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The author reflects on the effectivity of the vaccination program for the prevention of cervical cancer in Great Britain. The authors highlighted Cervarix™ vaccine from GlaxoSmithKline, which works against human papillomavirus (HPV) types 16 and 18. The authors opine that HPV immunization would decrease the incident of common malignancies related to HPV. According to the authors, the program did satisfactorily in its first year upon implementation.

The article presents a case study of a 71-year-old woman with stromal adenosarcoma of the uterus. She was suffering from a heavy postmenopausal bleeding though she did not have any significant past medical history and is not under any medication. Due to the inverted uterus being found, she under went radical hysterectomy and bilateral salpingo-oophorectomy approach. She made an excellent postoperative recovery with no recommended chemotherapy.

The article considers the role of vaginal microbiome in the aetiology of gynecological cancers. Topics discussed are factors that influence the acquisition of genital human papillomavirus (HPV) that are important in the pathogenesis of cervical cancer, efficacy of hysterectomy or salpingectomy with ovarian conservation and tubal ligation in reducing the risk of ovarian cancer, and role of vaginal microbiome in endometrial carcinogenesis.

The article presents information on a 82-year-old woman presented with a 3- month history of abdominal fullness and right-sided abdominal pain. The patient had no other symptoms and was systemically well. Medical scanning of the patient showed a complex pelvic mass with areas of calcification, likely to represent ovarian pathology.

Background: Constitutional mismatch repair deficiency syndrome results from bi-allelic inheritance of mutations affecting the key DNA mismatch repair genes: MLH1, MSH2, MSH6 or PMS2. Individuals with bi-allelic mutations have a dysfunctional mismatch repair system from birth; as a result, constitutional mismatch repair deficiency syndrome is characterised by early onset malignancies. Fewer than 150 cases have been reported in the literature over the past 20 years. This is the first report of the founder PMS2 mutation - NM_000535.5:c.1500del (p.Val501TrpfsTer94) in exon 11 and its associated cancers in this family. Case presentation: The proband is 30 years old and is alive today. She is of Pakistani ethnic origin and a product of consanguinity. She initially presented aged 24 with painless bleeding per-rectum from colorectal polyps and was referred to clinical genetics. Clinical examination revealed two café-au-lait lesions, lichen planus, and a dermoid cyst. Her sister had been diagnosed in childhood with an aggressive brain tumour followed by colorectal cancer. During follow up, the proband developed 37 colorectal adenomatous polyps, synchronous ovarian and endometrial adenocarcinomas, and ultimately a metachronous gastric adenocarcinoma. DNA sequencing of peripheral lymphocytes revealed a bi-allelic inheritance of the PMS2 mutation NM_000535.5:c.1500del (p.Val501TrpfsTer94) in exon 11. Ovarian tumour tissue demonstrated low microsatellite instability. To date, she has had a total abdominal hysterectomy, bilateral salpingo-oophorectomy, and a total gastrectomy. Aspirin and oestrogen-only hormone replacement therapy provide some chemoprophylaxis and manage postmenopausal symptoms, respectively. An 18-monthly colonoscopy surveillance programme has led to the excision of three high-grade dysplastic colorectal tubular adenomatous polyps. The proband's family pedigree displays multiple relatives with cancers including a likely case of 'true' Turcot syndrome. Conclusions: Constitutional mismatch repair deficiency syndrome should be considered in patients who present with early onset cancer, a strong family history of cancer, and cutaneous features resembling neurofibromatosis type I. Immunohistochemistry analysis of tumour and normal tissue is sensitive and specific for identifying patients with mismatch repair deficiency and should direct DNA sequencing of lymphocytic tissue to establish a diagnosis. Microsatellite instability status appears to be of little value in identifying patients who may have constitutional mismatch repair deficiency syndrome. [ABSTRACT FROM AUTHOR]

Background: Lynch syndrome is the most common genetic predisposition for hereditary cancer but remains underdiagnosed. Large prospective observational studies have recently increased understanding of the effectiveness of colonoscopic surveillance and the heterogeneity of cancer risk between genotypes. The need for gene- and gender-specific guidelines has been acknowledged. Methods: The European Hereditary Tumour Group (EHTG) and European Society of Coloproctology (ESCP) developed a multidisciplinary working group consisting of surgeons, clinical and molecular geneticists, pathologists, epidemiologists, gastroenterologists, and patient representation to conduct a graded evidence review. The previous Mallorca guideline format was used to revise the clinical guidance. Consensus for the guidance statements was acquired by three Delphi voting rounds. Results: Recommendations for clinical and molecular identification of Lynch syndrome, surgical and endoscopic management of Lynch syndrome-associated colorectal cancer, and preventive measures for cancer were produced. The emphasis was on surgical and gastroenterological aspects of the cancer spectrum. Manchester consensus guidelines for gynaecological management were endorsed. Executive and layperson summaries were provided. Conclusion: The recommendations from the EHTG and ESCP for identification of patients with Lynch syndrome, colorectal surveillance, surgical management of colorectal cancer, lifestyle and chemoprevention in Lynch syndrome that reached a consensus (at least 80 per cent) are presented. [ABSTRACT FROM AUTHOR]

Objective: To describe the current testing practice, referral pathways and gynaecological services available to women with Lynch syndrome (LS) in the UK.Design: Cross-sectional nationwide survey of gynaecological oncologists and women with LS.Setting: United Kingdom.Methods: Gynaecological oncologists were contacted directly. Women with LS were identified from national and regional clinical databases and the patient support group, Lynch syndrome UK.Main Outcome Measures: Gynaecological oncologists were asked to report rates of LS testing and current practice regarding risk-reducing strategies and gynaecological surveillance for women with LS. Women with LS were asked to describe their experiences of gynaecological care.Results: In total, 41 gynaecological oncologists and 298 women with LS responded to the survey. Of the gynaecological oncologists surveyed, 37% were unfamiliar with any clinical guidelines for the management of LS. Only 29% of gynaecological oncologists supported universal testing of endometrial cancer for LS; one centre routinely performed such testing. In all, 83% said they perform risk-reducing gynaecological surgery and 43% were aware of a local gynaecological surveillance service for women with LS. Of women with LS, most had undergone a hysterectomy (n = 191/64.1%), most frequently to reduce their gynaecological cancer risk (n = 86/45%). A total of 10% were initially referred for LS testing by their gynaecologist and 55% of those eligible regularly attended gynaecological surveillance; however, 62% wanted more regular surveillance. Regional variation was evident across all standards of care.Conclusions: There is widespread variation in the services offered to women with LS in the UK. As a community, gynaecological oncologists should move towards a nationally agreed provision of services.Tweetable Abstract: A mismatch in care for mismatch repair. Survey finds significant variation in gynaecological care for #Lynchsyndrome in the UK. [ABSTRACT FROM AUTHOR]

It is indeed plausible that women with certain vaginal microbiome CST groups are more prone to acquiring and failing to clear high-risk HPV and therefore identifying these CSTs is important to (1) predict cervical cancer risk, (2) develop targeted prevention strategies, and (3) test novel therapeutic strategies based on pre/probiotics. Well-designed longitudinal studies with adequate sample sizes, and using standardised sampling and analytical methods are now needed to provide robust evidence on what CST subtypes are linked with high-risk HPV and cervical cancer and importantly, to confirm causality. FundingKN is supported by a Cancer Research UK Manchester Cancer Research Centre Clinical Research Fellowship. [Extracted from the article]

Background: Developing a shared agenda is an important step in ensuring future research has the necessary relevance.Objective: To characterise research priority setting partnerships (PSPs) relevant to women's health.Search Strategy: Included studies were identified by searching MEDLINE and the James Lind Alliance (JLA) database.Selection Criteria: Priority setting partnerships using formal consensus methods.Data Collection and Analysis: Descriptive narrative to describe the study characteristics, methods, and results.Main Results: Ten national and two international PSPs were identified. All PSPs used the JLA method to identify research priorities. Nine PSPs had published a protocol. Potential research uncertainties were gathered from guidelines (two studies), Cochrane reviews (five studies), and surveys (12 studies). The number of healthcare professionals (31-287), patients (44-932), and others (33-139) who responded to the survey, and the number of uncertainties submitted (52-4767) varied. All PSPs entered confirmed research uncertainties (39-104) into interim priority setting surveys and healthcare professionals (31-287), patients (44-932), and others (33-139) responded. All PSPs entered a short list of research uncertainties into a consensus development meeting, which enabled healthcare professionals (six to 21), patients (eight to 14), and others (two to 13) to identify research priorities (ten to 15). Four PSPs have published their results.Conclusion: Future research priority setting studies should publish a protocol, use formal consensus development methods, and ensure their methods and results are comprehensively reported.Tweetable Abstract: Research published in @BJOGtweets highlights future research priorities across women's health, including @FertilityTop10, @jamesmnduffy. [ABSTRACT FROM AUTHOR]

The article focuses on extension of BRCA1/2 germline testing to all high-grade serous ovarian cancer (HGSOC) regardless of family history. It mentions benefits of poly ADP ribose polymerase inhibitor (PARPi) therapies and no endometrioid types were recorded and identify somatic mutations that would otherwise go undetected but may determine sensitivity to PARPi. It also mentions affected women would then only require germline testing if a pathogenic variant were identified in tumour material.

Objectives To measure the feasibility and effectiveness of interventions to increase cervical screening uptake amongst young women. Methods A two-phase cluster randomized trial conducted in general practices in the NHS Cervical Screening Programme. In Phase 1, women in practices randomized to intervention due for their first invitation to cervical screening received a pre-invitation leaflet and, separately, access to online booking. In Phase 2, non-attenders at six months were randomized to one of: vaginal self-sample kits sent unrequested or offered; timed appointments; nurse navigator; or the choice between nurse navigator or self-sample kits. Primary outcome was uplift in intervention vs. control practices, at 3 and 12 months post invitation. Results Phase 1 randomized 20,879 women. Neither pre-invitation leaflet nor online booking increased screening uptake by three months (18.8% pre-invitation leaflet vs. 19.2% control and 17.8% online booking vs. 17.2% control). Uptake was higher amongst human papillomavirus vaccinees at three months (OR 2.07, 95% CI 1.69–2.53, p < 0.001). Phase 2 randomized 10,126 non-attenders, with 32–34 clusters for each intervention and 100 clusters as controls. Sending self-sample kits increased uptake at 12 months (OR 1.51, 95% CI 1.20–1.91, p = 0.001), as did timed appointments (OR 1.41, 95% CI 1.14–1.74, p = 0.001). The offer of a nurse navigator, a self-sample kits on request, and choice between timed appointments and nurse navigator were ineffective. Conclusions Amongst non-attenders, self-sample kits sent and timed appointments achieved an uplift in screening over the short term; longer term impact is less certain. Prior human papillomavirus vaccination was associated with increased screening uptake. [ABSTRACT FROM AUTHOR]

Background: Preclinical studies in endometrial cancer (EC) show that metformin reduces cellular proliferation by PI3K-AKT-mTOR inhibition. We tested the hypothesis that short-term presurgical metformin reduces cellular proliferation in atypical endometrial hyperplasia (AEH) and endometrioid EC, and assessed the feasibility of using phosphorylated PI3K-AKT-mTOR proteins as tissue end points.Methods: Women with AEH or EC received metformin 850 mg twice a day or no drug in the presurgical window between diagnosis and hysterectomy. Before and after the window, tissue samples were obtained; serum markers of insulin resistance (e.g. homeostasis model of assessment of insulin resistance index) were determined; and anthropometrics measured (e.g. BMI). Cell proliferation (Ki-67) and PI3K-AKT-mTOR phosphostatus were assessed by immunohistochemistry and scored blinded to treatment.Results: Twenty-eight metformin-treated and 12 untreated patients, well matched for age and BMI, completed the study. Metformin treatment (median 20 days, range 7-34) was associated with a 17.2% reduction in tumour Ki-67 (95% CI -27.4, -7.0, P=0.002), in a dose-dependent manner. Tumour PI3K-AKT-mTOR protein phosphostatus varied but the effects were not significant after adjusting for changes in controls.Conclusions: Short-term metformin was associated with reduced Ki-67 expression in EC. Changes in tumour PI3K-AKT-mTOR protein phosphostatus were seen in both groups. Future studies should address the variability attributed to different sampling techniques including devascularisation of the uterus at hysterectomy. [ABSTRACT FROM AUTHOR]

The author discusses the study "Obesity and endometrial cancer: unanswered epidemiological questions," by A. G. Renehan, M. L. MacKintosh, and E. J. Crosbie, focuses on the epidemiology of endometrial cancer and obesity. Topics include the endometrial cancer in women in North America and European countries, the meta-analysis on the relationship between endometrial cancer risk and increasing body mass index (BMI), and the endometrial cancer prevention in population with obese or overweight.

Background:Adjuvant therapy increases disease-free survival in endometrial cancer (EC), but has no impact on overall survival and negatively influences the quality of life. We investigated the discriminatory power of classical and immunological predictors of recurrence in a cohort of EC patients and confirmed the findings in an independent validation cohort.Methods:We reanalysed the data from 355 EC patients and tested our findings in an independent validation cohort of 72 patients with EC. Predictors were selected and Harrell's C-index for concordance was used to determine discriminatory power for disease-free survival in the total group and stratified for histological subtype.Results:Predictors for recurrence were FIGO stage, lymphovascular space invasion and numbers of cytotoxic and memory T-cells. For high risk cancer, cytotoxic or memory T-cells predicted recurrence as well as a combination of FIGO stage and lymphovascular space invasion (C-index 0.67 and 0.71 vs 0.70). Recurrence was best predicted when FIGO stage, lymphovascular space invasion and numbers of cytotoxic cells were used in combination (C-index 0.82). Findings were confirmed in the validation cohort.Conclusions:In high-risk EC, clinicopathological or immunological variables can predict regional or distant recurrence with equal accuracy, but the use of these variables in combination is more powerful. [ABSTRACT FROM AUTHOR]

The authors examines whether disease management protocols in Great Britain are restricting innovations in the treatment of cancer, highlighting a legislative bill introduced by Lord Maurice Saatchi. The legislative bill is discussed which aims to promote responsible innovation in case the available treatment options are limited or are projected to fail. Other topics include the bill's section that prevents quackery, its possible impact on clinical trials, and stratification of medicine.

Background: MCM5 is a protein involved in DNA replication, facilitating cell proliferation. In normal epithelium MCM5 expression is restricted to the cells in the basal proliferative compartments, however in the presence of a tumour MCM5 positive cells are present at the surface epithelium and are shed into bodily fluids. The aim of this study was to determine the sensitivity of MCM5 as a biomarker for the detection of endometrial and ovarian cancer.Methods: Patients with known ovarian or endometrial cancers, or known benign gynaecological conditions, were enrolled. Informed consent was obtained prior to the collection of full void urine, and either a vaginal tampon (worn for 6-8 h), or a vaginal swab. Vaginal secretions were extracted from the tampon or swab, centrifuged and lysed. Urine samples were centrifuged and lysed. MCM5 levels were determined by MCM5-ELISA (Arquer Diagnostics Ltd).Results: 125 patients completed the study protocol, 41 patients had endometrial cancer, 26 ovarian cancer, and 58 benign controls. All patients provided a urine sample and either a tampon or vaginal swab sample. Urine MCM5 levels were higher in cancer patients than controls (p < 0.0001), there was no significant difference in levels between tampon samples or vaginal swab samples in cancer patients when compared to controls. Performance of MCM5 to discriminate cancer from benign disease was high with an area under the ROC curve of 0.83 for endometrial cancer and 0.68 for ovarian cancer. Using a cut off of 12 pg/mL, overall sensitivity for endometrial cancer was 87.8, and 61.5% for ovarian cancer with a specificity of 75.9%.Conclusions: MCM5 is a novel sensitive and specific biomarker for the detection of ovarian and endometrial tumours in urine samples, which is likely to have clinical utility as a diagnostic aid. [ABSTRACT FROM AUTHOR]

The article discusses the article by M. Zakhour and colleagues about women with atypical endometrial hyperplasia (AEH) or endometrial cancer (EC) who were treated with progestins. Topics include the use of immunohistochemistry to define lesions as mismatch repair (MMR)-competent or MMR-deficient, the senescence, differentiation, and apoptosis induced by progestin, and the response rate to intrauterine progestins.

Despite the success of cervical screening, cancer of the cervix is the fourth most common cancer affecting women worldwide (CRUK 2014). Rates are particularly high in developing nations, which lack the requisite infrastructure for cytology and colposcopy-based screening, and in certain demographic groups, where uptake of screening is poor. Recent research has focussed on developing less invasive and potentially more acceptable means of identifying women at high risk of cervical intraepithelial neoplasia (CIN). Urinary HPV testing has received particular attention because of the ease of obtaining samples and the opportunity this affords to overcoming barriers to cervical screening like embarrassment and discomfort. This article is protected by copyright. All rights reserved. [ABSTRACT FROM AUTHOR]