Introduction: Paget's disease of the vulva is an intraepithelial adenocarcinoma, primarily arising from vulvar skin glands, with or without an underlying invasive adenocarcinoma. It brings low mortality and a high local recurrence rate and mainly affects postmenopausal women. Case outline: This is a case report of a 57-year-old postmenopausal woman, who had histopathological (HP) verified Extramammary Vulvar Paget's disease (EVPD) in 2014, and underwent a radical vulvectomy with a right-sided inguinofemoral lymphadenectomy and V-Y flap at the Oncology Institute of Vojvodina. Nine years later, in 2023, the patient was presented with a biopsy HP proven EVPD recurrence. The recurrence was surgically treated with vulvectomy and bilateral fasciocutaneous V-Y flaps reconstruction. The operative HP specimen proved the EVPD recurrence with atypical cells on one edge of the specimen. Due to the infection-complicated healing and wound dehiscence, the first reoperation was performed, which included wound debridement and left-sided rotational flap. We carried out the wound care and toileting in the postoperative course, with antibiotic treatment. Due to infection-complicated healing, tissue necrosis and consequent dehiscence, the second reoperation was performed, which included wound debridement with granulation tissue excochleation and Tiersch-type skin graft. Conclusion: The patient was discharged 21 days after the second reoperation in good condition. A regular oncological postsurgical follow-up on the 3th and 6th month revealed no recurrence or deterioration of the general condition or local findings. The patient subjectively feels well and has no complaints or unwanted effects of the applied treatment.

This review examines hormone replacement therapy (HRT) in cases of surgical menopause following gynecological malignancies. It aims to capture current knowledge, summarize recent findings, and provide recommendations for clinical settings. Unlike natural menopause, surgical menopause occurs abruptly, without an adjustment period, and is associated with a notably higher risk of fractures, arthritis, cognitive decline, dementia, Parkinson’s disease, and various metabolic disorders affecting glucose and lipid levels—all of which contribute to an increased risk of major cardiovascular events. In 2017, The North American Menopause Society recommended that, barring contraindications, HRT should be initiated in women who enter surgical menopause before age 45. If these women do not experience vasomotor symptoms or other issues, HRT should be maintained consistently at least until age 52. This guideline reflects contemporary knowledge and is the result of a multidisciplinary consensus, based on a review of existing literature and several randomized clinical trials focusing on women who have survived gynecological cancers and whose quality of life is significantly impacted by surgical or early menopause. Estrogen supplementation is particularly beneficial, as it is linked to marked improvements in quality of life, including delayed onset of chronic cardiovascular issues, reduced fracture risk, enhanced cognitive function, reduced inflammation, and improved self-esteem, as well as better social and work performance. Clinical implementation of HRT, however, requires a highly individualized approach. This approach must consider the type and stage of malignancy, histopathological characteristics, risk factors for recurrence (such as diet, concurrent medications, medical history, and genetic predispositions), and a thorough assessment of the potential benefits and risks of HRT, as well as the patient’s personal wishes and expectations.

Neuroendocrine neoplasms (NENs) of the gynecological tract are a rare, heterogenous and aggressive group of neoplasms, with high recurrence rates and poor prognosis. In this review we focus on NENs of the gynecological system emphasizing the classification, epidemiological and clinical characteristics of NENs across the gynecological tract (cervix, endometrium, ovary, vagina, and vulva), risk/prognostic factors, pathology and molecular biology (including actionable genomic mutations), imaging, staging and the most effective treatment modalities in the "standard of care" approach as well as the pipeline products. We also focused on metastatic spreading patterns of gynecological NENs. We searched for all available literature reviews, interventional studies, short series, case reports and meta-analyses published from 1990 to 2024. Deteriorated survival rate is essentially impacted by early development of lymph node, distant organ metastases and vascular propagation toward rapid extra-pelvic metastasis to the brain, liver, lung, bone marrow, lymph nodes and bones. Management of NENs needs to be customized on a case-based manner and comprises a multidisciplinary approach that involves gynecologists, surgeons, medical oncologists, radiologists, radiation oncologists, nuclear medicine specialists, pathologists, molecular biologists, qualified nurses etc. The treatment of extrapulmonary NENs arising in the female genital tract is basically extrapolated from that for small cell lung cancer. This includes, but is not limited to: surgery, chemotherapy, radiotherapy, peptide receptor radionuclide therapy, somatostatin analogs, and immunotherapy as well as investigational drugs in rare prospective clinical trials. Establishing modern therapeutic thesaurus is conditioned by the existence of well-designed clinical trials targeting a tumor's genomic profile and the incorporation of these data into the actual treatment landscape.

Introduction. Low-grade serous ovarian carcinoma is a distinct and relatively uncommon histologic subtype of epithelial ovarian cancer, characterized by unique biological and clinical features that differentiate from high-grade and other epithelial subtypes. Material and Methods. A comprehensive literature search was performed to identify interventional studies, systematic reviews, case reports, and meta-analyses published between 2010 and 2024, focusing on the diagnosis, management, and outcomes of low-grade serous ovarian carcinoma. Diagnosis. Ultrasound is the first-line imaging modality for evaluating ovarian and adnexal lesions. Computed tomography remains the preferred method for staging, treatment planning, and posttherapy monitoring, while magnetic resonance imaging is recommended for characterizing indeterminate adnexal masses or for evaluating extensive disease visualized on ultrasound or computed tomography. Clinical management. For patients with advanced-stage disease (FIGO stages II-IV), maximal cytoreductive surgery followed by six cycles of carboplatin and paclitaxel remains the standard of care. Optimal cytoreduction is associated with significantly improved overall and progressionfree survival compared with suboptimal surgery. Given the intrinsic chemoresistance of low-grade serous ovarian carcinoma, primary cytoreductive surgery is generally favored over neoadjuvant chemotherapy. Emerging targeted therapies focusing on CDK4/6, MAPK, and PI3K/AKT/mTOR pathways, as well as hormonal treatments, are under investigation and have demonstrated encouraging preliminary results. Conclusion. The management of low-grade serous ovarian carcinoma increasingly necessitates an individualized, multidisciplinary approach. Future therapeutic strategies will likely integrate molecularly targeted and endocrine therapies with optimal cytoreductive surgery to improve outcomes for this chemoresistant and biologically distinct ovarian cancer subtype.

OBJECTIVE:Advances in tumor biology have transformed endometrial cancer management. Since 2021, ESGO-ESTRO-ESP (European Society of Gynaecological Oncology-European Society for Radiotherapy and Oncology-European Society of Pathology) guidelines have incorporated molecular classification, which is essential in the 2025 update. Its implementation in Eastern Europe remains unclear. This study evaluated the availability, reimbursement, and integration of molecular classification at national and institutional levels. METHODS:A 2-phase cross-sectional online survey was conducted from December 2024 to September 2025. National coordinators from 17 European Society of Gynaecological Oncology-affiliated countries reported on access, reimbursement, and guidelines. A second survey targeted 67 treatment centers to assess institutional practices. RESULTS:Full molecular profiling (p53-abnormal, POLE-ultra-mutated, mismatch repair-deficient) was available in 29.4% of countries, with partial access in 70.6%. Lack of reimbursement and accredited laboratories were the main barriers. At least 1 test was publicly funded in 58.8% of countries: p53 and mismatch repair-deficient immunohistochemistry in 70.0% and POLE-ultra-mutated next-generation sequencing in 29.4%. National guidelines existed in over half of the countries, but few included molecular classification. At the institutional level, testing was routine in 41.0% of centers, selective in 27.9%, and unavailable in 31.1%. Overall, 55.8% reported access via local or external laboratories. Comprehensive classification was significantly more available in settings with national/public reimbursement (79.2% vs 18.9%, p < .0001). POLE-ultra-mutated testing was more accessible in private than public hospitals (42.9% vs 33.3%, p = .006), while p53 immunohistochemistry was more common in high-volume centers (97.5% vs 76.2%, p = .01). CONCLUSIONS:Access to molecular classification in Eastern Europe remains limited because of insufficient reimbursement and laboratory resources. Addressing these disparities is essential to support equitable treatment and improve outcomes.

Obesity is a significant health issue associated with increased cancer risks, including gynecological malignancies. The worldwide rise in obesity rates is significantly impacting both cancer development and treatment outcomes. Adipose tissue plays a crucial role in metabolism, secreting various substances that can influence cancer formation. In obese individuals, dysfunctional adipose tissue can contribute to cancer development through inflammation, insulin resistance, hormonal changes, and abnormal cholesterol metabolism. Studies have shown a strong correlation between obesity and gynecological cancers, particularly endometrial and breast cancers. Obesity not only increases the risk of developing these cancers but is also associated with poorer outcomes. Additionally, obesity affects the perioperative management of gynecological cancers, requiring specialized care due to increased complications and resistance to therapy. Treatment strategies for managing metabolic dysregulation in patients with gynecological cancers include weight management, statin therapy, and insulin-sensitizing medications. Emerging studies suggest that interventions like intermittent fasting and caloric restriction may enhance the effectiveness of cancer treatments. Furthermore, targeting cholesterol metabolism, such as with statins or proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitors, shows potential in cancer therapy. In conclusion, addressing metabolic issues, particularly obesity, is crucial in preventing and treating gynecological malignancies. Personalized approaches focusing on weight management and metabolic reprogramming may improve outcomes in these patients.

Background/Aim. Carcinosarcoma of the uterus, formerly known as malignant mixed M?llerian tumor, is a rare, aggressive malignancy of the female genital tract. The aim of this study was to analyse most important clinical and pathohistological characteristics of carcinosarcomas on operated patients, as well as to determine which of those factors are affecting disease free survival and overall survival of patients. Methods. The study was conducted as a retrospective analysis of medical data documentation of patients with a diagnosis of carcinosarcoma of the uterus who were surgically treated at Department of Gynecology, Clinic for Operative Oncology, Oncology Institute of Vojvodina, Sremska Kamenica, Serbia, in a period of 10 years, from the beginning of 2009 to the end of 2018. Results. The analysis included data for a total of 31 patients. Of all the examined parameters (age of the patient, clinical stage of the disease, histological grade, depth of myometrial invasion and lymphovascular invasion) the greatest influence on the choice of therapeutic procedure had a histological tumor grade. Conclusion. Our research showed the joint influence of the examined clinical and pathohistological factors parameters on progressionfree survival (PFS) and overall survival (OS) of patients with carcinosarcoma of the uterus. The only independent parameter that showed statistically significant impact on survival is lymphovascular invasion.

Introduction Neuroendocrine tumors (NEC) were first described by Albores-Saavedra in 1972 and these tumors account for only 0.9% to 1.5% of all invasive cervical cancers.1,2 The most common type is small cell neuroendocrine carcinoma (SCNEC) of the cervix, which accounts for 80% of cases.2 The poor prognosis despite advances in treatment remains still a huge problem, so the aim of our review is to cover all current therapeutic options. Method We searched for all available interventional studies, reviews, case reports and meta-analyses published from 1995 to 2023. Results In 2017 Castle et al.9 published a systematic review and meta-analysis and concluded that SCNC and large cell neuroendocrine carcinoma (LCNC) are, in most cases, caused by HPV, primarily HPV18 and HPV16. Comparative genomics data suggest that cervical NEC may be genetically more similar to common cervical cancer subtypes than to extra-cervical SCNEC of the lung and bladder.13 Surgery is recommended as the primary treatment in early stages of disease, with radical hysterectomy and nodal assessment followed by adjuvant pelvic radiotherapy and/or chemotherapy. However, simple hysterectomy may be adequate when followed by adjuvant radiotherapy with concurrent cisplatin and etoposide as additional chemotherapy.15 Considering that pathologic and clinical behavior is similar to small cell lung cancer, patients usually receive platinum and etoposide as part of their primary therapy.16 The recurrent disease remains a major clinical problem, because there is no standard treatment modality for these patients, and individualized therapy is recommeded. Conclusion Current therapeutic modalities are mainly based on experience in the treatment of SCNEC of the lung. Certainly, a multidisciplinary approach is very important inorder to design a personalized management plan.

Introduction/Background It has been concluded that the occurrence, development, invasion, and metastasis of tumors are closely linked to angiogenesis which is reflected by the tumor microvessel density. To analyze microvascular density (MVD) in observed groups of patients with cervical carcinoma, and to compare MVD in relation to the degree of tumor differentiation, size, presence of lymphovascular invasion and the presence of lymph node metastases. Methodology The retrospective study was conducted on histopathological samples of 109 patients who underwent hysterectomy due to benign disease or due to dysplastic changes on the cervix. Data were collected from Oncology Institute of Vojvodina and divided into three groups depending on histopathological result. Based on H&E stain representative material was chosen for immunohistochemistry, therefore analysis of CD34 antigen expression and measurement of MVD was done. Results Calculated mean values for control group (2,2), group A-dysplasia in cervix (9,85) and group B-cervical cancer (17,19), a cut-off value was determined in order to make a division within the group into LMVD and HMVD. Statistically significant difference was observed by comparing these groups. There were 7 patients (21,21%) with the HMVD in group A and 29 patients (63,04%) in group B. Statistically significant difference was confirmed by comparing HMVD and LMVD in lymph nodes metastasis subgroup(p<0,029 ). In the subgroup of patients with other worse pathohistological prognostic factors, tumor size greater than 2 cm, depth of stromal invasion greater than 10 mm, infiltration of 'isthmus' of the uterus, HMVD was higher but with no statistical significance. Conclusion HMVD was statistical significance higher in cervical cancer comparing other two groups. In the comparison of histopathological parameters in group B it is demonstrated that subgroup with lymph nodes metastasis had higher percentages of HMVD with statistical significance. Disclosures Nothing to disclosures.

Human papillomaviruses (HPV) are the most common sexually transmitted pathogens worldwide, leading to infections with a wide range of clinical manifestations: from benign conditions to different types of cancer in women and men as well. Cervical cancer is highly correlated with persistent high-risk-HPV (HR-HPV) infection, which is the key factor in emergence of 99.99% of cervical cancer cases. The most effective way to prevent HPV-related cancers is vaccination. There are three available prophylactic HPV vaccines: bivalent, quadrivalent and nonavalent. The nonavalent vaccine is gradually replacing other HPV vaccines in most countries and can be given from year 9, but it is commonly routinely implemented at the age of 11 to 12. The World Health Organization has recognised cervical cancer as a global threat and has announced the so-called 90-70-90 strategy to reduce and even eliminate cervical cancer. This strategy implies that 90% of girls should be vaccinated by the age of 15, 70% of women should be screened for cervical cancer, and 90% of women diagnosed with cervical disease should receive adequate treatment. Although different treatment options are available: surgery, radiation therapy, chemotherapy, and advanced target therapy using monoclonal antibodies, great efforts are needed to achieve the goals set by the World Health Organization to eliminate cervical cancer.

Objective: The occurrence, development, invasion, and metastasis of tumors are closely linked to angiogenesis, which is reflected by tumor microvessel density. The aim is to analyze microvascular density (MVD) in groups of patients with high grade squamous intraepithelial lesions (H-SIL), and cervical carcinoma, and to compare MVD in relation to the degree of tumor differentiation, size, presence of lymphovascular invasion and lymph node metastases. Materials and methods: The study was retrospective, conducted on histopathological samples of 109 patients who underwent hysterectomy with/without adnexectomy. Patients were divided into two groups depending on the histopathological results: group A - patients with H-SIL, and B with cervical cancer. The control group included surgically treated patients with benign uterine diseases. Based on hematoxylin/eosine staining, representative sample was chosen for immunohistochemistry, and the analysis of CD34 antigen expression and measurement of MVD were done. Results: In order to subdivide groups according to the low (L) and high (H) MVD, in control, group A, and B, with mean MVDs 2.2; 9.85 and 17.19, respectively, a cut-off values were determined. In the control group, LMVD 100% was measured. There were 7 (21.21%) in group A and 29 patients (63.04%) in group B with HMVD. A statistically significant difference was confirmed by comparing HMVD and LMVD in cervical cancer patients with lymph nodes metastasis (p<0.029). In the subgroup of patients with other worse pathohistological prognostic factors, a tumor size greater than 2 cm, depth of stromal invasion >10 mm, infiltration of "isthmus" of the uterus, a difference with no statistical significance was confirmed. Conclusion: Invasive cervical cancers are characterised by a significantly higher mean values of MVD compared to H-SIL. Significantly more often, HMVD is associated with the presence of lymph node metastases and histopathological parameters of poor prognosis.

Lymphoepithelioma-like carcinoma of the cervix (LELC) is a rare subtype of squamous cell carcinoma. This is a case report of a 40-year-old female patient diagnosed with LELC. The tumor is clinically presented as an exophytic mass on the front lip of the cervix. Magnetic resonance imaging (MRI) of the pelvis revealed a cervical tumor mass with a diameter of 21 mm. The findings of the preoperative pathohistological analysis of the biopsy tissue indicated LELC. The disease was clinically and radiologically staged as IB1 stage according to the 2009 FIGO classification, and the patient underwent surgical treatment. A total radical hysterectomy with pelvic lymphadenectomy was performed, followed by external beam radiotherapy. The patient was regularly monitored with the last check-up on February 2024 (36 months) and MRI control of the pelvis and abdomen without signs of recurrence of the underlying disease. The patient is in good general condition, without subjective complaints and side effects of the applied therapy.

Background and Objectives: Human papillomavirus (HPV) infection and its etiological role in the development of cervical cancer are well established. The cervical cancer mortality rate in Serbia is one of the highest among European countries, and this cancer is the second-leading cause of death in Serbian women aged from 15 to 44. Materials and Methods: This retrospective study was conducted at the Institute of Public Health of Vojvodina. A total of 10,062 cervical specimens from Serbian women were collected and HPV tested in ten years. The study patients were divided into five age groups. HPV genotype testing was performed using a commercial kit to detect 14 high-risk (HR) HPV genotypes. Additionally, cervix cytology data have been available for patients tested in 2022 and 2023. Results: An overall positive rate was found in 43.3% of patients (4356/10,062). A single HPV infection (62.1%) was the main infection pattern. The most frequent HR HPV genotypes were HPV 16, 31, 52, 56, 39, and 51, comprising 62.3% of the detected genotypes, including multiple infections. A significant difference was noted in the HPV prevalence across the different age groups, with a bimodal distribution of HPV infection. The highest prevalence was recorded in the age group ≤ 30 and those after 61 years. Women diagnosed with high-grade squamous intraepithelial lesions (HSIL) were significantly older compared to others. HR HPV is the most prevalent in patients with HSIL cytological findings (76.5%). The most common type, according to age-specific distribution and cytological findings, was HR HPV 16. Conclusions: This study provides comprehensive data on HR HPV distribution among Serbian women, which can serve as a basis for subsequent monitoring of genotypic distribution. It is particularly significant considering they are missing in the updated ICO/IARC Report for Serbia, and the cervical cancer mortality rate in Serbia is one of the highest among European countries.

Background and Objectives: Burden of cervical cancer in Central and Eastern Europe is higher than in other parts of Europe. We analyzed cervical cancer epidemiology in Serbia and Bosnia and Herzegovina (the Federation of Bosnia and Herzegovina and the Republic of Srpska) from January 2016 to December 2020, exploring the role of available sociodemographic factors and healthcare service parameters on incidence and mortality rates, using an ecological approach based on aggregated data. Materials and Methods: Incidence and mortality rates are standardized using the method of direct standardization with the World-ASR-W. Administrative units are grouped by tertiles of incidence and mortality to explore sociodemographic factors and healthcare parameters across these groups. Results: Average age-standardized incidence rates of cervical cancer per 100,000 females were 19.28 in Serbia, 12.48 in the Federation of Bosnia and Herzegovina, and 22.44 in the Republic of Srpska. Mortality rates per 100,000 females were 6.67, 5.22, and 4.56 in Serbia, the Federation of Bosnia and Herzegovina, and the Republic of Srpska, respectively. Several parameters of sociodemographics and health service usage differed significantly across units grouped by tertiles based on incidence level, i.e., female population ≥ 15 years old (p = 0.028), population density (p = 0.046), percent of gynecologists in the primary healthcare (p = 0.041), number of gynecologists per 10,000 females ≥ 15 years (p = 0.007), and the area-to-gynecologist ratio (p = 0.010). A moderate negative correlation was found between incidence and population density (rho = −0.465, p = 0.017), and a moderate positive correlation between incidence and area-to-gynecologist ratio (rho = 0.534, p = 0.005). Conclusions: Cervical cancer remains a leading cause of cancer among women in developing countries. Implementing tailored activities, such as educational programs, preventive services, and investments in healthcare infrastructure, particularly at the administrative units’ level, can help in reducing health disparities and improving health outcomes.

This study assesses human papilloma virus Human (HPV) infection prevalence among women in Vojvodina, Serbia and North Macedonia, considering cytological status and cervix-related pathological changes. The main goal of this study is to compare the HPV status (types of HPV, age of patients, histopathology diagnosis, etc.) in these two populations. The EUROArray HPV test, detecting 30 genotypes, was utilized on 1562 women (740 in Vojvodina and Serbia, 822 in North Macedonia) aged 20 to 80 with various cytological results. 164 of the 576 Serbian/Vojvodina samples that were categorised as negative of intraepithelial lesion or malignacy (NILM) had aberrant histology low grade squamous intraepithelial lesion/high grade squamous intraepithelial lesion (LSIL/HSIL cervical malignancy). Carcinogenic HPV genotypes were found in 252 (55%) samples, with 76.2% in the LSIL/HSIL/cervical cancer category. Top abnormal histopathology genotypes included HPV 16, 33, 31 and 56, while 18 and 39 were equally verified. Genotype 16 prevalence increased with higher histopathological grades: 18.8% in LSIL, 31.9% in HSIL, and 75% in cervical cancer samples. Among the North Macedonian samples, 221 had aberrant histopathology and 601 displayed NILM. Carcinogenic HPV genotypes were found in 43.4% of cases, with 70.1% in the LSIL/HSIL/cervical cancer category. Predominant genotypes associated with abnormal histopathology results included HPV 16, 31 and 35, with 18 and 52 equally verified. The most frequent genotype associated with higher-grade histopathological findings was genotype16, found in 20.1% of LSIL, 34.3% of HSIL, and 78% of cervical cancer cases. Multiple associated HPV genotypes were not correlated with histopathology. Older patients tended to exhibit higher-grade lesions when comparing histopathological diagnosis and age.

The aim of our study was to measure the levels of 8-hydroxy-2-deoxyguanosine, malondialdehyde, and antioxidant enzymes in patients with locally advanced cervical cancer prior to treatment to determine how these evaluated biomarkers are associated with cervical cancer recurrence and to estimate their potential in further research and clinical use.MATERIALS AND METHODS:The study included 45 female patients with newly diagnosed advanced cervical cancer who underwent concomitant chemoradiotherapy. The blood and urine samples were collected prior to treatment, between December 2013 and April 2016, and subsequent laboratory analysis was performed. After the medium follow-up of 29 months, the patients were divided into 3 groups according to the time of disease recurrence. A statistical analysis was performed in order to evaluate the relationship between the previously measured biomarkers and recurrence.RESULTS:Taken individually, the parameters of oxidative stress did not reveal significant differences between the three groups in our study. Nevertheless, the catalase and glutathione S-transferase activities were the best predictors of the recurrence. Based on the activities of these two oxidative enzymes, it was possible to separate the group of patients without recurrence after follow-up from the other two groups of patients with recurrent disease.CONCLUSIONS:The parameters of oxidative stress have a certain predictive value on the outcome of patients with advanced cervical cancer after concomitant chemo-radiotherapy.