Exploring the perspectives of underrepresented voices: Perceptions and experiences of uterine cancer for black African, Caribbean, black British, and mixed-black women in the UK to develop strategies for early symptom presentation.

OBJECTIVES: The uterine cancer (UC) mortality rate in the UK is significantly higher for women who belong to a Black ethnic group compared to those from other ethnic groups. This study aimed to understand the views and experiences of UC amongst Black ethnic minority women in the UK, with a focus on awareness and presentation of red-flag symptoms. METHODS: Women of Black African, Caribbean, Black British and Mixed-Black ethnicity were purposefully recruited to participate in focus groups and individual semi-structured interviews. RESULTS: Twenty women from different regions in England participated in the study. Reflexive thematic analysis of the data led to the identification of three main themes: 1) Healthcare inequities; 2) Support and sense making with other Black women; and 3) Knowledge dissemination, mobilisation, and empowerment. Perceptions of inequitable healthcare provision and distrust influenced how participants, and their peer networks, approached seeking assistance from healthcare professionals. Concerns were also raised about culturally insensitive information resources, including issues of language, literacy, and representation, all of which served as potential barriers for women within Black ethnic minority groups. CONCLUSIONS: The deficiency of targeted knowledge mobilisation and specific UC information aimed at Black ethnicity women living in the UK, reportedly contributes to the dissemination of misconceptions and an atmosphere of apprehension around a UC diagnosis. The insights from this study highlight the significance of designing culturally sensitive strategies to promote informed decision-making and empower the dissemination of accurate health knowledge amongst Black women.

Genetic Diversity and Protective Efficacy of the RTS,S/AS01 Malaria Vaccine.

BACKGROUND: The RTS,S/AS01 vaccine targets the circumsporozoite protein of Plasmodium falciparum and has partial protective efficacy against clinical and severe malaria disease in infants and children. We investigated whether the vaccine efficacy was specific to certain parasite genotypes at the circumsporozoite protein locus. METHODS: We used polymerase chain reaction-based next-generation sequencing of DNA extracted from samples from 4985 participants to survey circumsporozoite protein polymorphisms. We evaluated the effect that polymorphic positions and haplotypic regions within the circumsporozoite protein had on vaccine efficacy against first episodes of clinical malaria within 1 year after vaccination. RESULTS: In the per-protocol group of 4577 RTS,S/AS01-vaccinated participants and 2335 control-vaccinated participants who were 5 to 17 months of age, the 1-year cumulative vaccine efficacy was 50.3% (95% confidence interval [CI], 34.6 to 62.3) against clinical malaria in which parasites matched the vaccine in the entire circumsporozoite protein C-terminal (139 infections), as compared with 33.4% (95% CI, 29.3 to 37.2) against mismatched malaria (1951 infections) (P=0.04 for differential vaccine efficacy). The vaccine efficacy based on the hazard ratio was 62.7% (95% CI, 51.6 to 71.3) against matched infections versus 54.2% (95% CI, 49.9 to 58.1) against mismatched infections (P=0.06). In the group of infants 6 to 12 weeks of age, there was no evidence of differential allele-specific vaccine efficacy. CONCLUSIONS: These results suggest that among children 5 to 17 months of age, the RTS,S vaccine has greater activity against malaria parasites with the matched circumsporozoite protein allele than against mismatched malaria. The overall vaccine efficacy in this age category will depend on the proportion of matched alleles in the local parasite population; in this trial, less than 10% of parasites had matched alleles. (Funded by the National Institutes of Health and others.).

Knowledge, attitudes and awareness of the human papillomavirus amongst primary care practice nurses: an evaluation of current training in England.

Background: The incorporation of Human papillomavirus (HPV) testing into the English cervical screening programme has been met with fear and anxiety. Healthcare professionals need to be adequately informed about HPV to help alleviate patient concerns. The aim of this study was to evaluate the HPV training provided to practice nurses (PNs) and determine their level of HPV knowledge. Method: A web-based survey was distributed to 147 General Practice surgeries in the Leicester, Leicestershire and Rutland regions, between May and July 2015. The survey explored four broad areas; demographics/level of experience, HPV knowledge, attitudes towards the HPV vaccine and self-perceived adequacy of HPV knowledge. Results: A total of 128 surveys were completed, with 94 complete responses. Overall awareness of basic HPV facts was adequate; however, detailed, and in some cases basic, knowledge was lacking. 9.6% failed to identify that HPV can cause cervical cancer and 62.8% believed that HPV requires treatment. Not all PNs felt adequately informed about HPV and a need to improve the provision of training was identified. Conclusion: PNs play a key role in increasing public awareness of HPV and implementing cervical cancer screening. The provision of education to PNs needs to be a priority and current methods of training need to be re-evaluated.

Cervical cancer still presents symptomatically 20 years after the introduction of a structured national screening programme.

OBJECTIVE: To investigate the pattern of presentation of cervical cancer and to identify the characteristics of women who present symptomatically with cervical cancer. METHODS: A retrospective study of all cervical cancer cases diagnosed over a 4-year period. Details of mode of presentation, stage at diagnosis and cytological/gynaecological history were collated. RESULTS: In total, 148 cases were identified with a median age of 46 years (range, 20-91 years). In this population, 112 (75.7%) women were within the screening age range. Forty-eight (33.6%) were asymptomatic at diagnosis and presented through the colposcopy clinic. All asymptomatic women (100%) had stage I disease at diagnosis, compared with 37.2% of the symptomatic group (P < 0.001). Postmenopausal bleeding was the most common presenting symptom (33%), followed by postcoital bleeding (14.2%), intermenstrual bleeding (12.2%) and increased vaginal discharge (3.4%). The majority of symptomatic women presented through colposcopy, gynaecological oncology or gynaecology clinics (87.6%); however, 6.5% presented through the emergency department. Women who presented symptomatically were significantly older than asymptomatic women (54.9 versus 38.1 years, P < 0.001). Women at risk of social isolation (non-English speakers, alcohol abusers, heavy smokers, receiving treatment for psychiatric disease) were more likely to present with symptoms, through the emergency department and with advanced disease at diagnosis (stage II+) (P < 0.001). CONCLUSIONS: A review of local cervical cancer cases can highlight areas of weakness in a screening programme and can identify populations who are at risk in presenting symptomatically with advanced disease.

Primary retroperitoneal mucinous cystadenocarcinoma (PRMCa): a systematic review of the literature and meta-analysis.

PURPOSE: Primary retroperitoneal mucinous cystadenocarcinoma (PRMCa) is a rare tumour. Prognosis and optimal management are not well established. In view of a case managed in our Centre, we performed a systematic review and meta-analysis. METHOD: Systematic review of medical electronic databases for published data (1950-12/10/2015). No RCTs identified. Individual patient data detracted from case reports and case series were analysed RESULTS: In total, 73 female and 5 male cases of PRMCa identified including our case. Median age at diagnosis was 42.0 years (range 18-86 years), with women being significantly younger than men at diagnosis (42.0 years versus 62.2 years, p = 0.005). A palpable abdominal mass and abdominal pain were the most common presentations in 42.9 and 23.8 % of cases, respectively. Twenty-six women were <38 years old. There were 16 women <38 years old that had surgical data reported, of which 14 underwent fertility-sparing surgery with excision of the mass. Adjuvant chemotherapy was given in 24.1 % (13/72) women. Follow-up ranged from 1 to 130 months with a median of 15 months. Of the 57 cases that had follow-up reported, recurrence occurred in 23 cases (40.4 %) within a median of 8 months from diagnosis. Median disease-free survival was 15 months (range 1-130 months). Of the women who recurred, 14 died of their disease giving 1, 2 and 5-year disease-specific survival rates of 85.9, 80.7 and 75.4 %, respectively. CONCLUSION: PRMCa are rare and potentially aggressive tumours that often occur in young women. Removal of the tumour, adequate staging and adjuvant chemotherapy needs to be considered.

The role of regional anaesthesia in the surgical management of vulval malignancy.

Abstract Surgical excision is the management of choice in vulval cancer however, the patient population are typically elderly and comorbid, for whom general anaesthesia (GA) carries considerable risk. The outcome of 107 procedures were reviewed in order investigate the postoperative complication rates associated with general and regional anaesthesia for the surgical management of vulval cancer. GA was used in 78 (72.9%) cases; 27 (22.9%) had a regional anaesthetic (spinal/epidural/ileoinguinal) and two women had a GA following a failed spinal anaesthetic. Women having a regional anaesthetic were significantly older (p = 0.0198), had a higher ACE (p = 0.0001) and ASA score (p < 0.0001) than those having a GA. There was an association between GA and grade II+ complications, compared with regional techniques (odds ratio, OR 2.72) but this was not significant due to the small number of events. Regional anaesthetic techniques are safe, well-tolerated alternatives to GA for the surgical management of vulval cancer, especially in an elderly and comorbid population.

Attitudes and barriers to participation in window-of-opportunity trials reported by White and Asian/Asian British ethnicity patients who have undergone treatment for endometrial cancer.

PURPOSE: Window-of-opportunity trials (WOT) are a study design that have been used to investigate drug activity in endometrial cancer (EC). Recruitment to cancer clinical trials by patients from ethnic minority groups is reported to be lower than for patients of White ethnicity. METHODS: A verbal questionnaire was conducted with White and Asian/Asian British ethnicity patients who had undergone treatment for EC. Strategic purposeful sampling was used to recruit patients from diverse social/educational backgrounds. Questions explored: background knowledge of clinical research, WOT study design, and views on medications that might be investigated. Thematic analysis was used to explore motivations for WOT participation and perceived barriers. RESULTS: In total, 21 patients were recruited to the study (15 White and 6 Asian/Asian British). Views on optimum time to receive trial information differed, preferences ranging from 'at the time of diagnosis' to 'a few days after diagnosis'. The choice of medication under investigation had a strong influence on potential willingness to participate, with greater interest reported in medications derived from vitamins or food supplements rather than hormone-based drugs. Potential barriers to participation included concern over potential side-effects and the emotional/physical burden of a cancer diagnosis prior to major surgery. DISCUSSION: This study provides important insights into patients' views on WOT participation in EC and raises issues that need to be considered for future trial design and participant recruitment materials. The timing and format of study information and type of substance under investigation were factors influencing potential participation. Future studies should consider using multi-lingual visual information videos to address information needs, as this may encourage participation by ethnic minority patients.

Accuracy of colposcopy-directed punch biopsies: a systematic review and meta-analysis.

BACKGROUND: The colposcopy-directed punch biopsy is widely used in the management of women with abnormal cervical cytology; however, its accuracy compared with definitive histology from an excision biopsy is not well established. OBJECTIVES: To assess the accuracy of the colposcopy-directed punch biopsy to diagnose high-grade cervical intraepithelial neoplasia (CIN) by performing a systematic review and meta-analysis. SEARCH STRATEGY: A systematic search of MEDLINE, EMBASE and the Cochrane Library was performed. SELECTION CRITERIA: Articles that compared the colposcopically directed cervical punch biopsy with definitive histology from an excisional cervical biopsy or hysterectomy. DATA COLLECTION AND ANALYSIS: Random effects and hierarchical summary receiver operating characteristic regression models were used to compute the pooled sensitivity and specificity applying different test cut-offs for outcomes of high-grade CIN. MAIN RESULTS: Thirty-two papers comprising 7873 paired punch/definitive histology results were identified. The pooled sensitivity for a punch biopsy defined as test cut-off CIN1+ to diagnose CIN2+ disease was 91.3% (95% CI 85.3-94.9%) and the specificity was 24.6% (95% CI 16.0-35.9%). In most of the studies, the majority of enrolled women had positive punch biopsies. Pooling of the four studies where the excision biopsy was performed immediately after the punch biopsy, and where the rate of positive punch biopsies was considerably lower, yielded a sensitivity of 81.4% and specificity of 63.3%. AUTHOR'S CONCLUSION: The observed high sensitivity of the punch biopsy derived from all studies is probably the result of verification bias.

Review of invasive cervical cancers and uptake of disclosure of results: an audit of procedures and response.

OBJECTIVE: To audit the process and outcome of case reviews performed for invasive cervical cancers diagnosed between 2003 and 2007, and the timely disclosure of results to the respective patients. METHODS: Invasive cervical cancer reviews were performed on all cases of cervical cancer diagnosed between 2003 and 2007. Following the review, women were classified into two categories: a group who developed invasive cancer despite adherence to the screening programme or in whom a management or diagnostic decision was determined to have been a principal factor in the development of their disease (Group A), and a second group who either had never undergone a cervical smear or had been established defaulters from the screening programme (Group B). RESULTS: Ninety-seven of the 98 cases of invasive cervical cancer diagnosed in the 4-year study period were reviewed. Sixty of the 61 women in Group A were sent an invitation to discuss the results of their case review. Thirty-six (37%) were classified as Group B, and it was deemed neither appropriate nor possible to invite the patients for a review consultation. Of the women sent an invitation, only 24 (40%) chose to attend. CONCLUSION: A policy of selective invitation for the disclosure of invasive review results is feasible. Less than one-half of patients diagnosed with cervical cancer appear to want to know how they developed cervical cancer despite previously participating in a screening programme.

Innovative Follow-up Strategies for Endometrial Cancer.

Increasing recognition of the heterogeneous nature of endometrial cancer, the excellent prognosis of low-risk cases and improvements in risk stratification offer opportunities for innovative, personalised follow-up strategies. This review article outlines the evidence base for alternative follow-up strategies in the different risk categories of endometrial cancer, cancer survivorship programmes and considers future directions in endometrial cancer follow-up, including emerging new techniques, such as the liquid biopsy, and opportunities for combining molecular and clinicopathological features to personalise endometrial cancer follow-up.

Implementing the national invasive cervical cancer audit: a local perspective.

OBJECTIVE: To monitor the effectiveness of the cervical screening programme and identify suboptimal management in order to improve patient care. DESIGN: Retrospective study. SETTING: A university hospital serving a population of 1 million people. POPULATION: All women diagnosed with a cervical cancer between 2003 and 2006. METHODS: Analysis of data from invasive cervical cancer reviews. MAIN OUTCOME MEASURE: Categorisation of cervical cancer cases according to the Invasive Cervical Cancer Audit classification. RESULTS: Eighty-seven women were diagnosed with cervical cancer during the 3-year study period. The 'lapsed attender' group accounted for the greatest number of cases (30%), followed by screen detected (26%), interval cancers (13%), never attended (12%), lost to follow-up (10%) and never invited (9%). Women who had never attended for cytology presented with higher stage disease, stage-II or above, compared with the screen-detected cases: 60% were stage II or above, compared with 13.0%, Chi-square P = 0.018. The most frequently identified screening programme problem was patient compliance, which was determined to be the principle contributing factor in 39 cases (45%) and a secondary factor in a further ten cases. CONCLUSIONS: The categorisation of cervical cancer cases has the potential of yielding invaluable information for improving programme effectiveness. Patient compliance is the greatest challenge to the screening programme, and the need for regular screening and adherence to follow-up regimens needs to be reinforced in order to maximise the efficacy of the national screening programme.

Cervical cytology/histology discrepancy: a 4-year review of patient outcome.

OBJECTIVE: To investigate the diagnosis, review and management of women identified as having a cytology/histology discrepancy. METHODS: A review of all patients diagnosed with a discrepancy between referral smear and cervical histology was performed between January 2003 and December 2004. Cases were followed for a minimum of 4 years and patient management and outcome reviewed. RESULTS: A significant discrepancy was identified in 79 cases, 0.1% of all smears (n = 80,926) analysed during the study period. A discrepancy between cytology and histology, obtained from large loop excision of the transformation zone (LLETZ), was confirmed by multidisciplinary review in 42 cases (53.2%). In 37 cases (46.8%) the cytological and/or histological diagnosis was revised; the cytology was significantly more likely than the histology to be amended (chi square P = 0.005), most often because cytology had been overcalled. Of the confirmed discrepancy cases, 33 (78.6%) were due to high-grade squamous cell or glandular abnormalities on cytology with a negative, inflammatory or human papillomavirus (HPV) infection on histology (HGC/NH). HGC/NH cases were managed by cytological follow-up in 29 (87.9%), of which 72.4% of the smears were negative when performed at least 6 months post-excision. During the 4-year follow-up period six women with a confirmed HGC/NH underwent a repeat cervical excision (hysterectomy or LLETZ), and of these, HPV effect was seen in two cases but no cervical intraepithelial neoplasia was detected in any of the histological specimens. CONCLUSION: Cytology overcall was responsible for the majority of cytology/histology discrepancies. A confirmed discrepancy is not an indication for a further excisional biopsy but follow-up is essential because a small percentage of patients may have disease that has been missed.

The use and understanding of CA125 as a tumor marker for ovarian cancer: a questionnaire-based survey.

The aim of this study was to assess the level of understanding of the role of the tumor marker CA125 in ovarian cancer among doctors of different grades specializing in obstetrics and gynecology (O&G), medicine, surgery, and primary care (general practitioners [GPs]). The study involves a questionnaire-based survey. Two hundred and fifty-nine questionnaires were distributed. An overall response rate of 47.1% was achieved. All grades of doctors and all major specialties were represented. There was a significant difference in the level of self-reported CA125 ordering between the medical specialties, O&G being the most frequent users and primary care the least (P < 0.001), and between the grade of doctors, senior house officers/preregistration house officers and GPs less than consultants and middle grade doctors (P < 0.001). Electronic literature was the first source of advice for the majority of respondents (38.5%). The knowledge of false-positive causes for a raised CA125 was low in medicine, surgery, and primary care specialties, as was the awareness of the sensitivity and specificity of CA125 in epithelial and nonepithelial ovarian cancers. The role of CA125 in ovarian cancer is poorly understood, especially among doctors working outside O&G. Guidelines should be developed to aid clinicians from all specialties in the most appropriate application of CA125 in their practice. Substantial cost savings could be made by the introduction of clear protocol-driven ordering in an attempt to reduce the number of inappropriate tests performed.

Knowledge of the risk factors and symptoms associated with endometrial cancer in British South Asian and British White women.

OBJECTIVE: To explore differences in the background knowledge of Endometrial Cancer (EC), its risk factors, symptoms and prognosis of Endometrial Cancer (EC) between British White (BW) and British South Asian (BSA) women who had undergone treatment for stage I endometrial cancer within the past 3-years. STUDY DESIGN: Face-to-face, semi-structured interviews exploring knowledge; diagnosis; treatment; follow-up; and survivorship were undertaken and analysed using Thematic Analysis. RESULTS: Twenty-one women were interviewed (13 BW and 8 BSA). BW and BSA women reported similar views, experiences and concerns with regards to EC. Knowledge appeared to differ amongst the two groups with BSA women reporting being more aware that unscheduled vaginal bleeding could be associated with a malignancy but having lower levels of knowledge of the risk factors that can lead to EC, compared to BW women. There was a lack of understanding of the difference between cervical cancer and EC and as a result, many women reported taking reassurance from negative cervical cytology as excluding EC. There was also the misconception amongst some of the women that there was a link between sexual behaviour and EC. Women from both groups used the lay healthcare system to discuss their situation/symptoms, however BSA women reported to have specifically sought out women within their social network who had previously undergone treatment for EC. CONCLUSIONS: Greater effort is needed to raise awareness in both the BW/BSA communities of the symptoms associated with EC that should prompt medical review. Educational efforts are required to overcome the reported perception that EC is synonymous with cervical cancer and cannot be detected by cervical screening.

Iatrogenic Menopause After Treatment for Cervical Cancer.

The ever-improving prognosis of women diagnosed with cervical cancer has meant that survivorship and treatment-related sequelae are being brought more into the spotlight in an attempt to try to reduce morbidity and improve women's long-term health. However, there are many issues surrounding an iatrogenic menopause in cervical cancer, a variety of potential management options and barriers to treatment. Women who have become menopausal under the age of 45 years as a result of cervical cancer are significantly less likely to start hormone replacement therapy (HRT) or continue it long term as compared with those who have undergone a surgical menopause for a benign reason. High profile media reports raising concerns about the safety of HRT use have left many women reluctant to consider HRT as a therapeutic option for menopausal symptoms and many are seeking to use complementary/alternative medicine, including non-pharmacological interventions, to alleviate symptoms. The benefits of HRT in this population have been shown to reduce these effects, although adherence to treatment regimens is a challenge due to poor compliance, which is in part due to the fear of a second malignancy. The development of non-HRT-based interventions to ameliorate menopausal symptoms and reduce the long-term health consequences are needed for women who choose not to take HRT.

The role of CA125 in clinical practice.

BACKGROUND: CA125 is a high molecular weight glycoprotein, which is expressed by a large proportion of epithelial ovarian cancers. The sensitivity and specificity of CA125 are poor and there are no guidelines produced by the Royal College of Pathologists or the Association of Clinical Biochemists to aid clinicians and laboratories in its most appropriate use. AIM: To identify the patient population having a CA125 measurement and to determine its contribution to individual patient management. METHODS: A retrospective case note audit looking at patients who had a CA125 measurement performed between April 2000 and April 2002. RESULTS: The study comprised 799 patients; 751 (94%) were female and 48 (6%) male; 221 (29%) females and 22 (46%) males had an abnormal result. CA125 was mainly used to investigate a wide range of signs and symptoms, and few tests were for follow up or screening of ovarian cancer. In female patients having a CA125 for suspicion of malignancy/ovarian cancer, only 39 (20%) of the abnormal results were caused by ovarian cancer. False positive results were largely caused by another malignancy (48 cases; 26%), benign ovarian disease (26 cases; 14%), and benign gynaecological conditions, particularly leiomyomas (18 cases; 9%). The specificity of CA125 for ovarian cancer increased with concentrations >1000 kU/litre. CONCLUSIONS: These results confirm the high false positive rate and poor sensitivity and specificity associated with CA125. The substantial inappropriate usage of CA125 has led to results that are useless to the clinician, have cost implications, and add to patient anxiety and clinical uncertainty.

Colposcopy training and assessment across the member countries of the European Federation for Colposcopy.

OBJECTIVES: Colposcopy training and assessment is not uniform across Europe with individual countries determining their own required standards and regulations. In light of the significant changes in colposcopic practice that have occurred over the past decade and the expansion of the European Federation for Colposcopy (EFC) membership, a study was conducted firstly, to assess the current requirements for training in each of the member countries and secondly, to review an EFC-approved core training curriculum for colposcopy. STUDY DESIGN: A questionnaire survey of the EFC representatives from all member countries investigating their country's current practices/requirements with regard to training, assessment and accreditation for colposcopy. A two-round Delphi consultation with representation from the full, associate and three potential member countries was conducted using a 5-point Likert scale for scoring opinions. The results were analysed with respect to each country's population size and World Bank economic classification. RESULTS: For the questionnaire survey, responses were received from 31/34 countries invited to participate. Training programmes were reported to be in place in 21 of the 31 countries but only 17 of the 21 countries had a committee overseeing the training programme. An assessment was part of the training programme in 20 countries with multiple choice questions and portfolios the most common assessment tools. Countries with a population size less than 2 million have a statistically significant lower probability of having a structured training/assessment programme, 1/5 compared to 20/26 for a populations greater than 2 million, p=0.013. For the Delphi study, responses were received from 34/39 countries invited to participate. Of the 51 competencies previously identified only 2 did not receive full support: 'perform bacterial swabs' and 'provide data to national body'. There was no significant difference in the responses given by member, associate member or potential member countries. CONCLUSIONS: There is considerable variation in colposcopy training and assessment across Europe. This study has enabled consensus opinion with the EFC on the contents of an EFC core curriculum. The revised curriculum has a mandate from the EFC member countries to be implemented across Europe as the standard for colposcopic training.

Semisynthetic aminoglycoside antibacterials. 6. Synthesis of sisomicin, Antibiotic G-52, and novel 6'-substituted analogues of sisomicin from aminoglycoside 66-40C.

The discovery of aminoglycoside 66-40C, a novel dimeric, unsaturated imine produced by Micromonospora inyoensis, afforded a versatile intermediate for the synthesis of a variety of sisomicin analogues modified at the 6' position. The conversion of 66-40C into sisomicin, antibiotic G-52, and a series of novel 6'-substituted analogues of sisomicin is described, and the biological activity of the products is discussed.