Maturitas

Gene-specific cancer risks in female Lynch syndrome carriers: A copula-based meta-analysis

Lynch syndrome, caused by germline pathogenic variants in mismatch repair genes, markedly increases risks of endometrial, ovarian, and possibly breast cancer in women. We aimed to establish gene-specific risk profiles for these cancers using a unified multivariate model accounting for correlated outcomes. Eligible studies reported frequencies of endometrial, ovarian, and breast cancer in female with Lynch syndrome carriers, for at least two mismatch repair genes. We applied a Bayesian multivariate random-effects meta-analysis with a copula model to jointly model prevalence and odds ratios across cancers, accounting for between-study heterogeneity and inter-cancer correlation. Using a copula-based multivariate meta-analysis to account for outcome interdependence, the estimated prevalence was 20% for endometrial cancer, 5.7% for ovarian cancer, and 11% for breast cancer. Gene-specific analyses showed increased endometrial cancer risk with MSH6 (OR = 1.46, 95% CrI 1.02-2.04) and reduced risk with PMS2, relative to other Lynch genes (OR = 0.36, 95% CrI 0.14-0.95). Ovarian cancer risk did not differ significantly by gene. For breast cancer, PMS2 (OR = 1.52, 95% CI 1.02-2.25) and MSH6 (OR = 2.27, 95% CrI 1.08-2.49) were associated with higher risk, while MLH1 and MSH2 carried significantly lower risk. This copula-based meta-analysis identifies gene-specific risks of endometrial and ovarian cancer in female Lynch syndrome carriers, supporting personalized gynecologic surveillance. It also notes higher breast cancer risks in MSH6 and PMS2 carriers, but conflicting evidence from large perspective databases prevents definitive conclusions about breast cancer as part of the Lynch syndrome spectrum.

Circulating biomarkers for the preoperative diagnosis of uterine sarcoma: A systematic review and meta-analysis

A way to improve the early diagnosis of uterine sarcoma is by identifying circulating protein biomarkers that allow for differentiation between uterine sarcoma and benign leiomyomas. However, to date, no systematic review has gathered data on the diagnostic accuracy of these biomarkers as diagnostic tools for uterine sarcomas. We performed a systematic review and meta-analysis. An electronic search was conducted using PubMed, EMBASE, Web of Science, and CENTRAL (Cochrane) to identify clinical studies investigating the potential role of circulating biomarkers for the diagnosis of uterine sarcoma. We selected only studies that compared patients with a histologically confirmed diagnosis of leiomyoma versus uterine sarcoma. This study was conducted according to the Preferred Reporting Items for a Systematic Review and Meta-analysis of Diagnostic Test Accuracy Studies statement. A total of 20 observational studies were included, with a total of 13 biomarkers. Five studies reported data on diagnostic accuracy, including sensitivity and specificity. Lactate dehydrogenase levels showed a statistically significant difference between patients with uterine sarcoma and controls with leiomyoma (p < 0.001), with a sensitivity and specificity ranging between 0.47 and 1.00 and 0.86 to 1.00, respectively. Three studies reported data on diagnostic accuracy of carbohydrate antigen 125: the estimates for sensitivity and specificity ranged from 0.43 to 0.64 and 0.50 to 0.77, respectively, with substantial heterogeneity between the studies. Data on diagnostic accuracy for C-reactive protein was available for two studies, with sensitivity and specificity ranging between 0.84 and 0.87 and 0.83 to 0.89, respectively. Data for two biomarkers, human epididymal protein 4 and D-dimer, were insufficient, as each was evaluated in only one study. This systematic review and meta-analysis showed that the most encouraging results were available for lactate dehydrogenase. Other biomarkers may also prove to be useful tools in differentiating between leiomyomas and uterine sarcomas; however, further studies are needed to replicate these findings.

Correlates of sexual and reproductive health service utilization among older adults in China: Findings from the sexual well-being (SWELL) study

Sexual and reproductive health (SRH) is critical to the overall health of older adults. We assessed the utilization of SRH services and its correlates among older adults in China. We recruited community-dwelling adults aged 50 and above in five Chinese cities between June 2020 and December 2022. In this study SRH services included reproductive health examination, cervical cancer screening, and sexual life counselling. Logistic regression was used to assess correlates of SRH services utilization. A total of 3001 older adults (1819 men and 1182 women) were enrolled. Among them, 11.4 % (343/3001) of participants received a reproductive health examination, 35.4 % (418/1182) of female participants received cervical cancer screening, and 30.1 % (401/1332) of sexually active participants sought help for their sexual lives. Older men with an annual income of USD 7500 or more (aOR = 3.21, 95%CI: 1.39-7.44), two or more chronic conditions (2.38, 1.39-4.08), and reproductive health problems (2.01, 1.18-3.43) were more likely to receive a urological examination. For older women, individuals who were younger (aged 50-59 years: 5.18, 2.84-9.43; aged 60-69 years: 2.67, 1.49-4.79), lived in an urban area (1.88, 1.31-2.71), were employed (1.73, 1.21-2.47), had two or more chronic conditions (2.04, 1.37-3.05), were sexually active (1.72, 1.15-2.58) and talked about sex (1.69, 1.21-2.36) were more likely to receive a gynecological examination. SRH services utilization among older adults was low, with urological examination among older men particularly low. SRH messages and services tailored for older adults are needed to enhance their utilization of SRH services.

Ten-point guide on the management of healthy women carrying BRCA1/2 mutations

Healthy women carrying pathogenic germline mutations in BRCA1 or BRCA2 genes have an increased risk of breast and ovarian cancer. Prophylactic gynecological surgery includes risk-reducing bilateral salpingo-oophorectomy, which, in selected cases, can be combined with hysterectomy. Prophylactic gynecological surgery is recommended after completion of childbearing and can be performed for women aged 35 or more for BRCA1 or 40 or more for BRCA2 mutation carriers. Risk-reducing bilateral salpingo-oophorectomy has several adverse effects related to estrogen deprivation, and so hormonal therapy could be the main strategy for healthy women. However, health professionals have many doubts about whether they are able to offer clear counseling on the management of early menopausal symptoms (i.e. vasomotor and genitourinary symptoms) in healthy women with a hereditary predisposition to female cancer. This 'Ten-Point Guide' summarizes the evidence regarding prophylactic gynecological surgery and supports healthcare providers in the management of healthy women carrying germline BRCA1 and BRCA2 mutations.

Cervical cancer in older women: Does age matter?

Cervical cancer is frequently diagnosed in older women, but few studies have focused on cervical cancer in this specific population. The objectives of this study were to provide an overview of the demographic profile and therapeutic care of women with cervical cancer, and to identify whether age is a prognostic factor. Retrospective population-based study from a gynecological cancer registry in a French Regional University Hospital and Comprehensive Cancer Center. 292 women diagnosed with cervical cancer between January 1, 2005, and December 31, 2015, were included. They were classified into younger women (YW), that is, under 70 years of age (N = 228), and older women (OW), that is, aged 70 years or more (N = 64). The primary outcome was overall survival (OS). Cox proportional hazards models were developed to assess the impact of age on OS. Compared with YW, larger proportions of OW had comorbidities (14% vs 7% with a score ≥ 2 on the Charlson Comorbidity Index, P <0.001) and more advanced tumors (37.3% vs 19.7% with FIGO IV, P <0.001); the OW group had a lower treatment rate (81.3% vs 95.6%, P <0.001), and a smaller proportion had undergone surgery (37.5% vs 81.7%, P<.001) but a larger proportion had radiotherapy (67.2% vs 49.6%, P = .01). One-year, 5-year and 10-year OS rates were: 91.6%, 74.1% and 63.9% for YW, and 69.9%, 36.4% and 12.3% for OW, respectively (P <0.001). The hazard ratio for death was twice as high in OW compared with YW with cervical cancer (HR = 2.19 [1.41 - 3.40], P <0.001), independently of FIGO stage, histology, and comorbidities. The prognosis for cervical cancer depends on age. Screening with the G8 tool followed by a comprehensive geriatric assessment could lead to more suitable treatment being offered to older patients.

Hormone replacement therapy in women with iatrogenic premature ovarian insufficiency after radiotherapy for cervical cancer: A retrospective cohort and survey study

This study assessed the uptake of hormone replacement therapy (HRT) in cervical cancer patients with iatrogenic menopause. Survival in relation to HRT use was assessed via a retrospective chart study, and the severity of menopausal symptoms, motivations and barriers to starting HRT were examined via questionnaires. In total, 293 women under the age of 51 and treated with radiotherapy for cervical cancer between 2010 and 2020 were identified. Medical records were searched for information on HRT use. If still living, women were sent digital questionnaires addressing menopausal symptoms, quality of life (QoL) and potential barriers and motivations concerning HRT use. Univariable data were analysed using Mann-Whitney U, chi-square, and Fisher's exact test, while logistical regression was used to analyse relationships between certain variables and use of HRT and survival. Overall HRT uptake was 78.1 %, which was related to age and Charlson Comorbidity Index, but independent of the duration of radiotherapy or FIGO stage. Overall survival was higher for HRT users (χ HRT prescription rate was inversely correlated with age. Survival was not negatively affected by HRT use. It is important to stress the benefits of HRT and address women's fears regarding its use.

Age-related differences in patient preferences for adjuvant chemotherapy for high-risk endometrial cancer

Adjuvant chemotherapy in the treatment of endometrial cancer can be difficult to tolerate for older women. This study examined age-related differences in patient preferences for chemotherapy in women with high-risk endometrial cancer. We re-analyzed data from the cross-sectional patient preference study PRETEC-2 to determine the difference between three age groups in minimally desired survival benefit of chemotherapy. For this, patients with high-risk endometrial cancer treated with adjuvant pelvic radiotherapy with or without chemotherapy completed a treatment trade-off questionnaire. Patients also rated the importance they attributed to treatment duration and acute and late side-effects for their decision on chemotherapy, which we analyzed by age group. A total of 171 patients (23% <60 years, 40% 60-69 years and 37% ≥70 years) were included in the analysis. Older patients had a significantly higher median minimally desired survival benefit for preferring chemoradiotherapy (5% for <60 years, 8% for 60-69 years and 15% for patients ≥70 years; (p<0.001)), and had the largest variability in minimally desired survival benefit. For a real-life five-year survival benefit of 5%, fewer older patients preferred the addition of chemotherapy to their treatment regimen (61.5% for <60 years, 45.6% for 60-69 years and 21.9% for ≥70 years; p<0.001). Furthermore, older patients rated both treatment duration (p=0.001) and long-term tingling or numbness (p=0.005) as significantly more important than their younger counterparts. There is more heterogeneity in the desired benefit of chemotherapy among patients aged 70 years or more compared to younger patients. This underlines the importance of recognizing individual differences and the need for shared decision-making.

Long-term outcomes of surgical menopause after risk-reducing salpingo-oophorectomy: results of the HARMOny study

Premenopausal risk-reducing salpingo-oophorectomy (RRSO), often performed for women at high familial risk of ovarian cancer, induces immediate menopause. Evidence about its long-term effects is scarce. We conducted a cross-sectional study (n = 740) nested in a nationwide cohort of women at high familial risk of ovarian cancer. Participants completed a cognition test and a questionnaire on lifestyle, sexual functioning, urinary incontinence and health-related quality of life (HRQOL, SF-36). Cardiovascular disease (CVD) risk and bone mineral density (BMD) were assessed during a clinical visit. In women aged 60-70 years at study visit (n = 330), we compared potential long-term health effects of RRSO between women who underwent the procedure before menopause (i.e. when aged ≤45years) and those who had the procedure after menopause (when aged ≥54years). Participants' median age was 64.3 years, and the median time since premenopausal RRSO was 21 years. A comprehensive overview of our (partially published) results showed that a premenopausal RRSO compared with a postmenopausal RRSO was not associated with long-term coronary artery calcification, objective cognitive functioning, urinary incontinence or impaired health-related quality of life. However, women in the premenopausal RRSO group had lower bone mineral density and reported more vaginal dryness and sexual discomfort compared with the postmenopausal RRSO group. Premenopausal RRSO does not appear to be associated with long-term cardiovascular disease risk, cognition or health-related quality of life. However, it negatively influences bone mineral density and vaginal dryness. Pre-registered clinical trial number: NCT03835793.

No increased arterial stiffness after premenopausal risk-reducing salpingo-oophorectomy (RRSO)

Women at high familial risk of ovarian cancer are recommended to undergo premenopausal risk-reducing salpingo-oophorectomy (RRSO). The procedure leads to immediate surgical menopause, and while early natural menopause is associated with an increase in the risk of cardiovascular disease (CVD), evidence on CVD risk after surgical menopause is inconsistent. To investigate the long-term CVD risk after surgical menopause we conducted a cross-sectional study comparing a group of women who underwent a premenopausal RRSO (≤45 years) with a group who underwent postmenopausal RRSO (≥54 years). We assessed arterial stiffness, measured by pulse wave velocity (PWV). Increased PWV has been shown to be an independent predictor for CVD. Age differences between the pre- and postmenopausal RRSO groups were accounted for by restricting analyses to women aged 60-70 at study visit (n = 307). Within the premenopausal RRSO group (n = 461), we also examined the effect of timing of premenopausal RRSO on PWV (RRSO 0). Our study does not support a long-term adverse effect of premenopausal RRSO on arterial stiffness, but increased arterial stiffness is associated with the presence of CAC in women who have undergone a premenopausal RRSO. The pre-registered clinical trial number is .

The effect of opportunistic salpingectomy for primary prevention of ovarian cancer on ovarian reserve: a systematic review and meta-analysis

Opportunistic salpingectomy (OS) is an attractive method for primary prevention of ovarian cancer. Although OS has not been associated with a higher complication rate, it may be associated with earlier onset of menopause. To provide a systematic review and meta-analysis of the effect of OS on both age at menopause and ovarian reserve. A search was conducted in the Cochrane Library, Embase and MEDLINE databases from inception until March 2022. We included randomized clinical trials and cohort studies investigating the effect of OS on onset of menopause and/or ovarian reserve through change in anti-Müllerian hormone (AMH), antral follicle count (AFC), estradiol (E2), follicle stimulating hormone (FSH) and luteinizing hormone (LH). Data was extracted independently by two researchers. Random-effects meta-analyses were conducted to estimate the pooled effect of OS on ovarian reserve. The initial search yielded 1047 studies. No studies were found investigating the effect of OS on age of menopause. Fifteen studies were included in the meta-analysis on ovarian reserve. Meta-analyses did not result in statistically significant differences in mean change in AMH (MD -0.07 ng/ml, 95%CI -0.18;0.05), AFC (MD 0.20 n, 95 % CI -4.91;5.30), E2 (MD 3.97 pg/ml, 95%CI -0.92;8.86), FSH (MD 0.33mIU/ml, 95%CI -0.15;0.81) and LH (MD 0.03mIU/ml; 95%CI -0.47;0.53). Our study shows that OS does not result in a significant reduction of ovarian reserve in the short term. Further research is essential to confirm the absence of major effects of OS on menopausal onset since clear evidence on this subject is lacking. Registration number PROSPERO CRD42021260966.

Long-term health consequences of childhood adverse events: A narrative review

Development of cardiovascular risk factors in women with a BRCA1/2 pathogenic variant within five years after tubo-ovarian cancer risk reduction in the TUBA study

The effects of risk-reducing salpingo-oophorectomy on the development of cardiovascular risk factors in women with BRCA1/2 pathogenic variants are unknown. We compared the development of cardiovascular risk factors 5 years post-surgery between participants who had risk-reducing salpingo-oophorectomy with and without hormonal replacement therapy and participants who had risk-reducing salpingectomy. Eligible participants with a BRCA1/2 pathogenic variant from the TUBA study were longitudinally followed and categorized into three groups: (1) salpingectomy without subsequent oophorectomy within 5 years, (2) salpingo-oophorectomy with hormonal replacement therapy (use ≥3 years), (3) salpingo-oophorectomy without hormonal replacement therapy (use <3 years). Development of cardiovascular risk factors between baseline and 5 years after salpingo-oophorectomy or salpingectomy. Of the 400 participants, 258 (64.5%) had salpingectomy, 93 (23.3%) had salpingo-oophorectomy and used hormonal replacement therapy ≥3 years, and 49 (12.2%) used it for <3 years. At 5-year follow-up, the cardiovascular risk factor hypercholesterolemia (increased LDLc) was observed more often after salpingo-oophorectomy with (18.8%, p ≤0.001) and without (17.1%, p = 0.03) hormonal replacement therapy compared with the salpingectomy group (5.7%). Larger proportions of participants after salpingo-oophorectomy with (47.1%) and without (50.0%) hormonal replacement therapy experienced an increase in the number of risk factors present compared with participants after salpingectomy (24.5%; p = 0.009, p = 0.02, respectively). Overall, only a small proportion of the study population developed cardiovascular risk factors within five years after salpingo-oophorectomy. However, participants developed the risk factor hypercholesterolemia more after salpingo-oophorectomy (irrespective of use of hormonal replacement therapy) compared with after salpingectomy. NCT02321228.

Exploring the influence of adenomyosis on endometrial cancer

To evaluate whether coexisting adenomyosis is associated with distinct clinicopathological features in women with endometrial cancer. This retrospective cohort included 399 women who had undergone hysterectomy for histologically confirmed endometrial carcinoma at a tertiary center between 2016 and 2024. Patients were stratified according to the presence or absence of adenomyosis on final pathology. Clinical and pathological characteristics were compared, and multivariable logistic regression was used to adjust for potential confounders. Associations between adenomyosis and tumor invasiveness, stage at diagnosis, and other pathological features. The cohort consisted predominantly of postmenopausal women, with a median age of 67 years. Adenomyosis was identified in 94 patients (23.6%). Women with adenomyosis were more likely to have non-invasive tumors (1.1% vs. 6.8%; p = 0.037) and early-stage disease (Stage I-II: 91.3% vs. 80.8%; p = 0.029). After adjustment for age, adenomyosis was associated with lower odds of advanced-stage disease (adjusted odds ratio 0.40; 95% confidence interval 0.17-0.91). In a comprehensive model including age, histologic subtype, and peritoneal cytology, this association remained significant (adjusted odds ratio 0.20; 95% confidence interval 0.05-0.78). Endometrioid histology was independently protective (adjusted odds ratio 0.32; 95% confidence interval 0.13-0.75), while positive cytology was linked to advanced-stage disease (adjusted odds ratio 4.40; 95% confidence interval 1.86-10.40). Coexisting adenomyosis is associated with less invasive tumors and a lower likelihood of advanced-stage endometrial cancer. These findings suggest adenomyosis may influence tumor progression, potentially through structural or biological mechanisms. Prospective studies are needed to clarify the underlying biology and long-term prognostic impact. This study was performed in line with the principles of the Declaration of Helsinki. Approval was granted by the Ethics Committee of Rabin Medical Center (Date 3 July 2025 /No RMC- 0037-25).

STop OVarian CAncer (STOPOVCA) young: Protocol for a multicenter follow-up study to determine the long-term effects of opportunistic salpingectomy on age at menopause

Opportunistic salpingectomy comprises additional bilateral salpingectomy during abdominal surgery as a prophylactic method to reduce the risk of ovarian cancer. However, opportunistic salpingectomy may potentially damage (micro)blood circulation to the ovaries, resulting in earlier onset of menopause. To evaluate the long-term effects of opportunistic salpingectomy on the onset of menopause in women who underwent sterilization through salpingectomy compared with a control group who underwent sterilization by tubal ligation or no surgery at all. Opportunistic salpingectomy does not lower the mean age at onset of menopause. In a multicenter observational noninferiority study, we will prospectively compare the age at menopause of women initially aged 35-45 who underwent sterilization through opportunistic salpingectomy with a similarly aged control group who underwent sterilization by tubal ligation or no sterilization. Participants will be asked to complete an annual questionnaire on onset of menopause to eventually determine whether there is more than a one-year decrease in mean age at onset of menopause in the opportunistic salpingectomy group. Follow-up will last until determination of menopause, with a maximum of 15 years. Inclusion criteria: pre-menopausal; age between 35 and 45; intact ovaries. post-menopausal; previous bilateral salpingectomy or oophorectomy; previous hysterectomy; abnormal karyotype; previous or current chemotherapy or pelvic radiation. Determination of age of menopause measured by annual questionnaire. 1200 (400 intervention group; 800 control group). It is estimated that recruitment will be completed by 2023 and results will be published by 2039. NCT04757922 PROTOCOL VERSION: : Version 1, February 2021.

Nutritional interventions during treatment for ovarian cancer: A narrative review and recommendations for future research

Most women with ovarian cancer are diagnosed at an advanced stage (stage III or IV), when the intraabdominal spread of the tumour impacts nutrient intake and absorption. Up to 70 % of women with ovarian cancer are malnourished and approximately 40 % are affected by muscle loss at the time of diagnosis. Women with ovarian cancer are at high risk of nutritional decline due to invasive treatment and the severity of side-effects. This review explores the evidence evaluating nutritional interventions during treatment for ovarian cancer and their effect on nutritional status, muscle mass, and clinical outcomes. Perioperative immunonutrition has been investigated with mixed results for immediate postoperative outcomes. Individualised nutrition counselling as part of a multimodal prehabilitation programme prior to surgery shows promising results; however, the effects are limited by sample size. Nutrition counselling as part of a mixed intervention with exercise shows high acceptability and suggests improvements in dietary intake and quality of life during chemotherapy treatment, while oral nutritional supplements and nutrition education appear to reduce symptom burden. Individualised nutrition counselling during treatment also appears to be associated with improved overall survival; however, the evidence is limited to a single retrospective study. A key finding from this review is that, despite the high prevalence of malnutrition and muscle loss in women with ovarian cancer and the critical importance of addressing these modifiable prognostic factors, nutrition intervention studies are limited. Prospective studies with samples large enough to provide adequate power to evaluate intervention effectiveness are urgently required to inform optimal management.

Are older women with early-stage endometrial cancer undertreated and more likely to die from their cancer?

Endometrial cancer is the most common gynecological malignancy in developed countries, mainly affecting older women and raising concerns about potential under-treatment. This study aimed to describe treatment patterns and assess net survival in older women with early-stage endometrial cancer. This French retrospective observational study used a gynecological cancer registry. Patients diagnosed with FIGO I-II endometrial cancer from 1998 to 2018 were included and stratified by age (a younger group, under 70 years, and an older group, aged 70 years or more). A multiple penalized splines model was used. A total of 828 patients were included: 448 women aged under 70 and 380 aged 70 or more. Older patients belonged to higher-risk groups as defined by ESGO-ESTRO-ESP 2021 criteria (p < 0.001) and had a lower rate of low-grade endometrioid carcinoma (75.1 % vs. 85.7 %, p = 0.003). Treatment patterns did not differ by age; surgery plus adjuvant therapy remained the main treatment (69.7 % vs. 70.8 % in the older and younger groups, respectively, p = 0.87). 5-year net survival was 95.0 % (95 % CI: 92.6-97.6) for younger and 84.3 % (95 % CI: 78.8-90.3) for older women. The univariate hazard ratio for death in older vs. younger women was 2.38 (95 % CI: 1.19-4.74; p = 0.02). Multivariate analysis attenuated age's effect: hazard ratio 1.38 (95 % CI: 0.97-3.31; p = 0.06). Charlson Comorbidity Index and non-low-grade endometrioid histology predicted poorer survival. Diagnosis period was not associated with survival. No significant difference in treatment was found according to age. Although age was associated with 5-year net survival in univariate analysis, this association was no longer observed after adjusting for diagnosis period, comorbidities, and histology.

Prophylactic risk-reducing salpingo-oophorectomy in BRCA mutation carriers: what is going on in a region of northern Italy?

BRCA1 mutation carriers are recommended to undergo prophylactic risk-reducing salpingo-oophorectomy (RRSO) between the ages of 35 and 40 or when child bearing is complete, with a possible delay until age 40-45 for BRCA2 mutation carriers. Primary outcome was the rate of unsuspected cancer findings during RRSO in a region of northern Italy (Emilia Romagna) and secondary outcomes were details of RRSO: age at surgical intervention, the venue of the procedures in relation to the surgical/pathological quality and the rate/role of concomitant opportunistic hysterectomies. Multicentre data collection by invitation to report current RRSO practices. A total of 222 RRSOs (54.5 % BRCA1, 34.7 % BRCA2, 1.8 % BRCA1 and BRCA2 combined, 5.8 % BRCA-VUS and 3.2 % BRCA not better specified) were reported from 9 different centres, half in non-university hospitals and the remainder in university hospitals. Breast cancer survivors (56.3 %) underwent the RRSO at a younger age (47.8 vs 50.6 years, p =  0.02). The mean and median ages at surgical intervention (49.0 and 48.0, respectively) were similar for BRCA1 and BRCA2 mutation carriers, as was the temporal trend in age distribution, and proportions treated in university and non-university hospitals. A diagnosis of ovarian invasive cancer was reported in 3.5 % of subjects, all BRCA1 or BRCA-combined subjects, at a median and mean age of 57 years (range 42-68). Abnormal tubal findings, such as serous tubal intraepithelial lesions (STIL) (100 %), secretory cell outgrowth (SCOUT) (100 %) and STIC (71.4 %), were mainly reported by pathologists in university hospitals. Of the 222 procedures, 15 (6.7 %) included hysterectomies: in none of these cases was a primitive uterine endometrioid or serous cancer found. The results from this multicentre regional study should guide future preventive health policies for RRSO in BRCA mutation carriers.

Reduction from 2011 to 2017 in adherence to breast cancer screening and non-improvement in the uptake of cervical cancer screening among women living in Spain

To analyze the uptake of breast and cervical cancer screening according to the 2017 Spanish National Health Survey (SNHS), to compare uptake rates with those obtained in the previous SNHS 2011 and to identify predictors for the uptake for these two screening tests. Cross-sectional study. Uptake rates of breast cancer and cervical cancer screening were analyzed for women aged 40-69 and aged 25-65 years, respectively. Independent variables included sociodemographic characteristics and factors related to health status and lifestyle. We found that 66.8 % of women aged 40-69 years had undergone mammography in the previous two years. Positive predictors for mammography uptake were age (50-69 years); marital status (married); Spanish nationality; university education; one or more chronic diseases; no alcohol consumption; physical activity; body mass index <30 kg/m The adherence rate for mammography in Spain in 2017 was below the recommended 70 % and was significantly lower than in 2011. The figures for cervical cancer screening were over 70 % and stable over time.

Trends in the incidence of vulvar malignant melanoma in Denmark and Sweden: Two nationwide studies covering &gt;40 years

Vulvar malignant melanoma (VuMM) represents a rare malignancy. This study examines and compares the incidence and trends in incidence of VuMM in Denmark and in Sweden over a period of >40 years. A nationwide, population-based registry study conducted in two countries. We identified incident VuMM cases in the Danish and Swedish Cancer Registries. Information on age at diagnosis, anatomical site, histology, and stage of disease was retrieved. We calculated age-specific and age-standardized incidence rates (ASRs) with temporal trends in incidence evaluated by estimated annual percent change (EAPC) with 95 % confidence intervals (CI). A total of 524 women with VuMM, encompassing 171 women in Denmark (1978-2022) and 353 women in Sweden (1978-2018), were included. The age-specific incidence rates increased with age throughout the study period in both countries. The ASR decreased in both countries: in Denmark, from 1.03 (95 % CI: 0.59-1.48) per 1,000,000 to 0.55 (95 % CI: 0.26-0.83); and in Sweden from 1.25 (95 % CI: 0.22-2.28) to 0.76 (95 % CI: 0.42-0.84). This corresponded to EAPCs of -1.65 (95 % CI: -2.45; -0.84) in Denmark and -1.22 (95 % CI: -1.69; -0.75) in Sweden. The age-standardized and age-specific VuMM incidence rates were nearly identical in Denmark and Sweden, which are countries with similar demographic characteristics, and a free-of-charge healthcare system. The incidence of VuMM showed an equal and statistically significant decrease in Denmark and Sweden during the last four decades. The explanation for the decrease is currently unknown.

Genital and extragenital oncological risk in women with vulvar lichen sclerosus: A multi-center Italian study

Vulvar lichen sclerosus is a chronic inflammatory disease involving vulvar skin. The risk of developing invasive vulvar cancer for women with LS is reported in the literature, but the risk of extra-vulvar tumors has been under-investigated. This multicentric study aims to estimate the risk of developing cancers in a cohort of women with a diagnosis of vulvar lichen sclerosus. A cohort of women diagnosed with and treated for vulvar lichen sclerosus in three Italian gynecological and dermatological clinics (Turin, Florence, and Ferrara) was retrospectively reviewed. Patient data were linked to cancer registries of the respective regions. The risk of subsequent cancer was estimated by dividing the number of observed and expected cases by the standardized incidence ratio. Among 3414 women with a diagnosis of vulvar lichen sclerosus corresponding to 38,210 person-years of follow-up (mean 11.2 years) we identified 229 cancers (excluding skin cancers and tumors present at the time of diagnosis). We found an increased risk of vulvar cancer (standardized incidence ratio = 17.4; 95 % CL 13.4-22.7), vaginal cancer (standardized incidence ratio = 2.7; 95 % CL 0.32-9.771), and oropharyngeal cancer (standardized incidence ratio = 2.5; 95 % CL 1.1-5.0), and a reduced risk of other gynecological tumors (cervical, endometrial, ovarian) and breast cancer. Patients with vulvar lichen sclerosus should undergo annual gynecological check-up with careful evaluation of the vulva and vagina. The increased risk of oropharyngeal cancer also suggests the need to investigate oropharyngeal cavity symptoms and lesions in patients with vulvar lichen sclerosus.

Vulvar Paget's disease: outcomes of 51 patients treated with imiquimod cream

Vulvar Paget's disease (VPD) is a rare neoplasm with high recurrence rates even after surgical treatment. Imiquimod topical cream is a promising therapy; however, experience with it is limited to small series or case reports. This study aims to analyze the effectiveness and safety of topical imiquimod in a large cohort of patients with VPD. Fifty-five cases of histologically proven- VPD treated with topical imiquimod at the Gynecologic and Obstetric Division 1 U, S. Anna Hospital, University of Turin were retrospectively reviewed. We investigated the potential factors related to clinico-pathological response to imiquimod using univariate and multivariate logistic regression to estimate odds ratios (ORs). Four women discontinued the treatment due to side-effects. Of the remaining 51 (42 in situ tumors, and 9 micro-invasive tumors) who completed treatment, 22 (43%) achieved a complete clinico-pathological response. Among the women who had a complete response, there were no cases of recurrence (mean follow-up: 66 months). Symptomatic lesions (burning: OR 0.15, CI 0.03-0.67; itching: OR 0.07, CI 0.008-0.64), smaller tumors <60 mm (OR 0.15, CI 0.006-0.43), non-recurrent VPD (OR 0.19, CI 0.04-0.43) and treatment frequency of three application per week (OR 0.13, CI 0.04-0.50) were associated with a lower risk of persistence. Perianal involvement was associated with treatment failure (OR 7.79, CI 1.88-32.2). Multivariate analysis confirmed a predictive role for smaller tumors, non-recurrent VPD, and a treatment frequency of three applications per week. Imiquimod can be safely used for the treatment of VPD, even for micro-invasive tumors. Furthermore, we report some potential predictors of treatment response.

Menopausal hormone therapy for BRCA mutation carriers: A case for precision medicine

Antidepressant use and ovarian cancer risk: Evidence from nationwide studies with &gt;14,000 cases from Denmark and Sweden

Given that the evidence regarding the link between antidepressant use and ovarian cancer risk is equivocal, we investigated this research question by conducting two nationwide nested case-control studies among the Danish and Swedish populations. Altogether, 14,121 women with epithelial ovarian cancer (30-84 years old) (Denmark: 8976 diagnosed 2000-2019, Sweden: 5145 diagnosed 2010-2018) were randomly age-matched with 564,840 female controls (359,040 from Denmark, and 205,800 from Sweden) using risk set sampling. We used conditional logistic regression to estimate odds ratios (OR) with 95 % confidence intervals (CI) and combined the estimates based on the fixed-effect assumption. We also investigated potential effect modification by well-established risk factors for ovarian cancer. Antidepressant use was associated with an overall reduced risk of ovarian cancer (OR = 0.92, 95%CI: 0.88-0.96), and that reduction was more pronounced in postmenopausal women and long-term users. The effect was most pronounced for serous ovarian tumors (OR = 0.90, 95%CI: 0.86-0.95) but was also observed in other subtypes, although not statistically significant. Among different types of antidepressants, selective serotonin reuptake inhibitors in general and citalopram in particular exhibited a noteworthy reduction in ovarian cancer risk (OR = 0.89, 95%CI: 0.82-0.96). Additionally, use of oral contraceptives and hormone replacement therapy individually modified the association between antidepressant use and ovarian cancer risk. Use of an antidepressant was associated with a slight, but statistically significant, decrease in ovarian cancer risk. Given the morbidity and mortality associated with ovarian cancer, and increasing use of antidepressants, these findings may be of significance to cancer prevention and should be studied in more detail mechanistically.

Thyroid cancer risk in women after hysterectomy: A nationwide cohort study

Risk of endometrial polyp and surgical intervention in postmenopausal women with proliferative endometrium

To study the long-term risks of postmenopausal women with proliferative endometrium developing benign uterine pathologies (endometrial polyps and uterine fibroids) and requiring future gynecological interventions, and to compare them with women with atrophic endometrium. Retrospective cohort study of all women aged 55 or over who underwent endometrial biopsy between 1/1997 and 12/2008. Outcome data were available through to 2/2018. Women with proliferative endometrium were compared with those with atrophic endometrium for the presence of endometrial polyps, uterine fibroids, future endometrial biopsy for recurrent vaginal bleeding, and future hysteroscopy or hysterectomy. Logistic regression models were used to evaluate the association of endometrial histology and other covariates with the risk of morbidities. Postmenopausal women with proliferative endometrium are at higher risk of developing endometrial polyps, uterine fibroids and need for surgical intervention. Of 1808 women who underwent endometrial biopsy during the study period, 962 met inclusion criteria: 278 had proliferative and 684 had atrophic endometrium. Length of surveillance was similar in the two groups (11.9 vs. 11.5 years, p = 0.2). Compared with women with atrophic endometrium, women with proliferative endometrium had significantly higher rates of endometrial polyps (17.3 % vs 9.7 % p = 0.001). Multivariable logistic regression confirmed that women with proliferative endometrium had more fibroids on ultrasound (62.1 % vs 50.3 % 3 = 0.02), and had increased risks of developing endometrial polyps (aOR 1.9, 95 % CI 1.28-3.07, p = 0.002), repeat endometrial biopsy (34.9 % vs. 16.8%p < 0.001) and future hysterectomy or hysteroscopy (26.6 % vs 16.2 % p < 0.001). In addition to the long-term increased risk of cancer, postmenopausal women with proliferative endometrium are more likely to have future bleeding, surgical interventions and diagnosis of endometrial polyps. Medical management to reduce estrogenic activity and associated risks may be considered in these cases.

Endometrial telomerase activity in women with either endometrial cancer or hyperplasia: A systematic review and meta-analysis

We performed a systematic review and meta-analysis to assess whether endometrial telomerase activity is associated with endometrial cancer or hyperplasia. PubMed, Web of Science, Embase, Scielo, LILAC, and CNKI databases were searched to obtain relevant literature for articles published through June 2022, following PRISMA guidelines and a registered PROSPERO protocol. We included observational studies reporting endometrial telomerase activity in patients with either endometrial cancer or hyperplasia compared with benign endometrial tissue (control women). The Newcastle-Ottawa Scale was used to evaluate the quality of studies. Data were expressed as the odds ratios (OR) and 95 % confidence intervals (CI). Random effects and inverse variance methods were used to meta-analyze associations. The I There were significant associations between endometrial telomerase activity and either endometrial cancer (20 studies, OR = 10.65, 95 % CI 6.39, 17.75, p = 0.00001, I Endometrial telomerase activity is higher in women with either endometrial cancer or endometrial hyperplasia compared to control women without those lesions.

The impact of the pandemic on gynecological oncology practice: Three years later

The diagnosis of endometrial cancer in women with asymptomatic endometrial polyp does not increase survival rates: an israel gynecologic oncology group study

To compare outcomes of symptomatic and asymptomatic women with endometrial cancer and a preoperative diagnosis of an endometrial polyp. An Israel Gynecologic Oncology Group multi-center retrospective cohort study. Of 635 patients with endometrial cancer and a preoperative diagnosis of an endometrial polyp who underwent surgery between 2002 and 2014 in one of 11 centers in Israel were divided into two groups according to the presence of bleeding symptoms. Outcome measures included recurrence-free survival, disease-specific survival and overall survival. Survival data were plotted according to the method of Kaplan and Meier and compared using the log-rank test. There were 513 symptomatic and 122 asymptomatic women with endometrial cancer and a preoperative diagnosis of an endometrial polyp. The median follow-up was 52 months (range 12-120 months). There were no differences between patients who experienced bleeding and those who did not in 5-year recurrence-free survival (85.2 % vs. 85.7 %; p=0.83, respectively), disease-specific survival (88.2 % vs. 89.2 %; p=0.71, respectively), or overall survival (80.2% vs. 78.4 %; p=0.97, respectively). The diagnosis of endometrial cancer in patients with asymptomatic endometrial polyps is not associated with improved outcomes as compared with patients with bleeding. In the absence of factors indicating a high risk of endometrial cancer, clinical and sonographic follow-up is the advised management strategy for these patients.