Fiona M. Walter

CanRisk Tool—A Web Interface for the Prediction of Breast and Ovarian Cancer Risk and the Likelihood of Carrying Genetic Pathogenic Variants

Abstract Background: The CanRisk Tool (https://canrisk.org) is the next-generation web interface for the latest version of the BOADICEA (Breast and Ovarian Analysis of Disease Incidence and Carrier Estimation Algorithm) state-of-the-art risk model and a forthcoming ovarian cancer risk model. Methods: The tool captures information on family history, rare pathogenic variants in cancer susceptibility genes, polygenic risk scores, lifestyle/hormonal/clinical features, and imaging risk factors to predict breast and ovarian cancer risks and estimate the probabilities of carrying pathogenic variants in certain genes. It was implemented using modern web frameworks, technologies, and web services to make it extensible and increase accessibility to researchers and third-party applications. The design of the graphical user interface was informed by feedback from health care professionals and a formal evaluation. Results: This freely accessible tool was designed to be user friendly for clinicians and to boost acceptability in clinical settings. The tool incorporates a novel graphical pedigree builder to facilitate collection of the family history data required by risk calculations. Conclusions: The CanRisk Tool provides health care professionals and researchers with a user-friendly interface to carry out multifactorial breast and ovarian cancer risk predictions. It is the first freely accessible cancer risk prediction program to carry the CE marking. Impact: There have been over 3,100 account registrations, and 98,000 breast and ovarian cancer risk calculations have been run within the first 9 months of the CanRisk Tool launch.

The diagnostic performance of CA125 for the detection of ovarian and non-ovarian cancer in primary care: A population-based cohort study

The serum biomarker cancer antigen 125 (CA125) is widely used as an investigation for possible ovarian cancer in symptomatic women presenting to primary care. However, its diagnostic performance in this setting is unknown. We evaluated the performance of CA125 in primary care for the detection of ovarian and non-ovarian cancers. We studied women in the United Kingdom Clinical Practice Research Datalink with a CA125 test performed between 1 May 2011-31 December 2014. Ovarian and non-ovarian cancers diagnosed in the year following CA125 testing were identified from the cancer registry. Women were categorized by age: <50 years and ≥50 years. Conventional measures of test diagnostic accuracy, including sensitivity, specificity, and positive predictive value, were calculated for the standard CA125 cut-off (≥35 U/ml). The probability of a woman having cancer at each CA125 level between 1-1,000 U/ml was estimated using logistic regression. Cancer probability was also estimated on the basis of CA125 level and age in years using logistic regression. We identified CA125 levels equating to a 3% estimated cancer probability: the "risk threshold" at which the UK National Institute for Health and Care Excellence advocates urgent specialist cancer investigation. A total of 50,780 women underwent CA125 testing; 456 (0.9%) were diagnosed with ovarian cancer and 1,321 (2.6%) with non-ovarian cancer. Of women with a CA125 level ≥35 U/ml, 3.4% aged <50 years and 15.2% aged ≥50 years had ovarian cancer. Of women with a CA125 level ≥35 U/ml who were aged ≥50 years and who did not have ovarian cancer, 20.4% were diagnosed with a non-ovarian cancer. A CA125 value of 53 U/ml equated to a 3% probability of ovarian cancer overall. This varied by age, with a value of 104 U/ml in 40-year-old women and 32 U/ml in 70-year-old women equating to a 3% probability. The main limitations of our study were that we were unable to determine why CA125 tests were performed and that our findings are based solely on UK primary care data, so caution is need in extrapolating them to other healthcare settings. CA125 is a useful test for ovarian cancer detection in primary care, particularly in women ≥50 years old. Clinicians should also consider non-ovarian cancers in women with high CA125 levels, especially if ovarian cancer has been excluded, in order to prevent diagnostic delay. Our results enable clinicians and patients to determine the estimated probability of ovarian cancer and all cancers at any CA125 level and age, which can be used to guide individual decisions on the need for further investigation or referral.

Effectiveness of interventions for improving timely diagnosis of breast and cervical cancers in low and middle-income countries: a systematic review protocol

Introduction Breast and cervical cancers pose a major public health burden globally, with disproportionately high incidence, morbidity and mortality in low- and middle-income countries (LMICs). The majority of women diagnosed with cancer in LMICs present with late-stage disease, the treatment of which is often costlier and less effective. While interventions to improve the timely diagnosis of these cancers are increasingly being implemented in LMICs, there is uncertainty about their role and effectiveness. The aim of this review is to systematically synthesise available evidence on the nature and effectiveness of interventions for improving timely diagnosis of breast and cervical cancers in LMICs. Methods and analysis A comprehensive search of published and relevant grey literature will be conducted. The following electronic databases will be searched: MEDLINE (via PubMed), Cochrane Library, Scopus, CINAHL, Web of Science and the International Clinical Trials Registry Platform (ICTRP). Evidence will be synthesised in accordance with the Preferred Reporting Items for Systematic Review and Meta-Analyses (PRISMA). Two reviewers will independently screen the search outputs, select studies using predefined inclusion criteria and assess each included study for risk of bias. If sufficient data are available and studies are comparable in terms of interventions and outcomes, a meta-analysis will be conducted. Where studies are not comparable and a meta-analysis is not appropriate, a narrative synthesis of findings will be reported. Ethics and dissemination As this will be a systematic review of publicly available data, with no primary data collection, it will not require ethical approval. Findings will be disseminated widely through a peer-reviewed publication and forums such as conferences, workshops and community engagement sessions. This review will provide a user-friendly evidence summary for informing further efforts at developing and implementing interventions for addressing delays in breast and cervical cancer diagnosis in LMICs. PROSPERO registration number CRD42020177232.

Timeliness of diagnosis of breast and cervical cancers and associated factors in low-income and middle-income countries: a scoping review protocol

Introduction Breast and cervical cancer are leading causes of morbidity and mortality in women globally, with disproportionately high burdens in low-income and middle-income countries (LMICs). While the incidence of both cancers increases across LMICs, many cases continue to go undiagnosed or diagnosed late. The aim of this review is to comprehensively map the current evidence on the time to breast or cervical cancer diagnosis and its associated factors in LMICs. Methods and analysis This scoping review (ScR) will be informed by Arksey and O"Malley’s enhanced ScR methodology framework. It will be reported in accordance with the Preferred Reporting Items for Systematic reviews and Meta-Analyses extension for Scoping Reviews. We will conduct a comprehensive search of the following electronic databases: MEDLINE (via PubMed), Cochrane Library, Scopus and the Cumulative Index to Nursing and Allied Health Literature (CINAHL). Two reviewers will independently screen all abstracts and full texts using predefined inclusion criteria. All publications describing the time to diagnosis and its associated factors in the contexts of breast or cervical cancer will be considered for inclusion. Evidence will be narratively synthesised and analysed using a predefined conceptual framework. Ethics and dissemination As this is a ScR of publicly available data, with no primary data collection, it will not require ethical approval. Findings will be disseminated widely through a peer-reviewed publication and forums such as conferences and community engagement sessions. This review will provide a user-friendly evidence summary for understanding the enormity of diagnostic delays and associated factors for breast and cervical cancers in LMICs, while helping to inform policy actions and implementation of interventions for addressing such delays.

Symptom appraisal, help-seeking and perceived barriers to healthcare seeking in Uganda: an exploratory study among women with potential symptoms of breast and cervical cancer

Objective We assessed the process of recognising abnormal bodily changes, interpretations and attributions, and help-seeking behaviour among community-based Ugandan women with possible symptoms of breast and cervical cancer, in order to inform health interventions aiming to promote timely detection and diagnosis of cancer. Design Qualitative in-depth interviews. Setting Rural and urban communities in Uganda. Participants Women who participated in the African Women Awareness of CANcer cross-sectional survey who disclosed potential breast and cervical cancer symptoms were eligible; recruitment was purposive. Interviews were conducted in women’s homes, lasted between 40 and 90 min, were audio-recorded, transcribed verbatim and translated to English. Thematic analysis was used to identify themes and subthemes, underpinned by the conceptual framework of the Model of Pathways to Treatment. Results 23 women were interviewed: 10 had potential symptoms of breast cancer and 13 of cervical cancer. Themes regarding symptom appraisal and help-seeking included the: (1) detection and interpretation of abnormal bodily sensations; (2) lay consultations regarding bodily changes; (3) iterative process of inferring and attributing illnesses to the bodily changes; (4) restricted disclosure of symptoms to lay people due to concerns about privacy and fear of stigmatisation; (5) help-seeking from multiple sources including both traditional and biomedical health practitioners, and (6) multiple perceived barriers to help-seeking including long waiting times, lack of medicines, absenteeism of healthcare professionals, and lack of money for transport and medical bills. Conclusion Women with potential symptoms of breast and cervical cancer undergo complex processes of symptom interpretation, attributing symptoms or inferring illness, and lay consultations before undertaking help-seeking and management. Increasing community understanding of breast and cervical cancer symptoms, and tackling perceived barriers to health-seeking, could lead to prompt and appropriate symptom appraisal and help-seeking, and contribute to improving cancer outcomes.

Effectiveness of interventions for improving timely diagnosis of breast and cervical cancers in low-income and middle-income countries: a systematic review

Objectives To systematically synthesise available evidence on the nature and effectiveness of interventions for improving timely diagnosis of breast and cervical cancers in low and middle-income countries (LMICs). Design A systematic review of published evidence. The review was conducted and reported in accordance with the Preferred Reporting Items for Systematic Review and Meta-Analyses. Data sources A comprehensive search of published literature was conducted. In addition, relevant grey literature sources and bibliographical references of included studies were searched for potentially eligible evidence. Study selection Studies published between January 2010 and November 2020 were eligible for inclusion. To be eligible, studies had to report on interventions/strategies targeted at women, the general public or healthcare workers, aimed at improving the timely diagnosis of breast and/or cervical cancers in LMIC settings. Data extraction and synthesis Literature search, screening, study selection, data extraction and quality appraisal were conducted by two independent reviewers. Evidence was synthesised and reported using a global taxonomy framework for early cancer diagnosis. Results From the total of 10 593 records identified, 21 studies conducted across 20 LMICs were included in this review. Most of the included studies (16/21) focused primarily on interventions addressing breast cancers; two focused on cervical cancer while the rest examined multiple cancer types. Reported interventions targeted healthcare workers (12); women and adolescent girls (7) and both women and healthcare workers (3). Eight studies reported on interventions addressing access delays; seven focused on interventions addressing diagnostic delays; two reported on interventions targeted at addressing both access and diagnostic delays, and four studies assessed interventions addressing access, diagnostic and treatment delays. While most interventions were demonstrated to be feasible and effective, many of the reported outcome measures are of limited clinical relevance to diagnostic timeliness. Conclusions Though limited, evidence suggests that interventions aimed at addressing barriers to timely diagnosis of breast and cervical cancer are feasible in resource-limited contexts. Future interventions need to address clinically relevant measures to better assess efficacy of interventions. PROSPERO registration number CRD42020177232.

Timeliness of diagnosis of breast and cervical cancers and associated factors in low-income and middle-income countries: a scoping review

Objectives Addressing the barriers to early breast and cervical cancer diagnosis in low and middle-income countries (LMICs) requires a sound understanding and accurate assessment of diagnostic timeliness. This review aimed to map the current evidence on the time to breast and cervical cancer diagnosis and associated factors in LMICs. Design Scoping review. Sources MEDLINE (via PubMed), Cochrane Library, Scopus and CINAHL. Eligibility criteria Studies describing the time to diagnosis and associated factors in the context of breast and cervical cancer in LMICs published from 1 January 2010 to 20 May 2021. Study selection and data synthesis Two reviewers independently screened all abstracts and full texts using predefined inclusion criteria. The review was reported in accordance with the Preferred Reporting Items for Systematic reviews and Meta-Analyses extension for Scoping Reviews. Evidence was narratively synthesised using predefined themes. Results Twenty-six studies conducted across 24 LMICs were included in the review, most (24/26) of which focused on breast cancer. Studies varied considerably in their conceptualisation and assessment of diagnostic time, events, intervals and delays, with a minority of the studies reporting the use of validated methods and tools. Patient-related intervals and delays were more frequently evaluated and reported than provider-related and health system-related intervals and delays. Across studies, there were variations in the estimated lengths of the appraisal, help-seeking, patient and diagnostic intervals for both cancers and the factors associated with them. Conclusions Despite the significant burden of breast and cervical cancer in LMICs, there is limited information on the timeliness of diagnosis of these cancers. Major limitations included variations in conceptualisation and assessment of diagnostic events and intervals. These underscore the need for the use of validated and standardised tools, to improve accuracy and translation of findings to better inform interventions for addressing diagnostic delays in LMICs.

Clinical and Pathological Characteristics of Women With Ovarian Cancers in Syria

the goal of this observational study is to describe ovarian cancer epidemiology and characteristics in Syrian women, especially during the war to do more research in the future about the risk factors of ovarian cancer.