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Cancers
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Biomarkers for Gynecological Cancers
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Biomarkers for Gynecological Cancers

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

Deadline for manuscript submissions: 31 March 2026 | Viewed by 8855

Special Issue Editor

Dr. Apriliana Kartikasari

E-Mail Website
Guest Editor
School of Health and Biomedical Sciences, RMIT University, Melbourne, VIC 3083, Australia
Interests: ovarian cancer; biomarkers; therapy
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

Gynecological cancers, such as cervical, ovarian, and endometrial cancers, pose significant challenges in early detection and treatment. Biomarkers, as biomolecules that can predict or indicate the risk, presence, or absence of a biological event, have emerged as a potential tool to indicate disease risk, presence, progression, response to therapy, and patient outcomes. Thus, identifications of reliable biomarkers in gynecological cancers are essential for improving their early and accurate detection, personalizing treatment regimens, and improving survival outcomes. These biomarkers could originate from the tumor tissues, whole body, or body fluid, including blood, urine, stool, and saliva. Such biomarkers could offer insights to guide clinical decisions and improve patient outcomes. However, high accuracy in the detection of biomarkers and the standardization of tests and the interpretation of their results is crucial to integrating them into routine clinical practice in order to enhance the precision of cancer detection and treatment.

We are pleased to invite you to participate in this Special Issue, focusing on the latest findings regarding biomarkers and their detection in gynecological cancers. Original research articles and reviews regarding biomarkers as susceptibility/risk, diagnosis, prognosis, or treatment response factors, as well as their detection and standardization approaches, are welcome. We look forward to receiving your contributions.

Dr. Apriliana Kartikasari
Guest Editor

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

  • biomarkers
  • cervical
  • ovarian
  • uterine
  • endometrial
  • vaginal
  • vulvar
  • fallopian tube

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Published Papers (6 papers)

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Research

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20 pages, 1622 KB  
Article
The DNA Methylation Marker ZNF671 Has Prognostic Value for Progressing Cervical Intraepithelial Neoplasia
by Lena Dübbel, Anna Göken-Riebisch, Kristin Knoll, Juliane Hippe, Charis Marticke, Meike Schild-Suhren and Eduard Malik
Cancers 2025, 17(19), 3095; https://doi.org/10.3390/cancers17193095 - 23 Sep 2025
Viewed by 288
Abstract
Background/Objectives: Most cervical intraepithelial neoplasias (CINs) regress over time. Diagnostic screenings are limited and cannot identify the disease trend, which leads to the risk of overtreatment. Reliable methods are needed to preselect patients who will probably progress. The diagnostic GynTect® assay offers [...] Read more.
Background/Objectives: Most cervical intraepithelial neoplasias (CINs) regress over time. Diagnostic screenings are limited and cannot identify the disease trend, which leads to the risk of overtreatment. Reliable methods are needed to preselect patients who will probably progress. The diagnostic GynTect® assay offers sensitive and specific CIN identification from cervical scrapes, measuring the methylation of six marker genes. We studied the main marker (ZNF671) methylation on formalin-fixed paraffin-embedded (FFPE) material to determine if the kit provides prognostic information too. Methods: We tested 289 FFPE samples from 139 patients with varying CIN grades and disease trends, including regressive, persistent, progressive, and recurrent disease. Additionally, we correlated age and human papillomavirus (HPV) status with the results. Results: Although there are differences between FFPE material and cervical scrapes, we achieved a similar increase in ZNF671 methylation with increasing neoplasia grade (dysplasia-free: 0%, CIN 1: 8.20%, CIN 2: 26.73%, CIN 3: 32.43%, carcinoma: 100%). In addition, ZNF671 is more likely to detect recurring (27.12% of positives) and progressive (59.32% of positives) neoplasia. Patients with regressive (1.69% of positives) or persistent (11.86% of positives) trends less frequently show ZNF671 methylation. Interestingly, patients with HPV 16 infection (52.54% of positives) and >30 years (89.83% of positives) are more likely to appear ZNF671 methylation-positive. However, patients < 30 years with persistent neoplasia (42.86% of positives) also show methylation more frequently. Conclusions: The methylation of ZNF671 is measurable in cervical FFPE material and has prognostic value. Since ZNF671-methylated samples are most likely to be progressing, we recommend the closer monitoring of patients with GynTect®-positive test results. Full article
(This article belongs to the Special Issue Biomarkers for Gynecological Cancers)
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22 pages, 5276 KB  
Article
Protein Biomarkers Enable Sensitive and Specific Cervical Intraepithelial Neoplasia (CIN) II/III+ Detection: One Step Closer to Universal Cervical Cancer Screening
by Samrin F. Habbani, Sayeh Dowlatshahi, Nathanael Lichti, Meaghan Broman, Lucy Tecle, Scott Bolton, Lisa Flowers, Rafael Guerrero-Preston, Jacqueline C. Linnes and Sulma I. Mohammed
Cancers 2025, 17(11), 1763; https://doi.org/10.3390/cancers17111763 - 24 May 2025
Viewed by 2407
Abstract
Background/Objectives: Cervical cancer (CC) is a significant global health challenge, particularly in low- and middle-income countries (LMICs), where limited access to human papillomavirus (HPV) vaccination and effective CC screening results in a majority of cases and fatalities among women. Moreover, existing vaccines do [...] Read more.
Background/Objectives: Cervical cancer (CC) is a significant global health challenge, particularly in low- and middle-income countries (LMICs), where limited access to human papillomavirus (HPV) vaccination and effective CC screening results in a majority of cases and fatalities among women. Moreover, existing vaccines do not target HPV-independent cancers. Current screening methods are expensive and time-consuming, with a limited emphasis on CC protein biomarkers. Therefore, we aimed to validate critical markers that allow the development of affordable point-of-care screening tests for resource-limited settings. Methods: This study first optimized a cell lysis and protein extraction protocol for CC cell lines and clinical cervical swabs. Subsequently, four proteins—topoisomerase II alpha (TOP2A), minichromosome maintenance complex component 2 (MCM2), valosin-containing protein (VCP), and cyclin-dependent kinase inhibitor 2A (p16INK4a)—were quantified in the resulting lysates using enzyme-linked immunosorbent assays, as well as in cervical tumors and squamous intraepithelial lesions (SILs) using immunohistochemistry for further validation. Results: Acetone precipitation allowed for efficient cell isolation, and radioimmunoprecipitation assay buffer yielded the highest protein recovery. VCP and p16INK4a were overexpressed across all cancer cell lines compared to primary cells. All four biomarkers were overexpressed in high-grade SIL (HSIL) swab specimens and tumor samples, including CC subtypes, G1–G3 tumor grades, and HSILs. Lastly, we showed that the proteins could accurately classify swabs and tissue specimens into clinically relevant groups. Conclusions: The quantitative analysis of these biomarkers, along with the subsequent sensitive and specific clinical classification, highlights their potential application in SIL early detection and CC prevention, particularly in LMICs. Full article
(This article belongs to the Special Issue Biomarkers for Gynecological Cancers)
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10 pages, 1308 KB  
Article
Evaluation of Tumor Budding and Poorly Defined Clusters as Histological Biomarkers in Squamous Cell Carcinomas of the Vulva
by Gilbert Georg Klamminger, Annick Bitterlich, Bashar Haj Hamoud, Erich-Franz Solomayer, Martin Ertz, Laura Schnöder, Bernd Holleczek, Walburgis Brenner, Annette Hasenburg, Mathias Wagner and Meletios P. Nigdelis
Cancers 2025, 17(10), 1718; https://doi.org/10.3390/cancers17101718 - 21 May 2025
Viewed by 780
Abstract
Background/Objectives: Several histopathological risk factors have been examined in vulvar cancer (VC) so far. However, the prognostic relevance of morphological biomarkers such as tumor budding (TB) and poorly defined clusters (PDCs) remains to be determined. Material and Methods: We histologically analyzed the [...] Read more.
Background/Objectives: Several histopathological risk factors have been examined in vulvar cancer (VC) so far. However, the prognostic relevance of morphological biomarkers such as tumor budding (TB) and poorly defined clusters (PDCs) remains to be determined. Material and Methods: We histologically analyzed the formation of peritumoral and intratumoral TB and PDCs in a cohort of 157 patients with VC. We assessed their association with clinico-pathological features and evaluated their prognostic impact in terms of the risk of local recurrence and occurrence of metastasis (Fisher’s exact test) as well as overall survival (Log-rank test). Results: We determined a distinct prognostic relevance of peritumoral TB with regard to occurrence of metastasis (Fisher’s exact test; p = 0.0415) as well as a significant reduced risk of local recurrence in the group with absent intratumoral TB (Fisher’s exact test; p = 0.0004). Furthermore, we showed that patients without peritumoral budding formation had a significant superior prognosis in terms of overall survival (p = 0.0366, x2 = 4.370). Conclusions: This study shows that several new histomorphological biomarkers may serve useful in predicting the clinical course of patients with VC, identifying patients at a lower risk of developing metastases/local recurrence as well as improved overall survival. Full article
(This article belongs to the Special Issue Biomarkers for Gynecological Cancers)
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12 pages, 4516 KB  
Article
Expression Characteristics of 3-Marker Panel (PAX2, PTEN, and β-Catenin) in Benign Interval and Secretory Endometrium and Secretory Endometrial Precancer
by Shuang Niu, Kyle Molberg, Jackson Chen, Lesley Conrad, Elena Lucas and Hao Chen
Cancers 2025, 17(9), 1495; https://doi.org/10.3390/cancers17091495 - 29 Apr 2025
Viewed by 1087
Abstract
Background/Objectives: Despite advancements in treatment options, endometrial cancer remains a significant threat to women, underscoring the importance of early detection of atypical hyperplasia/endometrioid intraepithelial neoplasia (AH/EIN), the widely accepted histological precursor to endometrial carcinoma. Even with refinements in morphological criteria for the [...] Read more.
Background/Objectives: Despite advancements in treatment options, endometrial cancer remains a significant threat to women, underscoring the importance of early detection of atypical hyperplasia/endometrioid intraepithelial neoplasia (AH/EIN), the widely accepted histological precursor to endometrial carcinoma. Even with refinements in morphological criteria for the diagnosis of AH/EIN, accurate diagnosis remains challenging for pathologists, particularly in cases with secretory changes. Morphological alterations resulting from secretory-related changes further complicate the application of diagnostic criteria, emphasizing the need for reliable biomarkers. Previous studies have demonstrated that a panel consisting of three immunohistochemical markers, PAX2, PTEN, and β-catenin, can be effectively utilized for the identification of AH/EIN in various non-secretory scenarios. Methods: In this study, a total of 69 AH/EIN within secretory endometrium were analyzed using this panel. Benign interval endometrium (n = 57) and secretory phase endometrium (n = 71) were also analyzed for PAX2, PTEN, and β-catenin expression as controls. Results: The 3-marker panel successfully identified 93% of secretory AH/EIN, comparable to its performance in identifying non-secretory bona fide AH/EIN (92.8%) and AH/EIN within endometrial polyps (92.4%). Of note, β-catenin expression in benign interval endometrium commonly displayed weak nuclear staining (67%), which could pose a diagnostic pitfall when using the 3-marker panel. Overall, the results demonstrate the diagnostic utility of the 3-marker panel in clinical practice in identifying AH/EIN within challenging secretory phase endometrium cases. Conclusions: Combined with previous research highlighting its effectiveness in other challenging contexts—such as AH/EIN in polyps, small-sized EIN (subdiagnostic EIN), and progestin-treated EIN—this study provides strong evidence supporting the panel’s broad applicability in resolving major diagnostic challenges related to the precise diagnosis of AH/EIN. Full article
(This article belongs to the Special Issue Biomarkers for Gynecological Cancers)
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Review

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19 pages, 1521 KB  
Review
Genetic Polymorphisms in Base Excision Repair (BER) and Nucleotide Excision Repair (NER) Pathways as Potential Biomarkers for Gynecological Cancers: A Comprehensive Literature Review
by Magdalena Szatkowska and Julita Zdrada-Nowak
Cancers 2025, 17(13), 2170; https://doi.org/10.3390/cancers17132170 - 27 Jun 2025
Viewed by 787
Abstract
In 2022, approximately 1.4 million new cases of gynecological cancers were diagnosed worldwide, accounting for a significant share of all female cancer cases, according to the World Cancer Research Fund. DNA repair mechanisms play a critical role in maintaining genomic integrity, and their [...] Read more.
In 2022, approximately 1.4 million new cases of gynecological cancers were diagnosed worldwide, accounting for a significant share of all female cancer cases, according to the World Cancer Research Fund. DNA repair mechanisms play a critical role in maintaining genomic integrity, and their dysfunction can lead to the accumulation of DNA damage, thereby increasing the risk of gynecological cancer development. Single nucleotide polymorphisms (SNPs) in genes involved in DNA repair pathways, such as Base Excision Repair (BER) and Nucleotide Excision Repair (NER), represent important biomarkers for gynecological malignancies. These polymorphisms can affect the efficiency of DNA repair processes, thereby influencing individual susceptibility to cancer. SNPs within the BER and NER pathways exhibit high specificity, enabling accurate detection and monitoring of gynecological cancers, as well as the identification of individuals at elevated risk. This facilitates early risk assessment and supports the implementation of preventive strategies. Compared to traditional biomarkers such as CA-125, SNPs allow for the detection of genomic alterations at an earlier, preclinical stage. Furthermore, the characterization of SNPs in BER and NER pathways may serve as a foundation for personalized therapy, allowing treatment to be tailored to the patient’s specific genetic mutations. To identify polymorphisms in the BER and NER pathways associated with gynecological cancer risk, a systematic analysis of 128 scientific articles was conducted, which may serve as a solid foundation for advancing precision oncology and improving the early diagnosis of gynecological cancers. Full article
(This article belongs to the Special Issue Biomarkers for Gynecological Cancers)
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Other

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18 pages, 2620 KB  
Systematic Review
Circulating microRNAs as Diagnostic Biomarkers to Detect Specific Stages of Ovarian Cancer: A Comprehensive Meta-Analysis
by Apriliana Ellya Ratna Kartikasari, Paul Michel-Lara, Hayden Exton, Kaan Tekin-Sari, Ebtesam Motlaq M. Alnefai, Arnan Mitchell, Cesar Sanchez-Huertas and Magdalena Plebanski
Cancers 2024, 16(24), 4190; https://doi.org/10.3390/cancers16244190 - 16 Dec 2024
Cited by 3 | Viewed by 2773
Abstract
Ovarian cancer (OC) is one of the most common gynecological cancers [...] Full article
(This article belongs to the Special Issue Biomarkers for Gynecological Cancers)
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