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Gynecological Cancer: Prevention, Diagnosis, Prognosis and Treatment

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A special issue of Cancers (ISSN 2072-6694). This special issue belongs to the section "Clinical Research of Cancer".

Deadline for manuscript submissions: closed (31 January 2026) | Viewed by 11601

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Dr. Joanna P. Kacperczyk-Bartnik

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II Department of Obstetrics and Gynecology, Medical University of Warsaw, Warsaw, Poland
Interests: gynecologic oncology; cervical cancer screening; cervical cancer prevention; quality of life during and after cancer treatment
Special Issues, Collections and Topics in MDPI journals

Dr. Tibor Andrea Zwimpfer

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Guest Editor

1. Gynecological Cancer Center, University Hospital Basel, Basel, Switzerland
2. Department of Biomedicine, University Hospital Basel, Basel, Switzerland
3. Cancer Research, Peter MacCallum Cancer Centre, Melbourne, VIC 3002, Australia
Interests: gynecological oncology; ovarian cancer; vulvar cancer; experimental cancer research; multi-omics; BRCA-deficiency; poor survivors; homologous recombination deficiency; minimal invasive surgical procedures

Prof. Dr. Michał Ciebiera

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Guest Editor

Second Department of Obstetrics and Gynecology, Center of Postgraduate Medical Education, 00-189 Warsaw, Poland
Interests: uterine fibroids; pharmacology; miminally invasive therapy; reproductive endocrinology
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

Gynecological cancers, including ovarian, cervical, endometrial, vaginal, and vulvar malignancies, represent a significant global health burden. Despite advancements in medical research, early detection, prevention strategies, and therapeutic options remain critical challenges in managing these malignancies. This Special Issue aims to bring together cutting-edge research on the prevention, diagnosis, prognosis, and treatment of gynecological cancers. We invite authors to explore innovative diagnostic tools, novel therapeutic approaches, and strategies to reduce the incidence of these cancers. The Special Issue will provide insights into molecular mechanisms, personalized medicine, and emerging trends in treatment, ultimately aiming to improve patient outcomes and survival rates.

Dr. Joanna P. Kacperczyk-Bartnik
Dr. Tibor Andrea Zwimpfer
Prof. Dr. Michał Ciebiera
Guest Editors

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Keywords

gynecological cancer
ovarian cancer
cervical cancer
endometrial cancer
early diagnosis
cancer prevention
prognosis
molecular mechanisms
personalized medicine
novel therapies

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Published Papers (9 papers)

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Research

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16 pages, 1888 KB

Open AccessArticle

Differentiating Borderline from Malignant Ovarian-Adnexal Tumours: A Multimodal Predictive Approach Joining Clinical, Analytic, and MRI Parameters

by Lledó Cabedo, Carmen Sebastià, Meritxell Munmany, Adela Saco, Eduardo Gallardo, Olatz Sáenz de Argandoña, Gonzalo Peón, Josep Lluís Carrasco and Carlos Nicolau

Cancers 2026, 18(3), 516; https://doi.org/10.3390/cancers18030516 - 4 Feb 2026

Viewed by 210

Abstract

Objectives: To improve the differentiation of borderline ovarian-adnexal tumours (BOTs) from malignant ovarian-adnexal masses, most of which fall into the indeterminate O-RADS MRI 4 category, by developing a multimodal predictive model that integrates clinical, analytic, and MRI parameters. Methods: This retrospective, single-centre study included 248 women who underwent standardised MRI for ovarian-adnexal mass characterisation between 2019 and 2024. Of these, 201 had true ovarian-adnexal masses (114 benign, 22 borderline, and 65 malignant), confirmed by histopathology or stability after ≥12-month follow-up. Forty-one clinical, laboratory, and imaging variables were initially assessed, and after a bivariate evaluation, 18 final predictors with clinical relevance were selected for model construction with thresholds learned from the data. A classification and regression tree (CART) model (“Full Model”) was applied as a second-stage tool after O-RADS MRI scoring, using 10-fold cross-validation to prevent overfitting. A pruned “Simplified Model” was also derived to enhance interpretability. Results: O-RADS MRI performed well at the extremes (scores 2–3 and 5) but showed limited discrimination between BOTs and malignancies within category 4 (PPV for borderline = 0.50). The decision-tree models significantly improved diagnostic performance, increasing overall accuracy from 0.856 with O-RADS MRI alone to 0.905 (Simplified Model) and 0.955 (Full Model). The PPV for BOTs within the intermediate O-RADS MRI 4 category increased from 0.49 with O-RADS MRI alone to 0.77 and 0.90 with the simplified and full models, respectively, while maintaining high accuracy for benign and malignant lesions. Conclusions: In this retrospective single-centre cohort, the addition of an interpretable rule-based predictive model as a second-line tool within O-RADS MRI category 4 was associated with improved discrimination between borderline and invasive malignant ovarian-adnexal tumours. These findings suggest that multimodal integration of clinical, laboratory, and MRI features may help refine risk stratification in indeterminate cases; however, external validation in prospective multicentre cohorts is required before clinical implementation. Full article

(This article belongs to the Special Issue Gynecological Cancer: Prevention, Diagnosis, Prognosis and Treatment)

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17 pages, 824 KB

Open AccessArticle

Pelvic Exenteration: An Ultimate Option in Advanced Gynecological Malignancies—A Single Center Experience

by Helmut Plett, Jan Philipp Ramspott, Ibrahim Büdeyri, Andrea Miranda, Jalid Sehouli, Ahmad Sayasneh and Mustafa Zelal Muallem

Cancers 2025, 17(14), 2327; https://doi.org/10.3390/cancers17142327 - 12 Jul 2025

Cited by 2 | Viewed by 2014

Abstract

Background/Objectives: Pelvic exenteration (PE) might be a curative option for patients with advanced pelvic malignancies. Due to its significant morbidity and mortality rates, PE necessitates meticulous patient selection, and a comprehensive understanding of disease spread. This study outlines the experience at a single tertiary referral center and investigates prognostic factors influencing survival post-PE, thereby guiding clinical decision-making processes. Methods: Patients undergoing PE for advanced pelvic gynecological malignancies between 01/2016 and 12/2023 were retrospectively analyzed using a prospectively managed database. Eligibility for PE was determined through individualized tumor board evaluations based on CT/MRI imaging, excluding patients with distant metastases. Baseline demographic and clinical characteristics, operative details, complication rates, and histopathological findings were assessed using univariate and multivariate regression analyses. Disease-free (DFS) and overall survival (OS) were assessed by Kaplan-Meier analysis. Poor outcome prognostic factors were identified, outlining an optimal candidate profile for PE. Results: A total of 70 patients were included. The median age was 54.5 years. Forty-three patients (61.4%) presented with recurrent disease and the majority were diagnosed with cervical cancer (n = 48, 68.6%). Total PE was performed in 40 patients (57.1%), with complete tumor resection achieved in 68.6% of patients (n = 48). Sixteen patients (22.8%) experienced grade IV/V complications. Median DFS and OS were 8.2 and 16.4 months, respectively. Multivariate analysis identified R1 resection status and para-aortic lymph node involvement as independent negative prognostic factors. Conclusions: PE is a viable option for selected patients with advanced primary and recurrent pelvic gynecological malignancies. When complete tumor resection is feasible, patients may derive benefit from PE, although the risk of severe perioperative complications must be carefully evaluated. Full article

(This article belongs to the Special Issue Gynecological Cancer: Prevention, Diagnosis, Prognosis and Treatment)

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17 pages, 566 KB

Open AccessArticle

Efficacy and Safety of Chemotherapy Combined with Hormonal Therapy in Heavily Pretreated Advanced Epithelial Ovarian, Fallopian Tube, or Primary Peritoneal Cancer (ELSA/KGOG3049): A Multicenter Pilot Study

by Kidong Kim, Chel Hun Choi, Sang-Yoon Park, Min Kyu Kim, Keun Ho Lee, Eun-Ju Lee, Myong Cheol Lim, Young Han Park, Min Sun Kyung, Jae Hong No, Dong Hoon Suh, Jeong-Won Lee, Sangjeong Ahn and Banghyun Lee

Cancers 2025, 17(14), 2320; https://doi.org/10.3390/cancers17142320 - 12 Jul 2025

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Abstract

Background/Objectives: The effects of combining chemotherapy with hormonal therapy based on hormone receptor (HR) expression in epithelial ovarian, fallopian tube, or primary peritoneal (EOC) remain unclear. This study evaluated the efficacy and safety of physician-chosen chemotherapy combined with hormonal therapy in patients with heavily pretreated advanced EOC, stratified by HR expression. Methods: This phase II, multicenter, pilot study included patients with heavily pretreated advanced EOC, allocated to estrogen receptor (ER)-dominant or progesterone receptor (PR)-dominant arms. Patients in the ER-dominant arm received tamoxifen plus physician-selected chemotherapy, while those in the PR-dominant arm received megestrol acetate (MA) plus chemotherapy. The primary outcome was the best objective response rate (ORR) for six months, assessed using an optimal two-stage Simon design. Results: Among 33 ER-dominant patients with high-grade serous carcinoma (HGSC), the six-month best ORR was 27.3% (3% complete response, 24.2% partial response). The six-month ORR and clinical benefit rate (CBR) were 18.8% and 37.5%, respectively, with 62.5% experiencing progressive disease (PD). Among three PR-dominant patients (two clear cell carcinoma and one HGSC), the six-month best ORR was 0%. The six-month ORR and CBR were also 0%, and all experienced PD within six months. No unacceptable toxicity related to tamoxifen or MA was encountered. Conclusions: In heavily pretreated advanced HGSC patients with ER-dominant expression, chemotherapy combined with tamoxifen showed encouraging clinical activity with favorable safety. While limited by the study design, these findings suggest a potential role for tailored hormonal therapy combined with chemotherapy based on HR expression in heavily pretreated advanced EOC. Clinical Trial Registration: KCT0004571 Full article

(This article belongs to the Special Issue Gynecological Cancer: Prevention, Diagnosis, Prognosis and Treatment)

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12 pages, 1654 KB

Open AccessFeature PaperArticle

Endocrine Maintenance Therapy in High-Grade Serous Ovarian Cancer: A Retrospective Off-Label Real-World Cohort Study

by Franziska Geissler, Flurina Graf, Tibor A. Zwimpfer, Ruth S. Eller, Bich Doan Nguyen-Sträuli, Andreas Schötzau, Viola Heinzelmann-Schwarz and Ursula Gobrecht-Keller

Cancers 2025, 17(8), 1301; https://doi.org/10.3390/cancers17081301 - 12 Apr 2025

Cited by 1 | Viewed by 2541

Abstract

Background: Endocrine therapy is the standard-of-care maintenance treatment for estrogen receptor (ER)-positive breast cancers and is increasingly used in low-grade serous ovarian cancer. However, its therapeutic role in the early maintenance setting for ER-positive high-grade serous ovarian cancer (HGSC) remains undefined. Methods: A retrospective analysis was conducted on clinicopathological data from patients with newly diagnosed ER-positive HGSC following completion of adjuvant chemotherapy. Patients received maintenance therapy either with or without the aromatase inhibitor letrozole, in addition to standard maintenance care. ER expression levels and the administration of letrozole were analyzed, along with outcome measures for the entire cohort, with stratification based on residual disease status. Results: A total of 102 patients with newly diagnosed HGSC were included in the analysis, with 64 (62.7%) receiving letrozole and 38 (37.3%) not receiving letrozole. The median ER expression was 70%, with higher expression observed in the letrozole group compared to the no letrozole group (77.5% vs. 60%). No significant correlation was found between ER expression status and therapy response (p = 0.295 and p = 0.176, respectively). Letrozole therapy was well tolerated with no major adverse effects reported. In the overall cohort, maintenance letrozole therapy did not confer a significant improvement in progression-free survival (median 20.56 months vs. 29.34 months, p = 0.53) or overall survival (OS) (median 79.48 months vs. 46.85 months, p = 0.71) over a median follow-up duration of 23.5 months. However, among patients with no residual disease, maintenance letrozole therapy was associated with a statistically significant improvement in OS compared to those not receiving letrozole (median 114 months vs. 46.9 months, p = 0.006). Conclusions: Maintenance letrozole therapy appears to be a well-tolerated and potentially beneficial intervention in a subset of patients with ER-positive HGSC with no residual disease post-treatment. These findings highlight the need for further validation through prospective randomized trials to comprehensively assess the efficacy of endocrine therapy in this setting and its implications for patient quality of life. Full article

(This article belongs to the Special Issue Gynecological Cancer: Prevention, Diagnosis, Prognosis and Treatment)

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Review

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27 pages, 4328 KB

Open AccessReview

Bartholin Gland Carcinoma: A State-of-the-Art Review of Epidemiology, Histopathology, Molecular Testing, and Clinical Management

by Stoyan Kostov, Yavor Kornovski, Vesela Ivanova, Dimitar Metodiev, Angel Yordanov, Stanislav Slavchev, Yonka Ivanova, Anke Seidel, Ingolf Juhasz-Böss, Ihsan Hasan, Ibrahim Alkatout and Rafał Watrowski

Cancers 2025, 17(23), 3819; https://doi.org/10.3390/cancers17233819 - 28 Nov 2025

Viewed by 1399

Abstract

Bartholin gland carcinoma (BGC) is a rare malignancy, comprising 3–7% of vulvar cancers and <1% of gynecologic tumors. Due to its low incidence, high-level evidence is lacking, and management is largely extrapolated from vulvar cancer guidelines. This comprehensive narrative review synthesizes current evidence on BGC, emphasizing histotype-specific features, diagnostic criteria, molecular profiling, and treatment strategies. The three most common subtypes are squamous cell carcinoma, adenoid cystic carcinoma (AdCC), and adenocarcinoma. HPV-associated tumors tend to occur in younger women and carry favorable prognoses. Accurate diagnosis requires exclusion of metastases and integration of clinical, imaging, and immunohistochemical data, including p16/HPV for squamous tumors, MYB/MYBL1 fusions for AdCC, and CK20/CDX2/SATB2 for intestinal-type adenocarcinoma. Approximately 50% of cases are diagnosed at an advanced stage due to misclassification as benign cysts or abscesses. Nodal metastasis occurs in >40% of cases, with histotype influencing prognosis. Adenocarcinoma and node-positive disease independently predict worse survival. Treatment hinges on complete surgical excision with 2–3 mm margins, bilateral groin evaluation, and histology-tailored adjuvant therapy. Emerging data support the use of immune checkpoint inhibitors in squamous BGC and targeted agents (e.g., mTOR/CDK4/6 inhibitors) in adenocarcinoma. We propose a practical molecular testing algorithm and highlight the urgent need for prospective, multinational collaboration to establish BGC-specific guidelines. Full article

(This article belongs to the Special Issue Gynecological Cancer: Prevention, Diagnosis, Prognosis and Treatment)

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18 pages, 747 KB

Open AccessReview

Adjuvant Treatment for Surgically-Treated Cervical Cancer Patients: A Comprehensive Review

by Stamatios Petousis, Aristarchos Almperis, Chrysoula Margioula-Siarkou, Frederic Guyon, Vasileios Pergialiotis, Nikolaos Thomakos, Konstantinos Dinas and Alexandros Rodolakis

Cancers 2025, 17(22), 3710; https://doi.org/10.3390/cancers17223710 - 20 Nov 2025

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Abstract

Background/Objectives: Cervical cancer (CC) is the fourth most common gynecologic malignancy, disproportionately affecting women in low- and middle-income countries. Despite the effectiveness of HPV vaccination and screening strategies, CC poses a major global health issue, accounting for approximately 94% of annual deaths. Τhis review aims to summarize the current evidence regarding adjuvant treatment indications for surgically treated cervical cancer patients and identify areas where further research is required. Methods: After a literature search, a comprehensive review of the existing guidelines, clinical trials, and cohort studies related to cervical cancer treatment was conducted, focusing on the role of adjuvant therapy in patients classified as at low, intermediate, and high risk for recurrence, who may require no further treatment. Results: Adjuvant therapy is generally unnecessary for low-risk patients, while high-risk patients with lymph node invasion, parametrial involvement, or large tumor size require chemoradiation (CRT). Ιntermediate-risk patients fall into a grey zone, where the necessity of adjuvant therapy is still debatable. Guidelines emphasize the need for individualization in treatment strategies, since, based on the published studies, careful surgery alone and observation can provide similar outcomes to adjuvant therapy. Conclusions: This review emphasizes that achieving monotherapy remains pivotal to optimize outcomes and minimize overtreatment. Definitive adjuvant treatment is indicated for high-risk cases, and intermediate-risk patients may benefit from careful observation following adequate surgical intervention, pointing out the necessity of well-designed clinical trials. Full article

(This article belongs to the Special Issue Gynecological Cancer: Prevention, Diagnosis, Prognosis and Treatment)

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Other

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35 pages, 7090 KB

Open AccessSystematic Review

Oncologic and Reproductive Outcomes of Fertility-Sparing Management in Early-Stage Endometrial Carcinoma: A Systematic Review and Meta-Analysis

by Pál Sebok, Márton Keszthelyi, Balázs Vida, Lotti Lőczi, Barbara Sebők, Petra Merkely, Nándor Ács, Ferenc Bánhidy, Attila Keszthelyi, Szabolcs Várbíró, Balázs Lintner and Richárd Tóth

Cancers 2026, 18(3), 399; https://doi.org/10.3390/cancers18030399 - 27 Jan 2026

Viewed by 189

Abstract

Endometrial carcinoma (EC) is the leading gynecologic malignancy in high-income countries, with a consistent upward trend in incidence observed among younger women, particularly in those younger than 50 years [...] Full article

(This article belongs to the Special Issue Gynecological Cancer: Prevention, Diagnosis, Prognosis and Treatment)

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25 pages, 3882 KB

Open AccessSystematic Review

Oncologic and Reproductive Outcomes After Fertility-Sparing Treatments for Endometrial Hyperplasia with Atypia: A Systematic Review and Meta-Analysis

by Pál Sebok, Márton Keszthelyi, Balázs Vida, Lotti Lőczi, Barbara Sebők, Petra Merkely, Nándor Ács, Attila Keszthelyi, Szabolcs Várbíró, Balázs Lintner and Richárd Tóth

Cancers 2025, 17(24), 3966; https://doi.org/10.3390/cancers17243966 - 12 Dec 2025

Cited by 1 | Viewed by 896

Abstract

Background: Atypical endometrial hyperplasia is a precursor of endometrial carcinoma, increasingly diagnosed in reproductive-aged women. Standard hysterectomy may constitute overtreatment. Fertility-sparing approaches, oral or local progestins, hysteroscopic resection, and combined regimens are widely used, though evidence largely derives from early-stage carcinoma. Methods: CENTRAL, EMBASE, Scopus, Web of Science, and PubMed were searched from inception to 13 April 2025. Eligible studies included premenopausal women with AEH treated with oral progestins, levonorgestrel intrauterine devices (LNG-IUDs), hysteroscopic resection, or combination regimens (e.g., oral progestins + metformin, LNG-IUD + GnRH analogues). Random-effects meta-analyses with multilevel modeling were applied. Risk of bias was assessed using RoB-2 and ROBINS-I; certainty of evidence was graded with GRADE-PRO. Results: Forty-nine studies (2313 women) were included. The pooled complete response (CR) rate was 85% (95% CI 80–89%). LNG-IUDs resulted in 88% CR and oral progestins in 80%. Combination therapies achieved up to 95% CR, though data were limited. Hysteroscopic resection combined with hormonal therapy reported high CR rates (96–97%) but relied on small, heterogeneous cohorts with uncertain reproducibility. The pooled recurrence rate was 19% (95% CI, 13–25%), lower with LNG-IUDs (14%) compared with oral progestins (22%). No response occurred in 14% overall and was lower with LNG-IUDs (13%) than oral progestins (19%). Among women attempting conception, the pooled pregnancy rate was 41%, and the live birth rate was 30%. The mean time to achieve CR was 5.6 months, whereas the mean time to recurrence was approximately 33 months. Conclusions: LNG-IUDs provide the most effective and well-supported fertility-sparing treatment for AEH, ensuring high remission with low recurrence. Despite favorable numerical outcomes, the evidence for hysteroscopic resection is limited and inconsistent, not supporting its routine use. Combination regimens may improve response but require confirmation in larger studies. Full article

(This article belongs to the Special Issue Gynecological Cancer: Prevention, Diagnosis, Prognosis and Treatment)

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23 pages, 1483 KB

Open AccessSystematic Review

Exosomes as Emerging Non-Invasive Biomarkers of Cervical Cancer: A Systematic Review and Meta-Analysis

by Fernanda Santos, Francisco A. Caramelo, Jorge M. P. Tomaz, Magda M. Santana, Rui J. Nobre, Luis P. Almeida and Margarida Figueiredo-Dias

Cancers 2025, 17(24), 3945; https://doi.org/10.3390/cancers17243945 - 10 Dec 2025

Cited by 1 | Viewed by 919

Abstract

Background/Objectives: Cervical cancer remains a significant global health burden, underscoring the imperative for refined diagnostic and prognostic methodologies. This study aimed to evaluate the potential of extracellular vesicles (EVs) as non-invasive biomarkers for cervical cancer, focusing on diagnosis and prognosis. Methods: We conducted a systematic review and meta-analysis in accordance with PRISMA guidelines to assess the diagnostic and prognostic accuracy of EV-based biomarkers. We searched PubMed, EMBASE, and Web of Science for relevant studies. Twelve articles met the inclusion criteria: eight related to diagnostic accuracy, three to prognosis, and one to both outcomes. Six studies met the criteria for meta-analysis. We used a random-effects model to synthesise diagnostic data, while prognostic data were synthesised narratively. Results: The meta-analysis yielded a pooled area under the receiver operating characteristic curve (AUC) of 0.87 (95% CI 0.80–0.92) for EVs in the diagnosis of cervical cancer, indicating high accuracy. The evaluated diagnostic biomarkers were primarily non-coding RNAs. For prognosis, data heterogeneity precluded quantitative synthesis; however, individual studies identified diverse EV-associated molecules correlated with recurrence and survival. GRADE assessment indicated a high risk of bias and heterogeneity across studies. Conclusions: Extracellular vesicles demonstrate robust promise as diagnostic biomarkers for cervical cancer; however, their prognostic utility remains inconclusive due to methodological and clinical heterogeneity. Future research must prioritise the standardisation of isolation protocols and the execution of large-scale, prospective studies to validate EV biomarkers for clinical application. Systematic Review Registration: PROSPERO, identifier: CRD420251014411. Full article

(This article belongs to the Special Issue Gynecological Cancer: Prevention, Diagnosis, Prognosis and Treatment)

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