Special Issue "Prevention and Diagnosis of Gynaecological Cancers"

A special issue of Biology (ISSN 2079-7737). This special issue belongs to the section "Cancer Biology".

Deadline for manuscript submissions: closed (31 March 2023) | Viewed by 9202

Special Issue Editors

1. Department of Metabolism, Digestion and Reproduction, Imperial College London, London SW7 2AZ, UK
2. School of Pharmacy and Biomedical Sciences, University of Central Lancashire, Preston PR1 2HE, UK
Interests: gynaecological cancers; clinical diagnostics; early detection; innovative diagnostics; metabolomics; vibrational spectroscopy; liquid biopsies
Prof. Dr. Evangelos Paraskevaidis
E-Mail Website
Co-Guest Editor
Department of Obstetrics and Gynaecology, Faculty of Medicine, University of Ioannina, 45110 Ioannin, Greece
Interests: gynaecological cancers; human pappilomavirus (HPV); HPV vaccination; cervical cancer; cervical intraepithelian neoplasia (CIN); cervical screening; colposcopy
Special Issues, Collections and Topics in MDPI journals
Institute of Chemistry, Federal University of Rio Grande do Norte, Natal, RN 59078-970, Brazil
Interests: microbiological assays; biospectroscopy; cancer and normal cells; pharmaceutical; gold nanoparticles for colorectal cancer cell imaging; proteomic and metabolomic approaches; multivariate data analysis; statistics; machine learning
1. Department of Metabolism, Digestion and Reproduction, Imperial College London, London SW7 2AZ, UK
2. Imperial College Healthcare NHS Trust, London W2 1NY, UK
Interests: gynaecological cancers; human pappilomavirus (HPV); HPV vaccination; cervical cancer; cervical intraepithelian neoplasia (CIN); cervical screening; ovarian cancer; endometrial cancer; microbiome; epigenetics; organoids
Special Issues, Collections and Topics in MDPI journals
1. Department of Metabolism, Digestion and Reproduction, Imperial College London, London SW7 2AZ, UK
2. Department of Obstetrics and Gynaecology, University of Helsinki, 00014 Helsinki, Finland
Interests: gynaecological cancers; human pappilomavirus (HPV); HPV vaccination; cervical cancer; cervical intraepithelian neoplasia (CIN); cervical screening; ovarian cancer; endometrial caner; systematic reviews; meta-analysis

Special Issue Information

Dear Colleagues,

Gynaecologic malignancies continue to be a major cause of cancer-related mortality. While only a fraction of gynaecological cancers is attributable to inherited genetic predisposition, other features have recently attracted the scientific interest as contributing factors toward malignant transformation. Recent advances in the fields of genomics, epigenetics, proteomics, metabolomics and microbiome, among others, have all contributed to the better understanding of carcinogenesis. Innovative approaches that can be used to unravel mechanisms of carcinogenesis, provide a timely and accurate diagnosis or allow the development of screening/prognostic biomarkers are urgently needed.

The aim of this Special Issue is to shed light on novel approaches and techniques that can be used in a series of clinical applications to improve the diagnosis and outcomes of patients affected by female cancers, making a difference with long-lasting impact in women’s health. We are especially interested in studies involving women who have developed or are at risk of developing vulval, vaginal, cervical, endometrial or ovarian cancer.

We welcome the submission of original research articles, short communications, and reviews focusing on current methodologies for the detection and better understanding of female cancers. Translational research with a focus on point-of-care diagnostics is also encouraged. This Special Issue will provide an overview of the current knowledge on this topic and promote innovative techniques for the screening, diagnosis and treatment of gynaecological malignancies.

Dr. Maria Paraskevaidi
Prof. Dr. Evangelos Paraskevaidis
Prof. Dr. Kassio Lima
Dr. Maria Kyrgiou
Dr. Ilkka Kalliala
Guest Editors

Manuscript Submission Information

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Keywords

  • screening
  • early diagnosis
  • cervical cancer
  • human papillomavirus (HPV)
  • endometrial cancer
  • ovarian cancer
  • vulval cancer
  • vaginal cancer
  • biomarker discovery
  • genomics, epigenetics
  • proteomics
  • metabolomics
  • microbiome

Published Papers (6 papers)

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Research

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Article
Demographic Factors Predict Risk of Lymph Node Involvement in Patients with Endometrial Adenocarcinoma
Biology 2023, 12(7), 982; https://doi.org/10.3390/biology12070982 - 10 Jul 2023
Viewed by 522
Abstract
The presence of lymph node positivity (LN+) guides adjuvant treatment for endometrial adenocarcinoma (EAC) patients, but recommendations regarding LN evaluation at the time of primary surgery remain variable. Sociodemographic factors in addition to pathologic tumor characteristics may more accurately predict risk of LN+ [...] Read more.
The presence of lymph node positivity (LN+) guides adjuvant treatment for endometrial adenocarcinoma (EAC) patients, but recommendations regarding LN evaluation at the time of primary surgery remain variable. Sociodemographic factors in addition to pathologic tumor characteristics may more accurately predict risk of LN+ in EAC patients. Patients diagnosed between 2004 and 2016 with pathologic T1-T2 EAC who had at least one lymph node sampled at the time of surgery in the National Cancer Data Base were included. Pathologic primary tumor predictors of LN+ were identified using logistic regression. To predict overall, pelvic only, and paraaortic and/or pelvic LN+, nomograms were generated. Among the 35,170 EAC patients included, 2864 were node positive. Using multivariable analysis, younger patient age (OR 0.98, 95% CI 0.98–0.99, p < 0.001), black versus white race (OR 1.19, 95% CI 1.01–1.40, p = 0.04), increasing pathologic tumor stage and grade, increase in tumor size, and presence of lymphovascular invasion were predictive of regional LN+. Both black versus white (OR 1.64, 95% CI 1.27–2.09, p < 0.001) and other versus white race (OR 1.54, 95% CI 1.12–2.07, p = 0.006) strongly predicted paraaortic LN+ in the multivariable analysis. Independent subset analyses of black and white women revealed that tumor grade was a stronger predictor of LN+ among black women. In addition to standard pathologic tumor features, patient age and race were associated with a higher risk of regional LN+ generally and paraaortic LN+ specifically. This information may inform adjuvant treatment decisions and guide future studies. Full article
(This article belongs to the Special Issue Prevention and Diagnosis of Gynaecological Cancers)
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Article
CCL21/CCR7 Axis Contributes to Trophoblastic Cell Migration and Invasion in Preeclampsia by Affecting the Epithelial Mesenchymal Transition via the ERK1/2 Signaling Pathway
Biology 2023, 12(2), 150; https://doi.org/10.3390/biology12020150 - 18 Jan 2023
Viewed by 1134
Abstract
Preeclampsia (PE) is a pregnancy-related disorder that is a leading cause of maternal death. The failure of spiral artery remodeling due to insufficient trophoblast migration and invasion is critical in the pathogenesis of PE. Recently, the CC motif chemokine ligand 21 (CCL21) has [...] Read more.
Preeclampsia (PE) is a pregnancy-related disorder that is a leading cause of maternal death. The failure of spiral artery remodeling due to insufficient trophoblast migration and invasion is critical in the pathogenesis of PE. Recently, the CC motif chemokine ligand 21 (CCL21) has been widely linked to cancer cell invasion and migration. However, their potential mechanisms are still unknown. In this study, we found that CCL21 expression was significantly lower in the PE group than that in the control group. In vitro experiments revealed that recombinant CCL21 could promote trophoblast cell epithelial-to-mesenchymal transitions (EMTs) and improve migration and invasion. Furthermore, an inhibitor of the ERK1/2 signaling pathway inhibited the CCL21-induced EMT process. Finally, a PE mouse model was established using the NOS inhibitor L-NAME, and we obtained similar results, with downregulated CCL21 and EMT biomarkers and upregulated CCR7. Taken together, these findings suggest that the CCL21/CCR7 axis influences EMT by activating the ERK1/2 signaling pathway, thereby affecting trophoblast cell migration and invasion, which may play a crucial role in the pathogenesis of PE. Full article
(This article belongs to the Special Issue Prevention and Diagnosis of Gynaecological Cancers)
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Article
Application of Multigene Panels Testing for Hereditary Cancer Syndromes
Biology 2022, 11(10), 1461; https://doi.org/10.3390/biology11101461 - 05 Oct 2022
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Abstract
Background: Approximately 5–10% of all cancers are associated with hereditary cancer predisposition syndromes (HCPS). Early identification of HCPS is facilitated by widespread use of next-generation sequencing (NGS) and brings significant benefits to both the patient and their relatives. This study aims to evaluate [...] Read more.
Background: Approximately 5–10% of all cancers are associated with hereditary cancer predisposition syndromes (HCPS). Early identification of HCPS is facilitated by widespread use of next-generation sequencing (NGS) and brings significant benefits to both the patient and their relatives. This study aims to evaluate the landscape of genetic variants in patients with personal and/or family history of cancer using NGS-based multigene panel testing. Materials and Methods: The study cohort included 1117 probands from Russia: 1060 (94.9%) patients with clinical signs of HCPS and 57 (5.1%) healthy individuals with family history of cancer. NGS analysis of 76 HCPS genes was performed using a custom Roche NimbleGen enrichment panel. Results: Pathogenic/likely pathogenic variants were identified in 378 of 1117 individuals (33.8%). The predominant number (59.8%) of genetic variants was identified in BRCA1/BRCA2 genes. CHEK2 was the second most commonly altered gene with a total of 28 (7.4%) variants, and 124 (32.8%) genetic variants were found in other 35 cancer-associated genes with variable penetrance. Conclusions: Multigene panel testing allows for a differential diagnosis and identification of high-risk group for oncological diseases. Our results demonstrate that inclusion of non-coding gene regions into HCPS gene panels is highly important for the identification of rare spliceogenic variants with high penetrance. Full article
(This article belongs to the Special Issue Prevention and Diagnosis of Gynaecological Cancers)
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Article
Intraoperative Flow Cytometry for the Characterization of Gynecological Malignancies
Biology 2022, 11(9), 1339; https://doi.org/10.3390/biology11091339 - 11 Sep 2022
Cited by 5 | Viewed by 1589
Abstract
Cell-cycle analysis has shown the presence of aneuploidy to be associated with poor prognosis. We developed an innovative rapid cell-cycle analysis protocol (the Ioannina protocol) that permitted the intraoperative identification of neoplastic cells in a plethora of malignancies. Herein, we aimed to investigate [...] Read more.
Cell-cycle analysis has shown the presence of aneuploidy to be associated with poor prognosis. We developed an innovative rapid cell-cycle analysis protocol (the Ioannina protocol) that permitted the intraoperative identification of neoplastic cells in a plethora of malignancies. Herein, we aimed to investigate the potential role of cell-cycle analysis in the intraoperative characterization of gynecological malignancies. Women who underwent surgery for gynecological malignancies in our institution over a three-year period were included in this study. Permanent section pathology evaluation was used as the gold standard for malignancy evaluation. Total accordance was observed between flow cytometry and pathology evaluation. In total, 21 aneuploid cancers were detected following DNA index calculation. Of these, 20 were hyperploid and 1 was hypoploid. In addition, tumor samples were characterized by a significantly lower percentage of cells in G0/G1, as well as an induced tumor index. The response time for flow cytometry to obtain results was 5–6 min per sample. It seems that flow cytometry analyses for intraoperative tumor evaluation can be safely expanded to gynecological malignancies. This is a novel practical approach that has been proven valuable in several tumor types to date, and also seems to be reliable for gynecological malignancies. Intraoperative flow cytometry is expected to be crucial in decisions of lymph node dissection in endometrial cancers, due to its rapid response regarding the tumor invasion of part or all of the myometrial thickness. In this way, the surgeon can quickly modify the plane of dissection. Our results warrant the further investigation of applying iFC in larger, multicenter studies. Full article
(This article belongs to the Special Issue Prevention and Diagnosis of Gynaecological Cancers)
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Article
The Influence of Sexual Behavior and Demographic Characteristics in the Expression of HPV-Related Biomarkers in a Colposcopy Population of Reproductive Age Greek Women
Biology 2021, 10(8), 713; https://doi.org/10.3390/biology10080713 - 26 Jul 2021
Cited by 4 | Viewed by 1727
Abstract
Despite the significant scientific evolution in primary and secondary cervical cancer prevention in the battle started by George Papanicolaou in the previous century, global cervical cancer mortality rates remain disappointing. The widespread implementation of HPV-related molecular markers has paved the way to tremendous [...] Read more.
Despite the significant scientific evolution in primary and secondary cervical cancer prevention in the battle started by George Papanicolaou in the previous century, global cervical cancer mortality rates remain disappointing. The widespread implementation of HPV-related molecular markers has paved the way to tremendous developments in cervical cancer screening, with the transition from cytological approach to the more accurate and cost-effective HPV testing modalities. However, the academic audience and different health systems have not yet adopted a universal approach in screening strategies, and even artificial intelligence modalities have been utilized from the multidisciplinary scientific armamentarium. Combination algorithms, scoring systems as well as artificial intelligent models have been so far proposed for cervical screening and management. The impact of sexual lifestyle inherently possesses a key role in the prevalence of HPV-related biomarkers. This study aimed to investigate any possible influence of sexual behavior and demographic characteristics in the expression of HPV-related biomarkers in a colposcopy population from October 2016 to June 2017, and corroborated the determining role of age at fist intercourse; the older the age, the lower the probability for DNA positivity. Multivariate analysis illustrated additionally that a number of sexual partners exceeding 4.2 was crucial, with women with ≤5 partners being approximately four times less likely to harbor a positive HPV DNA test (p < 0.0001). Similarly, a reported partner change during the last year before HPV DNA assessment contributed to 2.5 times higher odds for DNA positivity (p = 0.0006). From this perspective, the further development and validation of scoring systems quantifying lifestyle factors that could reflect cervical precancer risk seems paramount. Full article
(This article belongs to the Special Issue Prevention and Diagnosis of Gynaecological Cancers)
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Systematic Review
Primary Melanoma of the Cervix Uteri: A Systematic Review and Meta-Analysis of the Reported Cases
Biology 2023, 12(3), 398; https://doi.org/10.3390/biology12030398 - 02 Mar 2023
Viewed by 1626
Abstract
Primary malignant melanoma (MM) of the cervix uteri is a rare and aggressive malignancy of the female reproductive tract. Considering that clinical data on this cancer are scarce, we aimed to comprehensively examine the currently available literature and provide an overview of the [...] Read more.
Primary malignant melanoma (MM) of the cervix uteri is a rare and aggressive malignancy of the female reproductive tract. Considering that clinical data on this cancer are scarce, we aimed to comprehensively examine the currently available literature and provide an overview of the reported cases of cervical MM focusing on the clinical characteristics, diagnosis and therapeutic management. We conducted a systematic review of the literature by screening three electronic databases until June 2022. The critical appraisal checklist provided by the Joanna Briggs Institute was employed to evaluate the overall quality of the studies. We included 96 reports, which comprised 137 patients diagnosed with MM of the cervix. The mean age of the patients was 56.5 (median: 58, age range: 33–88). Data regarding menopausal status were provided for 98 patients with 15 being premenopausal and 83 being postmenopausal. The most common presenting symptom was vaginal bleeding (83%, 100/121). Biopsy (either excisional or punch biopsy) was used as the first diagnostic modality in most of the patients (67%, 64/95), followed by cytology (18%, 17/95). In 74 cases, the FIGO staging system for cervical cancer was used with the most common stage being FIGO stage I (38%, 28/74), followed by FIGO stage II (36%, 27/74), FIGO stage III (19%, 14/74) and FIGO stage IV (7%, 5/74). Most of the patients were managed surgically (90%, 119/131) with a hysterectomy (either radical or total), and a salpingo-oophorectomy with/without lymphadenectomy was the most common approach utilized (40%, 48/119). The data of clinical outcomes were provided for 105 patients, of whom 61 died (58%, 61/105) and 44 survived (42%, 44/105). Knowledge regarding the rare occurrence of MM in the cervix and the increased awareness of clinicians can prevent clinical misdiagnosis and ultimately improve further the clinical outcomes of patients developing this rare malignancy. Full article
(This article belongs to the Special Issue Prevention and Diagnosis of Gynaecological Cancers)
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