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Current and Future Approaches to Prevention and Early Detection of Women's Cancers

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A special issue of Diagnostics (ISSN 2075-4418). This special issue belongs to the section "Pathology and Molecular Diagnostics".

Deadline for manuscript submissions: closed (31 December 2023) | Viewed by 40082

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Special Issue Editors

Dr. Aleksandra Gentry-Maharaj

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Guest Editor

1. MRC Clinical Trials Unit at UCL, Institute of Clinical Trials & Methodology, London WC1V 6LJ, UK
2. Department of Women’s Cancer, Elizabeth Garrett Anderson Institute for Women’s Health, University College London, London, UK
Interests: screening for ovarian cancer; cancer biomarkers; genetic predisposition to ovarian cancer

Dr. Aarti Sharma

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Guest Editor

Cardiff and Vale University Health Board, University Hospital of Wales, Cardiff CF14 4XW, UK
Interests: gynecological cancers

Special Issue Information

Dear Colleagues,

The focus of this Special Issue is on the current advances in our understanding of women’s cancers. We welcome submissions discussing updates to the process of early detection and preventative approaches that have either been adopted (such as effectiveness and safety evaluation of HPV vaccination for cervical cancer) or are being explored at present (such as prophylactic salpingectomy for ovarian cancer in the context of hereditary conditions, the impact of obesity, and the potential of metformin in prevention and prognosis of endometrial cancer).

The issue will also address advances in our understanding of genetic predisposition to breast and ovarian cancer to inform future risk stratification strategies. In view of the recent introduction of the practice of assessing all endometrial cancers for the presence of Lynch syndrome, we welcome a review of the literature and a discussion about why this approach is important. Articles on rarer gynecological cancers, such as vulval cancer, will also be welcome.

Key to each submission is addressing the diagnostic pathway and how each of these approaches will impact earlier detection of women’s cancers. The requirement is that each article addresses this aspect in at least 50% of the individual submission.

The Special Issue will provide an insight into the current strategies being explored that may potentially be integrated into future management strategies of women’s cancers.

Dr. Aleksandra Gentry-Maharaj
Dr. Aarti Sharma
Guest Editors

Manuscript Submission Information

Manuscripts should be submitted online at www.mdpi.com by registering and logging in to this website. Once you are registered, click here to go to the submission form. Manuscripts can be submitted until the deadline. All submissions that pass pre-check are peer-reviewed. Accepted papers will be published continuously in the journal (as soon as accepted) and will be listed together on the special issue website. Research articles, review articles as well as short communications are invited. For planned papers, a title and short abstract (about 100 words) can be sent to the Editorial Office for announcement on this website.

Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are thoroughly refereed through a single-blind peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. Diagnostics is an international peer-reviewed open access semimonthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. The Article Processing Charge (APC) for publication in this open access journal is 2600 CHF (Swiss Francs). Submitted papers should be well formatted and use good English. Authors may use MDPI's English editing service prior to publication or during author revisions.

Keywords

screening
prevention
ovarian cancer
endometrial cancer
cervical cancer
vulval cancer
Human Papilloma Virus
familial risk

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Published Papers (10 papers)

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Research

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12 pages, 392 KiB

Open AccessArticle

Exploration of Preliminary Objective Triage by Menopause Score and CA 125 Result Prior to Accelerating Fast-Track Booking for Suspected Ovarian Cancer—A Role for the Pathway Navigator?

by Robert Woolas, Lisa Young, Dirk Brinkmann, Francis Gardner, Richard Hadwin, Thomas Woolas and Natalia Povolotskaya

Diagnostics 2024, 14(5), 541; https://doi.org/10.3390/diagnostics14050541 - 4 Mar 2024

Viewed by 1743

Abstract

The 28-days-to-diagnosis pathway is the current expected standard of care for women with symptoms of ovarian cancer in the UK. However, the anticipated conversion rate of symptoms to cancer is only 3%, and use of the pathway is increasing. A rapid triage at the moment of receipt of the referral might allow resources to be allocated more appropriately. In secondary care, multidisciplinary teams (MDTs) use the risk of malignancy index (RMI) score, (multiply menopausal status pre = 1 or post = 3 × ultrasound score = 0 − 3 × the CA 125 level), using a score of >200, to triage urgency and management in possible ovarian cancer cases. The most powerful determinant of the RMI score variables is CA 125 level, an objective number. Could a simple modification of the RMI score retain a high sensitivity for cancer whilst improving specificity and, consequently, decrease the morbidity of false-positive classification? To test this hypothesis, a retrospective evaluation of an ovarian two-week-wait telephone clinic of one consultant gynaecological oncologist was undertaken. Enquiry re menopause status was scored as one for pre- and three for postmenopausal or uncertain. CA 125 levels of >67 u/mL for premenopausal and >23 u/mL for postmenopausal women were used to precipitate urgent cross-sectional imaging requests and MDT opinions. These CA 125 cut thresholds were calculated using an assumption that the RMI imaging score, regardless of whether the result was available, could be three. We contemplate that women who did not exceed a provisional RMI score of >200 might be informed they are extremely unlikely to have cancer, removed from the malignancy tracker and appropriate follow-up arranged. One hundred and forty consecutive cases were analysed; 43% were deemed premenopausal and 57% postmenopausal. Twenty of the women had cancer, eighteen (90%) of whom had an RMI > 200. One hundred and twenty were benign, and only twenty-three (19%) classified as urgent cases in need of accelerated referral to imaging. In contrast, CA 125 > 35 u/mL, whilst retaining the sensitivity of 90%, misclassified 36 (30%) of the benign cases. It is possible that a telephone triage via a questionnaire determining menopausal status and the CA 125 result could offer a sensitivity for cancer of 90% and urgent expert review of under 20% of benign cases. This rapid initial telephone assessment could be presented by a trained pathway navigator, physician associate or nurse specialist. Substantial savings in NHS cancer services resources, anxieties all around and reduced patient morbidity may occur as a result. Full article

(This article belongs to the Special Issue Current and Future Approaches to Prevention and Early Detection of Women's Cancers)

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14 pages, 1269 KiB

Open AccessArticle

A Study on the Factors and Prediction Model of Triple-Negative Breast Cancer for Public Health Promotion

by Young-Hee Nam

Diagnostics 2023, 13(22), 3486; https://doi.org/10.3390/diagnostics13223486 - 20 Nov 2023

Cited by 1 | Viewed by 1566

Abstract

This study was conducted to identify the risk causes and predictive models based on the clinical features of patients with breast cancer classified as triple-negative breast cancer (TNBC) and non-triple-negative breast cancer (non-TNBCs) using Korean cancer statistics. A total of 2045 cases that underwent three types of hormone receptor tests were obtained from Korean cancer data in 2016. Research data were analyzed with the software SPSS Ver. 26.0. TNBC and non-TNBCs accounted for 12.4% and 87.6% of the data, respectively. Tubular and lobular tumors occurred most frequently in the external quadrant of the breast (C50.4–C50.5; 43.1%). Compared to non-TNBCs, the incidence of TNBC was the most common in patients under the age of 39 (19.5%), followed by those over the age of 70 (17.3%). Tumors larger than 2 cm accounted for 16.0%, which was higher than the number of tumors smaller than 2 cm. Cases in stage IV cancer represented 21.7% of the data. Additionally, 21.0% of the patients were in the SEER stage of distant metastasis, which was the most prevalent SEER (surveillance, epidemiology, and end outcomes) stage. Neoadjuvant therapy was administered more frequently, with a rate of 24.1%. In the logistic regression and decision-making tree model, the variables that affected TNBC were age, differentiation grade, and neoadjuvant therapy. The predictive accuracies of logistic regression and decision-making tree models were 87.8% and 87.6%, respectively. In a decision-marking tree model, the differentiation grades of TNBC affect neoadjuvant therapy, and neoadjuvant therapy affects the cancer stage. Therefore, in order to promote the health of breast cancer patients, it is urgent to apply an intensive early health check-up program for those in their 40s and 50s with a high prevalence of TNBC. For patients with breast cancer, in TNBC cases, except for poorly differentiated cases, neoadjuvant therapy must be applied first at all differentiation grades. The establishment of a policy system is necessary for the success of this process. Full article

(This article belongs to the Special Issue Current and Future Approaches to Prevention and Early Detection of Women's Cancers)

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11 pages, 2728 KiB

Open AccessArticle

Tissue Characteristics of Endometrial Carcinoma Analyzed by Quantitative Synthetic MRI and Diffusion-Weighted Imaging

by Yiang Wang, Mengge He, Peng Cao, Philip P. C. Ip, Chien-Yuan Lin, Weiyin Liu, Chia-Wei Lee and Elaine Y. P. Lee

Diagnostics 2022, 12(12), 2956; https://doi.org/10.3390/diagnostics12122956 - 25 Nov 2022

Cited by 2 | Viewed by 1798

Abstract

Background: This study investigates the association of T1, T2, proton density (PD) and the apparent diffusion coefficient (ADC) with histopathologic features of endometrial carcinoma (EC). Methods: One hundred and nine EC patients were prospectively enrolled from August 2019 to December 2020. Synthetic magnetic resonance imaging (MRI) was acquired through one acquisition, in addition to diffusion-weighted imaging (DWI) and other conventional sequences using 1.5T MRI. T1, T2, PD derived from synthetic MRI and ADC derived from DWI were compared among different histopathologic features, namely the depth of myometrial invasion (MI), tumor grade, cervical stromal invasion (CSI) and lymphovascular invasion (LVSI) of EC by the Mann–Whitney U test. Classification models based on the significant MRI metrics were constructed with their respective receiver operating characteristic (ROC) curves, and their micro-averaged ROC was used to evaluate the overall performance of these significant MRI metrics in determining aggressive histopathologic features of EC. Results: EC with MI had significantly lower T2, PD and ADC than those without MI (p = 0.007, 0.006 and 0.043, respectively). Grade 2–3 EC and EC with LVSI had significantly lower ADC than grade 1 EC and EC without LVSI, respectively (p = 0.005, p = 0.020). There were no differences in the MRI metrics in EC with or without CSI. Micro-averaged ROC of the three models had an area under the curve of 0.83. Conclusions: Synthetic MRI provided quantitative metrics to characterize EC with one single acquisition. Low T2, PD and ADC were associated with aggressive histopathologic features of EC, offering excellent performance in determining aggressive histopathologic features of EC. Full article

(This article belongs to the Special Issue Current and Future Approaches to Prevention and Early Detection of Women's Cancers)

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18 pages, 1084 KiB

Open AccessArticle

Serum CA125 and HE4 as Biomarkers for the Detection of Endometrial Cancer and Associated High-Risk Features

by Chloe E. Barr, Kelechi Njoku, Eleanor R. Jones and Emma J. Crosbie

Diagnostics 2022, 12(11), 2834; https://doi.org/10.3390/diagnostics12112834 - 17 Nov 2022

Cited by 11 | Viewed by 3339

Abstract

Early detection of endometrial cancer improves survival. Non-invasive diagnostic biomarkers would improve triage of symptomatic women for investigations. This study aimed to determine the diagnostic accuracy of serum Cancer Antigen 125 (CA125) and Human Epididymis 4 (HE4) for endometrial cancer and associated high-risk features. Serum samples from women investigated for gynaecological symptoms or diagnosed with endometrial cancer were analysed for CA125 and HE4. Conventional diagnostic metrics were calculated. In total, 755 women were included; 397 had endometrial cancer. Serum CA125 and HE4 were significantly elevated in cases compared with controls (both p < 0.001), and with pathological markers of disease severity (p < 0.05). A combination of CA125 and HE4 detected endometrial cancer with an area under the curve (AUC) of 0.77 (95% CI: 0.74–0.81). In a model with body mass index (BMI) and parity, HE4 predicted endometrial cancer in pre-menopausal women with an AUC of 0.91 [sensitivity = 84.5%, specificity = 80.9% (p < 0.001)]. In women with abnormal ultrasound, HE4 ≥ 77 pmol/L improved specificity compared with imaging alone [68.6% (95% CI: 75.0–83.6) vs. 34.4% (95% CI: 27.1–42.3), respectively], but at a cost to sensitivity. HE4 ≥ 77 pmol/L improved the detection of myometrial invasion ≥50% in women with stage I disease compared with magnetic resonance imaging (MRI) alone [sensitivity = 100% (95% CI: 54.1–100)]. CA125 ≥ 35 U/mL did not add to imaging. HE4 is a good predictor of poor prognostic features which could assist staging investigations. Full article

(This article belongs to the Special Issue Current and Future Approaches to Prevention and Early Detection of Women's Cancers)

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15 pages, 284 KiB

Open AccessArticle

Unselected Population Genetic Testing for Personalised Ovarian Cancer Risk Prediction: A Qualitative Study Using Semi-Structured Interviews

by Faiza Gaba, Samuel Oxley, Xinting Liu, Xin Yang, Dhivya Chandrasekaran, Jatinderpal Kalsi, Antonis Antoniou, Lucy Side, Saskia Sanderson, Jo Waller, Munaza Ahmed, Andrew Wallace, Yvonne Wallis, Usha Menon, Ian Jacobs, Rosa Legood, Dalya Marks and Ranjit Manchanda

Diagnostics 2022, 12(5), 1028; https://doi.org/10.3390/diagnostics12051028 - 19 Apr 2022

Cited by 6 | Viewed by 3570

Abstract

Unselected population-based personalised ovarian cancer (OC) risk assessments combining genetic, epidemiological and hormonal data have not previously been undertaken. We aimed to understand the attitudes, experiences and impact on the emotional well-being of women from the general population who underwent unselected population genetic testing (PGT) for personalised OC risk prediction and who received low-risk (<5% lifetime risk) results. This qualitative study was set within recruitment to a pilot PGT study using an OC risk tool and telephone helpline. OC-unaffected women ≥ 18 years and with no prior OC gene testing were ascertained through primary care in London. In-depth, semi-structured and 1:1 interviews were conducted until informational saturation was reached following nine interviews. Six interconnected themes emerged: health beliefs; decision making; factors influencing acceptability; effect on well-being; results communication; satisfaction. Satisfaction with testing was high and none expressed regret. All felt the telephone helpline was helpful and should remain optional. Delivery of low-risk results reduced anxiety. However, care must be taken to emphasise that low risk does not equal no risk. The main facilitators were ease of testing, learning about children’s risk and a desire to prevent disease. Barriers included change in family dynamics, insurance, stigmatisation and personality traits associated with stress/worry. PGT for personalised OC risk prediction in women in the general population had high acceptability/satisfaction and reduced anxiety in low-risk individuals. Facilitators/barriers observed were similar to those reported with genetic testing from high-risk cancer clinics and unselected PGT in the Jewish population. Full article

(This article belongs to the Special Issue Current and Future Approaches to Prevention and Early Detection of Women's Cancers)

14 pages, 3069 KiB

Open AccessArticle

miR-126 Decreases Proliferation and Mammosphere Formation of MCF-7 and Predicts Prognosis of ER+ Breast Cancer

by Zahraa S. Msheik, Farah J. Nassar, Ghada Chamandi, Abdul Rahman Itani, Emanuala Gadaleta, Claude Chalala, Nisreen Alwan and Rihab R. Nasr

Diagnostics 2022, 12(3), 745; https://doi.org/10.3390/diagnostics12030745 - 18 Mar 2022

Cited by 12 | Viewed by 3008

Abstract

Breast cancer (BC) is a major health burden that affects over one million women each year. It is the most prevalent cancer in women and the number one cancer killer of them worldwide. Of all BC subtypes, estrogen receptor-positive (ER+) BC is the most commonly diagnosed. The objective of this study is to investigate the contribution of miR-126 in the tumorigenesis of ER+ BC. miR-126 was downregulated in ER+ BC tissues from young breast cancer patients, as shown through miRNA microarray analysis and RT-qPCR. Subsequently, the effect of the modulation of miR-126 levels on the proliferation, cell cycle progression, and spheres formation of the ER+ BC cell line, MCF-7, was assessed by MTT assay, PI analysis, and mammosphere formation assay, respectively. miR-126 overexpression significantly decreased MCF-7 proliferation and mammosphere-forming ability, but did not affect cell cycle progression. Then, in silico analysis determined SLC7A5, PLXNB2, CRK, PLK2, SPRED1, and IRS1 as potential targets of miR-126. RT-qPCR data showed that miR-126 overexpression significantly downregulated SLC7A5 and PLXNB2 mRNA levels in MCF-7. Finally, in silico survival analysis showed that high expression of miR-126 or low expression of SLC7A5 correlated with better overall survival (OS) of ER+ BC patients. Overall, our study suggests that miR-126 might play a tumor suppressor role in ER+ BC. miR-126 and SLC7A5 might also be considered potential prognostic biomarkers in ER+ BC. Full article

(This article belongs to the Special Issue Current and Future Approaches to Prevention and Early Detection of Women's Cancers)

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Review

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19 pages, 1101 KiB

Open AccessReview

Racioethnic Disparities in Endometrial Cancer Outcomes

by Ojone Illah, Deborah Adeeko, Adeola Olaitan and Aleksandra Gentry-Maharaj

Diagnostics 2024, 14(4), 417; https://doi.org/10.3390/diagnostics14040417 - 14 Feb 2024

Cited by 3 | Viewed by 3540

Abstract

Black women are twice as likely to die from endometrial cancer (EC) compared with white women. This represents one of the worst racioethnic disparities amongst all cancers globally. Compared with white women, black women are more likely to be diagnosed with advanced EC, have more barriers to accessing care and experience increased delays in obtaining an EC diagnosis and commencing treatment. Histological and molecular differences place black women at higher risk of being diagnosed with more aggressive EC subtypes that carry less favourable outcomes. Furthermore, EC diagnostic pathways are less reliable in black women, and black women are less likely to receive evidence-based treatment for EC. This racioethnic disparity in EC outcomes exists both in the UK and US, despite differences in healthcare systems. This review methodically describes the key factors along the patient journey that contribute to the disparity in black women and proposes multifaceted approaches to lessen these gaps. Full article

(This article belongs to the Special Issue Current and Future Approaches to Prevention and Early Detection of Women's Cancers)

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11 pages, 1214 KiB

Open AccessReview

Molecular Testing in Ovarian Tumours: Challenges from the Pathologist’s Perspective

by Kate Dinneen and Rupali Arora

Diagnostics 2023, 13(12), 2072; https://doi.org/10.3390/diagnostics13122072 - 15 Jun 2023

Cited by 3 | Viewed by 2343

Abstract

The use of molecular testing to direct diagnosis and treatment options in ovarian tumours has rapidly expanded in recent years, in particular with regard to the recommendation for routine homologous recombination deficiency (HRD) testing in all patients with high-grade ovarian epithelial tumours. The implications of this increased level of testing upon the pathologist is significant in terms of increased workload, the provision of adequate tumour samples for molecular testing, and the interpretation of complex molecular pathology reports. In order to optimise the quality of reports generated, it is important to establish clear pathways of communication on both a local and national level between clinicians, pathology lab staff, and medical scientists. On a national level, in the United Kingdom, Genomic Laboratory Hubs (GLHs) have been established to provide a uniform high-quality molecular diagnostics service to all patients with ovarian tumours within the National Health services in the country. On a local level, there are a number of small steps that can be taken to improve the quality of tissues available for testing and to streamline the processes involved in generating requests for molecular testing. This article discusses these factors from the perspective of the clinical histopathologist. Full article

(This article belongs to the Special Issue Current and Future Approaches to Prevention and Early Detection of Women's Cancers)

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22 pages, 2012 KiB

Open AccessReview

Updates on HPV Vaccination

by Ojone Illah and Adeola Olaitan

Diagnostics 2023, 13(2), 243; https://doi.org/10.3390/diagnostics13020243 - 9 Jan 2023

Cited by 54 | Viewed by 13855

Abstract

Cervical cancer still poses a significant global challenge. Developed countries have mitigated this challenge by the introduction of structured screening programmes and, more recently, the HPV vaccine. Countries that have successfully introduced national HPV vaccination programmes are on course for cervical cancer elimination in a few decades. In developing countries that lack structured screening and HPV vaccination programmes, cervical cancer remains a major cause of morbidity and mortality. The HPV vaccine is key to addressing the disproportionate distribution of cervical cancer incidence, with much to be gained from increasing vaccine coverage and uptake globally. This review covers the history and science of the HPV vaccine, its efficacy, effectiveness and safety, and some of the considerations and challenges posed to the achievement of global HPV vaccination coverage and the consequent elimination of cervical cancer. Full article

(This article belongs to the Special Issue Current and Future Approaches to Prevention and Early Detection of Women's Cancers)

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14 pages, 1324 KiB

Open AccessReview

Protein Glycosylation as Biomarkers in Gynecologic Cancers

by Hung Shen, Chia-Yi Lee and Chi-Hau Chen

Diagnostics 2022, 12(12), 3177; https://doi.org/10.3390/diagnostics12123177 - 15 Dec 2022

Cited by 9 | Viewed by 3579

Abstract

Gynecologic cancers are the leading cause of death in women. Endometrial, ovarian, and cervical cancer are the three main types of gynecologic cancers. Poor prognoses and high mortality rates of advanced-stage cancer are still challenges of all three types. Diagnostic tools for early cancer detection could be the cornerstone for further cancer treatment and prevention. Glycosylation plays a vital role in cell proliferation, adhesion, motility, and angiogenesis, and is aberrantly expressed in cancer cells. Alterations of glycosylation may represent promising biomarkers with potential diagnostic and monitoring applications, as well as disease prognosis. Many glycosylated biomarkers, including glycoprotein, glycan, and enzyme, were discovered and well-studied for application in gynecologic cancers. Some of them have been developed as targets for cancer treatment. The use of certain biomarkers for diagnostics and monitoring of gynecologic cancers has clinical advantages, as it is quantitative, comparable, convenient, and inexpensive. However, one of the single markers have sufficient sensitivity for the screening of gynecologic cancers. In this review, we introduced the details of glycosylation and the current application of glycosylated biomarkers in these three cancers. Moreover, we also reviewed the different roles of each biomarker in other cancers and aimed to understand these glycosylated biomarkers comprehensively. Full article

(This article belongs to the Special Issue Current and Future Approaches to Prevention and Early Detection of Women's Cancers)

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