DNA methylation testing for vulvar cancer risk stratification in patients with high-grade vulvar intraepithelial neoplasia: a population-based cohort study.

Background: High-grade vulvar intraepithelial neoplasia (VIN) is the precursor of vulvar cancer and is divided into human papillomavirus (HPV)-associated high-grade squamous intraepithelial lesion (HSIL) and HPV-independent VIN, often clinically referred to as differentiated VIN (dVIN) and associated with vulvar dermatoses, usually lichen sclerosus. Surgical treatment of high-grade VIN often leads to genital deformity, reduced quality of life and reduced sexual function, which has a major impact on quality of life. To optimize clinical management, accurate biomarkers providing information on the cancer risk of high-grade VIN are needed.

Exercise effects on symptoms of depression and anxiety vary by patient, clinical, and intervention characteristics in cancer survivors: Results from pooled analyses of individual participant data of 26 RCTs.

Purpose: This study aimed to investigate whether socio-demographic, clinical, and intervention-related variables moderate the effects of exercise on depression and anxiety symptoms in cancer survivors.

Methods: Data from 26 RCTs in the POLARIS database were analyzed using a one-step individual participant data (IPD) meta-analytic approach with linear mixed models to assess exercise effects on depression and anxiety symptoms (z-scores). Interaction terms were added to these models to explore moderators.

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

Objective: 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.

Main Outcome Measures: 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).

Coronary Artery Calcium Scores After Prophylactic Premenopausal Bilateral Salpingo-Oophorectomy.

Background: Premenopausal risk-reducing salpingo-oophorectomy (RRSO) in women at high familial risk of ovarian cancer leads to immediate menopause. Although early natural menopause is associated with increased cardiovascular disease risk, evidence on long-term cardiovascular disease risk after early surgical menopause is scarce.

Objectives: We sought to determine the long-term influence of the timing of RRSO on the development of coronary artery calcium (CAC), an established marker for cardiovascular disease risk.

Prevalence and impact of vulvar lesions diagnosed prior to vulvar squamous cell carcinoma: A population-based cohort study.

Objective: To systematically explore vulvar pathology diagnosed prior to vulvar squamous cell carcinoma (VSCC), as well as the association with tumor characteristics, stage and survival outcome, with the aim of improving vulvar cancer prevention strategies.

Methods: VSCC diagnosed between 2005 and 2019 were identified from a population-based cohort provided by the Dutch Nationwide Pathology Databank. Pathology reports were reviewed to identify vulvar pathology diagnosed before primary VSCC.

DNA Methylation and p53 Immunohistochemistry as Prognostic Biomarkers for Vulvar Lichen Sclerosus.

Vulvar lichen sclerosus (LS) is an inflammatory dermatosis that can progress to human papillomavirus (HPV)-independent vulvar intraepithelial neoplasia (HPVi VIN) and vulvar squamous cell carcinoma (VSCC). Although LS has a much lower cancer risk compared with HPVi VIN (5% vs 50%, respectively), its incidence is significantly higher. Therefore, there is a clinical need to identify LS patients with an increased cancer risk.

Long-term outcome of high-grade serous carcinoma established in risk-reducing salpingo-oophorectomy specimens in asymptomatic BRCA1/2 germline pathogenic variant carriers.

Objective: The aim of this study was to describe the long-term outcome of asymptomatic BRCA1/2 germline pathogenic variant (GPV) carriers with high-grade serous carcinoma (HGSC) in their risk-reducing salpingo-oophorectomy (RRSO) specimen.

Methods: In a previously described cohort of asymptomatic BRCA1/2 GPV carriers derived from the Hereditary Breast and Ovarian cancer in the Netherlands (HEBON) study, women with HGSC at RRSO were identified. Main outcome was ten-year disease-free survival (DFS).

Incidence and Risk Factors for Recurrence and Progression of HPV-Independent Vulvar Intraepithelial Neoplasia.

Objectives: Human papillomavirus (HPV)-independent vulvar intraepithelial neoplasia (VIN) is a rare yet aggressive precursor lesion of vulvar cancer. Our objectives were to estimate its long-term incidence, the risk of recurrent disease and progression to vulvar cancer, and risk factors thereof.

Materials And Methods: Patients with HPV-independent VIN between 1991 and 2019 in a selected region were identified from the Dutch Nationwide Pathology Databank (Palga).

Dropout from exercise trials among cancer survivors-An individual patient data meta-analysis from the POLARIS study.

Introduction: The number of randomized controlled trials (RCTs) investigating the effects of exercise among cancer survivors has increased in recent years; however, participants dropping out of the trials are rarely described. The objective of the present study was to assess which combinations of participant and exercise program characteristics were associated with dropout from the exercise arms of RCTs among cancer survivors.

Methods: This study used data collected in the Predicting OptimaL cAncer RehabIlitation and Supportive care (POLARIS) study, an international database of RCTs investigating the effects of exercise among cancer survivors.

Urinary incontinence more than 15 years after premenopausal risk-reducing salpingo-oophorectomy: a multicentre cross-sectional study.

Objective: To study the impact of premenopausal risk-reducing salpingo-oophorectomy (RRSO), compared with postmenopausal RRSO, on urinary incontinence (UI) ≥10 years later.

Design: Cross-sectional study, nested in a nationwide cohort.

Setting: Multicentre in the Netherlands.

Clinical validation of methylation biomarkers for optimal detection of high-grade vulvar intraepithelial neoplasia.

The precursor lesions of vulvar squamous cell carcinoma (VSCC) include human papillomavirus (HPV)-associated and HPV-independent squamous neoplasia with a varying cancer risk. Our study aimed to validate the accuracy of previously identified DNA methylation markers for detection of such high-grade vulvar intraepithelial neoplasia (VIN). A large clinical series of 751 vulvar lesions, originally diagnosed as high-grade VIN, were reassessed and categorized into HPV-associated or HPV-independent vulvar disease categories.

Long-term effects of premenopausal risk-reducing salpingo-oophorectomy on cognition in women with high familial risk of ovarian cancer: A cross-sectional study.

Objective: To examine the effect of a premenopausal risk-reducing salpingo-oophorectomy (RRSO) in women at increased risk of ovarian cancer on objective and subjective cognition at least 10 years after RRSO.

Design: A cross-sectional study with prospective follow-up, nested in a nationwide cohort.

Setting: Multicentre in the Netherlands.

Sexual functioning more than 15 years after premenopausal risk-reducing salpingo-oophorectomy.

Background: Women with a BRCA1/2 pathogenic variant are advised to undergo premenopausal risk-reducing salpingo-oophorectomy after completion of childbearing, to reduce their risk of ovarian cancer. Several studies reported less sexual pleasure 1 to 3 years after a premenopausal oophorectomy. However, the long-term effects of premenopausal oophorectomy on sexual functioning are unknown.

The European Society of Gynaecological Oncology (ESGO), the International Society for the Study of Vulvovaginal Disease (ISSVD), the European College for the Study of Vulval Disease (ECSVD) and the European Federation for Colposcopy (EFC) Consensus Statements on Pre-invasive Vulvar Lesions.

The European Society of Gynaecological Oncology (ESGO), the International Society for the Study of Vulvovaginal Disease (ISSVD), the European College for the Study of Vulval Disease (ECSVD), and the European Federation for Colposcopy (EFC) developed consensus statements on pre-invasive vulvar lesions in order to improve the quality of care for patients with vulvar squamous intraepithelial neoplasia, vulvar Paget disease in situ, and melanoma in situ. For differentiated vulvar intraepithelial neoplasia (dVIN), an excisional procedure must always be adopted. For vulvar high-grade squamous intraepithelial lesion (VHSIL), both excisional procedures and ablative ones can be used.

The European Society of Gynaecological Oncology (ESGO), the International Society for the Study of Vulvovaginal Disease (ISSVD), the European College for the Study of Vulval Disease (ECSVD) and the European Federation for Colposcopy (EFC) consensus statements on pre-invasive vulvar lesions.

The European Society of Gynaecological Oncology (ESGO), the International Society for the Study of Vulvovaginal Disease (ISSVD), the European College for the Study of Vulval Disease (ECSVD), and the European Federation for Colposcopy (EFC) developed consensus statements on pre-invasive vulvar lesions in order to improve the quality of care for patients with vulvar squamous intraepithelial neoplasia, vulvar Paget disease in situ, and melanoma in situ. For differentiated vulvar intraepithelial neoplasia (dVIN), an excisional procedure must always be adopted. For vulvar high-grade squamous intraepithelial lesion (VHSIL), both excisional procedures and ablative ones can be used.

Changes in Sex Steroids and Relation With Menopausal Complaints in Women Undergoing Risk-reducing Salpingo-oophorectomy.

Context: Risk-reducing salpingo-oophorectomy (RRSO) is performed in BRCA1 or 2 mutant carriers to minimize ovarian cancer risk. Although studies have been performed investigating sex steroid levels, menopausal complaints, and sexual functioning in relation to RRSO, their exact relationship remains unknown.

Objectives: To investigate the impact of RRSO on serum sex steroid levels and their association with menopausal complaints and sexual functioning.

The Paget Trial: topical 5% imiquimod cream for noninvasive vulvar Paget disease.

Background: Vulvar Paget disease is an extremely rare skin disorder, which is most common in postmenopausal women. Most vulvar Paget disease cases are noninvasive; however, it may be invasive or associated with an underlying vulvar or distant adenocarcinoma. The current treatment of choice for noninvasive vulvar Paget disease is wide local excision, which is challenging because of extensive intraepithelial spread and may cause severe morbidity.

The Vulvar Cancer Risk in Differentiated Vulvar Intraepithelial Neoplasia: A Systematic Review.

Differentiated vulvar intraepithelial neoplasia (dVIN) is the precursor of human papillomavirus (HPV)-independent vulvar squamous cell carcinoma (VSCC). Given the rare incidence of dVIN, limited information on the exact cancer risk is available. We systematically reviewed the primary and recurrent VSCC risk in patients with dVIN, as well as the time to cancer development.

Biomarker Expression in Multifocal Vulvar High-Grade Squamous Intraepithelial Lesions.

In patients with high-grade squamous intraepithelial lesion (HSIL) of the vulva, the presence of multiple lesions, called multifocal HSIL, is common. The aim of this exploratory study was to investigate biomarker expression profiles in multifocal HSIL. In total, 27 lesions from 12 patients with high-risk human papillomavirus (HPV)-positive multifocal HSIL were tested for HPV genotype, expression of p16 and Ki-67, and DNA methylation of six genes.