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Risk Prediction for Gynecological Cancer

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A special issue of Journal of Clinical Medicine (ISSN 2077-0383). This special issue belongs to the section "Obstetrics & Gynecology".

Deadline for manuscript submissions: closed (20 March 2026) | Viewed by 20973

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Prof. Dr. Federico Ferrari

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Department of Clinical and Experimental Sciences, University of Brescia, 25136 Brescia, Italy
Interests: gynecological cancers; primary peritoneal cancer; tubo-ovarian cancer; uterine and cervical cancer; vaginal and vulvar cancer
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Special Issue Information

Dear Colleagues,

Risk prediction for gynaecological cancer is crucial for the early prevention, timely diagnosis, and effective treatment of cervical, endometrial and tubo-ovarian cancers. These cancers pose significant health threats to women worldwide, and understanding risk factors and tools to achieve early diagnosis can help researchers to reduce their incidence and mortality rates. Cervical cancer risk prediction relies heavily on screening and vaccination. Human papillomavirus (HPV) is the primary cause, so regular pap smears and HPV testing are essential, and screening programs and new assessments should be incorporated in clinical practice worldwide. Endometrial cancer, primarily affecting postmenopausal women, is often linked to obesity, diabetes, hypertension, and hormonal imbalances. Predictive models focus on these factors, as well as genetic predispositions and lifestyle choices. Early detection through symptom awareness and ultrasound assessment, both combined with timely endometrial biopsies, is crucial, and in this context, a hysteroscopic approach is of utmost importance. Ovarian cancer presents the greatest challenge due to its often-late diagnosis and subtle early symptoms. Risk factors include age, a family history of ovarian or breast cancer, and genetic mutations like BRCA1 and BRCA2. Risk prediction involves genetic testing, particularly for those with a family history, and regular pelvic exams. Prophylactic surgeries (such as salpingo-oophorectomy) are considered for high-risk individuals. Research into biomarkers and advanced imaging techniques continues to evolve, aiming to improve early detection rates. Integrating these risk prediction strategies into routine healthcare can significantly enhance the prevention and early diagnosis of gynaecological cancers. This Special Issue will highlight recent advances in the context of diagnosis, treatment, and the prediction of prognosis for these malignancies.

Dr. Federico Ferrari
Guest Editor

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Keywords

cervical cancer
endometrial cancer
tubo-ovarian cancer
diagnosis
treatment
prognosis

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Published Papers (11 papers)

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15 pages, 1413 KB

Open AccessArticle

The Impact of Osteopontin and Galectin-7 on the Preoperative Diagnosis of Ovarian Tumors: A Case–Control Study

by Foteini Chouliara, Aikaterini Sidera, Ioannis Tsakiridis, Areti Kourti, Georgios Michos, Evangelos Papanikolaou, Themistoklis Dagklis, Apostolos Mamopoulos, Kali Makedou and Ioannis Kalogiannidis

J. Clin. Med. 2026, 15(6), 2178; https://doi.org/10.3390/jcm15062178 - 12 Mar 2026

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Abstract

Background/Objectives: Accurate preoperative discrimination between women with ovarian pathology and healthy controls, as well as between benign and malignant ovarian tumors, remains challenging. This study aimed to evaluate the usefulness of osteopontin and galectin-7 on the diagnosis of ovarian tumors. Methods: This prospective single-center case–control study was conducted at the Third Department of Obstetrics & Gynecology, School of Medicine, Faculty of Health Sciences, Aristotle University of Thessaloniki, Greece, between 2018 and 2024. Preoperative serum levels of osteopontin, galectin-7, and established tumor markers (CA-125, CA19-9, CA15-3, CEA, AFP) were analyzed. Biomarker distributions were compared using non-parametric tests. Associations with clinical variables were explored using correlation analyses. Logistic regression and receiver operating characteristic (ROC) curve analyses were performed to assess diagnostic performance. Results: The study population included 116 women: 52 healthy controls, 45 patients with benign ovarian tumors, and 19 patients with malignant ovarian tumors. Serum osteopontin and galectin-7 levels did not differ significantly between control and study group (p = 0.562 and p = 0.138, respectively), nor between benign and malignant tumors (p = 0.784 and p = 0.140, respectively). Osteopontin showed no discriminatory ability (AUC = 0.47), while galectin-7 demonstrated weak discrimination (AUC = 0.63). A combined model yielded modest improvement (AUC = 0.69), remaining below clinically meaningful thresholds. CA-125 was the only biomarker significantly associated with malignancy (OR = 1.03, p = 0.038). Galectin-7 levels were higher in premenopausal women and inversely correlated with age, suggesting demographic rather than malignant influence. Conclusions: Despite strong biological relevance, circulating osteopontin and galectin-7 did not provide meaningful diagnostic discrimination between women with ovarian pathology and healthy controls or between benign and malignant ovarian tumors. CA-125 remained the most informative serum marker in this setting. Future efforts should focus on multi-marker strategies integrated with imaging and clinical assessment. Full article

(This article belongs to the Special Issue Risk Prediction for Gynecological Cancer)

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10 pages, 3840 KB

Open AccessArticle

The Pretreatment Glucose-to-Lymphocyte Ratio as an Independent Prognostic Biomarker in Ovarian Cancer

by Ece Baydar, Yasemin Bakkal Temi, İlkay Çıtakkul, Devrim Çabuk, Umut Kefeli and Kazım Uygun

J. Clin. Med. 2026, 15(5), 1999; https://doi.org/10.3390/jcm15051999 - 5 Mar 2026

Viewed by 264

Abstract

Background/Objectives: This study aimed to assess the prognostic significance of the glucose-lymphocyte ratio (GLR) prior to therapy in individuals with epithelial ovarian cancer. Methods: This retrospective cohort study included 326 patients with epithelial ovarian cancer who were treated from 2011 to 2025. The GLR was computed utilizing pre-treatment fasting blood glucose levels and absolute lymphocyte numbers. The optimal GLR cutoff value was established by receiver operating characteristic (ROC) analysis. Overall survival (OS) and disease-free survival (DFS) were assessed utilizing Kaplan–Meier analysis and Cox regression models. Additional sensitivity analyses were performed excluding patients with diabetes mellitus and by testing the interaction between GLR and neoadjuvant chemotherapy. Results: The optimal GLR cutoff value was 3.42. Patients were classified into low-GLR (≤3.42; n = 190) and high-GLR (>3.42; n = 136) groups. Patients with high GLR levels (>3.42) had a median OS of 58 months, which was significantly shorter than the 151 months for patients with low GLR levels (≤3.42) (p < 0.001). They also had a median DFS of 17 months, which was significantly shorter than the 49 months for patients with low GLR levels (p < 0.001). Multivariable Cox regression analysis showed that a higher GLR is an independent prognostic factor related to shorter overall survival (HR: 1.561; 95% CI: 1.078–2.261; p = 0.018). Findings remained consistent after excluding patients with diabetes mellitus. The group with a high GLR had a greater rate of disease progression (55.1% vs. 29.5%, p < 0.001). Conclusions: The pre-treatment GLR may serve as a simple and readily available prognostic biomarker in epithelial ovarian cancer, potentially supporting basic risk stratification; however, external validation is required. Full article

(This article belongs to the Special Issue Risk Prediction for Gynecological Cancer)

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10 pages, 816 KB

Open AccessArticle

Insights from the Pre-Molecular Era in Advanced Endometrial Cancer: Benchmarking Prognostic Indicators in High-Risk Tumours

by Jacopo Conforti, Sabina Ioana Nistor, Negin Sadeghi, Andreas Zouridis, Ammara Kashif, Ahmed Darwish, Sarah Louise Smyth, Alisha Sattar, Susan Addley, Christina Pappa, Stephen Damato, Mostafa Abdalla, Sean Kehoe, Andrea Giannini, Federico Ferrari and Hooman Soleymani Majd

J. Clin. Med. 2025, 14(24), 8726; https://doi.org/10.3390/jcm14248726 - 9 Dec 2025

Viewed by 450

Abstract

Background/Objectives: Although the binarism between type I and II endometrial cancer was dismissed and substituted with molecular classification, histopathological features remain of paramount importance. Hence, analysing survival outcomes according to histological type, our aim is to clarify whether the morphological features of the tumour retain prognostic relevance in the context of advanced disease. Methods: This is a retrospective analysis led within the Thames Valley Cancer Alliance Network. Results: We include 148 FIGO 2009 stage III–IV patients affected by endometrioid endometrial cancer (EEC) G1, G2, and G3, carcinosarcoma (CS), serous carcinoma (SC), and clear cell carcinoma (CCC) of the uterus. Five year overall survival (OS) is distinct among the histological groups (p-value < 0.001), being 73.3% for G2 endometrioid, 49.2% for G3 endometrioid, 8.3% for CS, and 28.4% for SC. The divergence was marked also for 5 year progression-free survival (PFS) (p-value < 0.001) as follows: for G2 endometrioid, was 76.4%; for G3 endometrioid, 52.7%; and for carcinosarcoma, 5.9%. PFS after 18 months for serous carcinoma was 5.7%. The multivariate analysis found G3 endometrioid (HR 2.91, 95% CI 1.20–7.11, p-value 0.018), carcinosarcoma (HR 12.15, 95% CI 5.07–29.11, p-value < 0.001), and serous carcinoma (HR 4.84, 95% CI 2.16–10.83, p-value < 0.001) as independent predictors of poor survival, as well as cervical invasion (HR 1.83, 95% CI 1.10–3.05, p-value 0.020) as the only histopathological feature confirmed. Regarding progression-free only carcinosarcoma (HR 14.91, 95% CI 5.28–41.11) and serous carcinoma (HR 17.68, 95% CI 6.41–48.75) were associated with an increased risk of recurrence. Conclusions: Our findings testify that, beyond the disease stage, histological subtype remains a major determinant of survival outcome. Cervical involvement is associated with a more aggressive disease, possibly correlated to death beyond relapse. Prospective trials involving advanced stage endometrial cancer, stratified by histological subtype and integrated with the molecular classification, are required. Full article

(This article belongs to the Special Issue Risk Prediction for Gynecological Cancer)

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13 pages, 12851 KB

Open AccessArticle

A Retrospective Analysis of Atypical Cervical Cytology: Correlating Bethesda Categories with HPV Genotyping and Histological Follow-Up

by Aleksandra Asaturova, Darya Dobrovolskaya, Andrew Zaretsky, Alina Badlaeva, Anna Tregubova, Aleksandra Rogozhina and Gennady Sukhikh

J. Clin. Med. 2025, 14(23), 8554; https://doi.org/10.3390/jcm14238554 - 2 Dec 2025

Viewed by 857

Abstract

Background/Objectives: Atypical cytological findings in cervical screening, such as ASC-US, ASC-H, and AGC, present a clinical challenge due to their variable risk of underlying high-grade lesions. The precise stratification of this risk is crucial for effective patient management. This study aimed to correlate Bethesda cytology categories with HPV genotyping, including viral load, and histological follow-up to improve risk prediction for cervical intraepithelial neoplasia grade 2 or worse (CIN2+). Materials and Methods: In this retrospective single-center study, we analyzed 407 patients with cytological reports of ASC-US, ASC-H, or AGC. All patients underwent HPV DNA testing with genotyping for 21 types, with viral load quantification for HPV16/18, and subsequent histological verification. Statistical analyses included non-parametric tests, correlation analysis, and multivariate logistic regression to identify independent predictors of CIN2+. Results: The prevalence of CIN2+ differed significantly among the cytological categories: 23.2% in ASC-US, 47.3% in ASC-H, and 19.5% in AGC. ASC-H and a high HPV16 viral load were identified as independent predictors of CIN2+ in the multivariate analysis. An ASC-H result increased the probability of CIN2+ by 2.5 times (aOR = 2.51; 95% CI: 1.28–4.94). For each 1 log10 increase in HPV16 viral load, the risk of CIN2+ increased by 30% (aOR = 1.30; 95% CI: 1.16–1.46). Stratification of ASC-US cases by HPV16 status revealed a dramatically higher positive predictive value (PPV) for CIN2+ in HPV16-positive patients (66%) compared to HPV16-negative patients (12.6%). The AGC category showed the strongest association with glandular pathology, including adenocarcinoma in situ. Conclusions: The combination of cytological findings and HPV16 viral load provides a powerful model for risk stratification. An ASC-H result is a strong independent risk marker, while the clinical significance of ASC-US is fundamentally determined by HPV16 status. These findings advocate for a risk-based management algorithm that integrates liquid-based cytology with extended HPV genotyping and viral load assessments to optimize patient triage and follow-up. Full article

(This article belongs to the Special Issue Risk Prediction for Gynecological Cancer)

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12 pages, 735 KB

Open AccessArticle

Clinical Utility of Pan-Immune Inflammation Value (PIV) in Predicting Prognosis of Endometrial Cancer

by Nurhan Onal Kalkan, Zuhat Urakcı, Berrak Mermit Erçek, Erkan Bilen, Hayati Arvas and Mehmet Hadi Akkuş

J. Clin. Med. 2025, 14(21), 7885; https://doi.org/10.3390/jcm14217885 - 6 Nov 2025

Cited by 2 | Viewed by 1175

Abstract

Background: Endometrial cancer (EC) is the most common gynecological malignancy in developed countries. While early-stage disease has favorable outcomes, advanced or recurrent EC remains associated with poor prognosis. Novel prognostic markers are needed to refine risk stratification. Systemic inflammation-based indices such as Pan-Immune Inflammation Value (PIV), Systemic Inflammation Response Index (SIRI), and Systemic Immune Inflammation Index (SII) have shown prognostic potential in solid tumors. Methods: We retrospectively evaluated 78 patients with endometrioid EC who had undergone hysterectomy with adnexectomy and lymphadenectomy. Demographic, clinicopathological, and laboratory data were extracted from electronic medical records. PIV, SII, and SIRI were calculated from the preoperative complete blood counts. Survival was assessed using Kaplan–Meier analysis, while prognostic factors were determined using univariate and multivariate Cox regression analyses. Results: The median age was 59 years, and 64.1% of the patients presented with early-stage disease. A high PIV (≥802) was significantly associated with a shorter overall survival (64 vs. 111 months, p < 0.001). PIV demonstrated the highest discriminatory accuracy (AUC = 0.776), followed by the SII (0.747) and SIRI (0.718). Univariate analysis identified that age, grade, LVSI, PNI, stage, distant metastasis, and high PIV, SII, SIRI, and NLR were predictors of poor survival. Multivariate analysis confirmed grade, distant metastasis and SIRI ≥ 1.5 as independent prognostic factors. Conclusions: Inflammation-based indices, particularly PIV and SIRI, correlated with survival outcomes in patients with EC. The SIRI retained an independent prognostic value, whereas PIV showed a strong discriminatory capacity. Incorporating these indices into established risk models may improve prognostic precision and support individualized management. Full article

(This article belongs to the Special Issue Risk Prediction for Gynecological Cancer)

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14 pages, 1612 KB

Open AccessArticle

A Competing-Risks Approach to the Progression, Regression and Persistence of High-Grade Cervical Dysplasia in Patients over 30 Years Old—A Prospective Study

by Iulian-Valentin Munteanu, Demetra Socolov, Razvan Socolov, Ana-Maria Adam, Gigi Adam, Ingrid-Andrada Vasilache, Petronela Vicoveanu, Valeriu Harabor, Anamaria Harabor and Alina-Mihaela Calin

J. Clin. Med. 2025, 14(17), 6303; https://doi.org/10.3390/jcm14176303 - 6 Sep 2025

Viewed by 1342

Abstract

Background/Objectives: In Romania, where cervical cancer incidence remains among the highest in the European Union, a risk-based management strategy could support more precise allocation of limited resources. The aim of this study was to test the prognostic utility of immediate pre-treatment and post-treatment risk predictions, derived from the American Society of Colposcopy and Cervical Pathology (ASCCP) risk-based management guidelines for the prediction of progression, regression or persistence of high-grade cervical dysplasia. Methods: In this prospective cohort study, we included 223 patients aged over 30 years who underwent self-referred or targeted screening with or without histologically confirmed cervical intraepithelial neoplasia (CIN) of any grade. We employed Fine and Gray’s subdistribution hazard model that evaluated the cumulative incidence function for each specific outcome, treating other outcomes as competing events. These outcomes were further stratified depending on the type of high-grade dysplasia. Results: The immediate post-treatment risk was significantly associated with subsequent progression of cervical dysplasia. For a cut-off of 60%, the immediate post-treatment risk was able to significantly predict the progression of both CIN2+ and CIN3+. On the other hand, the immediate pre-treatment risk > 60% was significantly associated with progression of CIN3+, but not of CIN2+. Also, the immediate pre-treatment risk was significantly associated with regression, but this observation did not persist at the >60% threshold. Both pre- and post-treatment risk > 60% were strongly associated with persistence across histologic subgroups. Conclusions: The ASCCP-derived immediate risk estimates, especially post-treatment risk > 60%, proved effective in predicting progression and persistence of high-grade cervical dysplasia. Full article

(This article belongs to the Special Issue Risk Prediction for Gynecological Cancer)

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15 pages, 2067 KB

Open AccessArticle

EphA5 Expression Predicts Better Survival Despite an Association with Proliferative Activity in Endometrial Cancer

by Shy-Yau Ang, Ching-Yu Shih, Hua Ho, Yen-Lin Chen, Jen-Tang Sun and Chiao-Yin Cheng

J. Clin. Med. 2025, 14(15), 5360; https://doi.org/10.3390/jcm14155360 - 29 Jul 2025

Viewed by 863

Abstract

Background/Objectives: Eph receptor A5 (EphA5) is a receptor tyrosine kinase that is implicated in multiple malignancies, although its role in endometrial cancer (EC) remains unclear. The aim of this study was to investigate the clinicopathological significance of EphA5 expression in EC and explore its association with proliferative and metabolic markers. Methods: We retrospectively analyzed 75 EC tissue samples from treatment-naïve patients by using immunohistochemistry and H-score quantification. Associations between EphA5 expression and clinicopathological parameters were assessed through logistic regression analysis. Kaplan–Meier analysis was used to evaluate survival outcomes. Correlation analysis, stratified according to cancer stage, was used to explore biomarker interactions. Results: High EphA5 expression levels were significantly associated with elevated Ki-67 expression (adjusted odds ratio (aOR): 1.08 per 1-point H-score increase, p = 0.024) and decreased pAMPK expression (aOR: 0.89 per 1-point H-score increase, p = 0.024), indicating its involvement in proliferative and metabolic pathways. Paradoxically, patients with high EphA5 levels had significantly better overall survival probabilities (H-score > 105, log-rank p = 0.007). Stage-specific analyses suggested that EphA5 levels correlated with proliferation in early-stage disease and epithelial–mesenchymal transition in advanced stages. Conclusions: EphA5 may act as a context-dependent biomarker in EC. Despite its positive correlation with proliferation and negative association with metabolic stress signaling, high EphA5 expression levels were predictive of a favorable prognosis. Full article

(This article belongs to the Special Issue Risk Prediction for Gynecological Cancer)

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Review

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13 pages, 1231 KB

Open AccessReview

Cervical Dysplasia and Cervical Cancer During Pregnancy: From Pathogenesis to Clinical Management

by Aleksandra Piórecka, Weronika Marcinkowska, Filip Gągorowski, Magdalena Gąsior, Katarzyna Kazimierczuk, Agnieszka Żalińska, Przemysław Oszukowski and Agnieszka Pięta-Dolińska

J. Clin. Med. 2025, 14(11), 3784; https://doi.org/10.3390/jcm14113784 - 28 May 2025

Cited by 3 | Viewed by 5172

Abstract

The incidence of malignancies diagnosed during pregnancy is estimated at 1 in 1000 pregnancies, with cervical cancer being the most common gynecological malignancy in this population. The increasing maternal age and widespread use of prenatal screening contribute to the rising detection rates. Early symptoms of cervical cancer, such as vaginal bleeding or discharge, often mimic normal pregnancy changes, leading to potential delays in diagnosis. Cervical dysplasia, a known precursor of cervical cancer, is closely associated with high-risk HPV infection, which affects approximately 25% of women of reproductive age. Screening using cytology and HPV testing is considered safe and effective during pregnancy in early detection. Colposcopy remains the gold standard in further diagnostics, with targeted biopsy indicated in selected cases. In cases of high-grade lesions (CIN II/III), conservative management is often preferred, as more than 60% of lesions regress postpartum. Invasive cervical cancer diagnosed during pregnancy is rare, with an estimated incidence of 1.4–4.6 per 100,000 pregnancies. Management decisions depend on gestational age, cancer stage, and the patient’s reproductive preference. Chemotherapy can be administered after the first trimester with acceptable maternal and fetal safety profiles. This review presents current evidence on screening, diagnostic pathways, and treatment strategies. It emphasizes the importance of individualized care, multidisciplinary collaboration, and shared decision-making to optimize outcomes for both mother and fetus. Full article

(This article belongs to the Special Issue Risk Prediction for Gynecological Cancer)

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14 pages, 613 KB

Open AccessReview

Advancements in Minimally Invasive Techniques and Biomarkers for the Early Detection of Endometrial Cancer: A Comprehensive Review of Novel Diagnostic Approaches and Clinical Implications

by Aleksandra Asaturova, Andrew Zaretsky, Aleksandra Rogozhina, Anna Tregubova and Alina Badlaeva

J. Clin. Med. 2024, 13(24), 7538; https://doi.org/10.3390/jcm13247538 - 11 Dec 2024

Cited by 6 | Viewed by 5800

Abstract

This review evaluates the advances in the early detection and diagnosis of endometrial cancer (EC), emphasizing the growing importance of minimally invasive techniques and novel biomarkers. Current diagnostic protocols for EC rely heavily on invasive procedures such as transvaginal ultrasound (TVU), hysteroscopy, and endometrial biopsy, which, although effective, can be overly burdensome for patients and inefficient for asymptomatic or low-risk populations. As there is no consensus on EC screening in high-risk or general populations, recent studies have explored alternative methods using biofluids and genomic biomarkers to improve sensitivity and specificity and facilitate access for patients. This review summarizes findings on DNA methylation markers, circulating tumor-derived nucleic acids, and the potential of liquid biopsy approaches for the early detection of EC. These innovations may not only streamline screening but also reduce the need for invasive procedures. This review highlights the potential of these biomarkers to be integrated seamlessly into the existing cervical cancer screening programs, which could transform screening methods for endometrial cancer and support the development of personalized, less invasive diagnostic procedures. Full article

(This article belongs to the Special Issue Risk Prediction for Gynecological Cancer)

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Other

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17 pages, 3628 KB

Open AccessSystematic Review

Role of L1 HPV Protein Expression in the Cytological Diagnosis of Precancerous Cervical Lesions

by Darya Dobrovolskaya, Aleksandra Asaturova, Alina Badlaeva, Anna Tregubova, Olga Mogirevskaya, Zaira Dzharullaeva, Yulia Davydova, Andrea Palicelli, Guldana Bayramova and Gennady Sukhikh

J. Clin. Med. 2025, 14(10), 3376; https://doi.org/10.3390/jcm14103376 - 12 May 2025

Cited by 2 | Viewed by 1699

Abstract

Human papillomavirus (HPV) infection is a major risk factor for cervical cancer, demanding improved diagnostic strategies to distinguish between transient infections and those requiring intervention. Background: This systematic review and meta-analysis evaluated the diagnostic accuracy of HPV L1 immunocytochemistry (ICC) in detecting high-grade cervical intraepithelial neoplasia (CIN2+). Methods: We systematically analyzed data from 15 studies (PROSPERO 2022 CRD42022375916) comprising 3804 cervical smears with varying cytological findings (NILM to ≥ASC-US). Results: The pooled sensitivity for detecting CIN2+ was 80.7% (95% CI: 76.2–84.4%); however, substantial heterogeneity was present (I² = 65.97%, p < 0.001). Similarly, the pooled specificity was 56.9% (95% CI: 49.6–64%), with even higher heterogeneity (I² = 90.46%, p < 0.001). This considerable heterogeneity, which may be attributable to methodological variations or regional differences in HPV prevalence and genotyping, limits the generalizability of these findings. Furthermore, the moderate specificity suggests a high rate of false positives, limiting the clinical utility of HPV L1 ICC as a standalone diagnostic test. Conclusions: In conclusion, although HPV L1 ICC exhibits acceptable sensitivity for detecting CIN2+, its limitations, including low specificity and substantial heterogeneity, necessitate its use as an adjunct to other established diagnostic methods, alongside further research to enhance its diagnostic performance, and necessitate its use as a supplementary test alongside established diagnostic methods, pending further research to refine its clinical utility. Full article

(This article belongs to the Special Issue Risk Prediction for Gynecological Cancer)

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16 pages, 2448 KB

Open AccessSystematic Review

Ki-67 as a Prognostic Marker in Squamous Cell Carcinomas of the Vulva: A Systematic Review

by Gilbert Georg Klamminger, Elke Eltze, Annick Bitterlich, Yaman Degirmenci, Annette Hasenburg, Mathias Wagner and Meletios P. Nigdelis

J. Clin. Med. 2025, 14(6), 2045; https://doi.org/10.3390/jcm14062045 - 17 Mar 2025

Viewed by 2149

Abstract

Background/Objectives: To evaluate the prognostic impact of immunohistochemical ki-67 staining analysis regarding lymph node involvement and survival data (overall/progression-free survival) in squamous cell carcinoma of the vulva. Methods: A systematic literature search of English and German articles was conducted (PubMed, Embase, Scopus, Web of Science) from 1980 to December 2023, including the search terms “vulvar Neoplasms”, “vulvar cancer”, “vulvar carcinoma”, “vulvar tumor”, ”vulvar tumour”, “vulvar malignancy”, “vulvar malignant”, “ki-67”, “MIB-1”, “MIB1”, “proliferative index”, “proliferative activity”, “mitotic index”, and “mitotic count”. Study quality was assessed using a two-step “mixed-criteria” approach; to synthesize study results, a narrative summary is provided. Results: In total, 13 studies were included in this systematic literature review. In general, two distinct methods of staining interpretation could be retrieved: A “pattern-based” method, as well as a cell count-based method. Ten of the included studies examined the relationship between ki-67 and lymph node involvement, nine studies included survival data as a parameter of interest; and only five studies defined both groin lymph node metastasis and survival data as outcome variables. While nine out of ten studies found no statistically significant association between ki-67 staining and lymph node metastasis, five out of nine studies determined an association between ki-67 status and overall survival, especially when employing a “pattern-based” method of staining interpretation. Conclusions: The prognostic value of ki-67 staining in terms of survival data has been reported ambivalently and should be subject to future studies. Furthermore, we did not find convincing evidence of an association between ki-67 and lymph node involvement. Full article

(This article belongs to the Special Issue Risk Prediction for Gynecological Cancer)

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