The Czech Republic is one of the countries with the highest incidence of endometrial cancer in the world. In June 2023, the Women's Cancer Committee of the International Federation of Gynaecology and Obstetrics (FIGO) introduced a new staging system for endometrial cancer, FIGO 2023, which replaced the 2009 version. The FIGO 2023 staging system differs significantly from the previous version by incorporating the result of molecular classification of the tumour and some histopathological parameters - histological type of tumour, tumour grade and presence of substantial lymphovascular invasion - into the definitions of stage I and stage II. For stage I and II tumours, specific separate stages are reserved when the molecular profile of POLEmut or TP53mut is detected. Stages III and IV have also been modified, but the result of the molecular classification of the tumour and other histopathological parameters do not influence the staging. However, the molecular classification result should be reported for all stages. These changes have further strengthened the role of the pathologist in staging. The changes, which are partly based on the recommendations of the three European professional societies ESGO/ESTRO/ESP for the diagnosis and treatment of endometrial cancer, better reflect the biological behaviour of the tumour and significantly refine the prognosis of the patient at a given stage. On the other hand, the FIGO 2023 staging system is quite complex and requires expensive tests, which may pose a problem for its routine use in a global context. The implementation of the FIGO 2023 endometrial cancer staging system in daily practice requires the full involvement of all stakeholders.

OBJECTIVE:To provide an overview of the most important histopathological characteristics and biomarkers of endometrial carcinoma that have clinical relevance for prognosis, prediction of treatment response, and decision-making regarding adjuvant therapy. METHODS AND RESULTS:Endometrial carcinoma represents the most common malignancy of the female reproductive tract in developed countries. Disease prognosis is determined not only by the anatomical extent, but also by a number of non-anatomical factors. The histological tumour type, presence of lymphovascular space invasion, and specific patterns of myometrial invasion (such as the MELF pattern) play major roles. Current molecular classification divides endometrial carcinomas into four groups (POLEmut, MMRd, NSMP, and TP53mut), which differ in prognosis as well as in therapeutic response. Additional clinically applicable biomarkers include oestrogen and progesterone receptors, L1CAM, HER2, CA125, and HE4. Emerging research focuses on novel biomarkers such as TROP2, circulating tumour DNA (ctDNA), circular RNA (circRNA), tumour- -infiltrating lymphocytes (TILs), and folate receptor alpha (FRa). These markers enable more precise risk stratification and identification of patients suitable for targeted therapies. Integration of multiple biomarkers with clinicopathological parameters further enhances the accuracy of risk assessment and prediction of treatment response. CONCLUSION:Incorporating histopathological features and biomarkers into routine clinical practice allows for a more accurate estimation of prognosis and a more rational selection of adjuvant therapy. An increasing number of non-anatomical biomarkers are becoming an integral part of the decision-making algorithm in endometrial carcinoma management.

Background: Human papillomavirus (HPV) is the most common sexually transmitted viral infection worldwide. Moreover, the prevalence of HPV infection is twice as high in pregnant women as in non-pregnant individuals. The aim of this review was to examine adverse pregnancy outcomes associated with cervicovaginal or placental HPV infection confirmed by a sensitive molecular method. Methods: We conducted searches on major medical databases including PubMed, EMBASE, Global Health, and the Cochrane Library to identify all studies examining HPV infection during pregnancy. Additionally, other online sources were consulted for relevant studies. Thirty-four records out of the initial 1868 identified were included in this review for thematic synthesis. The PRISMA-ScR guidelines were followed. Results: This scoping review included a total of 28 original observational studies, 1 systematic review, and 5 meta-analyses. Active HPV infection appears to significantly increase the risk of preterm premature rupture of membranes and preterm birth, as indicated by findings from published meta-analyses and systematic reviews. Determining the association of HPV infection with certain adverse pregnancy outcomes is challenging due to their frequency (such as miscarriage) or rarity (such as intrauterine fetal death). For conditions like preeclampsia and intrauterine fetal growth restriction, the limited number of heterogeneous studies precludes definitive conclusions. Moreover, the causes of these outcomes are typically multifactorial. The presence of HPV in trophoblasts and placental tissue is considered crucial for potential adverse pregnancy outcomes. There appears to be a strong correlation between cervicovaginal or urinary HPV infections and placental HPV infections in pregnant women. Conclusions: Persistent HPV infection seems to elevate the risk of preterm premature rupture of membranes and preterm birth. However, the currently available observational evidence does not allow for definitive conclusions regarding causality, and the reported findings should be interpreted as associations rather than proof of a causal relationship. The changes in frequency of certain perinatal complications in populations of women with high HPV vaccination rates may shed more light on this connection.

Background: Ectopic pregnancy (EP) remains a significant cause of maternal morbidity and mortality, with diverse clinical presentations and substantial variability in treatment strategies. Objectives: To assess current EP management approaches across gynecological inpatient departments of all sizes in the Czech Republic. Design: A nationwide cross-sectional observational questionnaire study. Methods: A survey was conducted in January 2025. All 92 registered inpatient gynecological wards in the Czech Republic were invited to participate in an anonymous online questionnaire on EP diagnosis and treatment. A total of 89 departments (96.7%) responded. Facilities were grouped into four categories based on annual hysterectomy volume. Statistical analyses included chi-squared and Fisher’s exact tests with adjustments for multiple comparisons. Results: Methotrexate (MTX) was available in 82.8% of high-volume centers, compared with 48.3% of smaller facilities ( p = 0.002). Despite this, 46.1% of institutions reported never using MTX. The use of MTX for all types of EP was significantly more common in larger centers (72.4% versus 45.0%, p = 0.023), although its use for tubal EP remained generally low (18.0%) with no significant difference by center size. Surgical treatment of tubal EP was consistently preferred by 36.0% of facilities, and 38.2% of surgeons occasionally performed salpingotomy. Laparoscopy was the dominant approach for interstitial pregnancies (86.5%), with universal adoption in high-volume centers ( p = 0.007). Suction and curettage were most commonly used for cesarean scar (47.2%) and cervical (60.7%) pregnancies, although treatment strategies varied considerably. Observational management was preferred in pregnancy of unknown location with declining human chorionic gonadotropin (hCG) levels (83.2%), while diagnostic laparoscopy was favored when hCG levels plateaued or rose (57.3%). Conclusion: EP management, even within a country with a homogeneous healthcare system, may demonstrate considerable heterogeneity, strongly influenced by institutional size. These findings highlight the need for national guidelines to ensure standardized and evidence-based care.

PURPOSE:Tumor Treating Fields (TTFields) are electric fields that disrupt processes critical for cancer cell viability and tumor progression. The pivotal, phase 3 ENGOT-ov50/GOG-3029/INNOVATE-3 study evaluated efficacy and safety of TTFields therapy with paclitaxel (PTX) vs PTX in patients with platinum-resistant ovarian cancer (PROC). PATIENTS AND METHODS:Adult patients with PROC with ≤ 5 total prior lines of therapy (LOT), including ≤ 2 prior LOT for platinum-resistant disease, and ECOG PS of 0-1 were randomized 1:1 to receive TTFields (200 kHz; ≥ 18 h/day) + PTX (80 mg/m2 weekly) or PTX. Primary endpoint was overall survival (OS). Exploratory post-hoc analyses assessed OS in pegylated liposomal doxorubicin (PLD)-naive patients. RESULTS:Between March 2019 and November 2021, 558 patients (ECOG PS 0, 60.2 %; median [range] age, 62 [22-91] years) were assigned TTFields+PTX (n = 280) or PTX (n = 278). 24.4 % had 4 + prior LOT. Median OS was 12.2 months with TTFields+PTX vs 11.9 months with PTX (HR, 1.01; 95 % CI, 0.83-1.24; p = 0.89). Grade ≥ 3 adverse events (AEs) were similar between treatment groups. Grade 1/2 device-related skin AEs occurred in 83.6 % of patients receiving TTFields therapy. In exploratory post-hoc analysis in PLD-naive patients, median OS was 16 months with TTFields+PTX (n = 113) vs 11.7 months with PTX (n = 88; nominal HR, 0.67; 95 % CI, 0.49-0.94; p = 0.03). CONCLUSIONS:No new safety signals were identified. TTFields+PTX did not significantly improve OS compared with PTX in the intent-to-treat population. An exploratory post-hoc analysis suggests a potentially favorable benefit-risk profile for TTFields therapy in PLD-naive patients.

This study aimed to evaluate the effectiveness of different tracers´ application techniques for sentinel lymph node (SLN) detection in women with endometrial cancer undergoing laparotomy. Additionally, potential risk factors for SLN detection failure were assessed. We retrospectively analyzed data from 248 endometrial cancer patients who underwent abdominal surgery with SLN mapping between January 2020 and March 2024. Statistical analyses were conducted using the Wilcoxon rank sum test for continuous variables and either Pearson’s chi-square test or Fisher’s exact test for categorical variables, with a significance level set at p < 0.05. Group I + S consisted of 147 women with intracervical and subserosal tracers´application and group I + I included 101 women with intracervical and intrafundal application. Successful detection of SLN on both sides was achieved in 39.9

OBJECTIVE:To map management of different types of ectopic pregnancies in the Czech Republic using a questionnaire-based study. METHODS:In 2023, a total of 95 obstetrics and gynecology departments across the Czech Republic were surveyed using an online questionnaire, which inquired about the management strategies for various types of ectopic pregnancies. The departments were categorized based on the number of hysterectomies performed annually. Differences in responses between large centers and other departments were statistically compared. RESULTS:A total of 45 departments of all sizes completed the questionnaire. Two-thirds of all departments always perform salpingectomy in cases of tubal pregnancy (78% of large, 58% of medium-sized, and 40% of small departments). Systemic methotrexate administration for the treatment of intact tubal pregnancy is used by one-fifth of departments (22% of large, 23% of medium-sized, and 0% of small departments). In cases of atypical ectopic pregnancy localization, methotrexate treatment is used by 33% of large, 42% of medium-sized, and 40% of small departments. A statistically significant difference was observed in the clearly preferred laparoscopic approach for surgical management of cesarean scar pregnancy in large centers compared to smaller departments (P = 0.036). No other statistically significant differences were observed between the departments in other parameters. CONCLUSION:In cases of intact tubal pregnancy, four-fifths of obstetric and gynecological departments perform laparoscopic salpingectomy, while only one-fifth utilize systemic methotrexate for treatment. On the other hand, methotrexate is used by one-third to two-fifths of departments of all sizes in cases of atypical ectopic pregnancy localization.

Concerning the dismal prognosis of chemoresistant patients with epithelial ovarian carcinoma (EOC), we aimed to follow up the findings of a previous whole-exome sequencing study using an orthogonal Sanger sequencing on the same patients and a separate set of 127 EOC patients (N = 177, all fresh frozen tumor samples). We focused on TP53 as a frequently mutated gene relevant for chemosensitivity, included KRAS as an additional therapeutically relevant target, complemented the study with transcript levels of both genes, and compared results with clinical parameters. All variants in TP53 and KRAS detected by exome sequencing were confirmed. KRAS mutated patients had significantly more frequent FIGO stages I or II (p = .002) and other than high-grade serous tumor subtypes (nonHGSCs) (p < .001), which was connected with lower KRAS transcript levels (p = .004). Patients with nonHGSC subtypes had less frequent TP53 mutations (p = .002). Carriers of TP53 variants disrupting the DNA binding loop had significantly longer platinum-free intervals than the rest (p = .037). Tumors bearing nonsense, frameshift, or splice site TP53 variants had a significantly lower TP53 transcript level, while those with missense variants had significantly higher levels than wild types (p < .001). The normalized intratumoral TP53 and KRAS transcript levels were correlated, and patients with co-mutated genes had poorer overall survival than others (p = .015). Protein levels of both genes significantly correlated with their respective transcripts (p = .028 and p = .001, respectively). Our study points to KRAS as a target for future therapy of nonHGSCs and reveals the prognostic value of TP53 variants in the DNA binding loop.

Patients with epithelial ovarian cancer (EOC) face high mortality due to late diagnosis, recurrence, metastasis, and drug resistance. The NOTCH signaling pathway plays a critical role in cancer progression. This study analyzed NOTCH pathway deregulation in EOC patients and its response to taxane treatment in vitro and in vivo. In tumor cells of EOC patients, a significant upregulation of NOTCH1/3/4 and JAG2 and a downregulation of the NOTCH2 gene were found. The observed high levels of NOTCH3 mRNA were also confirmed at the protein level. In contrast, we observed a significant association of low NOTCH4 expression with the presence of peritoneal metastasis and shortened platinum-free interval. In the resistant in vitro cell line model, significant upregulation of NOTCH signaling pathway, namely NOTCH3, was observed after treatment with experimental Stony Brook taxanes (SB-Ts), with high efficacy against paclitaxel-resistant ovarian tumor cells. The administration of SB-Ts also caused NOTCH3 upregulation in an effective combination regimen with paclitaxel in comparison to paclitaxel alone and untreated control in the in vivo cell-derived xenograft mouse model of resistant ovarian cancer. Knockdown of the NOTCH3 gene caused higher sensitivity of resistant cells to taxanes, suggesting that NOTCH3-specific inhibition may potentially bring therapeutic benefits in resistant ovarian carcinoma. Based on our results, we suggest the NOTCH3 gene as a potential target for preclinical studies on resistant ovarian tumors. The current study also highlights the NOTCH4 gene as a potential predictive biomarker of therapeutic response in ovarian cancer.

The International Federation of Gynaecology and Obstetrics (FIGO) introduced a new staging system for endometrial carcinoma FIGO 2023 in June 2023. The new staging system differs significantly from previous versions by incorporating other non-anatomical parameters (histological type of tumour, tumour grade and the presence of massive lymphovascular space involvement as well as the molecular classification of the tumour). The FIGO 2023 staging system enhances the accuracy of prognostic assessments for patients at a specific stage with better options for targeted treatment. Another objective was to synchronise staging as much as possible with the European oncogynaecological ESGO/ESTRO/ESP guidelines for the management of patients with endometrial carcinoma established in 2021. However, several changes are controversial. Routine molecular classification of endometrial carcinomas is not yet commonly available in most countries of the world. Another limitation of the FIGO 2023 staging system of endometrial cancer is the inclusion of variables whose definitions are still evolving, as well as variables that are subject to considerable interobserver variability in their assessment. Advantages, controversies, and limitations for clinical practice of the new FIGO 2023 endometrial cancer staging system are discussed.

Objective: The aim of this study was to determine how often changes the stage of the tumour in definitive histology against preoperative clinical stage in patient cohort with dia gnosed endometrial cancer. Methods: We evaluated prospectively a cohort of 166 patients with endometrial cancer. They all underwent abdominal hysterectomy, bilateral salpingo-oophorectomy, sentinel lymph node bio psy. Patients with high-risk tumours also pelvic lymfadenectomy. We collected data of preoperative dia gnostic bio psy and postoperative definitive histology. The data were statistically processed. Results: Detection of sentinel lymph node was successful in 71.1%, bilateral successful detection was in 40.6%. Discrepancy of tumour grade between preoperative bio psy and definitive histology was generally 31.4%. Upgrading of the tumour was in 22 (14.4%) cases, downgrading in 26 (17%) cases. Upgrade from low-risk to high-risk group of tumours was noticed in eight cases. Histopathological tumour type changed in 6.6%, 4.6% moved to histopathologic high-risk group. The tumour stage changed in definite histology in 57.3%, in 19.2% of cases moved from stage low/ intermediate-risk group to intermediate-high/ high-risk disease group. Conclusion: Correct assessment of preoperative clinical stage and histological grade of endometrial cancer is burdened with a high inaccuracy rate. A lot of cases is up-staged after surgical staging and moved to intermediate-high/ high-risk disease group. Results confirm the importance of oncogynaecologic centre II. evaluation of histopathology findings from dia gnostic bio psies made in referring hospitals. Sentinel lymph node bio psy should be performed even in clinically low/ intermediate-risk disease group.

Human papillomavirus (HPV) is the most common sexually transmitted viral infection worldwide, which may result in the development in benign lesions or malignant tumors. The prevalence of HPV infection is twice as high in pregnancy as in non-pregnant women. Additionally, there is a risk of vertical transmission of HPV from mother to fetus during pregnancy or childbirth. Various studies have reported an increased risk of adverse pregnancy outcomes in HPV-positive women, including miscarriage, preterm birth, premature rupture of membranes, preeclampsia, fetal growth restriction, and fetal death. HPV vaccination is not currently recommended during pregnancy. On the other hand, there is no evidence linking HPV vaccination during pregnancy with adverse pregnancy outcomes and termination of pregnancy is not justified in this case.

Aim: To review the changes in the new version of the FIGO 2023 staging system for endometrial cancer. Methods and results: The new FIGO 2023 endometrial cancer staging system provides key updates for the dia gnosis and treatment of endometrial cancer. An important step in dia gnosis is molecular classification, which allows more accurate risk stratification for recurrence and the identification of targeted therapies. The new staging system, based on the recommendations of the international societies ESGO, ESTRO and ESP, incorporates not only the description of the pathological and anatomical extent of the disease, but also the histopathological characteristics of the tumour, including the histological type and the presence of lymphovascular space invasion. In addition, the staging system uses molecular testing to classify endometrial cancers into four prognostic groups: POLEmut, MMRd, NSMP and p53abn. Each group has its own specific characteristics and prognosis. The most significant changes have occurred in stages I and II, in which the sub-staging better reflects the bio logical behaviour of the tumour. This update increases the accuracy of prognosis and improves individualized treatment options for patients with endometrial cancer. Conclusion: The updated FIGO staging of endometrial cancer for 2023 incorporates different histologic types, tumour features, and molecular classifications to better reflect the current improved understanding of the complex nature of several endometrial cancer types and their underlying bio logic behaviour. The aim of the new endometrial cancer staging system is to better define stages with similar prognosis, allowing for more precise indication of individualised adjuvant radiation or systemic treatment, including the use of immunotherapy.