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Prevention and Screening in Gynaecological Cancers

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A special issue of Cancers (ISSN 2072-6694). This special issue belongs to the section "Cancer Causes, Screening and Diagnosis".

Deadline for manuscript submissions: closed (30 September 2024) | Viewed by 12084

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Special Issue Editors

Dr. Raj Naik

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Queen Elizabeth Hospital, Gateshead, UK
Interests: gynaecological oncology; cervical cancer
Special Issues, Collections and Topics in MDPI journals

Dr. Pierre Martin-Hirsch

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Department of Gynaecological Oncology, Lancashire Teaching Hospitals NHS Foundation Trust, Preston PR2 9HT, UK
Interests: adjunctive technologies; screening in cervical pre-cancer; HPV vaccines & prevention
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Prof. Dr. Evangelos Paraskevaidis

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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
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Prof. Dr. Maria Kyrgiou

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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
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Special Issue Information

Dear Colleagues,

World Health Organization statistics show that Asia has the highest rate of gynaecological cancers, followed by Africa, Europe, Latin America, North America, and the lowest rate is observed in Oceania. The rates of gynaecological cancers are predicted to rise in forthcoming years. Appropriate strategies are desperately needed to control disease outcomes and it is widely accepted that these approaches should predominantly be preventative or screening.

Elimination of cervical cancer has become a global goal in cancer control over the past two decades due to effective human papillomavirus (HPV) vaccination and screening programmes. The secondary benefits of this are the reductions in vulvar cancer, which remains predominantly HPV related. Ovarian cancer still presents at a late stage due to a lack of effective screening tests or down-staging technologies. The association of rising endometrial cancer rates with an increased prevalence of obesity in the Western world is driving a greater population-based focus on improving diet, promoting exercise, weight-reduction programmes, and procedures.

Increased knowledge and research in genetic analysis at population and individual level is providing a greater ability to direct preventative and screening diagnostics to specifically target high-risk groups.

With so much that was once considered research now becoming standard clinical practice and in keeping with the “bench to clinic” concept and the explosion of personalized medicine, we, the Guest Editors, are delighted to bring to you this Special Themed Edition in the journal “Cancers”, focusing, specifically, on prevention and screening of gynaecological cancers.

Dr. Raj Naik
Dr. Pierre Martin-Hirsch
Prof. Dr. Evangelos Paraskevaidis
Prof. Dr. Maria Kyrgiou
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 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. Cancers 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 2900 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

cervical
uterine
endometrial
ovarian
vulvar
cancer
prevention
screening
epidemiology

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Published Papers (7 papers)

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18 pages, 765 KiB

Open AccessArticle

Detection of Mismatch Repair Deficiency in Endome-Trial Cancer: Assessment of IHC, Fragment Length Analysis, and Amplicon Sequencing Based MSI Testing

by Peter Sowter, Richard Gallon, Christine Hayes, Rachel Phelps, Gillian Borthwick, Shaun Prior, Jenny Combe, Holly Buist, Rachel Pearlman, Heather Hampel, Paul Goodfellow, D. Gareth Evans, Emma J. Crosbie, Neil Ryan, John Burn, Mauro Santibanez-Koref and Michael S. Jackson

Cancers 2024, 16(23), 3970; https://doi.org/10.3390/cancers16233970 (registering DOI) - 26 Nov 2024

Viewed by 309

Abstract

Background/Objectives: Mismatch repair (MMR) deficiency can be indicative of Lynch syndrome (LS) and guide treatment with immune checkpoint inhibitors. Colorectal cancers (CRCs) and endometrial cancers (ECs) are routinely screened to identify LS, primarily using immunohistochemistry (IHC) or microsatellite instability (MSI) testing, but concordance between these methods is variable in ECs. Here, we investigate this variability in 361 ECs from the Ohio OCCPI/OPTEC (n = 196) and Manchester PETALS (n = 165) trials, where concordance between assays differed significantly. Methods: Samples were re-tested using the amplicon-sequencing-based Newcastle MSI assay (NCL_MSI), and analysed with respect to existing IHC, MSI and MLH1 promoter hypermethylation data. Results: NCL_MSI showed consistency with the Ohio results (94% and 97% concordance with IHC and original MSI assays, respectively) and increased concordance within the Manchester cohort from 78% to 86% (MSI) and 84% (IHC). Among discordant Manchester samples, NCL_MSI was significantly associated with MLH1 promoter methylation status (p = 0.0028) and had the highest concordance with methylation, (62/69 samples, 90%), indicating utility as a screening tool in this tumour type. However, tumours with germline MSH6 defects were only detected efficiently with IHC; seven out of eight LS tumours classified as MSS by either MSI assay had isolated MSH6 loss, compared to four out of twelve classified as MSI-H by both (p = 0.028). Furthermore, reduced MSI signal was observed in tumours with isolated MSH6 loss (p = 0.009 Ohio, p = 6.2 × 10⁻⁵ Manchester) and in both ECs and CRCs with germline defects, although this only reached significance in CRCs (p = 0.002). Conclusions: These results provide further evidence that ECs with MSH6 loss in particular and LS tumours in general have an attenuated MSI signal, providing support for current guidelines specifically recommending IHC for LS detection and immune checkpoint therapy assessment in EC. Full article

(This article belongs to the Special Issue Prevention and Screening in Gynaecological Cancers)

16 pages, 1004 KiB

Open AccessArticle

Exploring Factors Influencing Cervical Cancer Screening Participation among Singaporean Women: A Social Ecological Approach

by Qing Huang and Li-Ying Tan

Cancers 2024, 16(20), 3475; https://doi.org/10.3390/cancers16203475 - 14 Oct 2024

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Abstract

Background/Objectives: Cervical cancer screening uptake in Singapore remains suboptimal. This study employed the Social Ecological Model (SEM) to investigate factors influencing cervical cancer screening participation among Singaporean women. Methods: The study included 665 women, aged 25–69 years, who reported awareness of cancer screening and no personal cancer history. Data were collected through a previously described online survey. Hierarchical logistic regression analysis was conducted to identify significant factors influencing screening participation. Results: Only 30% of participants reported cervical cancer screening participation. Women aged 25–29 years (OR = 0.33; 95% CI = 0.12–0.77), Malay women (OR = 0.42; 95% CI = 0.20–0.83), and unmarried women (OR = 0.30; 95% CI = 0.18–0.48) were less likely to be screened. Positive associations with screening participation were observed with good cervical cancer screening knowledge (OR = 2.90; 95% CI = 1.96–4.32), awareness of primary care providers’ role in delivering screening services (OR = 1.94; 95% CI = 1.24–3.10), cancer information seeking behavior (OR = 1.59; 95% CI = 1.07–2.39), and acceptance of self-sampling options (OR = 1.81; 95% CI = 1.22–2.70). Conclusions: Our study highlights the cumulative impact of factors at various SEM levels on screening participation and underscores the necessity for more targeted and multi-pronged strategies to improve cervical cancer screening uptake in Singapore. Full article

(This article belongs to the Special Issue Prevention and Screening in Gynaecological Cancers)

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19 pages, 427 KiB

Open AccessArticle

Concurrent Endometrial Cancer in Women with Atypical Endometrial Hyperplasia: What Is the Predictive Value of Patient Characteristics?

by Luca Giannella, Francesco Piva, Giovanni Delli Carpini, Jacopo Di Giuseppe, Camilla Grelloni, Matteo Giulietti, Francesco Sopracordevole, Giorgio Giorda, Anna Del Fabro, Nicolò Clemente, Barbara Gardella, Giorgio Bogani, Orsola Brasile, Ruby Martinello, Marta Caretto, Alessandro Ghelardi, Gianluca Albanesi, Guido Stevenazzi, Paolo Venturini, Maria Papiccio, Marco Cannì, Maggiorino Barbero, Massimiliano Fambrini, Veronica Maggi, Stefano Uccella, Arsenio Spinillo, Francesco Raspagliesi, Pantaleo Greco, Tommaso Simoncini, Felice Petraglia and Andrea Ciavattini Show full author list Hide full author list

Cancers 2024, 16(1), 172; https://doi.org/10.3390/cancers16010172 - 29 Dec 2023

Cited by 5 | Viewed by 1882

Abstract

Background: The rate of concurrent endometrial cancer (EC) in atypical endometrial hyperplasia (AEH) can be as high as 40%. Some patient characteristics showed associations with this occurrence. However, their real predictive power with related validation has yet to be discovered. The present study aimed to assess the performance of various models based on patient characteristics in predicting EC in women with AEH. Methods: This is a retrospective multi-institutional study including women with AEH undergoing definitive surgery. The women were divided according to the final histology (EC vs. no-EC). The available cases were divided into a training and validation set. Using k-fold cross-validation, we built many predictive models, including regressions and artificial neural networks (ANN). Results: A total of 193/629 women (30.7%) showed EC at hysterectomy. A total of 26/193 (13.4%) women showed high-risk EC. Regression and ANN models showed a prediction performance with a mean area under the curve of 0.65 and 0.75 on the validation set, respectively. Among the best prediction models, the most recurrent patient characteristics were age, body mass index, Lynch syndrome, diabetes, and previous breast cancer. None of these independent variables showed associations with high-risk diseases in women with EC. Conclusions: Patient characteristics did not show satisfactory performance in predicting EC in AEH. Risk stratification in AEH based mainly on patient characteristics may be clinically unsuitable. Full article

(This article belongs to the Special Issue Prevention and Screening in Gynaecological Cancers)

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15 pages, 2249 KiB

Open AccessArticle

Preoperative Serum Levels of PDGF-AB, PDGF-BB, TGF-α, EGF and ANG-2 in the Diagnosis of Endometrial Cancer

by Mateusz Kozłowski, Dominika Borzyszkowska, Justyna Mirko, Agnieszka Turoń-Skrzypińska, Katarzyna Piotrowska, Aleksandra Tołoczko-Grabarek, Sebastian Kwiatkowski, Maciej Tarnowski, Iwona Rotter and Aneta Cymbaluk-Płoska

Cancers 2023, 15(19), 4815; https://doi.org/10.3390/cancers15194815 - 30 Sep 2023

Cited by 2 | Viewed by 1151

Abstract

(1) Background: It is relevant to find new diagnostic biomarkers for endometrial cancer. This study aimed to investigate whether PDGF-AB, PDGF-BB, TGF-α, EGF and ANG-2 could be considered new useful markers for diagnosis and survival of endometrial cancer. (2) Methods: A total of 93 women diagnosed with endometrial cancer (EC) and 66 patients with non-cancerous endometrial lesions (NCEL) were included in this study. (3) Results: Median serum levels of PDGF-AB, PDGF-BB, TGF-α, EGF and ANG-2 were significantly higher in the EC group compared to the NCEL group (for PDGF-AB, PDGF-BB, TGF-α and ANG-2, p = 0.0000; for EGF, p = 0.0186). The cut-off level of PDGF-AB was set at 127.69 pg/mL with a sensitivity of 87.1% and a specificity of 66.67% (AUC = 0.78, p < 0.000001). The cut-off level of PDGF-BB was set at 207.86 ng/L with a sensitivity of 82.8% and a specificity of 75.76% (AUC = 0.85, p < 0.000001). The cut-off level of TGF-α was set at 33.85 ng/L with a sensitivity of 82.8% and a specificity of 75.76% (AUC = 0.82, p < 0.000001). The cut-off level of EGF was set at 934.76 pg/mL with a sensitivity of 83.87% and a specificity of 28.79% (AUC = 0.61, p = 0.018472). The cut-off level of ANG-2 was set at 3120.68 pg/mL with a sensitivity of 72.04% and a specificity of 93.94% (AUC = 0.87, p < 0.000001). (4) Conlusion: It was concluded that all the proteins studied could be potential diagnostic markers in endometrial cancer. Full article

(This article belongs to the Special Issue Prevention and Screening in Gynaecological Cancers)

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14 pages, 1509 KiB

Open AccessArticle

Cost-Effectiveness Analysis of HPV Extended versus Partial Genotyping for Cervical Cancer Screening in Singapore

by Brandon Chua, Li Min Lim, Joseph Soon Yau Ng, Yan Ma, Hwee Lin Wee and J. Jaime Caro

Cancers 2023, 15(6), 1812; https://doi.org/10.3390/cancers15061812 - 16 Mar 2023

Cited by 7 | Viewed by 3041 | Correction

Abstract

Human papillomavirus (HPV) partial genotyping (PGT) identifies HPV16 and HPV18 individually, alongside 12 other high-risk HPV genotypes (hrHPV) collectively. HPV extended genotyping (XGT) identifies four additional hrHPV individually (HPV31, 45, 51, and 52), and reports the remaining eight in three groups (HPV33|58; 56|59|66; 35|39|68). Quality-adjusted life years (QALY), health care resource use, and costs of XGT were compared to PGT for cervical cancer screening in Singapore using DICE simulation. Women with one of the three hrHPV identified by XGT (HPV35|39|68; 56|59|66; 51), and atypical squamous cells of undetermined significance (ASCUS) on cytology, are recalled for a repeat screening in one year, instead of undergoing an immediate colposcopy with PGT. At the repeat screening, the colposcopy is performed only for persistent same-genotype infections in XGT, while with PGT, all the women with persistent HPV have a colposcopy. Screening 500,122 women, aged 30–69, with XGT, provided an incremental cost-effectiveness ratio (ICER) versus PGT of SGD 16,370/QALY, with 7130 (19.4%) fewer colposcopies, 6027 (7.0%) fewer cytology tests, 9787 (1.6%) fewer clinic consultations, yet 2446 (0.5%) more HPV tests. The XGT ICER remains well below SGD 100,000 in sensitivity analyses, (-SGD 17,736/QALY to SGD 50,474/QALY). XGT is cost-effective compared to PGT, utilizes fewer resources, and provides a risk-based approach as the primary cervical cancer screening method. Full article

(This article belongs to the Special Issue Prevention and Screening in Gynaecological Cancers)

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16 pages, 1280 KiB

Open AccessArticle

The Risk of Endometrial Cancer and Uterine Sarcoma Following Endometriosis or Pelvic Inflammatory Disease

by Jing-Yang Huang, Kevin Sheng-Kai Ma, Li-Tzu Wang, Cho-Han Chiang, Shun-Fa Yang, Chun-Hao Wang and Po-Hui Wang

Cancers 2023, 15(3), 833; https://doi.org/10.3390/cancers15030833 - 29 Jan 2023

Cited by 11 | Viewed by 3084

Abstract

The relationship between uterine corpus cancer and endometriosis was conflicting. We aimed to determine the risk of uterine cancer in patients with endometriosis or pelvic inflammatory disease (PID). In this population-based cohort study, a total of 135,236 females with endometriosis (n = 20,510) or PID (n = 114,726), as well as 135,236 age-matched controls, were included. Cox regression models estimated the risk of uterine cancer in each group. Sub-outcomes of risk for uterine corpus cancer included endometrial cancer and uterine sarcoma were analyzed. An age subgroup analysis was performed to determine the moderator effect of age. A landmark analysis depicted the time varying effect of endometriosis and PID. A propensity score matching analysis was conducted to validate the findings. Patients with endometriosis had significantly higher risk of endometrial cancer (adjusted hazard ratio, aHR = 2.92; 95% CI = 2.12–4.03) and uterine sarcoma (aHR = 5.83; 95% CI = 2.02–16.89), while PID was not associated with the risk of uterine cancer. The increased risk of uterine cancer in patients with endometriosis persisted after propensity score matching (aHR = 2.83, 95%CI = 1.70–4.71). The greatest risk of endometrial cancer occurred in patients who had endometriosis for 37 to 60 months (adjusted relative risk, aRR = 9.15, 95% CI = 4.40–19.02). Females aged 12 to 35 years were at the greatest risk of endometriosis-associated uterine cancer (RR = 6.97, 95% CI = 3.41–14.26). In conclusion, patients with endometriosis were at great risk of uterine cancer, including endometrial cancer and uterine sarcoma, compared with propensity score-matched populations and compared with patients of PID. Younger females with endometriosis and patients who had endometriosis for three to five years were at the greatest risk of endometriosis-associated uterine cancer. Full article

(This article belongs to the Special Issue Prevention and Screening in Gynaecological Cancers)

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Open AccessCorrection

Correction: Chua et al. Cost-Effectiveness Analysis of HPV Extended versus Partial Genotyping for Cervical Cancer Screening in Singapore. Cancers 2023, 15, 1812

by Brandon Chua, Li Min Lim, Joseph Soon Yau Ng, Yan Ma, Hwee Lin Wee and J. Jaime Caro

Cancers 2023, 15(18), 4658; https://doi.org/10.3390/cancers15184658 - 21 Sep 2023

Viewed by 982

Abstract

The authors wish to revise two words in Table 1 row 3, and the first paragraph of Section 2 [...] Full article

(This article belongs to the Special Issue Prevention and Screening in Gynaecological Cancers)

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