing positive for human papillomavirus

Impact of lymphadenectomy and lymphoedema on health‐related quality of life 1 year after surgery for endometrial cancer. A prospective longitudinal multicentre study

ObjectiveTo assess the impact of lymphadenectomy and lymphoedema of the lower limbs (LLL) on health‐related quality of life (HRQoL) 1 year after surgery for endometrial cancer (EC).DesignProspective longitudinal cohort multicentre study.SettingDepartments of obstetrics and gynaecology at four university hospitals, six central hospitals and four county hospitals in Sweden.PopulationTwo‐hundred‐and‐thirty‐five women with early stage EC were included; 116 with high‐risk EC underwent surgery including lymphadenectomy (+LA), and 119 with low‐risk EC had surgery without lymphadenectomy (−LA).MethodsThe generic SF‐36 and EQ‐5D‐3L and the lymphoedema‐specific LYMQOL questionnaire were used to assess HRQoL. LLL was assessed by systematic circumferential measurements of the legs enabling volume estimation, clinical evaluation and patient‐reported perception of leg swelling. All assessments were carried out on four occasions; preoperatively, and 4–6 weeks, 6 months and 1 year postoperatively.Main outcome measureHRQoL scores.ResultsNo significant differences were seen in HRQoL between the +LA and –LA groups 1 year postoperatively. Irrespective of method of determining LLL, women with LLL were significantly more affected in the LYMQOL domains Function, Appearance/body image and Physical symptoms, but not in the domain Emotion/mood, than women without LLL. No such differences were seen in the generic HRQoL or in the LYMQOL global score between the groups with and without LLL.ConclusionsLymphadenectomy did not seem to affect generic HRQoL adversely. Irrespective of the method of measuring, LLL affected the lymphoedema‐specific HRQoL negatively, mainly in physical domains, but had no impact on the generic HRQoL.Tweetable abstractLymphoedema has impact on lymphoedema‐specific, but not on generic, HRQoL, 1 year after surgery for EC.

Diagnosis and management of isolated serous tubal intraepithelial carcinoma: A qualitative focus group study

Abstract Objective A Serous Tubal Intraepithelial Carcinoma (STIC) without concomitant invasive carcinoma is occasionally identified and associated with a high risk of subsequent peritoneal carcinomatosis. Management needs optimisation. This study explores professionals' opinions and clinical practices regarding the diagnosis, counselling, treatment and follow‐up of isolated STIC to facilitate clinical decision making and optimise the direction of future research. A secondary aim is to assess international clinical guidelines. Design Focus group study. Setting Four online sessions. Population International panel ( n  = 12 countries) of gynaecologists, gynaecologic oncologists, pathologists and medical oncologists ( n  = 49). Methods A semi‐structured interview guide was used. Two independent researchers analysed transcripts by open and axial coding. Results were organised in domains. Relevant (inter)national guidelines were screened for recommendations regarding isolated STIC. Main Outcome Measures Professionals' opinions and clinical practices regarding isolated STIC management. Results Regarding pathology, most professionals identified the SEE‐FIM protocol as standard of care for high‐risk patients, whereas variation exists in the histopathological examination of fallopian tubes in the general population. Confirmation of STIC diagnosis by a specialised pathologist was recommended. Regarding work‐up and follow‐up after STIC diagnosis, there was variety and discordance. Data on outcomes is limited. As for treatment, chemotherapy and PARP inhibitors were not recommended by most. Eleven guidelines provided limited recommendations. Conclusions We identified recommendations and highlighted knowledge gaps in the diagnosis and management of isolated STIC. Moreover, recommendations in clinical guidelines are limited. There is an agreed need for international collaboration for the prospective registration of isolated STIC.

Prognostic impact of cytoreductive surgery conducted with primary intent, versus cytoreductive surgery after neoadjuvant chemotherapy, in the management of patients with advanced epithelial ovarian cancers: a multicentre, propensity score‐matched study from the FRANCOGYN group

AbstractObjectiveTo compare survival and morbidity rates between primary cytoreductive surgery (pCRS) and interval cytoreductive surgery (iCRS) for epithelial ovarian cancer (EOC), using a propensity score.DesignWe conducted a propensity score‐matched cohort study, using data from the FRANCOGYN cohort.SettingRetrospective, multicentre study of data from patients followed in 15 French department specialized in the treatment of ovarian cancer.SamplePatients included were those with International Federation of Gynaecology and Obstetrics (FIGO) stage III or IV EOC, with peritoneal carcinomatosis, having undergone CRS.MethodsThe propensity score was designed using pre‐therapeutic variables associated with both treatment allocation and overall survival (OS).Main Outcome MeasuresThe primary outcome was OS. Secondary outcomes included recurrence‐free survival (RFS), quality of CRS and other variables related to surgical morbidity.ResultsA total of 513 patients were included. Among these, 334 could be matched, forming 167 pairs. No difference in OS was found (hazard ratio, HR = 0.8, p = 0.32). There was also no difference in RFS (median = 26 months in both groups) nor in the rate of CRS leaving no macroscopic residual disease (pCRS 85%, iCRS 81.4%, p = 0.76). The rates of gastrointestinal tract resections, stoma, postoperative complications and hospital stay were significantly higher in the pCRS group.ConclusionsAnalysis of groups of patients made comparable by propensity score matching showed no difference in survival, but lower postoperative morbidity in patients treated with iCRS.

Serum HE4 predicts progestin treatment response in endometrial cancer and atypical hyperplasia: A prognostic study

AbstractObjectiveTo investigate serum human epididymis‐4 (HE4) as a predictive biomarker of intrauterine progestin response in endometrial cancer and atypical endometrial hyperplasia (AEH).DesignProspective prognostic factor study.SettingConsecutive sample of women attending a tertiary gynaecological oncology centre in northwest England.PopulationWomen with AEH or early‐stage, low‐grade endometrial cancer who were unfit for or declined primary surgical management.MethodsA 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 MeasuresProgestin response at 12 months defined by histology and imaging.ResultsThe 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).ConclusionSerum HE4 shows promise as a predictive biomarker of progestin treatment response in endometrial cancer and AEH.

Salpingo‐oophorectomy and effects on cognition

The diagnostic and therapeutic prospects of exosomes in ovarian cancer

AbstractExosomes are nano‐sized vesicles derived from the endosomal system and are involved in many biological and pathological processes. Emerging evidence has demonstrated that exosomes with cell‐specific constituents are associated with the tumorigenesis and progression of ovarian cancer. Therefore, exosomes derived from ovarian cancers can be potential diagnostic biomarkers and therapeutic targets. In this review, we briefly present the biological characteristics of exosomes and the recent advances in isolating and detecting exosomes. Furthermore, we summarise the many functions of exosomes in ovarian cancer, hoping to provide a theoretical basis for clinical applications of exosomes in the diagnosis and treatment of ovarian cancer.

Ambient particulate matter air pollution exposure and ovarian cancer incidence in the USA: An ecological study

AbstractObjectiveTo investigate associations between air particulate matter of ≤2.5 μm in diameter (PM2.5) and ovarian cancer.DesignCounty‐level ecological study.SettingSurveillance, epidemiology, and end results from a collection of state‐level cancer registries across 744 counties. Data from the Environmental Protection Agency's network for PM2.5 monitoring was used to calculate trailing 5‐ and 10‐year PM2.5 county‐level values. County‐level data on demographic characteristics were obtained from the American Community Survey.PopulationA total of 98 751 patients with histologically confirmed ovarian cancer as a primary malignancy from 2000 to 2016.MethodsGeneralised linear regression models were developed to estimate the association between PM2.5 and PM10 levels, over 5‐ and 10‐year periods of exposure, and ovarian cancer risk, after accounting for county‐level covariates.Main outcome measuresRisk ratios for associations between ovarian cancer (both overall and specifically epithelial ovarian cancer) and PM2.5 levels.ResultsFor the 744 counties included, the average PM2.5 level from 1990 through 2018 was 11.75 μg/m3 (SD = 3.7) and the average PM10 level was 22.7 μg/m3 (SD = 5.7). After adjusting for county‐level covariates, the overall annualised ovarian cancer incidence was significantly associated with increases in 5‐year PM2.5 (RR = 1.11 per 10 units (μg/m3) increase, 95% CI 1.06–1.16). Similarly, when the analysis was limited to epithelial cell tumours and adjusted for county‐level covariates there was a significant association with trailing 5‐year PM2.5 exposure models (RR = 1.12 per 10 units increase, 95% CI 1.08–1.17). Likewise, 10‐year PM2.5 exposure was associated with ovarian cancer overall and with epithelial ovarian cancer.ConclusionsHigher county‐level ambient PM2.5 levels are associated with 5‐ and 10‐year incidences of ovarian cancer, as measurable in an ecological study.

The use of biomarkers to stratify surgical care in women with ovarian cancer

Plain language summaryBiomarkers may offer unforeseen insights into clinical diagnosis, as well as the likely course and outcome of a condition. In this paper, the focus is on the use of biological molecules found in body fluids or tissues for diagnosis and prediction of outcome in ovarian cancer patients.In cancer care, biomarkers are being used to develop personalised treatment plans for patients based on the unique characteristics of their tumour. This tailoring of care can be used to pursue specific targets identified by biomarkers, or treat the patient according to specific tumour characteristics.Surgery is one of the core treatments for ovarian cancer, whether it is offered in primary surgery or following chemotherapy in delayed surgery. Biomarkers already exist to guide the treatment of tumours with chemotherapy, but very little research has determined the value of biomarkers in tailoring surgical care for ovarian cancer. Such research is required to identify new biomarkers and assess their effectiveness in a clinical setting as well as to help identify specific tumour types to guide surgery. Biomarkers could help to determine the success of removing the disease surgically, or help to identify tumour deposits that persist after chemotherapy. All of these aspects would improve current practice.This Scientific Impact Paper highlights research that may pave the way towards bespoke surgery according to the biological characteristics of a tumour and aid gynaecological oncologists to provide surgical treatment according to individual need, rather than a blanket approach for all.

Time interval from biopsy of endometrial atypical hyperplasia to surgery and risk for concurrent endometrial carcinoma – A retrospective study

Immune checkpoint inhibitors plus chemotherapy in first‐line endometrial cancer treatment: Still the era of microsatellites?

AbstractObjectiveThe combination of immune checkpoint inhibitors (ICIs) plus chemotherapy is currently being tested as the first‐line treatment of advanced endometrial. We aimed to evaluate the efficacy and safety of this combination.DesignWe performed a meta‐analysis of randomized clinical trials.Population and settingPatients with advanced endometrial carcinoma receiving ICIs plus chemotherapy in the experimental arm, compared with chemotherapy plus placebo in the control arm, were included.Methods and OutcomesWe evaluated the progression‐free survival (PFS) as an efficacy outcome and the number and grades of adverse events (AEs) for safety. Hazard ratios (HR) for PFS and risk ratios (RR) for AEs, with 95% confidence intervals (CI), were calculated.Results1303 patients were treated in the included studies. Adding ICIs to chemotherapy significantly improved PFS in mismatch repair deficient (dMMR—HR 0.29; 95% CI, 0.20–0.42; p < 0.00001) and in mismatch repair proficient (pMMR—HR 0.64; 95% CI, 0.46–0.90; p = 0.01) patients. No difference emerged for all‐grades AEs (RR 1.00; p = 0.98), but the risk of ≥G3 AEs was increased in the ICIs + chemotherapy group (RR 1.22; 95% CI, 1.11–1.34; p < 0.0001).ConclusionsAdding ICIs to chemotherapy significantly improves PFS in first‐line endometrial cancer, regardless of MMR status.

Predicting risk of endometrial cancer in asymptomatic women (PRECISION): Model development and external validation

AbstractObjectivesDevelop an endometrial cancer risk prediction model and externally validate it for UK primary care use.DesignCohort study.SettingThe 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.PopulationWomen aged 45–60 years with no history of endometrial cancer or hysterectomy.MethodsModel 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 measuresEndometrial cancer diagnosis within 1–10 years of the index date.ResultsModel 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.ConclusionsThe 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.

Attitudes towards risk‐reducing salpingectomy: listen to the patients

Ovarian cancer risk in Lynch syndrome: it's time to individualise

Front‐line ovarian cancer maintenance therapy: PARP inhibitors for all?

PARP inhibitors as maintenance therapy in newly diagnosed advanced ovarian cancer: a meta‐analysis

BackgroundUp to 70% of patients with advanced ovarian cancer have a relapse after primary therapy. New agents and approaches are urgently needed to avoid or slow down this recurrence.ObjectivesTo investigate the efficacy of PARP inhibitors (PARPis) as maintenance treatment in patients with newly diagnosed advanced ovarian cancer.Search strategyPubMed, MEDLINE, EMBASE, Cochrane Library and Web of Science databases.Selection criteriaAll randomised clinical trials (RCTs) that compared PARPis with placebo as first‐line maintenance therapy in ovarian cancer.Data collection and analysisTwo reviewers extracted data. Pooled hazard ratio (HR) and risk ratio (RR) with 95% confidence interval (CI) were calculated.Main resultsPARPis were associated with significant improvement of progression‐free survival (PFS) in advanced epithelial ovarian cancer (AeOC) (HR = 0.53, 95% CI 0.40–0.71; P < 0.0001). The benefit was not only in women with BRCA mutations (HR = 0.35, 95% CI 0.29–0.42; P < 0.00001) and homologous recombination deficiency (HRD) (HR = 0.43, 95% CI 0.32–0.60; P < 0.00001), but also in those with nonmutated BRCA (HR = 0.72, 95% CI 0.63–0.82; P < 0.00001) and even non‐HRD (HR = 0.83, 95% CI 0.70–0.99; P = 0.04).ConclusionsPARP inhibitors are effective as maintenance therapy among patients with newly diagnosed advanced ovarian cancer after platinum‐based chemotherapy, regardless of BRCA mutation or HRD status.Tweetable abstractPARPis provide a significant PFS benefit as first‐line maintenance therapy in patients with newly diagnosed advanced ovarian cancer.

The effect of progestin therapy in advanced and recurrent endometrial cancer: A systematic review and meta‐analysis

AbstractBackgroundFifteen percent of patients with endometrial cancer (EC) have advanced stage disease or develop a recurrence. Progestins have been applied as systemic treatment for decades, but there is limited evidence on response prediction with biomarkers and toxicity.ObjectivesTo review the response and toxicity of progestin therapy and stratify response to progesterone receptor (PR) expression and tumour grade.Search strategyWe used the search terms ‘Endometrial cancer’, ‘Progestins’, ‘Disease progression’, ‘Recurrence’ and related terms in Pubmed, Embase and Cochrane databases.Selection criteriaStudies on patients with advanced stage or recurrent EC treated with progestin monotherapy were included. Studies on adjuvant therapy, with fewer than ten cases and with sarcoma histology were excluded.Data collection and analysisEvaluation for bias was performed with the Revised Cochrane RoB2 tool for randomised studies and the ROBINS‐I tool for non‐randomised studies. A random effects meta‐analysis was performed with the overall response rate (ORR), clinical benefit rate and toxicity as primary outcome measures.Main resultsTwenty‐six studies (1639 patients) were included. The ORR of progestin therapy was 30% (95% CI 25–36), the clinical benefit rate was 52% (95% CI 42–61). In PR‐positive EC, the ORR was 55%, compared with 12% in PR‐negative disease (risk difference 43%, 95% CI 15–71). Severe toxicity occurred in 6.5%.ConclusionsProgestin therapy is a viable treatment option in patients with advanced stage and recurrent EC with low toxicity and high ORR in PR‐positive disease. The role of PR expression in relation to progression‐free survival and overall survival is unclear.

Treatment methods for cervical intraepithelial neoplasia in England: A cost‐effectiveness analysis

AbstractObjectiveTo compare the cost‐effectiveness of different treatments for cervical intraepithelial neoplasia (CIN).DesignA cost‐effectiveness analysis based on data available in the literature and expert opinion.SettingEngland.PopulationWomen treated for CIN.MethodsWe developed a decision‐analytic model to simulate the clinical course of 1000 women who received local treatment for CIN and were followed up for 10 years after treatment. In the model we considered surgical complications as well as oncological and reproductive outcomes over the 10‐year period. The costs calculated were those incurred by the National Health Service (NHS) of England.Main outcome measuresCost per one CIN2+ recurrence averted (oncological outcome); cost per one preterm birth averted (reproductive outcome); overall cost per one adverse oncological or reproductive outcome averted.ResultsFor young women of reproductive age, large loop excision of the transformation zone (LLETZ) was the most cost‐effective treatment overall at all willingness‐to‐pay thresholds. For postmenopausal women, LLETZ remained the most cost‐effective treatment up to a threshold of £31,500, but laser conisation became the most cost‐effective treatment above that threshold.ConclusionsLLETZ is the most cost‐effective treatment for both younger and older women. However, for older women, more radical excision with laser conisation could also be considered if the NHS is willing to spend more than £31,500 to avert one CIN2+ recurrence.

Improving outcomes in ovarian cancer: a work in progress

Clinical Practice of Poly ( ADP ‐Ribose) Polymerase Inhibitors for Maintenance Treatment of Platinum‐Sensitive Recurrent Ovarian Cancer in China

ABSTRACT Clinical trials of three poly (ADP‐ribose) polymerase (PARP) inhibitors, olaparib, niraparib and fuzuloparib, in platinum‐sensitive recurrent ovarian cancer (PSR OC) in China showed that PARP inhibitors improved progression‐free survival and achieved an all‐comer indication in this population. We reviewed the efficacy and safety of these PARP inhibitors in patient populations studied in clinical trials and highlighted the positive role of PARP inhibitors in improving patient outcomes using clinical trials and real‐world studies conducted in China. This article also discusses the issues encountered in clinical practice and how to evaluate the different indications for PSR OC in China and abroad.

Effects of neoadjuvant hyperthermic intraperitoneal chemotherapy on chemotherapy response score and recurrence in high‐grade serous ovarian cancer patients with advanced disease: A multicentre retrospective cohort study

AbstractObjectiveTo investigate whether the combination of neoadjuvant hyperthermic intraperitoneal chemotherapy (NHIPEC) plus intravenous neoadjuvant chemotherapy (IV NACT) has superior efficacy to IV NACT alone.DesignRetrospective cohort study.SettingTwo tertiary referral university hospitals.PopulationPatients with ovarian cancer who received NACT‐interval debulking surgery (IDS) between 2012 and 2020.MethodsThe tumour response to NACT was evaluated with the chemotherapy response score (CRS) system. Survival outcomes were compared.Main outcome measuresCRS 3, progression‐free survival (PFS), and overall survival (OS).ResultsIn total, 127 patients were included, and 46 received NHIPEC plus IV NACT. The addition of NHIPEC was independently associated with an increased likelihood of CRS 3 (p = 0.033). Patients who received NHIPEC + IV NACT had significantly improved PFS compared with those who received IV NACT alone (median PFS: 22 versus 16 months, p < 0.001). The use of NHIPEC was identified as an independent predictor of PFS (p < 0.0001). OS did not differ significantly between treatment groups (p = 0.062), although a trend favouring NHIPEC was noted. Incidence of grade 3–4 adverse events and the surgical complexity score of IDS were similar between the two groups.ConclusionsCompared with IV NACT alone, the combination of NHIPEC and IV NACT resulted in improved tumour response and longer PFS. The addition of NHIPEC did not increase the risk of adverse effects or affect the complexity of IDS.

Risk‐Reducing Salpingo‐Oophorectomy and the Use of Hormone Replacement Therapy Below the Age of Natural Menopause

Plain language summaryThis paper deals with the use of hormone replacement therapy (HRT) after the removal of fallopian tubes and ovaries to prevent ovarian cancer in premenopausal high risk women. Some women have an alteration in their genetic code, which makes them more likely to develop ovarian cancer. Two well‐known genes which can carry an alteration are the BRCA1 and BRCA2 genes. Examples of other genes associated with an increased risk of ovarian cancer include RAD51C, RAD51D, BRIP1, PALB2 and Lynch syndrome genes. Women with a strong family history of ovarian cancer and/or breast cancer, may also be at increased risk of developing ovarian cancer. Women at increased risk can choose to have an operation to remove the fallopian tubes and ovaries, which is the most effective way to prevent ovarian cancer. This is done after a woman has completed her family. However, removal of ovaries causes early menopause and leads to hot flushes, sweats, mood changes and bone thinning. It can also cause memory problems and increases the risk of heart disease. It may reduce libido or impair sexual function. Guidance on how to care for women following preventative surgery who are experiencing early menopause is needed.HRT is usually advisable for women up to 51 years of age (average age of menopause for women in the UK) who are undergoing early menopause and have not had breast cancer, to minimise the health risks linked to early menopause. For women with a womb, HRT should include estrogen coupled with progestogen to protect against thickening of the lining of the womb (called endometrial hyperplasia). For women without a womb, only estrogen is given. Research suggests that, unlike in older women, HRT for women in early menopause does not increase breast cancer risk, including in those who are BRCA1 and BRCA2 carriers and have preventative surgery.For women with a history of receptor‐negative breast cancer, the gynaecologist will liaise with an oncology doctor on a case‐by‐case basis to help to decide if HRT is safe to use. Women with a history of estrogen receptor‐positive breast cancer are not normally offered HRT. A range of other therapies can be used if a woman is unable to take HRT. These include behavioural therapy and non‐hormonal medicines. However, these are less effective than HRT. Regular exercise, healthy lifestyle and avoiding symptom triggers are also advised. Whether to undergo surgery to reduce risk or not and its timing can be a complex decision‐making process. Women need to be carefully counselled on the pros and cons of both preventative surgery and HRT use so they can make informed decisions and choices.

Impact of socio‐economic deprivation on endometrial cancer survival in the North West of England: a prospective database analysis

ObjectiveTo assess the impact of socio‐economic deprivation on endometrial cancer survival.DesignSingle‐centre prospective database study.SettingNorth West England.PopulationWomen with endometrial cancer treated between 2010 and 2015.MethodsAreal‐level socio‐economic status, using the English indices of multiple deprivation from residential postcodes, was analysed in relation to survival using Kaplan–Meier estimation and multivariable Cox regression.Main outcome measuresOverall survival, cancer‐specific survival and patterns and rates of recurrence.ResultsA total of 539 women, with a median age of 66 years (interquartile range, IQR 56–73 years) and a body mass index (BMI) of 32 kg/m2 (IQR 26–39 kg/m2), were included in the analysis. Women in the most deprived social group were younger (median 64 years, IQR 55–72 years) and more obese (median 34 kg/m2, IQR 28–42 kg/m2) than women in the least deprived group (median age 68 years, IQR 60–74 years; BMI 29 kg/m2, IQR 25–36 kg/m2; P = 0.002 and <0.001, respectively). There were no differences in endometrial cancer type, stage or grade between social groups. There was no difference in recurrence rates, however, women in the middle and most deprived social groups were more likely to present with distant/metastatic recurrence (80.6 and 79.2%, respectively) than women in the least deprived group (43.5%, P < 0.001). Women in the middle and most deprived groups had a two‐fold (adjusted hazard ratio, HR = 2.00, 95% CI 1.07–3.73, P = 0.030) and 53% (adjusted HR = 1.53, 95% CI 0.77–3.04, P = 0.221) increase in cancer‐specific mortality compared with women in the least deprived group. There were no differences in overall survival.ConclusionsWe found that socio‐economically deprived women with endometrial cancer were more likely to develop fatal recurrence. Larger studies are needed to confirm these findings and to identify modifiable contributing factors.Tweetable abstractSocio‐economic deprivation is linked to an increased risk of death from endometrial cancer in the North West of England.

The detection of germline and somatic BRCA1/2 genetic variants through parallel testing of patients with high‐grade serous ovarian cancer: a national retrospective audit

ObjectiveTo determine the frequency of germline and somatic pathogenic BRCA1 and BRCA2 variants in patients with high‐grade serous ovarian cancer tested by next‐generation sequencing (NGS), with the aim of defining the best strategy to be implemented in future routine testing.DesignNational retrospective audit.SettingThe All Wales Medical Genomics Service (AWMGS).PopulationPatients with high‐grade serous ovarian/fallopian tube/peritoneal cancer referred by oncologists to the AWMGS between February 2015 and February 2021 for germline and/or tumour testing of the BRCA1 and BRCA2 genes by NGS.MethodsAnalysis of NGS data from germline and/or tumour testing.Main outcome measuresFrequency of BRCA1 and BRCA2 pathogenic variants.ResultsThe overall observed germline/somatic pathogenic variant detection rate was 11.6% in the 844 patients included in this study, with a 9.2% (73/791) germline pathogenic variant detection rate. Parallel tumour and germline testing was carried out for 169 patients and the overall pathogenic variant detection rate for this cohort was 14.8%, with 6.5% (11/169) shown to have a somatic pathogenic variant. Two BRCA1 dosage variants were found during germline screens, representing 2.0% (2/98) of patients with a pathogenic variant that would have been missed through tumour testing alone.ConclusionsParallel germline and tumour BRCA1 and BRCA2 testing maximises the detection of pathogenic variants in patients with high‐grade serous ovarian cancer.Tweetable abstractParallel germline and tumour testing maximises BRCA pathogenic variant detection in ovarian cancer.

Association of hysterectomy and invasive epithelial ovarian and tubal cancer: a cohort study within UKCTOCS

ObjectiveTo investigate the association between hysterectomy with conservation of one or both adnexa and ovarian and tubal cancer.DesignProspective cohort study.SettingThirteen NHS Trusts in England, Wales and Northern Ireland.PopulationA total of 202 506 postmenopausal women recruited between 2001 and 2005 to the UK Collaborative Trial of Ovarian Cancer Screening (UKCTOCS) and followed up until 31 December 2014.MethodsMultiple sources (questionnaires, hospital notes, Hospital Episodes Statistics, national cancer/death registries, ultrasound reports) were used to obtain accurate data on hysterectomy (with conservation of one or both adnexa) and outcomes censored at bilateral oophorectomy, death, ovarian/tubal cancer diagnosis, loss to follow up or 31 December 2014. Cox proportional hazards regression models were used to assess the association.Main outcome measuresInvasive epithelial ovarian and tubal cancer (WHO 2014) on independent outcome review.ResultsHysterectomy with conservation of one or both adnexa was reported in 41 912 (20.7%; 41 912/202 506) women. Median follow up was 11.1 years (interquartile range 9.96–12.04), totalling >2.17 million woman‐years. Among women who had undergone hysterectomy, 0.55% (231/41 912) were diagnosed with ovarian/tubal cancer, compared with 0.59% (945/160 594) of those with intact uterus. Multivariable analysis showed no evidence of an association between hysterectomy and invasive epithelial ovarian/tubal cancer (hazard ratio 0.98, 95% CI 0.85–1.13, P = 0.765).ConclusionsThis large cohort study provides further independent validation that hysterectomy is not associated with alteration of invasive epithelial ovarian and tubal cancer risk. These data are important both for clinical counselling and for refining risk prediction models.Tweetable abstractHysterectomy does not alter risk of invasive epithelial ovarian and tubal cancer.

Inch by inch; Row by row

Deputy Editor‐in‐Chief, Dr John M Thorp Jr, discusses his top articles from this issue in an audio podcast available at: https://soundcloud.com/bjog/februaryeditors-choice-2021.

Editorial: Towards better and personalized management of ovarian cancer in China

The first Chinese National Union of Real‐world Gynaecological Oncology Research and Patient Management Platform: A retrospective study

AbstractObjectiveTo produce high‐quality, real‐world evidence for oncologists by collating scattered gynaecologic oncology (GO) medical records in China.DesignRetrospective study.SettingThe National Union of Real‐world Gynaecological Oncology Research and Patient Management Platform (NUWA platform).SamplePatient‐centred data pool.MethodsThe NUWA platform integrated inpatient/outpatient clinical, gene and follow‐up data. Data of 11 456 patients with ovarian cancer (OC) were collected and processed using 91 345 electronic medical records. Structured and unstructured data were de‐identified and re‐collated into a patient‐centred data pool using a predefined GO data model by technology‐aided abstraction.Main Outcome MeasuresRecent treatment pattern shifts towards precision medicine for OC in China.ResultsThirteen first‐tier hospitals across China participated in the NUWA platform up to 7 December 2021. In total, 3504 (30.59%) patients were followed up by a stand‐alone patient management centre. The percentage of patients undergoing breast cancer gene (BRCA) mutation tests increased by approximately six‐fold between 2017 and 2018. A similar trend was observed in the administration rate of poly(ADP‐ribose) polymerase inhibitors as first‐line treatment and second‐line treatment after September 2018, when olaparib was approved for clinical use in China.ConclusionThe NUWA platform has great potential to facilitate clinical studies and support drug development, regulatory reviews and healthcare decision‐making.

Risk stratification of HPV‐positive women in routine cervical screening

Assessing the Accuracy of Large Language Models on European Guidelines for Cervical Cancer: An In Silico Benchmarking Study

ABSTRACT Objective Although large language models are increasingly used in clinical and research settings, the validity of the information they provide remains uncertain. This study aimed to evaluate the accuracy, consistency, and reliability of three large language models—ChatGPT 4.0, DeepSeek R1, and Gemini 2.0—in answering cervical cancer‐related questions based on the ESGO/ESTRO/ESP guidelines. Design Prospective, comparative in silico benchmarking study. Setting Fondazione Policlinico Universitario A. Gemelli, Rome, Italy. Population or Sample: Fifty questions derived from the ESGO/ESTRO/ESP (European Society of Gynaecologic Oncology/European Society for Radiotherapy and Oncology/European Society of Pathology) Guidelines for Cervical Cancer. Methods Each question was submitted simultaneously to ChatGPT 4.0, DeepSeek R1, and Gemini 2.0, and re‐entered twice to assess response repeatability. Answers were evaluated for accuracy using a Global Quality Score (GQS) from 1 (poor) to 5 (completely accurate). Consistency (intra‐model response stability) and reliability (alignment with guidelines) were assessed using binary classification. Main Outcome Measures: Median GQS, percentage of GQS 5 responses, consistency between repeated answers, and reliability. Results ChatGPT 4.0 achieved the highest performance, with 42% of responses rated GQS 5, followed by Gemini 2.0 (30%) and DeepSeek R1 (28%). DeepSeek R1 and Gemini 2.0 scored lower in median GQS (3.50) compared to ChatGPT 4.0 (4.00). Response consistency varied significantly, with ChatGPT 4.0 and DeepSeek R1 showing differences from Gemini 2.0 ( p  = 0.034 and p  = 0.044, respectively). No significant difference was observed in reliability ( p  = 0.602). Conclusion All models demonstrated suboptimal accuracy in aligning with clinical guidelines. ChatGPT 4.0 was the most accurate and consistent whereas DeepSeek R1 underperformed. Despite similar reliability across models, expert oversight remains essential to ensure safe clinical application and prevent misinformation.

Survival after minimally invasive radical hysterectomy without using uterine manipulator for early‐stage cervical cancer: A systematic review and meta‐analysis

AbstractBackgroundMinimally invasive radical hysterectomy has been reported to increase the risk of cancer relapse and death compared with open surgery in women with early‐stage cervical cancer. The use of a uterine manipulator is considered one of the risk factors.ObjectivesTo investigate whether women with early‐stage cervical cancer treated with minimally invasive radical hysterectomy without using uterine manipulator have oncological outcomes similar to those of open surgery.Search strategySearches were performed in MEDLINE, Embase and CENTRAL from their inception until 31 March 2022.Selection criteriaInclusion criteria were: (1) randomised controlled trials or observational cohort studies published in English, (2) studies comparing minimally invasive radical hysterectomy without using a uterine manipulator with open radical hysterectomy in women with early‐stage cervical cancer, and (3) studies comparing survival outcomes.Data collection and analysisTwo authors independently conducted data extraction and assessed study quality. We calculated the hazard ratios (HR) and the 95% confidence intervals (CI) using the inverse variance approach for survival outcome.Main resultsSix observational studies with 2150 women were included. The minimally invasive surgery group had a significantly higher risk of cancer relapse compared with open surgery group (HR 1.55, 95% CI 1.15–2.10).ConclusionsMinimally invasive radical hysterectomy without using a uterine manipulator resulted in an inferior recurrence‐free survival compared with open radical hysterectomy in the treatment of women with early‐stage cervical cancer.

Investigating older women with an abnormal cervical screening test: Is anxiety an issue?

Linked article: This is a mini commentary on Gustafson et al., pp. 192–200 in this issue. To view this article visit https://doi.org/10.1111/1471-0528.17299

Salpingectomy With Delayed Oophorectomy Versus Salpingo‐Oophorectomy in BRCA1/2 Carriers: Three‐Year Outcomes of a Prospective Preference Trial

ABSTRACTObjectiveTo compare menopause‐related quality of life (QoL) after risk‐reducing salpingectomy (RRS) versus risk‐reducing salpingo‐oophorectomy (RRSO) until 3 years of post‐surgery.DesignA prospective study (TUBA study) with treatment allocation based on patients' preference. Data were collected pre‐surgery and at 3 months, 1 and 3 years of post‐surgery.SettingMulticentre prospective preference trial in thirteen hospitals in the Netherlands.Population BRCA1/2 pathogenic variant (PV) carriers aged 25–40 (BRCA1) or 25–45 (BRCA2), who were premenopausal, without a future child wish and without current (treatment for) malignancy.MethodsTreatment allocation was based on patients' preference: either RRS from the age of 25 years with delayed oophorectomy at the maximum age of 45 (BRCA1) or 50 (BRCA2), or RRSO between the ages of 35–40 (BRCA1) or 40–45 (BRCA2). After RRSO, hormone replacement therapy (HRT) was recommended, if not contraindicated. Primarily, menopause‐related QoL as measured with the Greene Climacteric Scale (GCS) was compared between the RRS and RRSO without HRT group. Secondarily, GSC‐scores of the RRS group were compared with the scores of the RRSO with HRT after surgery group. A higher GSC‐score reflects more climacteric symptoms.ResultsUntil April 2023, 410 participants had undergone RRS and 160 RRSO. The BRCA1/BRCA2 proportions were 51.4%/48.6%. The mean age at surgery (SD) was 37.9 (3.5) years. Participants 3 years after RRSO without HRT had a 4.3 (95% CI 2.1–6.5; p < 0.001) point higher increase in GCS‐score from baseline compared to those after RRS, while the difference was 7.9 (95% CI 5.9–9.8) and 8.5 (95% CI 6.5–10.5) points at 3 and 12 months, respectively. Among participants with HRT after surgery, the RRSO group had a 2.4 (95% CI 0.8–3.9; p = 0.002) point higher increase in GCS‐score from baseline compared to the RRS group.ConclusionsIn this multicentre preference trial, menopause‐related QoL was better after RRS than after RRSO, even with HRT after RRSO. Differences between arms were most pronounced until one‐year post‐surgery.

Pain Reduction in Linzagolix‐Treated Patients With Uterine Fibroids: A Secondary Mediation Analysis of the PRIMROSE 1 and 2 Phase 3 Trials

ABSTRACTObjectiveAmong women with uterine fibroids (UFs), we assess the extent to which the linzagolix effect on pain alleviation is explained by its effect on reducing heavy menstrual bleeding (HMB) and fibroid volume (FV).DesignPost hoc analysis on the pooled data from two randomised double‐blind placebo‐controlled phase 3 trials.Setting94 sites in the US (PRIMROSE 1 trial) and 95 sites in Europe/US (PRIMROSE 2 trial).PopulationWomen aged ≥ 18 years with ultrasound‐confirmed UFs and HMB (n = 1012).MethodsParticipants were randomised to linzagolix (100 mg and 200 mg, with and without hormonal add‐back therapy) versus placebo. A post hoc mediation analysis was conducted on the pooled PRIMROSE 1 and PRIMROSE 2 data. The effect of linzagolix versus placebo on pain reduction was divided into three components (effect explained by HMB reduction associated with linzagolix, FV reduction associated with linzagolix, and remaining [not yet explained] treatment effect), with proportions of each component reported.Main Outcome MeasuresThe mediation analysis outcome was clinically significant pain reduction, defined as a change of ≥ 2 pain categories from baseline to Week 24 using the Numeric Rating Scale (pain categories: no pain (0), and mild (1–3), moderate (4–6), severe pain (7–10)).ResultsIn the mediation analysis, 28%–51% (depending on treatment arm) of linzagolix effect on pain reduction was explained by its effect on HMB reduction, while 2%–8% was explained by its effect on FV reduction. The residual proportion ranged between 44% and 67%, depending on treatment arm, and was statistically significant only in the linzagolix 200 mg without add‐back therapy arm (p = 0.002).ConclusionsThis analysis showed that reductions in pain were significantly mediated by reductions in HMB (all doses) and FV (200 mg alone) in linzagolix‐treated women with UFs. Further research is needed to identify additional mediating factors.Trial RegistrationClinicalTrials.gov: NCT03070899 and NCT03070951

The Swedescore: Does structured image scoring improve colposcopy performance?

Linked article: This is a mini commentary on Emilia Alfonzo et al., pp. 1261–1267 in this issue. To view this article visit https://doi.org/10.1111/1471-0528.17054.

Investigating harms of testing for ovarian cancer – psychological outcomes and cancer conversion rates in women with symptoms of ovarian cancer: A cohort study embedded in the multicentre ROCkeTS prospective diagnostic study

AbstractObjectiveTo investigate psychological correlates in women referred with suspected ovarian cancer via the fast‐track pathway, explore how anxiety and distress levels change at 12 months post‐testing, and report cancer conversion rates by age and referral pathway.DesignSingle‐arm prospective cohort study.SettingMulticentre. Secondary care including outpatient clinics and emergency admissions.PopulationA cohort of 2596 newly presenting symptomatic women with a raised CA125 level, abnormal imaging or both.MethodsWomen completed anxiety and distress questionnaires at recruitment and at 12 months for those who had not undergone surgery or a biopsy within 3 months of recruitment.Main outcome measuresAnxiety and distress levels measured using a six‐item short form of the State–Trait Anxiety Inventory (STAI‐6) and the Impact of Event Scale – Revised (IES‐r) questionnaire. Ovarian cancer (OC) conversion rates by age, menopausal status and referral pathway.ResultsOverall, 1355/2596 (52.1%) and 1781/2596 (68.6%) experienced moderate‐to‐severe distress and anxiety, respectively, at recruitment. Younger age and emergency presentations had higher distress levels. The clinical category for anxiety and distress remained unchanged/worsened in 76% of respondents at 12 months, despite a non‐cancer diagnosis. The OC rates by age were 1.6% (95% CI 0.5%–5.9%) for age <40 years and 10.9% (95% CI 8.7%–13.6%) for age ≥40 years. In women referred through fast‐track pathways, 3.3% (95% CI 1.9%–5.7%) of pre‐ and 18.5% (95% CI 16.1%–21.0%) of postmenopausal women were diagnosed with OC.ConclusionsWomen undergoing diagnostic testing display severe anxiety and distress. Younger women are especially vulnerable and should be targeted for support. Women under the age of 40 years have low conversion rates and we advocate reducing testing in this group to reduce the harms of testing.

Secondary Cytoreductive Surgery for Ovarian Cancer With Second Platinum‐Sensitive Recurrence: A Multicentre Retrospective Cohort Study

ABSTRACTObjectiveTo compare survival outcomes between patients with ovarian cancer with platinum‐sensitive recurrence (PSR) who underwent secondary cytoreductive surgery (SCS) at the first recurrence and those who underwent SCS at the second recurrence.DesignMulticentre cohort study.SettingData were retrospectively collected from five hospitals in China.PopulationPatients with ovarian cancer who underwent SCS at either the first or second PSR.MethodsOverall survival (OS) and time to second progression (PFS2), calculated from the time of recurrence to the next progression following SCS, were compared between the groups. Postsurgical complications were categorised according to the Clavien–Dindo classification system.Main Outcome MeasuresOS, PFS2, and postsurgical complications.ResultsAmong the 231 patients included, 175 underwent SCS at the first PSR (Group 1) while 56 underwent SCS at the second PSR (Group 2). Complete resection was achieved in 84.0% of patients in Group 1 and 78.6% in Group 2. Postsurgical complication rates were similar between the groups. The median OS was not reached in Group 1, whereas Group 2 had a median OS of 77.3 months. Patients who underwent SCS at the second PSR had an OS comparable to that of those who underwent SCS at the first PSR. Multivariate analyses revealed that complete resection (hazard ratio [HR] = 0.120, p = 0.002) and optimal resection (HR = 0.228, p = 0.046) were independently associated with improved survival.ConclusionsSCS is a safe and effective treatment for patients with platinum‐sensitive recurrent ovarian cancer, regardless of whether it is performed at the first or second recurrence.

Combination of PARP Inhibitor and Antiangiogenic Therapy Following Disease Progression in Patients With Epithelial Ovarian Cancer Undergoing PARP Inhibitor Maintenance Therapy: A Real‐World Study

ABSTRACTObjectiveTo investigate whether the combination of antiangiogenic therapy and poly‐ADP‐ribose polymerase inhibitors (PARPi) can enhance the effectiveness of maintenance therapy in patients with progressive ovarian cancer who are progressing after PARPi maintenance therapy.DesignRetrospective cohort study.SettingSingle‐centre tertiary hospital in Beijing, China.PopulationPatients treated with combination therapy.MethodsWe retrospectively reviewed the clinicopathological data of patients with epithelial ovarian cancer. Telephone follow‐ups were performed for eligible participants to verify disease progression and survival status.Main Outcome MeasuresClinical endpoints included objective response rate (ORR), disease control rate (DCR), time‐to‐symptomatic progression (TTSP), and progression‐free survival.ResultsOverall, 25 patients were analysed. Overall confirmed ORR was 44%, and the DCR was 68%. The median TTSP was 12.0 months (95% CI: 2.05–24.73). In the progression‐free interval (PFI) > 12 months group (n = 15), the ORR was 60% (9/15), and the DCR was 73.3%. In the PFI ≤ 12 months group (n = 10), the ORR was 20% (2/10), and the DCR was 60%. The median TTSP was not reached in the PFI > 12 months group and was 4.0 months (95% CI: 2.988–5.012) for the PFI ≤ 12 months group. The 6‐month progression‐free survival rates were 58% and 40%, respectively. Among the 10 patients who received subsequent chemotherapy, seven achieved partial response (PR), and one had stable disease. The respective ORR and DCR values were 70% and 80%.ConclusionsCombining antiangiogenic therapy with the original PARPi may benefit patients with ascites‐free ovarian cancer and a low tumour burden who experience disease progression following PARPi maintenance therapy.

The Forefront of Maintenance Therapy for Newly Diagnosed Advanced Ovarian Cancer in China: A Review of Updated Evidence With PARP Inhibitors

ABSTRACTBackgroundIn the first‐line (1L) maintenance treatment of newly diagnosed advanced ovarian cancer (OC), poly (ADP‐ribose) polymerase inhibitors (PARPi) have demonstrated significant benefits in progression‐free survival (PFS) and an encouraging trend in overall survival (OS).ObjectivesTo provide a summary of advances and evidence regarding the use of PARPi in the maintenance treatment of newly diagnosed advanced OC in the Chinese population.Search StrategySystematic search of PubMed from January 2016 to June 2024.Selection CriteriaPhase III randomized trials and real‐world studies conducted in China were included.Main ResultsPARPi 1L maintenance studies conducted in China have shown that PARPi can prolong PFS in OC patients with manageable safety. Chinese patients differ from foreign patients in baseline characteristics and safety data. Given the current situation of 1L maintenance therapy in China, recommendations are made for maintenance strategies based on different biomarker status.ConclusionsPARPi 1L maintenance therapy offers survival benefit to Chinese patients with newly diagnosed advanced OC. OC has become a chronic disease that requires the selection of appropriate maintenance regimens based on multiple factors.

PAX1/SOX1 DNA Methylation Versus Cytology and HPV16/18 Genotyping for the Triage of High‐Risk HPV‐Positive Women in Cervical Cancer Screening: Retrospective Analysis of Archival Samples

ABSTRACTObjectiveTo compare the performance of cytology, HPV16/18 genotyping and PAX1/SOX1 methylation for the triage of high‐risk HPV‐positive cervical samples.DesignRetrospective analyses of archival samples collected from a large‐scale prospective randomised controlled trial.Setting/SampleHPV‐positive women recruited from the general cervical screening population.Methods403 HPV‐positive samples including 113 normal, 173 low‐grade cervical intraepithelial neoplasia (LG‐CIN), 114 HG‐CIN and three cervical cancers. All samples were assessed by liquid‐based cytology, HPV genotyping and PAX1/SOX1 methylation.Main Outcome MeasuresAUC (area under the curve), sensitivity and specificity for cytology, HPV16/18 genotyping and PAX1/SOX1 methylation for high‐grade (HG) premalignant cervical lesions.ResultsPAX1 was more sensitive than cytology and HPV16/18 genotyping in detecting a HG lesion (CIN2+). The sensitivity for PAX1, SOX1, cytology and HPV16/18 were 73.5% (95% CI: 65.5–81.5), 41.9% (95% CI: 32.9–50.8), 48.7% (95% CI: 39.7–57.8) and 36.8% (95% CI: 28.0–45.5), respectively, and their respective specificities were 70.3% (95% CI: 65.0–75.6), 83.6% (95% CI: 79.3–87.9), 77.6% (95% CI: 72.8–82.5) and 67.1% (95% CI: 61.7–72.6), respectively. Overall, PAX1 gave the best AUC at 0.72. Adding SOX1 to PAX1 did not improve the AUC (0.68). Three hundred and twenty‐two women who did not have a HG lesion at baseline were followed up for two rounds of screening. Fewer women developed a HG lesion with a normal baseline PAX1 compared to women with a normal baseline cytology or negative HPV16/18 (8.4% vs. 14.5% and 17.5%, respectively).ConclusionPAX1 triage for referral to colposcopy in HPV‐positive women may be superior to cytology and HPV16/18 genotyping.

Fertility and Miscarriage Incidence After Cervical Intraepithelial Neoplasia Treatment by Thermal Ablation: A Cohort Study

ABSTRACTObjectiveTo assess the impact of thermal ablation (TA) for the treatment of cervical dysplasia on fertility and pregnancy outcomes among women screened for cervical cancer in Cameroon.DesignRetrospective cohort study.SettingDschang health district, Cameroon.PopulationParticipants aged 30–45 years from two screening trials conducted between 2015 and 2020 in Dschang District Hospital.MethodsParticipants were primarily screened for human papillomavirus infection, triaged by visual inspection and treated by TA if needed. Between October 2021 and March 2022, interviews on subsequent fertility were conducted with participants treated by TA and a control group of untreated women.Main Outcome MeasuresPregnancy and miscarriage after screening/treatment.ResultsA total of 760 participants (219 treated and 541 untreated) completed the survey, with a mean follow‐up time of 1297 days. Sixty‐two women (28.3%) treated by TA reported a pregnancy postscreening versus 165 (30.5%) in the control group (p = 0.550). Adjusted for potential confounders, the hazard ratio of pregnancy for treated compared with untreated women was 0.82 (0.54–1.24, p = 0.350). Among women reporting pregnancies with a known outcome and which were not voluntarily terminated, 18 (35.3%) treated participants had a miscarriage versus 31 (21.4%) in the control group (p = 0.048). In the adjusted model, no association remained between TA and miscarriage (1.04, 0.39–2.78, p = 0.935).ConclusionsIn our study population, TA did not significantly impact fertility nor miscarriage risk. Our results support the widespread use of TA as a treatment of choice for precancerous cervical lesions in low‐income settings.

Randomised trial of population‐based BRCA testing in Ashkenazi Jews: long‐term outcomes

ObjectiveUnselected population‐based BRCA testing provides the opportunity to apply genomics on a population‐scale to maximise primary prevention for breast‐and‐ovarian cancer. We compare long‐term outcomes of population‐based and family‐history (FH)/clinical‐criteria‐based BRCA testing on psychological health and quality of life.DesignRandomised controlled trial (RCT) (ISRCTN73338115) GCaPPS, with two‐arms: (i) population‐screening (PS); (ii) FH/clinical‐criteria‐based testing.SettingNorth London Ashkenazi‐Jewish (AJ) population.Population/SampleAJ women/men.MethodsPopulation‐based RCT (1:1). Participants were recruited through self‐referral, following pre‐test genetic counselling from the North London AJ population.Inclusion criteria: AJ women/men >18 years old; exclusion‐criteria: prior BRCA testing or first‐degree relatives of BRCA‐carriers.Interventions: Genetic testing for three Jewish BRCA founder‐mutations: 185delAG (c.68_69delAG), 5382insC (c.5266dupC) and 6174delT (c.5946delT), for (i) all participants in PS arm; (ii) those fulfilling FH/clinical criteria in FH arm. Linear mixed models and appropriate contrast tests were used to analyse the impact of BRCA testing on psychological and quality‐of‐life outcomes over 3 years.Main outcome measuresValidated questionnaires (HADS/MICRA/HAI/SF12) used to analyse psychological wellbeing/quality‐of‐life outcomes at baseline/1‐year/2‐year/3‐year follow up.ResultsIn all, 1034 individuals (691 women, 343 men) were randomised to PS (n = 530) or FH (n = 504) arms. There was a statistically significant decrease in anxiety (P = 0.046) and total anxiety‐&‐depression scores (P = 0.0.012) in the PS arm compared with the FH arm over 3 years. No significant difference was observed between the FH and PS arms for depression, health‐anxiety, distress, uncertainty, quality‐of‐life or experience scores associated with BRCA testing. Contrast tests showed a decrease in anxiety (P = 0.018), health‐anxiety (P < 0.0005) and quality‐of‐life (P = 0.004) scores in both PS and FH groups over time. Eighteen of 30 (60%) BRCA carriers identified did not fulfil clinical criteria for BRCA testing. Total BRCA prevalence was 2.9% (95% CI 1.97–4.12%), BRCA1 prevalence was 1.55% (95% CI 0.89–2.5%) and BRCA2 prevalence was 1.35% (95% CI 0.74–2.26%).ConclusionPopulation‐based AJ BRCA testing does not adversely affect long‐term psychological wellbeing or quality‐of‐life, decreases anxiety and could identify up to 150% additional BRCA carriers.Tweetable abstractPopulation BRCA testing in Ashkenazi Jews reduces anxiety and does not adversely affect psychological health or quality of life.

Gene sequencing in ovarian cancer: continually moving targets

Linked article: This is a mini commentary on B Frugtniet et al., pp. 433‐442 in this issue. To view this article visit https://doi.org/10.1111/1471-0528.16975

Minimally invasive surgery for suspected early‐stage ovarian cancer; a cost‐effectiveness study

ObjectiveWhile there are a number of benefits to minimally invasive surgery (MIS) for women with ovarian cysts, there is an increased risk of ovarian capsule rupture during the procedure, which could potentially seed the abdominal cavity with malignant cells. We developed a decision model to compare the risks, benefits, effectiveness and cost of MIS versus laparotomy in women with ovarian masses.DesignCost‐effectiveness studyPopulationHypothetical cohort of 10 000 women with ovarian masses who were undergoing surgical management.MethodsThe initial decision point in the model was performance of surgery via laparotomy or a MIS approach. Model probabilities, costs and utility values were derived from published literature and administrative data sources. Extensive sensitivity analyses were conducted to assess the robustness of the findings.Main outcome measuresThe primary outcome was the cost‐effectiveness of MIS versus laparotomy for women with a pelvic mass measured by incremental cost‐effectiveness ratios (ICERs).ResultsMIS was the least costly strategy at $7,732 per women on average, compared with $17,899 for laparotomy. In our hypothetical cohort of 10 000 women, there were 64 cases of ovarian rupture in the MIS group and 53 in the laparotomy group, while there were 26 cancer‐related deaths in the MIS group and 25 in the laparotomy group. MIS was more effective than laparotomy (188 462 QALYs for MIS versus 187 631 quality adjusted life years [QALYs] for laparotomy). Thus, MIS was a dominant strategy, being both less costly and more effective than laparotomy. These results were robust in a variety of sensitivity analyses.ConclusionMIS constitutes a cost‐effective management strategy for women with suspicious ovarian masses.Tweetable abstractMIS is a cost‐effective management strategy for women with suspicious ovarian masses.

Does the primary treatment sequence affect post‐relapse survival in recurrent epithelial ovarian cancer? A real‐world multicentre retrospective study

AbstractObjectiveTo explore the impact of the primary treatment sequence (primary debulking surgery, PDS, versus neoadjuvant chemotherapy and interval debulking surgery, NACT‐IDS) on post‐relapse survival (PRS) and recurrence characteristics of recurrent epithelial ovarian cancer (REOC).DesignReal‐world retrospective study.SettingTertiary hospitals in China.PopulationA total of 853 patients with REOC at International Federation of Gynaecology and Obstetrics stages IIIC–IV from September 2007 to June 2020. Overall, 377 and 476 patients received NACT‐IDS and PDS, respectively.MethodsPropensity score‐based inverse probability of treatment weighting (IPTW) was performed to balance the between‐group differences.Main Outcome MeasuresClinicopathological factors related to PRS.ResultsThe overall median PRS was 29.3 months (95% CI 27.0–31.5 months). Multivariate analysis before and after IPTW adjustment showed that NACT‐IDS and residual R1/R2 disease were independent risk factors for PRS (p < 0.05). Patients with diffuse carcinomatosis and platinum‐free interval (PFI) ≤ 12 months had a significantly worse PRS (p < 0.001). Logistic regression analysis revealed that NACT‐IDS was an independent risk factor for diffuse carcinomatosis (OR 1.36, 95% CI 1.01–1.82, p = 0.040) and PFI ≤ 12 months (OR 1.59, 95% CI 1.08–2.35, p = 0.019). In IPTW analysis, NACT‐IDS was still significantly associated with diffuse carcinomatosis (OR 1.29, 95% CI 1.05–1.58, p = 0.015) and PFI ≤ 12 months (OR 1.90, 95% CI 1.52–2.38, p < 0.001).ConclusionsThe primary treatment sequence may affect the PRS of patients with REOC by altering the recurrence pattern and PFI duration.

FOR: Fertility preservation for women with ovarian endometriosis: It is time to adopt it as routine practice

The risk of vaginal cancer is associated with a history of cervical neoplasia

An evolution in sentinel node mapping for cervical cancer

Human papillomavirus vaccine effectiveness within a cervical cancer screening programme: cohort study

ObjectiveTo assess the effectiveness of an HPV vaccination programme in reducing the risk of cervical abnormalities identified at subsequent screening.DesignRetrospective cohort study using administrative health data.SettingGeneral population of Ferrara Province, Italy.PopulationFemale residents born in 1986–1993 and participating in the organized cervical screening programme in 2011–2018, who were eligible for HPV vaccination in catch‐up cohorts.MethodsLogistic regression to evaluate the potential association between abnormal cervical cytology and one, two, three or at least one dose of HPV vaccine.Main outcome measuresCervical abnormalities, as predicted by low‐grade or high‐grade cytology, by number of vaccine doses, stratified by age.ResultsThe sample consisted of 7785 women (mean age 27.5 years, SD 2.3). Overall, 391 (5.0%) were vaccinated with ≥1 dose and 893 (11.5%) had abnormal cytology. Women receiving at least one vaccine dose were significantly less likely to have an abnormal cytology (adjusted odds ratio 0.52; 95% confidence interval 0.34–0.79). Similar results were observed for women receiving a single dose, for both bivalent and quadrivalent vaccines, and applying buffer periods (excluding cytological outcomes within 1 month, 6 months and 1 year of the first dose).ConclusionsIn the context of an organised cervical screening programme in Italy, catch‐up HPV vaccination almost halved the risk of cytological abnormalities.Tweetable abstractAmong Ferrara women, vaccination against human papillomavirus halved the risk of screening cervical abnormalities.

The influence of learning curve of robot‐assisted laparoscopy on oncological outcomes in early‐stage cervical cancer: an observational cohort study

ObjectiveTo investigate the learning curve of robot‐assisted laparoscopy in early‐stage cervical cancer and quantify impact on oncological outcomes.DesignObservational cohort study.SettingTertiary referral centre with one surgical team.PopulationAll women with early‐stage cervical cancer treated consecutively with robot‐assisted laparoscopy between 2007 and 2017.MethodsWith multivariate risk‐adjusted cumulative sum analysis (RA‐CUSUM), we assessed the learning curve of robot‐assisted laparoscopy of a single surgical team based on cervical cancer recurrence. Subsequently, a survival analysis was conducted comparing oncological outcomes of women treated during different phases of the learning curve.Main outcome measuresSurgical proficiency based on recurrence, survival rates in the different learning phases.ResultsOne hundred and sixty‐five women with cervical cancer underwent robot‐assisted laparoscopy, with a median follow up of 57 months (range 3–132 months). The RA‐CUSUM analysis demonstrated two phases of the learning curve: a learning phase of 61 procedures (group 1) and an experienced phase representing the 104 procedures thereafter (group 2). The 5‐year disease‐free survival was 80.2% in group 1 and 91.1% in group 2 (P = 0.040). Both the 5‐year disease‐specific survival and overall survival significantly increased after the learning phase.ConclusionThe learning phase of robot‐assisted laparoscopy in early‐stage cervical cancer in this institutional cohort is at least 61 procedures, with higher survival rates in the women treated thereafter. The learning curve of robot‐assisted laparoscopy affects oncological outcomes and warrants more attention in the design of future studies.Tweetable abstractThe learning curve of robot‐assisted laparoscopy in early‐stage cervical cancer affects oncological outcomes and warrants more attention.

Better triage tests needed for HPV‐positive women

Long‐term predictors of residual or recurrent cervical intraepithelial neoplasia 2–3 after treatment with a large loop excision of the transformation zone: a retrospective study

ObjectiveTo assess the long‐term risk factors predicting residual/recurrent cervical intraepithelial neoplasia (CIN 2–3) and time to recurrence after large loop excision of the transformation zone (LLETZ).DesignRetrospective study.SettingColposcopy clinic.Population242 women with CIN 2–3 treated between 1996 and 2006 and followed up until June 2016.MethodsAge, margins, and high‐risk human papillomavirus (HR‐HPV) were estimated using Cox proportional hazard and unconditional logistic regression models. The cumulative probability of treatment failure was estimated by Kaplan–Meier analysis.Main outcome measureHistologically confirmed CIN 2–3, HR‐HPV, margins, age.ResultsCIN 2–3 was associated with HR‐HPV (HR = 30.5, 95% confidence interval [CI] = 3.80–246.20), age >35 years (HR = 5.53, 95% CI = 1.22–25.13), and margins (HR = 7.31, 95% CI = 1.60–33.44). HR‐HPV showed a sensitivity of 88.8% and a specificity of 80%. Ecto+/endocervical+ (16.7%), uncertain (19.4%) and ecto−/endocervical+ margins (9.1%) showed a higher risk of recurrence (odds ratio [OR] = 13.20, 95% CI = 1.02–170.96; OR = 15.84, 95% CI = 3.02–83.01; and OR = 6.60, 95% CI = 0.88–49.53, respectively). Women with involved margins and/or who were HR‐HPV positive had more treatment failure than those who were HR‐HPV negative or had clear margins (P‐log‐rank <0.001).ConclusionsHR‐HPV and margins seem essential for stratifying post‐LLETZ risk, and enable personalised management. Given that clear margins present a lower risk, a large excision may be indicated in older women to reduce the risk.Tweetable abstractAfter LLETZ for CIN 2–3, recurrences appear more often in women with positive HR‐HPV and involved margins and aged over 35.

Intraoperative human papillomavirus testing: earlier prediction of treatment failure

Does the vaginal microbiome drive cervical carcinogenesis?

Cost‐effectiveness of HPV‐based cervical screening based on first year results in the Netherlands: a modelling study

ObjectiveWe aim to compare the cost‐effectiveness of the old cytology programme with the new high‐risk human papillomavirus (hrHPV) screening programme, using performance indicators from the new Dutch hrHPV screening programme.DesignModel‐based cost‐effectiveness analysis.SettingThe Netherlands.PopulationDutch 30‐year‐old unvaccinated females followed up lifelong.MethodsWe updated the microsimulation screening analysis (MISCAN) model using the most recent epidemiological and screening data from the Netherlands. We simulated both screening programmes, using the screening behaviour and costs observed in each programme. Sensitivity analyses were performed on screening behaviour, utility losses and discount rates.Main outcome measuresCervical cancer incidence and mortality rates, number of screening tests and repeat tests, colposcopy referrals by lesion grade, costs from a societal perspective, quality‐adjusted life years (QALYs) gained and cost‐effectiveness.ResultsThe new Dutch cervical cancer screening programme decreased the cervical cancer mortality by 4% and the incidence by 1% compared with the old programme. Colposcopy referrals of women without cervical intra‐epithelial neoplasia grade 2 or worse, increased by 172%, but 13% more QALYs were still achieved. Total costs were reduced by 21%, mainly due to fewer screening tests. Per QALY gained, the hrHPV programme cost 46% less (€12,225) than the cytology programme (€22,678), and hrHPV‐based screening remained more cost‐effective in all sensitivity analyses.ConclusionsThe hrHPV‐based screening programme was found to be more effective and cost‐effective than the cytology programme. Alternatives for the current triage strategy should be considered to lower the number of unnecessary referrals.Tweetable abstractFirst results after implementation confirm that HPV screening is more cost‐effective than cytology screening.

Vulval Flap Reconstruction in Women With Benign, Preneoplastic and Malignant Vulval Conditions: A Prospective Study

ABSTRACTObjectivesTo (i) evaluate the surgical morbidity, (ii) identify correlates of these and, (iii) explore whether flap reconstruction following vulvectomy improves patient symptoms and quality of life.DesignSingle arm prospective study.SettingSingle tertiary vulval centre, UK.PopulationConsecutive cases of women undergoing radical vulvectomy and flap reconstructions for benign and (pre)invasive vulval conditions.MethodsProspective data collection from April 2020–February 2024. All women were given two validated questionnaires preoperatively and at 3‐, 6‐ and 12‐months to evaluate their satisfaction with the aesthetic, genitourinary and psychosexual outcomes.Main Outcome MeasuresEarly and late complications within 30 days. Patient reported outcome measures preoperatively and post‐reconstruction.Results136 flaps in 69 women were analysed. 92.6% (126/136) and 83.1% (113/136) flaps developed none‐to‐mild complications at 7 days, and between days 8 to 30, respectively. Five necrotic flaps in two patients were surgically debrided. All flaps had healed/healing at 30 days. We did not identify any correlates of complications. At 12 months, women reported an improvement in genital symptoms (p < 0.001). 80.4% (37/46) reported no urinary incontinence vs. 48.1% (26/54) preoperatively, p = 0.0038. 24.4% (11/45) were sexually active vs. 9.3% (5/54) preoperatively, p = 0.0410. More women felt attractive (p = 0.0498), were satisfied with their body (p = 0.0407) and comfortable in intimate situations (p = 0.0273). 88.9% (40/45) stated that reconstruction helped with acceptance of their cancer diagnosis and surgery.ConclusionsLocoregional flap reconstruction has low surgical morbidity, leads to a significant improvement in genitourinary and psychosexual functions. In women with cancer, reconstruction supports women to cope with their diagnosis.

Patterns of cervical cancer screening among Medicaid beneficiaries

AbstractObjectiveCervical cancer screening guidelines have evolved over time with the incorporation of human papillomavirus (HPV) testing along with cytology. Current screening guidelines recommend cytological screening every 3 years or HPV testing with or without cytology every 5 years in women age 30–65 years. We examined the use of cervical cancer screening among average‐risk Medicaid beneficiaries.DesignRetrospective cohort study.PopulationWomen age 30–64 years at average risk for cervical cancer who underwent cervical cancer screening with cytology, co‐testing or primary HPV testing from 2013 to 2016.MethodsThe IBM Watson Health Multi‐State Medicaid MarketScan Database was used. Subsequent screening rates within 3 years of the index test were examined.Main outcome measureThe rate of repeat cervical cancer screening was analysed using a cumulative incidence function.ResultsA total of 265 083 patients were identified. Overall, 43.1% (n = 114 312) had index co‐testing, 55.2% (n = 146 309) had cytology and 1.7% (n = 4462) had primary HPV testing. The cumulative incidence of early, repeat cervical cancer screening was 3.9% at 12 months, 22.7% at 24 months and 33.3% at 36 months. During the period from 12 to 24 months after follow up, 20.9% of women underwent repeat screening while 19.4% underwent repeat screening 24–36 months after the index test. Among women who did not undergo repeat cervical cancer screening, a yearly gynaecological examination was performed in only 16 627 (10.7%) during year 2 and in 11 116 (8.8%) during year 3.ConclusionAmong average‐risk Medicaid beneficiaries, cervical cancer screening is frequently overused. Women who do not undergo cervical cancer screening are unlikely to undergo routine gynaecological examination.Tweetable AbstractAmong average‐risk Medicaid beneficiaries, cervical cancer screening is frequently overused.

Sinecatechins ointment as a potential novel treatment for usual type vulval intraepithelial neoplasia: a single‐centre double‐blind randomised control study

ObjectiveTo compare the safety and efficacy of 10% sinecatechins (Veregen®) ointment against placebo in the treatment of usual type vulvar intraepithelial neoplasia (uVIN).DesignA Phase II double‐blind randomised control trial.SettingA tertiary gynaecological oncology referral centre.PopulationAll women diagnosed with primary and recurrent uVIN.MethodsEligible patients were randomised 1:1 to receive either sinecatechins or placebo ointment (applied three times daily for 16 weeks) and were followed up at 2, 4, 8, 16, 32 and 52 weeks.Main outcome measuresThe primary outcome measure, recorded at 16 and 32 weeks, was histological response (HR). Secondary outcome measures included clinical (CR) response, toxicity, quality of life and pain scores.ResultsThere was no observed difference in HR between the two arms. However, of the 26 patients who were randomised, all 13 patients who received sinecatechins showed either complete (n = 5) or partial (n = 8) CR, when best CR was evaluated. In placebo group, three patients had complete CR, two had partial CR, six had stable disease and two were lost to follow up. Patients in the sinecatechins group showed a statistically significant improvement in best observed CR as compared with the placebo group (P = 0.002). There was no difference in toxicity reported in either group.ConclusionAlthough we did not observe a difference in HR between the two treatment arms, we found that 10% sinecatechins application is safe and shows promise in inducing clinical resolution of uVIN lesions and symptom improvement, thus warranting further investigation in a larger multicentre study.Tweetable abstractA randomised control study indicating that sinecatechins ointment may be a novel treatment for uVIN.

Clinical outcomes of conventional HDR intracavitary brachytherapy combined with complementary applicator‐guided intensity modulated radiotherapy boost in patients with bulky cervical tumour

AbstractObjectiveTo investigate the clinical outcomes and toxicity in patients with locally advanced cervical cancer treated with supplementary applicator guided‐intensity modulated radiation therapy (IMRT) based on conventional intracavitary brachytherapy (IC/IMRT).DesignA retrospective cohort study.SettingSichuan Cancer Hospital & Institute, Sichuan Cancer Centre, China.PopulationLarge high‐risk clinical target volume (HR‐CTV) volume (>40 ml) at the time of brachytherapy cervical cancer patients were recruited.MethodsThis study is a retrospective analysis of 76 patients with locally advanced cervical cancer (FIGO IIB‐IVA) treated with concurrent chemoradiotherapy followed by IC/IMRT between June 2010 and October 2016. External radiotherapy (45 Gy in 25 fractions) was adminstered with cisplatin chemotherapy treatment before IC/IMRT. The IMRT plan was optimised using the ICBT plan base dose plan by an inverse dose optimisation tool which allows the use of DVH constraints on the total dose of ICBT. A seven‐field gantry angle IMRT plan was devised to avoid hotspots when optimising the boost plan. The prescription dose for HR‐CTV and IR‐CTV were 6 and 5 Gy per fraction for five fractions, respectively.ResultsMean HR‐CTV was 65.8 ± 23.6 ml at the time of brachytherapy. D90 for HR‐CTV and IR‐CTV were 88.7 ± 3.6 Gy and 78.1 ± 2.5 Gy. D2cc for bladder, rectum, sigmoid and small intestine were 71.8 ± 3.8, 64.6 ± 4.9, 63.9 ± 5.3 and 56.7 ± 8.7 Gy, respectively. Median follow‐up was 85 months (47.9–124.2 months). Five‐year local recurrence‐free survival rate, metastasis recurrence‐free survival rate, disease‐free survival rate and cancer‐special survival rate were 87.6, 82.4, 70.9 and 76.3%, respectively. The grade 1 + 2 gastrointestinal and urinary late toxicities were 15.8 and 21.1%, and grade 3 late toxicities were 3.9 and 5.2%, respectively. Neither acute nor late grade 4 gastrointestinal or urinary toxicities were seen.ConclusionsThe combination of ICBT with an applicator‐guided supplementary IMRT boost achieved excellent local control and overall survival with low toxicity for bulky residual cervical tumour.

Recent advances in the cervical screening programme

Treatment planning computed tomography radiomics for predicting treatment outcomes and haematological toxicities in locally advanced cervical cancer treated with radiotherapy: A retrospective cohort study

AbstractObjectiveWe evaluated whether radiomic features extracted from planning computed tomography (CT) scans predict clinical end points in patients with locally advanced cervical cancer (LACC) undergoing intensity‐modulated radiation therapy and brachytherapy.DesignA retrospective cohort study.SettingXiangya Hospital of Central South University, Changsha, Hunan, China.PopulationTwo hundred and fifty‐seven LACC patients who were treated with intensity‐modulated radiotherapy from 2014 to 2017.MethodsPatients were allocated into the training/validation sets (3:1 ratio) using proportional random sampling, resulting in the same proportion of groups in the two sets. We extracted 254 radiomic features from each of the gross target volume, pelvis and sacral vertebrae. The sequentially backward elimination support vector machine algorithm was used for feature selection and end point prediction.Main outcomes and measuresClinical end points include tumour complete response (CR), 5‐year overall survival (OS), anaemia, and leucopenia.ResultsA combination of ten clinicopathological parameters and 34 radiomic features performed best for predicting CR (validation balanced accuracy: 80.8%). The validation balanced accuracy of 54 radiomic features was 85.8% for OS, and their scores can stratify patients into the low‐risk and high‐risk groups (5‐year OS: 95.5% versus 36.4%, p < 0.001). The clinical and radiomic models were also predictive of anaemia and leucopenia (validation balanced accuracies: 71.0% and 69.9%).ConclusionThis study demonstrated that combining clinicopathological parameters with CT‐based radiomics may have value for predicting clinical end points in LACC. If validated, this model may guide therapeutic strategy to optimise the effectiveness and minimise toxicity or treatment for LACC.

Current and prior human papillomavirus (HPV) type and cytology results enable risk assessment for triage to colposcopy

Linked article: This is a mini commentary on Gustafson et al., pp. 2132–2141. in this issue. To view this article visit https://doi.org/10.1111/1471‐0528.17200

Cervical ablation versus excision for CIN2/3: What is the current evidence?

Linked article: This is a mini commentary on Zhang et al., pp. 153–161 in this issue. To view this article visit https://doi.org/10.1111/1471-0528.17251

Impacts of the COVID‐19 pandemic on cervical cancer will be severe

Linked article: This is a mini commentary on Jennifer M. Davies et al., pp. 1133–1139 in this issue. To view this article visit https://doi.org/10.1111/1471-0528.17098

Adherence to a Cholesterol‐Lowering Diet and the Risk of Female Hormone‐Related Cancers: An Analysis From a Case–Control Study Network

ABSTRACTObjectiveWe investigated the association between a cholesterol‐lowering diet score and the risk of female hormone‐related cancers.DesignWe used data on 2108 breast, 367 endometrial, 869 ovarian cancer cases and corresponding controls from an Italian network of case–control studies.SettingHospital‐based.SampleBreast, endometrial, and ovarian cancer cases and controls.MethodsWe assessed the adherence to a cholesterol‐lowering diet using a score based on seven dietary components: high intake of non‐cellulosic polysaccharides, monounsaturated fatty acids, legumes, seeds/corn oil; low intake of saturated fatty acids, dietary cholesterol, and glycaemic index. We assigned one point for each component if the requirement was met; otherwise, we assigned zero. The overall score was calculated by summing up points over the seven components, ranging from 0 (null) to 7 (complete adherence).Main Outcome MeasuresOdds ratios (ORs) and 95% confidence intervals (CIs) were estimated through unconditional logistic regression models including terms for potential confounders.ResultsCompared to a low adherence to a cholesterol‐lowering diet (0–2 points), the ORs for a higher adherence (5–7 points) were 0.74 (95% CI: 0.60–0.92) for breast, 0.48 (95% CI: 0.30–0.77) for endometrial, and 0.77 (95% CI: 0.57–0.99) for ovarian cancer. The ORs for a 1‐point increment in the score were 0.87 (95% CI: 0.97–0.80), 0.80 (95% CI: 0.72–0.90), and 0.90 (95% CI: 0.84–0.97) for breast, endometrial, and ovarian cancers, respectively.ConclusionsA cholesterol‐lowering diet may favourably affect the risk of female hormone‐related cancers.

PARP Inhibitors Rechallenge in Patients With Recurrent Ovarian Cancer: A Multicentre Real‐World Study in China

ABSTRACTObjectiveTo evaluate the treatment pattern, outcomes, safety and identify patient populations benefiting from PARP inhibitor (PARPi) rechallenge for recurrent ovarian cancer.DesignA multicentre, retrospective, real‐world study.SettingTwelve hospitals in China.PopulationSeventy patients with recurrent ovarian cancer underwent PARPi rechallenge between 1 June 2019 and 10 March 2023.MethodsData, including demographic, clinical characteristics and treatment‐related information, were retrospectively collected from electronic health records.Main Outcome MeasuresThe primary outcome was progression‐free survival (PFS) of PARPi rechallenge (PARPi2) as maintenance therapy. We also conducted exploratory analysis to identify factors influencing PFS and characteristics associated with favourable outcomes.ResultsOf the 70 patients, 37.1% had BRCA1/2 mutations. PARPi2 was used as a maintenance therapy in 81.4% of patients, with a median PFS of 8.6 months (95% confidence interval [CI]: 6.0–13.5). PFS did not significantly differ by BRCA status (hazard ratio = 1.25 [95% CI: 0.60–2.60], p = 0.55). Achieving complete response (CR) to the last chemotherapy was a significant predictor for receiving PARPi2 for ≥ 6 months (vs. partial response, odds ratio = 4.25 [95% CI: 1.21–14.9], p = 0.02). Patients receiving combination therapies (33.3%) had longer median PFS than those receiving monotherapy (11.0 [95% CI: 5.2–15.3] vs. 7.7 [95% CI: 5.0–13.5] months). Overall, 2.9% of patients discontinued PARPi2 due to adverse events.ConclusionsPARPi rechallenge as maintenance therapy may be feasible and tolerable. Achieving CR after the last chemotherapy is associated with longer PFS and combined therapies may improve outcomes, indicating potential to overcome PARPi resistance.

CDK4/6 Inhibitor Can Improve Niraparib Sensitivity and Reverse Acquired Drug Resistance Through Endonuclease G Nuclear Translocation in BRCA Wild‐Type Ovarian Cancer: A Vitro Study

ABSTRACTObjectiveTo investigate whether the CDK4/6 inhibitor TQB‐3616 has synergistic effects with niraparib ZL‐2306 in suppressing BRCA wild‐type ovarian cancer and to explore the mechanisms of combined therapy.DesignIn vitro study.SettingLaboratory of a tertiary hospital and Experimental Animal Centre of Shanghai Jiaotong University School of Medicine.SampleSKOV3 (human ovarian cancer cell line).MethodsThe BRCA wild‐type ovarian cancer cell line, SKOV3, was used, and the niraparib‐resistant cell line (SKOV3‐NR) was generated using a concentration‐increasing method. The effects of combined therapy with TQB‐3616 and ZL‐2306 on cell viability, long‐term survival, apoptosis and cell cycle were studied in vitro and in vivo, and DNA damage was detected. Proteomic mass spectrometry was performed to determine the mechanism of action underlying combined therapy.Main Outcome MeasureCDK4/6 and niraparib efficacy.ResultsA niraparib‐resistant strain of the wild‐type BRCA ovarian cancer cell line SKOV3 was generated, and the CDK4/6 inhibitor TQB‐3616 was combined with niraparib ZL‐2306 to inhibit the growth of ovarian cancer cells and reverse drug resistance. The feasibility and effectiveness of ZL‐2306 in combination with TQB‐3616 were demonstrated in a tumour‐bearing nude mouse model.ConclusionsCombined therapy with the CDK4/6 inhibitor TQB‐3616 and niraparib ZL‐2306 showed synergistic antitumour effects against BRCA wild‐type ovarian cancer without increasing the toxicity of each drug. The antitumour effect may be related to mitochondrial apoptosis, where EndoG nuclear translocation plays a critical role. This study proposes combined therapy of CDK4/6 and PARP inhibitors as a novel approach for the treatment of refractory ovarian cancer.

The global burden, trends and cross‐country inequalities of female breast and gynaecologic cancers: A population based study

AbstractObjectiveTo analyse the global burden, trends and cross‐country inequalities of female breast and gynaecologic cancers (FeBGCs).DesignPopulation‐Based Study.SettingData sourced from the Global Burden of Disease Study 2019.PopulationIndividuals diagnosed with FeBGCs.MethodsAge‐standardised mortality rates (ASMRs), age‐standardised Disability‐Adjusted Life Years (DALYs) rates (ASDRs) and their 95% uncertainty interval (UI) described the burden. Estimated annual percentage changes (EAPCs) and their confidence interval (CI) of age‐standardised rates (ASRs) illustrated trends. Social inequalities were quantified using the Slope Index of Inequality (SII) and Concentration Index.Main Outcome MeasuresThe main outcome measures were the burden of FeBGCs and the trends in its inequalities over time.ResultsIn 2019, the ASDRs per 100 000 females were as follows: breast cancer: 473.83 (95% UI: 437.30–510.51), cervical cancer: 210.64 (95% UI: 177.67–234.85), ovarian cancer: 124.68 (95% UI: 109.13–138.67) and uterine cancer: 210.64 (95% UI: 177.67–234.85). The trends per year from 1990 to 2019 were expressed as EAPCs of ASDRs and these: for Breast cancer: −0.51 (95% CI: −0.57 to −0.45); Cervical cancer: −0.95 (95% CI: −0.99 to −0.89); Ovarian cancer: −0.08 (95% CI: −0.12 to −0.04); and Uterine cancer: −0.84 (95% CI: −0.93 to −0.75). In the Social Inequalities Analysis (1990–2019) the SII changed from 689.26 to 607.08 for Breast, from −226.66 to −239.92 for cervical, from 222.45 to 228.83 for ovarian and from 74.61 to 103.58 for uterine cancer. The concentration index values ranged from 0.2 to 0.4.ConclusionsThe burden of FeBGCs worldwide showed a downward trend from 1990 to 2019. Countries or regions with higher Socio‐demographic Index (SDI) bear a higher DALYs burden of breast, ovarian and uterine cancers, while those with lower SDI bear a heavier burden of cervical cancer. These inequalities increased over time.

Measuring HE4 alongside CA125 for ovarian cancer diagnosis: A pilot clinical study

The role of neoadjuvant chemotherapy in advanced ovarian cancer: The right treatment to the right patient – Ensuring optimal outcomes in advanced ovarian cancer

Dostarlimab for recurrent mismatch repair‐deficient endometrial cancer: A cost‐effectiveness study

AbstractObjectivePatients with recurrent endometrial cancer treated with carboplatin and paclitaxel whose disease progresses have few effective treatment options. Based on promising clinical trial data, the anti‐programmed cell death 1 (anti‐PD‐1) antibody dostarlimab was recently granted accelerated approval for endometrial cancer by the US Food and Drug Administration. We developed a decision model to examine the cost‐effectiveness of dostarlimab for patients with progressive/recurrent deficient mismatch repair (dMMR) endometrial cancer whose disease has progressed with first‐line chemotherapy.DesignCost‐effectiveness study.PopulationHypothetical cohort of 6000 women with progressive/recurrent dMMR endometrial cancer.MethodsThe initial decision point in the Markov model was treatment with dostarlimab, pembrolizumab or pegylated liposomal doxorubicin (PLD). Model probabilities, and cost and utility values were derived with assumptions drawn from published literature. Effectiveness was estimated as average quality‐adjusted life years (QALYs) gained. One‐way, two‐way and probabilistic sensitivity analyses were performed to vary the assumptions across a range of plausible values.Main outcome measuresThe primary outcome was the incremental cost‐effectiveness ratio (ICER).ResultsPegylated liposomal doxorubicin (PLD) was the least costly strategy, at $55,732, followed by dostarlimab ($151,533) and pembrolizumab ($154,597). Based on a willingness‐to‐pay threshold of $100,000/QALY, PLD was cost‐effective compared with dostarlimab, with an ICER of $331,913 per QALY gained for dostarlimab, whereas pembrolizumab was ruled out by extended dominance (less effective, more costly), compared with dostarlimab. In one‐way sensitivity analyses, dostarlimab was cost‐effective when its cost was reduced to $4905 (52% reduction). These results were robust in a variety of sensitivity analyses.ConclusionsDostarlimab is associated with greater survival compared with other treatments for women with recurrent dMMR endometrial cancer. Although the agent is substantially more costly, dostarlimab became cost‐effective when its cost was reduced to $5489 per cycle.

Uptake and outcomes of sentinel lymph node mapping in women undergoing minimally invasive surgery for endometrial cancer

AbstractObjectiveTo examine the patterns and outcomes of sentinel lymph node (SLN) assessment in women with endometrial cancer.DesignRetrospective cohort study.SettingUnited States inpatient and outpatient hospital services.PopulationWomen with endometrial cancer who underwent a laparoscopic or robotic‐assisted hysterectomy.MethodsThe Perspective Database from 2012 to 2018 was used. Performance of lymph node dissection was classified as SLN mapping, lymph node dissection or no nodal evaluation. Adjusted regression models were developed to examine the association between SLN mapping and morbidity and cost.Main Outcome MeasuresUtilisation rates, morbidity and cost of both lymph node dissection and SLN mapping.ResultsAmong 45 381 patients, SLN mapping was performed for 7768 patients (17.1%), lymph node dissection was performed for 23 214 patients (51.2%) and no lymphatic evaluation was performed for 14 399 patients (31.7%). SLN mapping increased from 1.8% in 2012 to 35.3% in 2018, whereas the rate of lymph node dissection decreased from 63.5% to 39.1% (p < 0.001). Among women who underwent nodal evaluation, residence in the west, White race and use of robotic‐assisted hysterectomy were associated with SLN mapping (p < 0.05 for all). The complication rate was 5.9% for SLN mapping, compared with 7.3% in those that underwent lymph node dissection (aRR 0.85, 95% CI 0.77–0.95). The median hospital costs for women who underwent SLN mapping ($10 479) and lymph node dissection ($10 747) were higher than for those who did not undergo nodal assessment ($9149) (p < 0.001).ConclusionsThe performance of SLN mapping is increasing for endometrial cancer. Compared with lymph node dissection, SLN mapping is associated with lower morbidity. SLN mapping significantly increases the costs compared with hysterectomy alone.Tweetable AbstractSLN mapping is increasing rapidly for endometrial cancer and is associated with decreased perioperative morbidity.

Adult lifetime body mass index trajectories and endometrial cancer risk

AbstractObjectiveTo identify body mass index (BMI) trajectories in adult life and to examine their association with endometrial cancer (EC) risk, also exploring whether relations differ by hormonal replacement therapy use.DesignPooled analysis of two case–control studies.SettingItaly and Switzerland.PopulationA total of 458 EC cases and 782 controls.MethodsWe performed a latent class growth model to identify homogeneous BMI trajectories over six decades of age, with a polynomial function of age. Odds ratios (ORs) and the corresponding 95% CI for EC risk were derived through a multiple logistic regression model, correcting for classification error.Main outcome measuresThe relation of BMI trajectories with endometrial cancer.ResultsWe identified five BMI trajectories. Compared with women in the ‘Normal weight‐stable’ trajectory, a reduction by about 50% in the risk of EC emerged for those in the ‘Underweight increasing to normal weight’ (95% CI 0.28–0.99). The ‘Normal weight increasing to overweight’ and the ‘Overweight‐stable’ trajectories were associated with, respectively, an excess of 3% (95% CI 0.66–1.60) and of 71% (95% CI 1.12–2.59) in cancer risk. The OR associated to the trajectory ‘Overweight increasing to obese’ was 2.03 (95% CI 1.31–3.13). Stronger effects emerged among hormonal replacement therapy never users (OR 2.19 for the ‘Overweight‐stable’ trajectory and OR 2.49 for the ‘Overweight increasing to obese’ trajectory).ConclusionsOur study suggests that longer exposure to overweight and obesity across a lifetime is associated with an increased risk of endometrial cancer. Weight during adulthood also appears to play an important role.Tweetable abstractLonger exposure to overweight and obesity across a lifetime is associated with an increased risk of endometrial cancer.

Authors' reply re: Mirena Coil is a suitable treatment of early‐stage endometrial cancer in obese women: FOR or AGAINST?

The Mirena coil is a suitable treatment of early‐stage endometrial cancer in obese women

Atypical endometrial polyps and the incidence of endometrial cancer: a retrospective cohort study

ObjectiveThe aim of this study was to evaluate the incidence of endometrial carcinoma, proven after hysterectomy, in patients diagnosed with atypical endometrial hyperplasia confined to a polyp. A secondary aim was to establish factors associated with (pre‐)malignant alterations in a polyp.DesignA retrospective cohort study.SettingMaastricht University Medical Centre (MUMC+) and Máxima Medical Centre in Eindhoven/Veldhoven (Máxima MC).PopulationWomen who underwent a hysteroscopic polyp resection between 2008 and 2016.MethodsPatient characteristics and histopathology results of the polyp and, in the case of a hysterectomy, uterus were collected from patients’ charts.ResultsA total of 1445 complete hysteroscopic polyp resections were included. Of those, 1390 polyps showed benign histopathology results, 39 polyps contained atypical hyperplasia and 16 polyps contained endometrial carcinoma. A hysterectomy was performed in 35 women who were diagnosed with atypical hyperplasia confined to a polyp after hysteroscopic polyp resection. Histopathological assessment showed no additional (pre‐)malignant changes of the endometrium in 12 women (30.8%), atypical hyperplasia in 11 women (28.2%) and endometrial carcinoma in 12 women (30.8%). None of the prognostic factors under consideration were significantly associated with (pre‐)malignant changes in a polyp.ConclusionThe incidence of endometrial carcinoma in the surrounding endometrium after complete resection of a polyp with atypical hyperplasia is 30.8% in this study. This supports the current advice to perform a hysterectomy and bilateral salpingo‐oophorectomy. No prognostic factor for (pre‐)malignant changes in a polyp was established.Tweetable abstractThe incidence of endometrial carcinoma after complete resection of a polyp with atypical hyperplasia is high.

‘First do no harm’ revisited in ovarian cancer cytoreduction

Linked article: This is a mini commentary on Marchetti et al., pp.1579–1588 in this issue. To view this article visit https://doi.org/10.1111/1471‐0528.17558.

Paracetamol use and risk of epithelial ovarian cancer: A nationwide nested case–control study

AbstractObjectiveTo investigate whether paracetamol use is associated with a reduced risk of epithelial ovarian cancer (EOC).DesignA nationwide nested case–control study.SettingDanish female population.PopulationA total of 9589 EOC cases diagnosed from 2000 to 2019 were age‐matched with 383 549 randomly selected female controls using risk set sampling.MethodsParacetamol use, reproductive history, history of medication and history of surgery were retrieved from Danish national registers. Paracetamol use was defined as at least two prescriptions for up to 1 year before the index date, and was further classified according to recency, duration, cumulative dose and intensity of dose.Main outcome measuresConditional logistic regression was used to estimate odds ratios and 95% confidence intervals for the association between paracetamol and EOC risk, overall and by histological subtypes.Results‘Ever’ use of paracetamol was associated with a reduced EOC risk after adjusting for potential confounding factors (OR 0.92, 95% CI 0.87–0.97). The association was only significant among recent users (OR 0.89, 95% CI 0.84–0.95). The risk declined further with the increasing level of cumulative dose and intensity; women from the group with a high cumulative dose and a high intensity had a 13% (OR 0.87, 95% CI 0.80–0.94) and 14% (OR 0.86, 95% CI 0.79–0.93) reduced risk, respectively. In the histological subtype analysis, reduced risk with ‘ever’ use was most pronounced for serous and clear cell tumours.ConclusionsParacetamol use was associated with a decreased risk of EOC in a dose–response manner. Future studies are needed to validate the findings and investigate the mechanisms behind the association.

Extending vaccination periods against human papillomavirus: Lessons from the SARS‐CoV‐2 pandemic

A Cost Consequence Analysis of Seven Diagnostic Strategies for Ovarian Cancer: A Model‐Based Economic Evaluation

ABSTRACT Objective To assess the costs and consequences of seven diagnostic strategies for ovarian cancer in pre‐ and post‐menopausal women with symptoms in secondary care. Design Economic evaluation alongside a prospective single‐arm diagnostic accuracy study. Setting NHS secondary care outpatients (2‐week referrals, clinics, GP referrals, cross‐specialty referrals) and inpatients (emergency presentations to secondary care). Sample Two cohorts of 857 pre‐menopausal and 1242 post‐menopausal women newly presenting to secondary care with symptoms of suspected ovarian cancer. Methods A model‐based cost‐consequence analysis (CCA) was conducted using a decision tree simulating patient pathways over 12 months. Diagnostic accuracy data were sourced from the ROCkeTS study and supplemented by literature. Main Outcome Measures Cancer deaths, correct diagnosis proportion, and diagnostic yield. Results No diagnostic strategy was optimal across all outcomes. Across both cohorts, the Risk of Malignancy Index (RMI) 200 was least expensive but had poor cancer death and diagnostic yield outcomes. The ADNEX 3% strategy had the highest diagnostic yield and lowest cancer mortality but was the most expensive. For pre‐menopausal women, the IOTA ADNEX 10% strategy outperformed ORADS, ROMA, and CA125 in cost and outcomes. For post‐menopausal women, the high cancer prevalence required a trade‐off. In sensitivity analysis, a two‐step IOTA ADNEX 10% strategy outperformed ORADS, ROMA, and CA125 across all three outcomes, making the strategy a more balanced choice in both cohorts. Conclusion At 12 months, no single diagnostic strategy was superior. Early diagnosis requires balancing cancer mortality, diagnostic yield, and cost. The IOTA ADNEX two‐step strategy at a 10% threshold provided the best trade‐off across these factors and is recommended for practice.

A comparison of the carbon footprint of alternative sampling approaches for cervical screening in the UK: A descriptive study

AbstractObjectiveTo 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.DesignDescriptive study.SettingNational Health Service (NHS), United Kingdom (UK).Population or SamplePatients aged 25–64 years eligible for cervical screening in the UK.MethodsA 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 MeasuresWe 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.ResultsThe 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.ConclusionsRoutine 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.

The CryoPop study: Screening for high‐grade cervical dysplasia in Karnataka, India

AbstractObjectiveTo describe our experience of screening with visual inspection with acetic acid (VIA) and colposcopy to identify women with high‐grade precancerous cervical lesions who were candidates for cryotherapy. Women were screened to determine eligibility for a clinical trial testing the safety and efficacy of a new, simple and inexpensive cryotherapy device (CryoPop®) targeted for use in low and middle‐income countries (LMICs).DesignProspective cohort study.SettingPrimary and urban health centres in Belagavi, Hubballi and Vijayapur, India.PopulationWomen in the age‐group 30–49 years, premenopausal, with no prior hysterectomy and no known HIV infection were eligible for screening.MethodsVisual inspection with acetic acid was performed on eligible women following informed consent. VIA‐positive women were referred for colposcopy and biopsy. Biopsies were read by two pathologists independently, with a third pathologist acting as tie‐breaker if needed.Main outcome measuresThe primary outcome measures were the number/proportion of women screening positive by VIA and the number/proportion of those women screening VIA‐positive found to have high‐grade cervical lesions on biopsy (cervical intraepithelial neoplasia 2/3 [CIN 2/3]). Demographic variables were compared between women who screened VIA‐positive and those who screened VIA‐negative; a separate comparison of demographic and limited reproductive variables was performed between women who had CIN 2/3 on biopsy and those without CIN 2/3 on biopsy. Chi‐square or Fisher's exact tests for categorical data andt‐tests or analysis of variance for numeric data were used with all tests two‐sided and performed at an alpha 0.05 level of statistical significance.ResultsA total of 9130 women were screened with VIA between 4 July 2020 and 31 March 2021. The mean age of all women screened was 37 years (standard deviation = 5.6 years) with 6073 of the women (66.5%) in the 30–39 year range. Only 1% of women reported prior cervical cancer screening. A total of 501 women (5.5%) were VIA‐positive; of these, 401 women underwent colposcopy. Of those who had colposcopy, 17 (4.2%) had high‐grade lesions on biopsy, an additional 164 (40.9%) had low‐grade cervical lesions on biopsy or endocervical curettage and one woman (0.2%) was found to have invasive cancer. VIA‐positive women were younger and had higher levels of education and income; however, women who were VIA‐positive and found to have CIN 2/3 were older, were more likely to be housewives and had higher household income than those without CIN 2/3.ConclusionDespite the COVID‐19 pandemic, over 9100 women were screened with VIA for precancerous lesions. However, only 17 (4.2%) were found to have biopsy‐proven high‐grade cervical lesions, underscoring the subjective performance of VIA as a screening method. Given that this is significantly lower than rates reported in the literature, it is possible that the prevalence of high‐grade lesions in this population was impacted by screening a younger and more rural population. This study demonstrates that screening is feasible in an organised fashion and can be scaled up rapidly. However, while inexpensive and allowing for same‐day treatment, VIA may be too subjective and have insufficient accuracy clearly to identify lesions requiring treatment, particularly in low‐prevalence and low‐risk populations, calling into question its overall cost‐effectiveness.

Testing for viral DNA integration among HPV‐positive women to detect cervical precancer: An observational cohort study

AbstractObjectiveHuman papillomavirus (HPV) integration is a crucial genetic step in cervical carcinogenesis. This study aimed to evaluate the performance of an HPV integration test for the triage of HPV‐positive women.DesignAn observational cohort study.SettingA cervical cancer screening programme in China.Population1393 HPV‐positive women aged 25–65 years undergoing routine cervical cancer screening and HPV integration testing with 1‐year follow‐up.MethodsThe sensitivity, specificity, positive predictive value and negative predictive value between HPV integration and cytology were compared.Main outcome measuresCervical intraepithelial neoplasia grade 3 or more severe (CIN3+).ResultsAmong 1393 HPV‐positive patients, 138 (9.9% [8.3–11.5%]) were HPV integration test positive compared with 537 who had abnormal cervical cytology (38.5% [36.0–41.1%]). Compared with cytology, HPV integration exhibited higher specificity (94.5% [93.3–95.8%] versus 63.8% [61.2–66.4%]) and equivalent sensitivity (70.5% [61.4–79.7%] versus 70.5% [61.4–79.7%]) for detection of CIN3+. HPV integration‐negative women accounted for 90.1% (1255/1393) of the total population and had a low immediate CIN3+ risk (2.2%). At 1‐year follow‐up, the progression rate in the HPV integration‐positive women was higher than in the HPV integration‐negative women (12.0% versus 2.1%, odds ratio 5.6, 95% CI, 2.6–11.9). In 10 conservatively managed integration‐negative CIN2 patients, all showed spontaneous regression and seven showed HPV clearance after 1‐year follow‐up.ConclusionThe HPV integration test may be a precise risk stratification tool for HPV‐positive women and could avoid excessive use of invasive biopsies.

Incidence and prevalence of drugs used for chronic diseases in survivors of adult‐onset gynaecological cancer – A nationwide cohort study

AbstractObjectivesTo evaluate both incidence and prevalence of drugs used for chronic diseases in survivors of adult‐onset gynaecological cancer.DesignA prospective study.SettingPopulation‐based registries.Population1.76 million women, including 17 500 women with gynaecological cancers.MethodsData from the Cancer Registry of Norway was linked to the Norwegian Prescription Database and other national databases.Main Outcome MeasuresPrevalence ratios (PRs) and hazard ratios (HRs), with 95% confidence intervals (CIs), of dispensed drugs in gynaecological cancer patients (up to 15 years after diagnosis) were estimated by log‐binomial and Cox regression, respectively, with cancer‐free women as reference.ResultsFor gynaecological cancer patients, the incidence of drugs used for pain control was higher than in cancer‐free women, especially the first 5 years after diagnosis, and the prevalence was high at least 10 years after. The prevalence of sex hormones was high in women with gynaecological cancer at least 10 years after diagnosis (cervical and ovarian cancer PR = 23, 95% CI 18–30 and PR = 24, 95% CI 15–38, respectively), but low in cancer‐free women (0.3%). Patients with uterine corpus cancer had a higher prevalence of antidiabetics before and at least 10 years after diagnosis, most pronounced in women diagnosed before age 50 (PR = 10, 95% CI 5.0–21). The prevalence of antidepressants was moderately elevated in women with gynaecological cancers.ConclusionsGynaecological cancer survivors, particularly cervical and ovarian cancer survivors, had an increased long‐term use of drugs for pain control and sex hormones. Survivors of uterine corpus cancer used antidiabetics more often, both before and after diagnosis.

Attitudes towards risk‐reducing early salpingectomy with delayed oophorectomy for ovarian cancer prevention: a cohort study

ObjectiveTo determine risk‐reducing early salpingectomy and delayed oophorectomy (RRESDO) acceptability and effect of surgical prevention on menopausal sequelae/satisfaction/regret in women at increased ovarian cancer (OC) risk.DesignMulticentre, cohort, questionnaire study (IRSCTN:12310993).SettingUnited Kingdom (UK).PopulationUK women without OC ≥18 years, at increased OC risk, with/without previous RRSO, ascertained through specialist familial cancer/genetic clinics and BRCA support groups.MethodsParticipants completed a 39‐item questionnaire. Baseline characteristics were described using descriptive statistics. Logistic/linear regression models analysed the impact of variables on RRESDO acceptability and health outcomes.Main outcomesRRESDO acceptability, menopausal sequelae, satisfaction/regret.ResultsIn all, 346 of 683 participants underwent risk‐reducing salpingo‐oophorectomy (RRSO). Of premenopausal women who had not undergone RRSO, 69.1% (181/262) found it acceptable to participate in a research study offering RRESDO. Premenopausal women concerned about sexual dysfunction were more likely to find RRESDO acceptable (odds ratio [OR] = 2.9, 95% CI 1.2–7.7, P = 0.025). Women experiencing sexual dysfunction after premenopausal RRSO were more likely to find RRESDO acceptable in retrospect (OR = 5.3, 95% CI 1.2–27.5, P < 0.031). In all, 88.8% (143/161) premenopausal and 95.2% (80/84) postmenopausal women who underwent RRSO, respectively, were satisfied with their decision, whereas 9.4% (15/160) premenopausal and 1.2% (1/81) postmenopausal women who underwent RRSO regretted their decision. HRT uptake in premenopausal individuals without breast cancer (BC) was 74.1% (80/108). HRT use did not significantly affect satisfaction/regret levels but did reduce symptoms of vaginal dryness (OR = 0.4, 95% CI 0.2–0.9, P = 0.025).ConclusionData show high RRESDO acceptability, particularly in women concerned about sexual dysfunction. Although RRSO satisfaction remains high, regret rates are much higher for premenopausal women than for postmenopausal women. HRT use following premenopausal RRSO does not increase satisfaction but does reduce vaginal dryness.Tweetable abstractRRESDO has high acceptability among premenopausal women at increased ovarian cancer risk, particularly those concerned about sexual dysfunction.

Patterns of clinicopathological features and outcome in epithelial ovarian cancer patients: 35 years of prospectively collected data

ObjectiveInvestigate the clinical landscape of ovarian carcinoma (OC) over time.DesignRegister‐based prospectively collected data.SettingSouth East Scotland.SampleA total of 2805 OC patients diagnosed in 1981–2015.MethodsSurvival times were visualised using the Kaplan–Meier method; median survival, 5‐year survival probabilities and associated restricted mean survival time analyses were used to quantify survival differences.Main outcome measuresDisease‐specific survival.ResultsA significant increase in disease‐specific survival (DSS) from 1981–1985 to 2011–2015 was observed (median 1.73 versus 4.23 years, P < 0.0001). Corresponding increase in progression‐free survival (PFS) was not statistically significant (median 1.22 versus 1.58 years, P = 0.2568). An increase in the proportion of cases with low residual disease volume (RD) (<2 cm RD) following debulking was observed (54.0% versus 87.7%, P < 0.0001). The proportion of high grade serous (HGS) cases increased (P < 0.0001), whereas endometrioid and mucinous cases decreased (P = 0.0005 and P = 0.0002). Increases in stage IV HGS OC incidence (P = 0.0009) and stage IV HGS OC DSS (P = 0.0122) were observed. Increasing median age at diagnosis correlated with increasing Eastern Cooperative Oncology Group Performance Status (ECOG PS) over time (r = 0.86).ConclusionsOC DSS has improved over the last 35 years. PFS has not significantly increased, highlighting that improvement in outcome has been limited to extending post‐relapse survival. Distribution of stage at diagnosis, histological subtype and RD following debulking has changed over time, reflecting evolution in tumour classification, staging and optimal debulking definitions (from low RD to minimal or zero RD). Histology, stage, RD and ECOG PS remain reliable outcome predictors. Increasing median age at diagnosis and ECOG PS indicates demographic shifts in the clinical population.Tweetable abstractSignificant improvement in ovarian carcinoma survival has been seen over time. Most of this improvement is due to an extension of survival following disease relapse.

Recovery After Transcervical Fibroid Ablation Versus Minimally Invasive Myomectomy for Symptomatic Uterine Fibroids: A Randomised Controlled Trial

ABSTRACT Objective To evaluate early recovery outcomes with transcervical fibroid ablation (TFA) compared to minimally invasive myomectomy (MIM) in women with symptomatic uterine fibroids. Design Randomised controlled trial. Setting Tübingen University Hospital (Tübingen, Germany). Sample Premenopausal women aged 18–50 years with symptomatic uterine fibroids. Methods Participants were randomised to undergo TFA or MIM. The MIM group underwent laparoscopic myomectomy with concurrent hysteroscopic myomectomy if submucosal fibroids were present. Main Outcome Measures The primary endpoint was the time to return to normal activities. Secondary outcomes included procedure time, postprocedural pain, hospital discharge readiness, time to return to 10 additional activities of daily living, and adverse events. Clinical outcomes through 7 weeks of follow‐up were reported. The primary endpoint was evaluated at p  < 0.028 due to a pre‐planned interim analysis; secondary outcomes were evaluated at p  < 0.05. Results Among 144 randomised patients, 119 provided follow‐up data (58 TFA; 61 MIM). The primary endpoint was met with the median time to return to normal activities favouring TFA (5.5 vs. 13 days; log‐rank p  < 0.001). Procedure time (51 ± 21 vs. 95 ± 37 min; p  < 0.001), postprocedural pain through discharge (all p  < 0.01), opioid utilisation (25.9% vs. 49.2%, p  = 0.009), and time to discharge readiness (22.9 ± 13.2 vs. 58.9 ± 33.1 h; p  < 0.001) favoured TFA. Nine of 10 treatment recovery metrics statistically favoured TFA with none favouring MIM. One serious adverse event occurred in a patient treated with MIM (diagnostic laparoscopy for postoperative bleeding). Conclusions TFA offers a faster recovery than MIM for the treatment of symptomatic uterine fibroids, with a comparable short‐term safety profile. Trial Registration This trial was prospectively registered on the German Clinical Trials Register; https://drks.de/search/de/trial/DRKS00028847

The Use of First‐Void Urine to Screen Women Aged 60–79 for HPV in the UK: The Catch‐Up Screen Study

ABSTRACT Objective Almost half the deaths from cervical cancer in the UK are among women aged over 65 who were already above the upper age of screening when primary HPV screening was introduced in the UK in 2019. Our aim is to test the feasibility of a national catch‐up HPV testing programme. Design This first phase of the Catch‐Up Screen study involved randomizing over 3000 invited participants to receive a urine HPV test and a follow‐up telephone call or text message. Setting GP practices in Hull and Manchester, UK. Population Women aged 60–79 who have not undergone primary HPV screening. Methods Eligible women were selected from GP practice records, and 3074 were invited to provide an at‐home first‐void urine sample for HPV testing. Main Outcome Measures Uptake of at‐home urine screening according to screening history, area‐level index of deprivation, and randomised follow‐up method. Results Overall, 59% (1816) of invited women returned a urine sample for HPV testing. Response varied by screening history and index of area‐level deprivation, but 39% of those who declined their last invited NHS screen responded favorably and took part in Catch‐Up Screen. Telephone reminders yielded a 5% absolute increase in response compared to the text message arm ( p  = 0.007). Conclusions An at‐home first‐void urine sample is a viable method for a national catch‐up HPV test and has the potential to address decreasing national coverage among older women being invited for their last screen.

A commentary on the discrepancy between blood and tumour BRCA testing: An open question

The impact of surgical learning curve on survival – reopening the door for minimally invasive surgery in the management of cervical cancer?

Reflex cytology for triage of high‐risk human papillomavirus positive self‐sampled material in cervical cancer screening: a prospective cohort study

ObjectiveHigh‐risk human papillomavirus (HrHPV)‐positive women detected by self‐sampling require an extra visit at the general practitioner for additional cytology testing, but the loss to follow up within this triage is substantial. The aim of this study was to evaluate the clinical utility of reflex cytology on hrHPV‐positive self‐samples for immediate stratification of women who need referral for colposcopy.DesignA prospective cohort study.SettingTwo Dutch cervical cancer‐screening laboratories.Population1014 screenees who tested hrHPV‐positive on self‐samples between 1 December 2018 and 1 August 2019.MethodsSelf‐samples were directly used for cytological analysis. Cytological and histological outcomes during follow up were obtained from the Dutch Pathology Registry (PALGA).Main outcome measuresTest performance of reflex cytology on self‐samples was determined for different thresholds and compared with physician‐taken cytology and histological outcomes.ResultsReflex cytology on self‐samples for detecting abnormal cytology showed a sensitivity of 26.4% (95% CI 21.8–31.3) and specificity of 90.5% (95% CI 87.7–92.8). Of all ≥CIN2 cases, 29.4% (95% CI 22.5–37.1) were detected with reflex cytology on self‐samples. The positive predictive value for detection of ≥CIN2 was higher with cytology on self‐collected samples than on physician‐collected samples. Of women who were lost to follow up, 12.9% were found to have abnormal cytology on their self‐sampled material.ConclusionCytology testing is achievable on hrHPV‐positive self‐samples, could decrease the loss to follow up in screening and is easily implementable in the current clinical practice. Of all hrHPV‐positive women with abnormal cytology on additional physician‐collected samples, 26.4% could have been directly referred for colposcopy if triage with reflex cytology on self‐sampled material had been performed.Tweetable abstractReflex cytology for triage of hrHPV+ self‐samples is of added value for direct referral of women for colposcopy.

Low incidence of pulmonary metastases in vulvar cancer patients: limited value of routine chest imaging based on a cohort study

ObjectiveTo evaluate the incidence of pulmonary metastases in the preoperative work‐up of patients with primary vulvar squamous cell carcinoma (SCC).DesignRetrospective cohort study.SettingTertiary referral centre.PopulationPatients treated for primary vulvar SCC from 2000 to 2018.MethodsThe pre‐operative chest imaging of 452 consecutively treated patients was documented with a minimal follow‐up period of 2 years.Mean outcome measuresIncidence of pulmonary metastases, frequency of chest imaging and subsequent coincidental findings.ResultsIn total, 80.8% of patients underwent pre‐operative chest imaging. Seven patients (1.9%), with a median tumour size of 80 mm, presented with pulmonary metastases. None of the patients with early stage disease and tumour size <40 mm who underwent radical local excision (RLE) with sentinel node (SN)‐procedure, was diagnosed with pulmonary metastasis. Chest imaging was performed by radiography (58.9%) and computerised tomography (CT) (41.1%). Coincidental findings were reported in 40.7% of patients who underwent CT, compared with 15.8% of patients undergoing radiography, resulting in additional diagnostics in 14.7 and 19.7% and being of limited consequence for outcome in 2.9 and 3.3%, respectively.ConclusionsThe incidence of pulmonary metastases in patients with primary vulvar SCC is extremely low, and none in patients with early stage disease undergoing the SN procedure. Chest imaging was performed in the majority of patients and was associated with frequent coincidental findings leading to clinically irrelevant diagnostic procedures. Therefore, we recommend omitting chest imaging in patients with early stage disease and tumours <40 mm, considering chest CT only in patients with large tumours and/or advanced stage disease.Tweetable abstractThe incidence of pulmonary metastases is 1.9%, none in early stage disease planned for SN. Omitting chest imaging in this group is advised.

Natural history of pelvic floor disorders before and after hysterectomy for gynaecological cancer

AbstractObjectiveTo investigate the prevalence and severity of pelvic floor disorders (PFD), and the associations between treatment type and PFD, and cancer stage and PFD in patients before and after hysterectomy for gynaecological cancer; and the changes in outcomes over time.DesignLongitudinal cohort study.SettingGynaecological oncology outpatient clinics.PopulationPatients undergoing hysterectomy for endometrial, uterine, ovarian or cervical cancer.MethodsParticipants were assessed before, and 6 weeks and 3 months after hysterectomy. Changes over time were analysed using generalised estimating equations or linear mixed models. Associations were analysed using logistic regression models and analyses of variance.Main outcome measuresIncontinence Severity Index, Pelvic Floor Distress Inventory‐short form (PFDI‐20), Female Sexual Function Index.ResultsOf 277 eligible patients, 126 participated. Prevalence rates of PFD were high before (urinary incontinence [UI] 66%, faecal incontinence [FI] 12%, sexual inactivity 73%) and after (UI 59%, FI 14%, sexual inactivity 58%) hysterectomy. Receiving adjuvant therapy led to moderate‐to‐very severe UI 3 months after surgery compared with surgery only (odds ratio 4.98, 95% CI 1.63–15.18). There was no association between treatment type and other PFD, or cancer stage and any PFD.ConclusionPrevalence of PFD was high before and after hysterectomy for gynaecological cancer. Moderate‐to‐very‐severe UI was associated with adjuvant therapy.

Metformin plus megestrol acetate compared with megestrol acetate alone as fertility‐sparing treatment in patients with atypical endometrial hyperplasia and well‐differentiated endometrial cancer: a randomised controlled trial

ObjectiveTo assess the efficacy of metformin in megestrol acetate (MA)‐based fertility‐sparing treatment for patients with atypical endometrial hyperplasia (AEH) and endometrioid endometrial cancer (EEC).DesignA randomised, single‐centre, open‐label, controlled trial conducted between October 2013 and December 2017.SettingShanghai OBGYN Hospital of Fudan University, China.PopulationA total of 150 patients (18–45 years old) with primary AEH or well‐differentiated EEC were randomised into an MA group (n = 74) and an MA plus metformin group (n = 76).MethodsPatients with AEH or EEC were firstly stratified, then randomised to receive MA (160 mg orally, daily) or MA (160 mg orally, daily) plus metformin (500 mg orally, three times a day).Main outcomes and measuresThe primary efficacy parameter was the cumulate complete response (CR) rate within 16 weeks of treatment (16w‐CR rate); the secondary efficacy parameters were 30w‐CR rate and adverse events.ResultsThe 16w‐CR rate was higher in the metformin plus MA group than in the MA‐only group (34.3 versus 20.7%, odds ratio [OR] 2.0, 95% confidence interval [CI] 0.89–4.51, P = 0.09) but the difference was more significant in 102 AEH patients (39.6 versus 20.4%, OR 2.56, 95% CI 1.06–6.21, P = 0.04). This effect of metformin was also significant in non‐obese (51.4 versus 24.3%, OR 3.28, 95% CI 1.22–8.84, P = 0.02) and insulin‐sensitive (54.8 versus 28.6%, OR 3.04, 95% CI 1.03–8.97, P = 0.04) subgroups of AEH women. No significant result was found in secondary endpoints.ConclusionAs a fertility‐sparing treatment, metformin plus MA was associated with a higher early CR rate compared with MA alone in AEH patients.Tweetable abstractFor AEH patients, metformin plus MA might be a better fertility‐sparing treatment to achieve a higher early CR rate compared with MA alone.

Who really benefits from intraperitoneal chemotherapy for advanced ovarian cancer? A treatment‐free survival analysis of the AICE trial

AbstractObjectiveTo investigate whether peritoneal disease extent can predict the survival benefit of intraperitoneal/intravenous (IP/IV) chemotherapy in ovarian cancer.DesignA treatment‐free survival (TFS) analysis.SettingFive‐centre trial.PopulationAn extended follow‐up of the Additional Intraperitoneal Cisplatin and Etoposide in ovarian cancer (AICE) trial (NCT01669226), with data cut‐off on 27 August 2020. Patients were categorised into subgroups with high tumour burden (HTB) and low tumour burden (LTB).MethodsOverall survival (OS) was divided into time on protocol treatment exposure (T), time free of subsequent treatment or death (TFS) and time after the first subsequent therapy (REL). TFS analyses and quality‐adjusted OS were calculated by multiplying the mean time in each health state by its assigned utility: quality‐adjusted OS = ut × T + TFS + urel × REL.Main outcome measuresThe area under each Kaplan–Meier curve was estimated using the 96‐month restricted mean time, with threshold utility analyses used to illustrate quality‐adjusted OS comparisons.ResultsIn the HTB subgroup, the restricted mean TFS was 33.9 months and 18.7 months in the IP/IV and IV groups, respectively (p = 0.005), with a significant quality‐adjusted OS gain (13.2–16.0 months). In the LTB subgroup, IP/IV therapy yielded no survival benefit in either TFS (p = 0.268) or quality‐adjusted OS (range: 1.4–6.3 months).ConclusionsBoth TFS and quality‐adjusted OS was longer across all utility weight values with IP/IV than with standard IV therapy in the HTB subgroup, whereas patients in the LTB subgroup did not benefit from the therapy. The tumour burden of ovarian cancer should be assessed before deciding on IP/IV versus IV treatment.

High co‐expression of SLC7A11 and GPX4 as a predictor of platinum resistance and poor prognosis in patients with epithelial ovarian cancer

AbstractObjectiveThe aim was to assess the expression levels of SLC7A11 and GPX4 in relation to platinum resistance and prognosis in patients with epithelial ovarian cancer (EOC).DesignA retrospective cohort study.SettingWomen's Hospital, Zhejiang University School of Medicine, Hangzhou, China.Population or SampleWe included 192 eligible patients from hospital between January 2002 and December 2018.MethodsWe retrospectively analysed the medical records of patients with EOC. Surgical specimens of EOC were stained for SLC7A11 and GPX4. Survival analysis was performed using the Kaplan–Meier and Cox regression methods.Main Outcome MeasuresClinical end points include platinum‐free interval (PFI), progression‐free survival (PFS) and overall survival (OS).ResultsPatients with high co‐expression levels of SLC7A11 and GPX4 had a 60‐fold higher risk of platinum resistance compared with those with low co‐expression (risk ratio, 60.46; 95% confidence interval [CI] 22.76–160.58; p < 0.001). Moreover, high co‐expression level of SLC7A11 and GPX4 was an independent prognostic factor for poor OS (p < 0.001, hazard ratio [HR] 4.44, 95% CI, 2.77–7.14) and poor PFS (p < 0.001, HR = 5.73, 95% CI, 3.86–8.73). For in vitro experiments, SLC7A11 and GPX4 expression were both upregulated in platinum‐resistant cells compared with their parental ovarian cancer cells, and siRNA‐induced SLC7A11 and GPX4 inhibition decreased platinum resistance.ConclusionsHigh expression levels of SLC7A11 and GPX4 are associated with platinum resistance in EOC patients. High co‐expression of SLC7A11 and GPX4 may be a significant independent prognostic factor and a potential therapeutic target for platinum resistance in EOC patients.

Updates on fluorescent probes and open‐field imaging methods for fluorescence‐guided cytoreductive surgery for epithelial ovarian cancer: A review

AbstractFluorescence‐guided surgery has emerged as a promising imaging technique for real‐time intraoperative tumour delineation and visualisation of submillimetre tumour masses in cytoreductive surgery for epithelial ovarian cancer (EOC). Researchers have developed several EOC‐targeted fluorescent probes, most of which are currently in the preclinical stage. Interestingly, imaging devices designed for open surgery are proof of concept. This review summarises the recent advances in EOC‐targeted fluorescent probes and open‐field fluorescence imaging strategies and discusses the challenges and potential solutions for clinical translation.

Patient decision aids in mainstreaming genetic testing for women with ovarian cancer: A prospective cohort study

AbstractObjectiveTo evaluate patient preference for short (gist) or detailed/extensive decision aids (DA) for genetic testing at ovarian cancer (OC) diagnosis.DesignCohort study set within recruitment to the Systematic Genetic Testing for Personalised Ovarian Cancer Therapy (SIGNPOST) study (ISRCTN: 16988857).SettingNorth‐East London Cancer Network (NELCN) population.Population/SampleWomen with high‐grade non‐mucinous epithelial OC.MethodsA more detailed DA was developed using patient and stakeholder input following the principles/methodology of IPDAS (International Patients Decision Aids Standards). Unselected patients attending oncology clinics evaluated both a pre‐existing short and a new long DA version and then underwent mainstreaming genetic testing by a cancer clinician. Appropriate inferential descriptive and regression analyses were undertaken.Main outcome measuresSatisfaction, readability, understanding, emotional well‐being and preference for long/short DA.ResultsThe mean age of patients was 66 years (interquartile range 11), and 85% were White British ethnicity. Of the participants, 74% found DAs helpful/useful in decision‐making. Women reported higher levels of satisfaction (86% versus 58%, p < 0.001), right amount of information provided (76.79% versus49.12%, p < 0.001) and improved understanding (p < 0.001) with the long DA compared with the short DA. There was no statistically significant difference in emotional outcomes (feeling worried/concerned/reassured/upset) between ‘short’ and ‘long’ DA; 74% of patients preferred the long DA and 24% the short DA. Patients undergoing treatment (correlation coefficient (coef) = 0.603; 95% CI 0.165–1.041, p = 0.007), those with recurrence (coef = 0.493; 95% CI 0.065–0.92, p = 0.024) and older women (coef = 0.042; 95% CI 0.017–0.066, p = 0.001) preferred the short DA. Ethnicity did not affect outcomes or overall preference for long/short DA.ConclusionsA longer DA in OC patients has higher satisfaction without increasing emotional distress. Older women and those undergoing treatment/recurrence prefer less extensive information, whereas those in remission preferred a longer DA.

Quality of life in patients with advanced ovarian cancer after primary debulking surgery versus neoadjuvant chemotherapy: Results from the randomised SCORPION trial (NCT01461850)

AbstractObjectiveTo investigate the effect of treatment with neoadjuvant chemotherapy (NACT) followed by interval debulking surgery (IDS), versus primary debulking surgery (PDS), on quality of life (QoL) in patients with advanced epithelial ovarian cancer (EOC).DesignRandomised trial conducted in a single institution.SettingDivision of Gynaecologic Oncology, Fondazione Policlinico Universitario A. Gemelli IRCCS, Rome, Italy.SamplePatients with stage‐IIIC/IV EOC and high tumour load.MethodsPatients were randomised (1:1) to undergo either PDS (PDS group) or NACT followed by IDS (NACT/IDS group).Main outcome measuresQuality‐of‐life (QoL) data, assessed using the European Organization for Research and Treatment of Cancer core QoL questionnaire (QLQ‐C30) and ovarian cancer module (OV28); co‐primary outcomes were the QLQ‐C30 global health score at 12 months (cross‐sectional analysis) and the difference in mean QLQ‐C30 global health score over time between treatment groups (longitudinal analysis).ResultsFrom October 2011 to May 2016, 171 patients were enrolled (PDS = 84; NACT/IDS = 87). We observed no clinical or statistically significant difference between treatment groups in any of the QoL functioning scales at 12 months, including QLQ‐C30 global health score (NACT/IDS group vs PDS group, mean difference 4.7, 95% CI −4.99 to 14.4, p = 0.340). Over time, we found lower global health scores for those undergoing PDS than for those receiving NACT (difference in mean score 6.27, 95% CI 0.440–12.11, p = 0.035), albeit this was not clinically relevant.ConclusionsWe found no difference in global QoL related to treatment approach at 12 months, even though patients in the NACT/IDS group reported better global health scores across the 12‐month period compared with the PDS group; these findings further confirm that NACT/IDS might be a feasible option for patients unsuitable for PDS.

Risk of vaginal cancer among hysterectomised women with cervical intraepithelial neoplasia: a population‐based national cohort study

ObjectiveTo study the risk of vaginal cancer among hysterectomised women with and without cervical intraepithelial neoplasia (CIN).DesignPopulation‐based national cohort study.Setting and populationAll Swedish women, 5 million in total, aged 20 and up, 1987–2011 using national registries.MethodsThe study cohort was subdivided into four exposure groups: hysterectomised with no previous history of CIN3 and without prevalent CIN at hysterectomy; hysterectomised with a history of CIN3/adenocarcinoma in situ (AIS); hysterectomised with prevalent CIN at hysterectomy; non‐hysterectomised.Main outcome measureVaginal cancer.ResultsWe identified 898 incident cases of vaginal cancer. Women with prevalent CIN at hysterectomy and those with a history of CIN3/AIS had incidence rates (IR) of vaginal cancer of 51.3 (95% CI 34.4–76.5) and 17.1 (95% CI 12.5–23.4) per 100 000, respectively. Age‐adjusted IR‐ratios (IRRs) compared with hysterectomised women with benign cervical history were 21.0 (95% CI 13.4–32.9) and 5.81 (95% CI 4.00–8.43), respectively. IR for non‐hysterectomised women was 0.87 (95% CI 0.81–0.93) and IRR was 0.37 (95% CI 0.30–0.46). In hysterectomised women with prevalent CIN, the IR remained high after 15 years of follow up: 65.7 (95% CI 21.2–203.6).ConclusionsOur findings suggest that hysterectomised women with prevalent CIN at surgery should be offered surveillance. Hysterectomised women without the studied risk factors have a more than doubled risk of contracting vaginal cancer compared with non‐hysterectomised women in the general population. Still, the incidence rate does not justify screening.Tweetable abstractHigh risk of contracting vaginal cancer among hysterectomised women having prevalent CIN at surgery.

Global impacts of COVID‐19 pandemic on sexual and reproductive health services: An international comparative study on primary care from the INTRePID Consortium

AbstractObjectiveTo understand how the COVID‐19 pandemic has impacted sexual and reproductive health (SRH) visits.DesignAn ecological study comparing SRH services volume in different countries before and after the onset of the COVID‐19 pandemic.SettingSeven countries from theINTernational ConsoRtium ofPrimary Care BIgData Researchers (INTRePID) across four continents.PopulationOver 3.8 million SRH visits to primary care physicians in Australia, China, Canada, Norway, Singapore, Sweden and the USA.MethodsDifference in average SRH monthly visits before and during the pandemic, with negative binomial regression modelling to compare predicted and observed number of visits during the pandemic for SRH visits.Main outcome measuresMonthly number of visits to primary care physicians from 2018 to 2021.ResultsDuring the pandemic, the average volume of monthly SRH visits increased in Canada (15.6%, 99% CI 8.1–23.0%) where virtual care was pronounced. China, Singapore, Sweden and the USA experienced a decline (−56.5%, 99% CI −74.5 to −38.5%; −22.7%, 99% CI −38.8 to −6.5%; −19.4%, 99% CI −28.3 to −10.6%; and −22.7%, 99% CI −38.8 to −6.5%, respectively); while Australia and Norway showed insignificant changes (6.5%, 99% CI −0.7 to –13.8% and 1.7%, 99% CI −6.4 to –9.8%). The countries that maintained (Australia, Norway) or surpassed (Canada) pre‐pandemic visit rates had the greatest use of virtual care.ConclusionsIn‐person SRH visits to primary care decreased during the pandemic. Virtual care seemed to counterbalance that decline. Although cervical cancer screening appeared insensitive to virtual care, strategies such as incorporating self‐collected samples for HPV testing may provide a solution in a future pandemic.

Beyond P16/Ki67 dual‐stain cytology: Exploring alternative biomarkers for diagnosing cervical cancer and its precursors

Incidence distributions, risk factors and trends of vaginal cancer: A global population‐based study

AbstractObjectiveThis study aimed to investigate the incidence, risk factors and trends for vaginal cancer.DesignRetrospective observational design.SettingData were collected from multiple sources, including the Global Cancer Observatory, Cancer Incidence in Five Continents Plus, Global Burden of Disease, World Bank and the United Nations.PopulationIndividuals diagnosed with vaginal cancer.MethodsThe study collected data on vaginal cancer from the specified sources. The age‐standardised rate (ASR) of vaginal cancer was calculated for different regions and age groups. Multivariable and univariable linear regression analyses were performed to examine the associations between risk factors and the incidence of vaginal cancer. Trend analysis was conducted using joinpoint regression analysis, and the average annual percentage change (AAPC) was calculated to quantify the temporal trend.Main Outcome MeasuresThe main outcome measures of the study were the incidence of vaginal cancer, risk factors associated with the disease and the trend of its incidence over time.ResultsThere were 17 908 newly reported cases of vaginal cancer (ASR = 0.36, 95% CI 0.30–0.44) in 2020, with the highest ASRs reported in South–Central Asia and Southern Africa. Risk factors associated with a higher incidence of vaginal cancer included a higher prevalence of unsafe sex and human immunodeficiency virus (HIV) infection. The temporal trend showed an overall rising incidence globally, with Iceland (AAPC = 29.56, 95% CI 12.12–49.71), Chile (AAPC = 22.83, 95% CI 13.20–33.27), Bahrain (AAPC = 22.05, 95% CI 10.83–34.40) and the UK (AAPC = 1.40, 95% CI 0.41–2.39) demonstrating the most significant rising trends.ConclusionsThe significant regional disparities and risk factors associated with vaginal cancer underscore the necessity for targeted interventions and education, particularly in regions with a lower human development index (HDI) and a higher prevalence of human papillomavirus (HPV) infection. The increasing incidence trend emphasises the need for enhanced HPV vaccination rates to prevent the development of vaginal cancer.

Hysterectomy and ovarian cancer: further research is needed to inform clinical decision making

Linked article: This is a mini commentary on JA Taylor et al., pp. 110–118 in this issue. To view this article visit https://doi.org/10.1111/1471‐0528.16943

Randomised trial of population‐based BRCA testing in Ashkenazi Jews: long‐term secondary lifestyle behavioural outcomes

AbstractObjectiveAshkenazi‐Jewish (AJ) population‐based BRCA testing is acceptable, cost‐effective and amplifies primary prevention for breast & ovarian cancer. However, data describing lifestyle impact are lacking. We report long‐term results of population‐based BRCA testing on lifestyle behaviour and cancer risk perception.DesignTwo‐arm randomised controlled trials (ISRCTN73338115, GCaPPS): (a) population‐screening (PS); (b) family history (FH)/clinical criteria testing.SettingNorth London AJ‐population.Population/SampleAJ women/men >18 years. Exclusions: prior BRCA testing or first‐degree relatives of BRCA‐carriers.MethodsParticipants were recruited through self‐referral. All participants received informed pre‐test genetic counselling. The intervention included genetic testing for three AJ BRCA‐mutations: 185delAG(c.68_69delAG), 5382insC(c.5266dupC) and 6174delT(c.5946delT). This was undertaken for all participants in the PS arm and participants fulfilling FH/clinical criteria in the FH arm. Patients filled out customised/validated questionnaires at baseline/1‐year/2‐year/3‐year follow‐ups. Generalised linear‐mixed models adjusted for covariates and appropriate contrast tests were used for between‐group/within‐group analysis of lifestyle and behavioural outcomes along with evaluating factors associated with these outcomes. Outcomes are adjusted for multiple testing (Bonferroni method), with P < 0.0039 considered significant.Outcome measuresLifestyle/behavioural outcomes at baseline/1‐year/2‐year/3‐year follow‐ups.Results1034 participants were randomised to PS (n = 530) or FH (n = 504) arms. No significant difference was identified between PS‐ and FH‐based BRCA testing approaches in terms of dietary fruit/vegetable/meat consumption, vitamin intake, alcohol quantity/ frequency, smoking behaviour (frequency/cessation), physical activity/exercise or routine breast mammogram screening behaviour, with outcomes not affected by BRCA test result. Cancer risk perception decreased with time following BRCA testing, with no difference between FH/PS approaches, and the perception of risk was lowest in BRCA‐negative participants. Men consumed fewer fruits/vegetables/vitamins and more meat/alcohol than women (P < 0.001).ConclusionPopulation‐based and FH‐based AJ BRCA testing have similar long‐term lifestyle impacts on smoking, alcohol, dietary fruit/vegetable/meat/vitamin, exercise, breast screening participation and reduced cancer risk perception.

Future of HIPEC for ovarian cancer

Quality of life from cytoreductive surgery in advanced ovarian cancer: Investigating the association between disease burden and surgical complexity in the international, prospective, SOCQER‐2 cohort study

AbstractObjectiveTo investigate quality of life (QoL) and association with surgical complexity and disease burden after surgical resection for advanced ovarian cancer in centres with variation in surgical approach.DesignProspective multicentre observational study.SettingGynaecological cancer surgery centres in the UK, Kolkata, India, and Melbourne, Australia.SamplePatients undergoing surgical resection (with low, intermediate or high surgical complexity score, SCS) for late‐stage ovarian cancer.Main Outcome MeasuresPrimary: change in global score on the European Organisation for Research and Treatment of Cancer (EORTC) core quality‐of‐life questionnaire (QLQ‐C30). Secondary: EORTC ovarian cancer module (OV28), progression‐free survival.ResultsPatients’ preoperative disease burden and SCS varied between centres, confirming differences in surgical ethos. QoL response rates were 90% up to 18 months. Mean change from the pre‐surgical baseline in the EORTC QLQ‐C30 was 3.4 (SD 1.8, n = 88) in the low, 4.0 (SD 2.1, n = 55) in the intermediate and 4.3 (SD 2.1, n = 52) in the high‐SCS group after 6 weeks (p = 0.048), and 4.3 (SD 2.1, n = 51), 5.1 (SD 2.2, n = 41) and 5.1 (SD 2.2, n = 35), respectively, after 12 months (p = 0.133). In a repeated‐measures model, there were no clinically or statistically meaningful differences in EORTC QLQ‐C30 global scores between the three SCS groups (p = 0.840), but there was a small statistically significant improvement in all groups over time (p < 0.001). The high‐SCS group experienced small to moderate decreases in physical (p = 0.004), role (p = 0.016) and emotional (p = 0.001) function at 6 weeks post‐surgery, which resolved by 6–12 months.ConclusionsThe global QoL of patients undergoing low‐, intermediate‐ and high‐SCS surgery improved at 12 months after surgery and was no worse in patients undergoing extensive surgery.Tweetable AbstractCompared with surgery of lower complexity, extensive surgery does not result in poorer quality of life in patients with advanced ovarian cancer.

Psychosexual distress following routine primary human papillomavirus testing: a longitudinal evaluation within the English Cervical Screening Programme

ObjectiveTo assess psychosexual distress over a 12‐month period among women receiving different human papillomavirus (HPV) and cytology results in the context of the English HPV primary screening pilot.DesignLongitudinal, between‐group study.SettingFive sites in England where primary HPV testing was piloted.PopulationWomen aged 24–65 years (n = 1133) who had taken part in the NHS Cervical Screening Programme.MethodsWomen were sent a postal questionnaire soon after receiving their screening results (baseline) and 6 and 12 months later. Data were analysed using linear regression models to compare psychosexual outcomes between groups receiving six possible combinations of HPV and cytology screening results, including a control group with normal cytology and no HPV test.Main outcome measuresPsychosexual distress, assessed using six items from the Psychosocial Effects of Abnormal Pap Smears Questionnaire (PEAPS‐Q).ResultsAt all time points, there was an association between screening result group and psychosexual distress (all P < 0.001). At baseline, mean psychosexual distress score (possible range: 1–5) was significantly higher among women with HPV and normal cytology (B = 1.15, 95% CI 0.96–1.34), HPV and abnormal cytology (B = 1.02, 95% CI: 0.78–1.27) and persistent HPV (B = 0.90, 95% CI 0.70–1.10) compared with the control group (all P < 0.001). At the 6 and 12 month follow ups the pattern of results were similar, but coefficients were smaller.ConclusionsOur findings suggest receiving an HPV‐positive result can cause psychosexual distress, particularly in the short‐term. Developing interventions to minimise the psychosexual burden of testing HPV‐positive will be essential to avoid unnecessary harm to the millions of women taking part in cervical screening.Tweetable abstractReceiving an HPV‐positive result following primary HPV testing can cause psychosexual distress, particularly in the short‐term.

Cervical screening with human papillomavirus primary testing: the way forward

Role of carbon nanoparticle suspension in sentinel lymph node biopsy for early‐stage cervical cancer: a prospective study

ObjectiveTo evaluate the clinical diagnostic validity of carbon nanoparticle suspension (CNS) in sentinel lymph node biopsy (SLNB) for assessing lymphatic spread of early‐stage cervical cancer.DesignA prospective study.Setting and population356 cases.MethodsWe enrolled 356 stage Ia2‐IIa2 cervical cancer patients to undergo SLNB using CNS, followed by systematic pelvic lymphadenectomy. All lymph node specimens were assessed using conventional histopathologic ± pathologic ultrastaging analyses.Main outcome measuresSentinel lymph node detection rate (DR), clinical diagnostic validity and various related factors were analysed.ResultsCNS identified 1456 SLNs in 325 patients. The overall SLN DR was 91.29%. A significantly higher DR was found for patients with tumours <20 mm (97.75% versus 71.91%; P < 0.001). Two patients had false‐negative results. SLNB with CNS had sensitivity of 96.65%, false‐negative rate (FNR) of 4.35% and negative predictive value (NPV) of 99.29%. Importantly, sensitivity (100%), NPV (100%) and FNR (0%) were improved when testing the subgroup of patients with tumours <20 mm (267 cases). There were no observed differences in DR based on pathological type or grade, stage, depth of stromal invasion, surgical approach, menopausal status or prior treatment with chemotherapy (P > 0.05).ConclusionsSentinel lymph node biopsy with CNS results in favourable DR, sensitivity and NPV for women with early‐stage cervical cancer with small tumour sizes. SLNB with CNS is safe, feasible and relatively effective for guiding precise surgical treatment of early‐stage cervical cancer.Tweetable abstractSentinel lymph node biopsy with carbon nanoparticle suspension is safe and feasible for early‐stage cervical cancer.

Authors' reply re: Reflex cytology for triage of high‐risk human‐papillomavirus‐positive self‐sampled material in cervical cancer screening: a prospective cohort study

Re: Reflex cytology for triage of high‐risk human papillomavirus positive self‐sampled material in cervical cancer screening: a prospective cohort study

Can DNA methylation tests improve the accuracy of cervical screening?

Cervical self‐sampling yields useful cytology

The impact of age and high‐risk human papillomavirus (hrHPV) status on the prevalence of high‐grade cervical intraepithelial neoplasia (CIN2+) in women with persistent hrHPV‐positive, cytology‐negative screening samples: a prospective cohort study

ObjectiveTo establish the prevalence of high‐grade cervical intraepithelial neoplasia (CIN2+) in women referred to colposcopy with persistent high‐risk human papillomavirus (hrHPV) cytology‐negative screening sample according to hrHPV genotype, age at referral and colposcopic performance.DesignProspective cohort study.SettingSingle colposcopy clinic linked to a population‐based screening programme.PopulationWomen referred with persistent hrHPV cytology‐negative routine screening samples.MethodsProspective study with descriptive statistics from a single colposcopy unit between June 2014 and July 2019.Main outcome measuresPrevalence of hrHPV genotypes and CIN2+, positive predictive value for colposcopic impression, and inadequate colposcopic examinations.ResultsA total of 3107 women were referred. Prevalence of CIN2+ was highest for persistent HPV16 infections (10.7%) compared with HPV18 (3.6%) or HPVO (4.7%). Prevalence of CIN2+ declined with age (25–34 years 14.2% to 55–64 years 1.1%) whereas the percentage of women with an inadequate colposcopic examination increased (25–34 years 0.9% to 55–64 years 29.5%). High‐grade colposcopic impression fell over time during the study from 16.1 to 5.1%. The positive predictive value for colposcopic impression of CIN2+ was affected by hrHPV genotype (57.3% for HPV16 versus 32.1% for nonHPV16). The adjunctive use of electrical impedance spectroscopy detected an extra 42 cases of CIN2+, which was irrespective of hrHPV genotype.ConclusionsPrimary hrHPV cervical screening increases detection of CIN2+; however, low specificity results in more women being referred to colposcopy with a low prevalence of CIN2+. Colposcopy performs poorly in some groups, particularly with HPVO infections and women over 50 years of age. An appropriate threshold for referral to colposcopy in primary hrHPV screening has not been established.Tweetable abstractLow prevalence of CIN2+ in HPV‐positive negative cytology samples. HPV genotype, age and prevalence of CIN2+ affect colposcopic performance.

Preservation of the mesureter to reduce urinary complications: analysis of data from the observational Leipzig School MMR study

ObjectiveTo evaluate the feasibility and effect of mesureteral preservation on urinary complications in the context of total mesometrial resection (TMMR), a surgical treatment for cervical cancer.DesignRetrospective cohort study with historic control.SettingSingle tertiary academic centre.PopulationWomen older than 18 with primary cervical cancer staged FIGO IB1–IIB enrolled in the prospective Leipzig School MMR study and underwent total mesometrial resection (TMMR) without adjuvant radiation.MethodWe retrospectively analysed 100 consecutive TMMR procedures which were performed for cancer of the uterine cervix and in which the mesureter was preserved (intervention group, 01/2014–06/2017). We compared this group with the previous 100 consecutive TMMRs, which were performed before the introduction of mesureteral preservation (control group, 09/2010–01/2014).Main outcome measuresThe occurrence of urological and specifically ureteral complications.ResultsMesureteral preservation was feasible and was associated with a significant decrease in ureteral complications (11% without mesureteral preservation versus 3% with mesureteral preservation, P = 0.049). Furthermore, we found a significant decrease in the number of postoperative percutaneous nephrostomies and re‐operations (7% versus none, P = 0.014). There was also a trend towards a decrease in other urinary complications such as postoperative bladder atony and uretero‐vaginal fistulas.ConclusionThe mesureter constitutes a convenient dissection plane enabling the preservation of lateral ureteral blood supply during TMMR. In our study, maintenance of mesureteral integrity was associated with a significant reduction in ureteral complications. Mesureteral preservation might also be useful in other types of pelvic surgeries that carry a high risk of ureteral damage.Tweetable abstractSurgical preservation of the mesureter in cervical cancer patients was associated with a reduction in urinary complications.

Persistence and clearance of high‐risk human papillomavirus and cervical dysplasia at 1 year in women living with human immunodeficiency virus: a prospective cohort study

ObjectiveEvaluate 1‐year outcomes of cervical cancer screening and treatment using primary high‐risk human papillomavirus (HPV) testing in women living with human immunodeficiency virus (HIV).DesignProspective cohort study.SettingHIV treatment centre in Botswana.PopulationWomen living with HIV.MethodsParticipants underwent cervical cancer screening with high‐risk HPV testing and triage evaluation at baseline and 1‐year follow up. Excisional treatment was offered as indicated. Histopathology was the reference standard.Main outcome measuresPersistence, clearance and incidence of high‐risk HPV infection; and persistence, progression, regression, cure and incidence of cervical dysplasia.ResultsAmong 300 women screened at baseline, 237 attended follow up (79%). High‐risk HPV positivity significantly decreased from 28% at baseline to 20% at 1 year (P = 0.02). High‐risk HPV persistence was 46% and clearance was 54%; incidence was high at 9%. Prevalence of cervical intraepithelial neoplasia Grade 2 (CIN2) or higher was most common in participants with incident high‐risk HPV (53%). CIN2 or higher was also common in those with persistent high‐risk HPV (32%) and even in those who cleared high‐risk HPV (30%). Of the high‐risk HPV‐positive participants at baseline with <CIN2, 40% progressed to CIN2 or higher at follow up.ConclusionThe high incidence of high‐risk HPV and high‐grade cervical dysplasia in women living with HIV after one round of high‐risk HPV‐based screening and treatment raises concern about the rate of progression of high‐risk HPV infection to dysplasia. Persistent disease is common. Caution in spacing cervical cancer screening intervals using high‐risk HPV testing in women living with HIV is warranted.Tweetable abstractHigh incidence and persistence of HPV and CIN2+ in women living with HIV 1 year after screening and treatment.

Conservative management of women with cervical intraepithelial neoplasia grade 2 in Denmark: a cohort study

ObjectiveAssess the progression, persistence, and regression of cervical intraepithelial neoplasia grade 2 (CIN2) after new guidelines on conservative treatment, compared with previous practice.DesignNationwide register‐based cohort study.SettingDenmark.PopulationWomen aged 18–44 years diagnosed with CIN2 on biopsy: 6721 in 2008–2011 and 6399 in 2014–2017.MethodsRegister data were retrieved from before (2008–2011) and after (2014–2017) the introduction of new guidelines. Histology diagnoses at second visit were used to assess progression (CIN3+), persistence (CIN2), or regression (CIN1/normal).Main outcome measuresProportion of CIN2 by type of management. Relative risk (RR) and corresponding 95% confidence intervals (95% CIs) for progression, persistence, and regression at second visit in 2014–2017, versus 2008–2011.ResultsThe proportion of CIN2 managed conservatively increased from 29.6% in 2008–2011 to 53.3% in 2014–2017 (RR 1.81, 95% CI 1.73–1.89). Time to second visit increased by 2 months. Regression increased from 23.5 to 30.2% (RR 1.29, 95% CI 1.22–1.36), whereas persistence and progression decreased, from 42.6 to 34.9% (RR 0.82, 95% CI 0.78–0.86) and from 28.0 to 22.8% (RR 0.81, 95% CI 0.77–0.86), respectively. In 2008–2011, women managed conservatively had a regression rate of 41.8%, persistence rate of 40.9%, and progression rate of 16.6%. In 2014–2017, these rates were 46.7, 35.5, and 17.1%, respectively.ConclusionAfter implementation of the new guidelines, conservative management became more frequent, and is now used for more than half of women with CIN2. Lesion regression became more frequent, now experienced by 47% of women managed conservatively. Similar regression rates were seen in women younger and older than 30 years, suggesting that conservative management is justifiable for women of childbearing age.Tweetable abstractIn Denmark, more than half of women with CIN2 are managed conservatively, and half of these women experience lesion regression.

Radical hysterectomy for cervical cancer: reducing ureteric injuries

Beyond the scope of the HPV triage strategy – proposals for consideration

Stuck in the middle: diagnostic and clinical management challenges surrounding CIN2

Triaging women with human papillomavirus infection and normal cytology or low‐grade dyskaryosis: evidence from 10‐year follow up of the ARTISTIC trial cohort

ObjectivesTo estimate long‐term cervical intraepithelial neoplasia grade 3 (CIN3) risks associated with different triage strategies for human papillomavirus positive (HPV+) women with a view to reducing unnecessary referrals.DesignThe ARTISTIC trial cohort was recruited in Manchester in 2001–03 and was followed up for CIN3 and cancer notification through national registration until December 2015.ResultsThe 10‐year cumulative risk of CIN3+ was much higher for women with HPV16/18 infection (19.4%, 95% CI 15.8–23.8% with borderline/low‐grade cytology and 10.7%, 95% CI 8.3–13.9% with normal cytology) than for those with other HPV types (7.3%, 95% CI 5.4–9.7% with borderline/low‐grade cytology and 3.2%, 95% CI 2.2–4.5% with normal cytology). Among the 379 women with normal to low‐grade cytology and new HPV infection, the 10‐year cumulative CIN3+ risk was 2.9% (95% CI 1.6–5.2%).ConclusionsThe CIN3 risk is confined to women with persistent type‐specific HPV so partial genotyping test assays identifying HPV16/18 as a minimum are essential for efficient risk stratification. Immediate referral to colposcopy for HPV+ women with borderline or low‐grade cytology and referral after a year if still HPV+ with normal cytology may be unnecessary. Low‐grade lesions can safely be retested to identify those with persistent HPV. Recall intervals of 1 year for HPV16/18 and 2 years for other high‐risk HPVs are justified for women with normal cytology and might also be considered for women with borderline/low‐grade cytology. The minimal risk of invasive cancer that has progressed beyond stage 1A must be weighed against the advantages for patients and the NHS of reducing the number of referrals to colposcopy.Tweetable abstractCervical screening would be better for women and cheaper for the NHS if women with HPV and normal to low‐grade cytology were retested after a year or two when many infections will have cleared.

Long‐term prediction of failure after treatment of cervical precancer

Colposcopic assessment by Swedescore, evaluation of effectiveness in the Swedish screening programme: a cross‐sectional study

AbstractObjectiveTo evaluate the effectiveness and performance of Swedescore in the Swedish screening programme.DesignCross‐sectional register study.Setting and PopulationAll Swedish women aged over 18 years with a colposcopic assessment linked to a biopsy in the Swedish National Cervical Screening Registry, 2015–20.MethodsColposcopies with Swedescore were compared with the histopathological diagnosis of cervical intraepithelial neoplasia grade 2 or higher (CIN2+). The respective influence of cytology and human papillomavirus (HPV) testing, at referral for colposcopy and concurrently with colposcopy, were investigated in regression models.Main Outcome MeasuresCIN2+.ResultsA total of 11 317 colposcopic assessments with Swedescore were included. Odds ratios for CIN2+ increased for every step in the Swedescore scale. At Swedescore ≥0–1, the proportion of CIN2+ was 9.8%. At Swedescore ≥8, the specificity was 93.3% and the positive predictive value was 60.1%, Area under the receiver operating characteristics curve (AUC) was 0.71. If the smear had been abnormal at referral, a normal colposcopy (Swedescore 0–1) was still associated with a CIN2+ risk of more than 5%. In the regression model, cytology and HPV had higher odds ratio for CIN2+ than colposcopy; the combination resulted in an AUC of 0.88.ConclusionsSwedescore works well in a routine clinical setting but colposcopy assessed with Swedescore was inferior to that reported in previous clinical studies. No safe cutoff level was identified for refraining from biopsy. See‐and‐treat at Swedescore 8–10 is feasible only if referral cytology showed high‐grade squamous intraepithelial lesion.Tweetable AbstractNo safe cutoff level for refraining from biopsy nor for see‐and‐treat with Swedescore.

Assessing novel therapies for vulval neoplasia

Risk of adverse obstetric outcomes in patients with a history of endometrial cancer: A nationwide population‐based cohort study

AbstractObjectiveTo evaluate adverse obstetric outcomes in women with a history of endometrial cancer (EC).DesignPopulation‐based cohort study.SettingThe Korean National Health Insurance (KNHI) claims database.PopulationWomen who gave birth between 2009 and 2016, with a history of EC prior to pregnancy.MethodsThe KNHI database was used to compare obstetric outcomes of women with and without a history of EC, using the ICD‐10 codes. Multivariable logistic regression models were used to determine the associations between a history of EC and adverse obstetric outcomes.Main outcomes measuresAdverse obstetric outcomes.ResultsOverall, 248 and 3 335 359 women with and without a history of EC, respectively, gave birth. When adjusted for age, primiparity and comorbidities, an increased risk of multiple gestations (odds ratio [OR] 4.925, 95% confidence interval [CI] 3.394–7.147), caesarean delivery (OR 2.005, 95% CI 1.535–2.62) and preterm birth (OR 1.941, 95% CI 1.107–3.404) was observed among women with a history of EC. We were unable to demonstrate significant differences in the risk of pre‐eclampsia, gestational diabetes, vacuum delivery, placenta praevia, placenta accreta spectrum, placental abruption and postpartum haemorrhage between the groups. In the sensitivity analyses excluding multiple gestations, an increased risk of preterm birth was not observed among women with a history of EC (OR 1.276, 95% CI 0.565–2.881).ConclusionsThere is no convincing evidence of an increased risk of adverse obstetric outcomes among women with a history of EC. Our findings would be useful in counselling of patients with EC who are undergoing fertility‐sparing treatment.

Identifying symptoms of ovarian cancer: a qualitative and quantitative study

Introduction  Symptoms of ovarian cancer are often vague and consequently a high proportion of women with ovarian cancer are not referred to the appropriate clinic.Objective  To identify diagnostic factors for ovarian cancer.Design  A qualitative and quantitative study.Setting  Four UK hospitals.Sample  One hundred and twenty‐four women referred to hospital with suspected ovarian malignancy.Methods  Women were interviewed prior to diagnosis (n = 63), or soon after. A thematic analysis was conducted. Emergent symptoms were quantitatively analysed to identify distinguishing features of ovarian cancer.Main outcomes  Symptoms in women with and without ovarian cancer.Results  Diagnoses comprised 44 malignancies, 59 benign gynaecological pathologies and 21 normal findings. Of the malignancies, 25 women had stage III or more disease, with an average age of 59 years. The benign/normal cohort was significantly younger (48 years). Multivariate analysis revealed persistent abdominal distension (OR 5.2, 95% CI 1.3–20.5), postmenopausal bleeding (OR 9.2, 95% CI 1.1–76.1), appetite loss (OR 3.2, 95% CI 1.1–9.2), early satiety (OR 5.0, 95% CI 1.6–15.7) and progressive symptoms (OR 3.6, 95% CI 1.3–9.8) as independent, statistically significant variables associated with ovarian cancer. Fluctuating distension was not associated with ovarian cancer (OR 0.4, 95% CI 0–4.1). Women frequently used the term bloating, but this represented two distinct events: persistent abdominal distension and fluctuating distension/discomfort.Conclusions  Ovarian cancer is not a silent killer. Clinicians should distinguish between persistent and fluctuating distension. Recognition of the significance of symptoms described by women could lead to earlier and more appropriate referral.

Questions remain on progestin effectiveness for advanced and recurrent endometrial cancer

Survival from ovarian and endometrial cancer

Levels of anxiety in women aged ≥45 years undergoing diagnostic large loop excision of the transformation zone: A longitudinal study

AbstractObjectiveTo measure anxiety levels in women aged ≥45 years undergoing diagnostic large loop excision of the transformation zone (LLETZ) at the first colposcopy visit.DesignLongitudinal study.SettingThree colposcopy clinics in the Central Denmark Region.PopulationWomen aged ≥45 years undergoing diagnostic LLETZ.MethodsWomen completed the State–Trait Anxiety Inventory (STAI) and Short Form 12 (mental and physical health) questionnaires before, immediately after, and at 1 and 6 months after LLETZ.Main outcome measuresSTAI state anxiety median scores were calculated and stratified by health status, by letter with information about screening result and by LLETZ results.ResultsOf 109 eligible women, 11 were excluded, leaving 98 women for the final analyses. Response rates ranged from 84.7% to 100%. Overall, state anxiety levels were low; however, a decrease was observed from before to immediately after the LLETZ (33.4 vs 29.3, p < 0.001). The anxiety levels remained stable up to 6 months after LLETZ. Women with poor mental health were more likely to have higher anxiety levels compared with women with good mental health (before LLETZ, RR 3.77, 95% CI 2.12–6.70; 1 month after LLETZ, RR 3.37, 95% CI 1.59–7.15; 6 months after LLETZ, RR 1.93, 95%CI 1.06–3.51).ConclusionsOverall, colposcopy and diagnostic LLETZ in women aged ≥45 years were not associated with high levels of anxiety. Anxiety levels were highest before colposcopy, and the women seemed to experience immediate relief afterwards. Women with poor mental health had the highest anxiety levels throughout the study, which might call for special attention.

The added value of digital imaging to reflex cytology for triage of high‐risk human papillomavirus positive self‐sampled material in cervical cancer screening: A prospective cohort study

AbstractObjectiveCytology performed directly on hrHPV‐positive self‐samples (reflex cytology) is feasible and for women with abnormal cytology, an additional cytology test at the general practitioner could be omitted. The aim of this study is to assess the added value of digital imaging (ThinPrep® Imaging System) on the clinical utility of reflex cytology by reducing screening error.DesignA secondary analysis of a prospective cohort study.SettingOne of five Dutch screening laboratories.PopulationWomen tested hrHPV‐positive on self‐samples between December 2018 and August 2019.MethodsSelf‐samples were used for reflex cytology with and without digital imaging. The follow‐up data (cytological and histological results within 1 year of follow‐up) were obtained through the Dutch Pathology Registry (PALGA).Main outcome measuresTest performance of the reflex cytology was determined by comparing it with physician‐collected follow‐up results.ResultsThe sensitivity for detecting abnormal cells by reflex cytology on self‐samples increased significantly from 26.3% (42/160; 95% confidence interval [CI] 19.6–33.8) without digital imaging to 35.4% (56/158; 95% CI 28–43.4) with digital imaging (P < 0.05) without compromising specificity. Importantly, 41.7% of women with ≥CIN2 (35/84) and 45.6% with ≥CIN3 (26/57) were detected by reflex cytology with digital imaging on hrHPV‐positive self‐samples.ConclusionDigital imaging is of added value to reflex cytology on hrHPV‐positive self‐samples with a 9% increase in sensitivity. If reflex cytology on self‐samples analysed with digital imaging had been implemented in the screening programme, 35.4% of the hrHPV‐positive women with abnormal cytology on additional physician‐collected samples could have been referred directly for colposcopy.

Clinical utility of p16/Ki67 dual‐stain cytology for detection of cervical intraepithelial neoplasia grade two or worse in women with a transformation zone type 3: A cross‐sectional study

AbstractObjectiveTo evaluate the clinical utility of p16/Ki67 dual‐stain (DS) compared with cytology for detecting cervical intraepithelial lesion grade two or worse (CIN2+) in women with a transformation zone type 3 (TZ3).DesignCross‐sectional study.SettingColposcopy clinics in Central Denmark Region.PopulationWomen aged 45 years or older referred for colposcopy because of an abnormal screening test.MethodsAll women had a cervical sample collected for cytology and DS testing and underwent large‐loop excision of the transformation zone (LLETZ).Main outcome measureSensitivity, specificity and negative (NPV) and positive (PPV) predictive values of DS for CIN2+ detection were compared to those of cytology.ResultsOf 166 women eligible, 93 (56.0%) were included in the final analysis. Median age was 68 years (interquartile range [IQR] 63.4–70.5 years). Most women were postmenopausal (95.7%) and referred based on a positive human papillomavirus screening test (86.0%). Fifty‐two women (55.9%) were DS‐positive, 29 (55.8%) of whom had CIN2+ detected. Twenty‐seven (29.0%) women had atypical squamous cells of undetermined significance or worse (ASC‐US+), and CIN2+ was detected in 21 women (77.8%). DS had a higher sensitivity (96.7% versus 70.0% p = 0.021) and NPV (97.6% versus 86.4%, p = 0.018) compared with cytology for CIN2+ detection. In contrast, the specificity (63.5% versus 90.5% p < 0.001) and PPV (55.8% versus 77.8%, p = 0.001) were lower for DS compared with cytology.ConclusionsDual stain may be a valuable risk marker to guide clinical management of women with a TZ3. The superior NPV of DS suggests that a diagnostic excision may safely be avoided in DS‐negative women.

Factors Impacting Live Birth Probability After In Vitro Fertilisation and Embryo Transfer in Women With Endometrial Cancer Following Conservative Therapy: A Retrospective Cohort Study

ABSTRACTObjectiveThis study aimed to elucidate the factors influencing live birth outcomes following in vitro fertilisation/intracytoplasmic sperm injection (IVF/ICSI) after conservative therapy in women with early‐stage endometrioid endometrial cancer (EEC).DesignSingle‐centre retrospective cohort study.SettingReproductive Center, Peking University Third Hospital.PopulationOne hundred and seventeen women with Stage IA EEC who received conservative treatment and achieved complete remission.MethodsMedical records from our database were retrospectively analysed.Main Outcome MeasuresCumulative live births and endometrial cancer recurrence rates.ResultsThe cumulative live birth rate of women who underwent controlled ovarian stimulation (COS) was significantly higher than in those who did not (43.7% vs. 20.0%; p = 0.021), whereas the endometrial cancer recurrence rate was similar (26.1% vs. 30%; p = 0.812). Of 87 patients who received COS cycles, 71 underwent embryo transfer, of which 38 resulted in live birth and 33 did not. There was a significant association between live births and both endometrial thickness (odds ratio [OR] 1.753, 95% confidence interval [CI] 1.174–2.616, p = 0.006) and the number of transferable embryos (OR 1.270, 95% CI 1.017–1.587, p = 0.035).ConclusionsThe chances of successful live births following IVF/ICSI‐ET are encouraging for women diagnosed with EEC. Endometrial thickness and the number of transferable embryos are crucial factors associated with the success rate of live births in women with EEC undergoing IVF‐ET.

Cervical intraepithelial neoplasia in women with transformation zone type 3: cervical biopsy versus large loop excision

AbstractObjectiveTo compare the proportion of cervical intraepithelial neoplasia grade 2 or higher (CIN2+) in cervical biopsies with that in large loop excision of the transformation zone (LLETZ) specimens in women aged ≥45 years with transformation zone type 3 (TZ3).DesignMulticentre cross‐sectional study.SettingThree colposcopy clinics in the Central Denmark Region.PopulationWomen aged ≥45 years referred to colposcopy as a result of a positive human papillomavirus (HPV) test and/or abnormal cytology and with TZ3 at colposcopy.MethodsWomen had multiple biopsies taken and an LLETZ was performed.Main outcome measuresHistologically confirmed CIN2+ in biopsies compared with that in LLETZ specimens.ResultsOf 166 eligible women at colposcopy, 102 women with paired data from biopsies and LLETZ specimens were included for final analysis. The median age was 67.7 years (IQR 62.6–70.4 years), and most were postmenopausal (94.1%) and had undergone HPV‐based screening (81.3%). The CIN2+ detection rate was significantly higher in LLETZ specimens than in biopsies (32.4% vs 14.7%, difference 17.7%, 95% CI 6.3–29.0%), resulting in more than half of CIN2+ cases being missed in biopsies (54.5%, 95% CI 36.4–71.9%). The overall agreement between biopsies and LLETZ was 82.4% (95% CI 73.6–89.2%).ConclusionsCIN2+ detection is underestimated in women aged ≥45 years with TZ3 if detection relies on the results of biopsies alone. To reduce the risk of underdiagnosis and overtreatment, future studies should explore the use of new biomarkers for risk stratification to improve discrimination between women at increased risk of CIN2+ who need to undergo LLETZ and women who may undergo follow‐up.

Shift in harms and benefits of cervical cancer screening in the era of HPV screening and vaccination: a modelling study

AbstractObjectiveTo calculate the changes in harms and benefits of cervical cancer screening over the first three screening rounds of the Dutch high‐risk human papillomavirus (hrHPV) screening programme.DesignMicrosimulation study.SettingDutch hrHPV screening programme; women are invited for screening every 5 or 10 years (depending on age and screening history) from age 30 to 65.PopulationPartly vaccinated population of 100 million Dutch women.MethodsMicrosimulation model MISCAN was used to estimate screening effects. Sensitivity analyses were performed on test characteristics and attendance.Main outcome measuresHarms (screening tests, unnecessary referrals, treatment‐related health problems), benefits (CIN2+ diagnoses) and programme efficiency (number needed to screen [NNS]) over the first (period 2017–2021), second (period 2022–2026) and third (period 2027–2031) rounds of hrHPV‐based screening.ResultsThe number of screening tests and CIN2+ diagnoses decreased from the first to the second round (−25.8% and −23.6%, respectively). In the third screening round, these numbers decreased further, albeit only slightly (−2.7% and −5.3%, respectively). NNS to detect a CIN2+ remained constant over the rounds; however, it increased in younger age groups while decreasing in older age groups.ConclusionBoth harms and benefits of hrHPV screening decreased over the first screening rounds. For younger women, the efficiency would decrease, whereas longer screening intervals would lead to increased efficiency in older women. Programme efficiency overall remained stable, showing the importance of longer intervals for low‐risk women.Tweetable abstract:Cervical cancer screening: both harms and benefits of hrHPV screening will decrease in the future.

Patient‐initiated follow‐up in women with early‐stage endometrial cancer: A long‐term follow‐up of the OPAL trial

AbstractObjectiveA long‐term follow‐up of the OPAL trial to compare the effect of patient‐initiated (PIFU) versus hospital‐based (HBFU) follow‐up on fear of cancer recurrence (FCR), quality of life (QoL) and healthcare use after 34 months of follow‐up.DesignPragmatic, multicentre randomised trial.SettingFour Danish departments of gynaecology between May 2013 and May 2016.Population212 women diagnosed with stage I low‐intermediate risk endometrial carcinoma.MethodsThe control group attended HBFU with regular outpatient visits (i.e., 8) for 3 years after primary treatment. The intervention group underwent PIFU with no prescheduled visits but with instructions about alarm symptoms and options of self‐referral.Main outcome measuresThe endpoints were FCR as measured by the Fear of Cancer Recurrence Inventory (FCRI) and QoL as measured by the European Organisation for Research and Treatment of Cancer Quality of Life Core Questionnaire C‐30 (EORTC QLQ C‐30), and healthcare use as measured by questionnaires and chart reviews after 34 months of follow‐up.ResultsFCR decreased from baseline to 34 months in both groups and no difference was found between allocations (difference −6.31 [95% confidence interval −14.24 to 1.63]). QoL remained stable with no difference in any domains between the two arms at 34 months using a linear mixed model analysis. The use of healthcare was significantly lower in the PIFU group (P < 0.01).ConclusionPatient‐initiated follow‐up is a valid alternative to hospital‐based follow‐up for people who have been treated for endometrial cancer and have low risk of recurrence.

Cervical cancer and COVID—an assessment of the initial effect of the pandemic and subsequent projection of impact for women in England: A cohort study

AbstractObjectiveTo review the effect of the COVID‐19 pandemic on the diagnosis of cervical cancer and model the impact on workload over the next 3 years.DesignA retrospective, control, cohort study.SettingSix cancer centres in the North of England representing a combined population of 11.5 million.MethodsData were collected retrospectively for all diagnoses of cervical cancer during May–October 2019 (Pre‐COVID cohort) and May–October 2020 (COVID cohort). Data were used to generate tools to forecast case numbers for the next 3 years.Main outcome measuresHistology, stage, presentation, onset of symptoms, investigation and type of treatment. Patients with recurrent disease were excluded.Results406 patients were registered across the study periods; 233 in 2019 and 173 in 2020, representing a 25.7% (n = 60) reduction in absolute numbers of diagnoses. This was accounted for by a reduction in the number of low stage cases (104 in 2019 to 77 in 2020). Adding these data to the additional cases associated with a temporary cessation in screening during the pandemic allowed development of forecasts, suggesting that over the next 3 years there would be 586, 228 and 105 extra cases of local, regional and distant disease, respectively, throughout England. Projection tools suggest that increasing surgical capacity by two or three cases per month per centre would eradicate this excess by 12 months and 7 months, respectively.ConclusionsThere is likely to be a significant increase in cervical cancer cases presenting over the next 3 years. Increased surgical capacity could mitigate this with little increase in morbidity or mortality.Tweetable AbstractCovid will result in 919 extra cases of cervical cancer in England alone. Effects can be mitigated by increasing surgical capacity.

Age‐specific outcomes from the first round of HPV screening in unvaccinated women: Observational study from the English cervical screening pilot

AbstractObjectiveTo report detailed age‐specific outcomes from the first round of an English pilot studying the implementation of high‐risk human papillomavirus (HR‐HPV) testing in primary cervical screening.DesignObservational study with screening in 2013–2016, followed by two early recalls and/or colposcopy until the end of 2019.SettingSix NHS laboratory sites.PopulationA total of 1 341 584 women undergoing screening with HR‐HPV testing or liquid‐based cytology (LBC).MethodsEarly recall tests and colposcopies were recommended, depending on the nature of the screening‐detected abnormality.Main outcome measuresWe reported standard screening process indicators, e.g. proportions with an abnormality, including high‐grade cervical intraepithelial neoplasia (CIN2+) or cancer, and the positive predictive value (PPV) of colposcopy for CIN2+, by screening test and age group.ResultsAmong unvaccinated women screened with HR‐HPV testing at age 24–29 years, 26.9% had a positive test and 10.4% were directly referred to colposcopy following cytology triage, with a PPV for CIN2+ of 47%. At 50–64 years of age, these proportions were much lower: 5.3%, 1.2% and 27%, respectively. The proportions of women testing positive for HR‐HPV without cytological abnormalities, whose early recall HR‐HPV tests returned negative results, were similar across the age spans: 54% at 24–29 years and 55% at 50–64 years. Two‐thirds of infections at any age were linked to non‐16/18 genotypes. Among women with CIN2, CIN3 or cervical cancer, however, the proportion of non‐16/18 infections increased with age. As expected, the detection of abnormalities was lower following screening with LBC.ConclusionsThese data provide a reliable reference for future epidemiological studies, including those concerning the effectiveness of HPV vaccination.Tweetable abstractData from the English pilot study provide a comprehensive overview of abnormalities detected through HPV screening.

Miles to go: social inequity and endometrial cancer survival