Current Problems in Cancer

Do estrogen, progesterone, P53 and Ki67 receptor ratios determined from curettage materials in endometrioid-type endometrial carcinoma predict lymph node metastasis?

Estrogen receptor (ER), progesterone receptor (PR), and Ki-67 and P53 receptor levels in endometrial curettage material were investigated for their ability to predict lymph node (LN) involvement in patients with endometrioid-type endometrial cancer (EEC). This retrospective study was based on a review of the records of patients who were diagnosed with EEC and underwent both hysterectomy and systematic retroperitoneal lymphadenectomy at the Gynecologic Oncology Clinic of Tepecik Training and Research Hospital, Turkey, between January 2008 and August 2017. The curettage materials of 138 EEC patients were analyzed for ER, PR and P53 and Ki-67 receptor levels. According to the pathology results, the median pelvic LN count was 20 (range: 12-49) and the para-aortic LN count was 14 (10-46). Retroperitoneal LN involvement was present in 18 patients (13.0%). The association of LN involvement with all receptors was significant. The combined ratio of the 2 groups of markers ([P53 + Ki67]/[ER + PR]) (≥0.71) was an independent risk factor for LN involvement. In addition, in a univariate logistic regression analysis all receptors were significant predictors of LN involvement. In the detection of LN involvement, determination of the receptor status in curettage material has a high sensitivity and specificity. In EEC patients, receptor levels in curettage materials can be evaluated to detect LN involvement preoperatively.

Women's ignorance and misperception of cervical cancer: Evidence-based analysis from low- and middle-income countries

Cervical cancer is a major cause of morbidity and mortality particularly in low- and mid-income countries. This review synthesizes existing knowledge on cervical cancer, HPV infection, and HPV vaccination accumulated over the past decade (2015-2024), highlighting disparities in awareness and prevention strategies globally. Education level correlates with HPV vaccine awareness, yet mere familiarity with cervical cancer doesn't ensure understanding of its severity. Notably, prevention measures, including screening and HPV testing, varied significantly across countries during this period. To enhance HPV vaccine uptake moving forward, targeted efforts are necessary to educate women, particularly in low- and mid-income countries, about HPV risks as a sexually transmitted disease and the availability of affordable vaccines in government clinics.

Primary and secondary prevention of cervical cancer among Italian AFAB transgender people

Currently, available data on preventive measures for Human Papillomavirus (HPV) infection and cervical cancer in the transgender assigned female at birth (AFAB) community are extremely limited. Our aim was to analyze adherence to primary and secondary cervical cancer prevention screening programs among transgender AFAB people attending our gender clinic. Transgender AFAB people attending our center were recruited. Anamnestic data were collected for each person through completion of a medical history form and medical records. Variables recorded included previous HPV vaccination, adherence to regional screening programs (Pap smear or HPV DNA test), subject age, duration of current or prior gender-affirming hormone therapy (GAHT) and whether gender affirmation surgery (GAS) with hysterectomy had been performed. Open questions regarding reasons for not undergoing screening tests were also included. In this cross-sectional study, 263 AFAB transgender people were included, with a mean age of 30.6 ± 10.5 years. GAS with hysterectomy had been performed on 37.6 % of these people. Of our participants, 71.7 % who were born after 1998 (the first cohort to receive HPV vaccination invitations in Italy) had been vaccinated for HPV. Seventy-four-point-nine percent of participants who were still eligible for cervical screening had never undergone Pap smear or HPV DNA testing, whereas those who had undergone at least one cervical screening had done so on average 4.2 ± 4.5 years ago. HPV vaccination prevalence in the AFAB transgender population born after 1998 is in line with the Italian AFAB general population. However, adherence to cervical cancer screening programs in the transgender AFAB population appears to be lower in comparison to the cisgender population. Further efforts are required from the medical community to enhance AFAB transgender people's adherence to HPV vaccination and to cervical screening.

Impact of non-BRCA genes in the indication of risk-reducing surgery in hereditary breast and ovarian cancer syndrome (HBOC)

Hereditary breast and ovarian cancer syndrome (HBOC) is associated with other genes beyond BRCA. The performance of prophylactic bilateral mastectomy (PBM) and risk-reducing salpingo-oophorectomy (RRSO) are primary prevention measures that can be recommended depending on the type of pathogenic/likely pathogenic (P/LP) variant detected or family history. Descriptive, retrospective, and observational audit. Between the years 2015 to May 2023, a total of 288 families were studied by a multigene panel using NGS. Statistical analysis was performed using IBM SPSS Statistics 22. Non-BRCA P/LP variants were detected in 38 families (84.2% females and 15.8% males); 18 in ATM (44.7 %), 7 in CHEK2 (18.4%), 5 in TP53 (13.2%), 2 in PTEN (5.3%), 2 in PALB2 (5.3%), 1 in RAD51C (2.6%), 1 in BRIP1 (2.6%), 1 in CDH1 (2.6%) and 1 in RAD51D (2.6%). Risk-reducing surgery was recommended in 18 patients (PBM in 18 [46.2 %] and RRSO in 5 [13.2%]). Given the results of our study, we support the recommendations of the guidelines on the use of multigene panels in the study of HBOC. Knowing P/LP variants beyond BRCA1 and 2 has an impact on the follow-up and primary and secondary prevention of affected families.

Impact of nonspecific death on overall survival in early-stage epithelial ovarian cancer patients

To estimate the impacts of nonovarian cancer-specific death (non-OCSD) and ovarian cancer-specific death (OCSD) on early-stage patients, and to determine which statistical method yielded survival results most similar to real-world situations. Data of patients with early-stage epithelial ovarian cancer from 1988 to 2015 registered in the Surveillance, Epidemiology, and End Results database were analyzed. The primary outcome events of epithelial ovarian cancer were OCSD, non-OCSD, or alive. Incidences of non-OCSD and OCSD with different clinicopathological factors, cumulative incidences of non-OCSD and OCSD, and overall survival impact of non-OCSD were analyzed. A total of 1606 non-OCSD (8.9%) and 3022 OCSDs (16.8%) were analyzed. Several independent features were associated with non-OCSD, including age (>60 years), radiotherapy, and marital status. In patients with histology (eg, endometrioid or mucinous), well-differentiated cells, stage I disease, or widowed marital status, as well as age older than 60, non-OCSD rates of all causes of death notably distorted overall survival, resulting in inaccurate and biased interpretations. Overall survival was greatly influenced by non-OCSD in early epithelial ovarian cancer. Future clinical trials should consider non-OCSD as a competing risk event, especially among patients older than 60 years and those with well-differentiated cells, no chemotherapy, and widowed marital status.

The role of changes in systemic inflammatory response markers during neoadjuvant chemotherapy in predicting suboptimal surgery in ovarian cancer

The aim of this study was to investigate the possibility of using the neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio, and platelet count and their dynamic changes during chemotherapy to predict suboptimal interval debulking surgery (IDS) in stage IIIC-IVA serous ovarian cancer (OC). Patients who underwent IDS after neoadjuvant chemotherapy (NAC) for stage IIIC-IVA serous OC at 3 centers between January 2008 and March 2018 were analyzed retrospectively. All women with complete blood counts both at diagnosis (T0) and after the completion of NAC but prior to IDS (T1) were included. An average of 3 weeks passed between IDS and the last cycle of NAC. A total of 214 patients were found suitable for the study. Suboptimal surgery was performed in 25.2% of the patients and optimal surgery was performed in 74.8%. The rate of change in NLR was calculated as [(NLR T0 - NLR T1)/NLR T0] × 100. A higher rate of change in NLR was found in the optimal surgery group. Recovery of thrombocytosis (When platelet count before NAC was >400,000/mm To identify the likelihood of suboptimal surgery in advanced stage OC patients who undergo IDS after NAC, the dynamic change in NLR values can be examined.

CAR-T/NK/M-based combination therapies in cancer: A comprehensive review

Mapping the expression and functional landscape of key enzymes in glucose metabolism within human gynecological tumors

Comparison of CA 125 alone and risk of ovarian malignancy algorithm (ROMA) in patients with adnexal mass: A multicenter study

This multicenter study aimed to evaluate the performance of CA 125 and risk of ovarian malignancy algorithm (ROMA) in differentiating epithelial ovarian cancer (EOC) from benign adnexal mass. We consecutively enrolled 782 patients referred to tertiary hospitals with adnexal mass requiring surgical treatment. A total 322 of patients with benign adnexal disease and 327 patients with EOC were included in the analysis. Using reference cut-off values in premenopausal women, ROMA had better specificity (0.926 vs. 0.787, P < 0.001) and accuracy (0.875 vs. 0.777, P < 0.001) than CA 125 alone and comparable sensitivity (0.707 vs. 0.747, P = 0.549). Using optimum cut-off values in premenopausal women, CA 125 and ROMA had comparable specificity (0.922 vs. 0.947, P < 0.001) and accuracy (0.871 vs. 0.868, P = 0.879); however, sensitivity for CA 125 was inferior to that of ROMA (0.707 vs. 0.613, P = 0.039). In postmenopausal women, sensitivity, specificity, and accuracy were comparable between CA 125 alone and ROMA using either reference cut-off values or optimum cut-off values.ROMA showed better diagnostic performance in differentiating EOC from benign adnexal tumors among premenopausal women. However, in postmenopausal women, ROMA did not show any benefit over CA 125 alone.

Central nervous system metastasis from epithelial ovarian cancer- predictors of outcome

Management of central nervous system (CNS) metastases from epithelial ovarian cancer (EOC) is an unmet need. We analyzed data on 41 such patients to evaluate predictors of outcome. Between January, 2010 and December 2020, among 1028 patients with EOC treated at our institute 41 (3.98%) developed CNS metastasis. Median age of patients was 48 years, ranging from 22 to 75 years. Primary outcome measure was progression free survival (PFS). Overall survival (OS), and analysis of prognostic factors were secondary outcome measures. An intention to treat analysis was done. We also performed review the literature (n=2253) as regards to clinicopathological and radiological features, treatment received, survival outcomes and prognostic factors. Median time from diagnosis of EOC to CNS metastasis was 27 months (range: 0 to 101 months). 33(80.5%) patients had FIGO stage III-IV at baseline and serous carcinoma (75.6%) was common pathology subtype. Thirteen (31.7%) patients had isolated CNS metastasis and 28 (68.3%) had intra-abdominal disease in addition. Nineteen (46.3%) patients achieved complete response post treatment with surgery, radiation and chemotherapy. Median PFS and OS from the time of CNS metastasis is 12 (range:1 to 51) months and 33 (range: 1 to 71) months, respectively. Absence of extracranial disease and lower serum CA-125 at diagnosis of CNS metastasis were predictive of superior PFS and OS on multivariate analysis. CNS metastasis is a late event in EOC, post multiple lines of treatment. Patients with disease limited to brain and treated with surgical resection and chemoradiation have best outcome.

Recurrence of high-grade vaginal intraepithelial neoplasia after various treatments

To assess the recurrence of high-grade vaginal intraepithelial neoplasia (VAIN) after various treatments and to determine the factors affecting recurrence. A retrospective cohort study was conducted in patients with a histologic diagnosis of high-grade VAIN who underwent treatment between 1986 and 2013. Recurrence rates, life table analysis of recurrence-free intervals following treatment, and factors affecting recurrence were analyzed. Of the 104 included patients, the mean age was 50.8± 13.4 years; 21.1% and 78.8% had VAIN2 and VAIN3, respectively. Overall, the recurrence rate of high-grade VAIN was 33.2 incidence density rate (IDR)% per year, and the median time to recurrence was 23.6 months. Observation, topical treatment, laser vaporization, electrosurgical ablation, electrosurgical excision, knife excision, and radiation were associated with recurrence rates of 65.4, 70.0, 38.0, 22.6, 43.1, 18.5, and 0 IDR% per year, respectively. The median times to recurrence for each treatment were 16.2, 18.8, 26.5, >35.8, 6.6, 39.8, and >57.3 months, respectively, but the differences in recurrence-free intervals among treatments were not statistically significant (P = 0.06). Patients in the treatment intervention group were less likely to experience recurrence than those in the untreated group (HR = 0.44, CI: 0.23-0.87, P = 0.018). A history of pelvic radiation was associated with a higher risk of recurrence (OR = 4.14, 95% CI: 1.06-16.16, P = 0.030). Although treatments for high-grade VAIN significantly decreased the risk of recurrence, approximately one-third of patients had recurrence after therapy. No treatment modality was superior to the others with respect to the recurrence rate. A history of radiation therapy was associated with higher recurrence.

Correlation of human papillomavirus 16 and 18 with cervical cancer and their diagnosis methods in Iranian women: A systematic review and meta-analysis

Human papillomavirus (HPV) is a sexually transmitted virus and related to the development of cervical cancer (CC). To determine the association between high-risk HPV types and CC, we undertook a systematic review and meta-analysis of recently reported prevalence of HPV16 and 18 in Iranian women identified with cervical infections. Prevalence studies were identified between 2002 and 2018 using several databases including Medline, Web of Science, Embase, Google Scholar, Iranmedex, and Scientific Information Database. For patients with CC, 57% (95% confidence interval [95% CI] = 43.7%-70.4%) were HPV positive, 48.5% (95% CI = 31.8%-65.2%) were HPV16 and 12.5% (95% CI = 8.8%-16.2%) were HPV18 positive. The results from meta-analysis indicate a relatively high prevalence of high-risk HPV among women infected with CC.

Conditional survival for high-risk early-stage cervical cancer patients with lymph node metastasis after hysterectomy

To estimate conditional survival (CS) for high-risk early-stage cervical cancer patients with lymph node metastasis after hysterectomy. 1964 T CDS5 and CRS5 increased from 71.0% and 73.7% at 0-year to 89.2% and 91.7% at 5-year, respectively. Inversely, the actuarial disease-specific survival and RS dropped from 71.0% and 73.7% at 5-year to 63.3% and 67.6% at 10-year, respectively. Patients with unfavorable factors had a bigger gap between actuarial survival and CS. Both CDS5 and CRS5 curves across stratas of each prognostic factor had a tendency to level off with time elapsing. Notably, CRS5 couldn't exceed 95% even after 5-year follow-up except for patients with grade I disease (CRS5 at 5-year: 100%) or tumor size less than 2 cm (CRS5 at 5-year: 96%). CS increased over time while actuarial survival decreased as time passed. Patients with unfavorable factors had bigger improvement in CS than those with favorable factors. Excess mortality still existed in these patients after 5-year follow-up compared to the general population except for patients with grade I disease or tumor size <2 cm, who might gradually decrease follow-up times after 5-year.

Chemotherapy and immune check point inhibitors in the management of cervical cancer

Management of locally advanced cervix cancer underwent major change 2 decades back when concurrent chemotherapy (CCRT) (with cisplatin alone or in combination) along with definite radiation therapy (external + brachytherapy) was found to be superior compared to radiation alone in a series of randomized trials. Since then CCRT has been the standard treatment approach; this has resulted in 5-year overall survival rate of 66% and disease-free survival (DFS) of 58%. About 30% to 40% of patients with locally advanced cervical cancer continue to have treatment failure. Also, some patients experience early and late side effects of treatment with negative impact on quality of life. To improve the outcome further - recent approaches have explored use of weekly paclitaxel and carboplatin for 4 to 6 weeks as dose dense chemotherapy prior to CCRT, adjuvant chemotherapy after CCRT in high risk patients. For patients with early stage disease (IA2-IIA), short course chemotherapy prior to surgery is associated with improved outcome in many studies. Bevacizumab- an inhibitor of vascular endothelial growth factor - is associated with improved survival. More recently, addition of treatment with immune check inhibitors (to boost the ability of T cells to destroy cancer cells) have improved responses and survival in the treatment of recurrent and metastatic cervical cancer. Whether these and other similar novel agents targeting molecular pathways could be brought in front line treatment along with cytotoxic chemotherapy along with bevacizumab are potential areas of current research.

The vaginal microbiome: A complex milieu affecting risk of human papillomavirus persistence and cervical cancer

The purpose of this review is to describe the existing literature regarding the relationship between the vaginal microbiome, human papillomavirus persistence, and cervical cancer risk, as well as to discuss factors that mediate these relationships. Data suggest that alterations in the vaginal microbiome affect the risk of human papillomavirus infection and persistence, which has downstream effects on cervical dysplasia and cancer risk. The homeostatic Lactobillus species L. crispatus, L. gasseri, L. jensenii act to promote a healthy vaginal environment, while L. iners and pathogens causing bacterial vaginosis are associated with increased inflammation, human papillomavirus infection, cervical dysplasia, and potentially cancer. There are, however, still several large gaps in the literature, particularly related to the modifiable and non-modifiable factors that affect the vaginal microbiome and ensuing risk of pre-cancerous and cancerous lesions. Evidence currently suggests that endogenous and exogenous hormones, tobacco products, and sexual practices influence vaginal microbiome composition, but the nuances of these relationships and how changes in these factors affect dysplasia risk are yet to be delineated. Other studies examining how diet, exercise, race, socioeconomic status, and genetic factors influence the vaginal microbiome are difficult to interpret in the setting of multiple confounders. Future studies should focus on how changes in these modulatory factors might promote a healthy vaginal microbiome to prevent or treat dysplasia in the lower female genital tract.

hsa_circ_0008285: Circular RNA with potential as a biomarker in ovarian cancer

Liquid biopsy has emerged as a non-invasive cancer diagnosis and prognosis tool. Circular RNAs (circRNAs) have become promising biomarkers due to their stability and regulatory roles in cancer biology. This study aimed to evaluate the potential of hsa_circ_0008285 as a diagnostic biomarker for ovarian cancer (OC). 102 paired cancer and adjacent normal tissue samples, along with plasma from 98 OC patients, 42 polycystic ovary syndrome (PCO) patients, 35 endometriosis patients, and 93 healthy donors, were analyzed. Differentially expressed circRNAs were identified using Illumina HiSeq 2000 high-throughput sequencing in OC tissue samples (n = 4). Quantitative real-time polymerase chain reaction (qRT-PCR) was employed to validate the expression of hsa_circ_0008285. Diagnostic efficacy and sensitivity were assessed using receiver operating characteristic (ROC) analysis. High-throughput sequencing identified hsa_circ_0008285 as the most significantly upregulated circRNA (P = 0.000012). qRT-PCR results confirmed increased expression of hsa_circ_0008285 in OC tissues and plasma compared to healthy controls (P < 0.0001). ROC analysis demonstrated an area under the curve (AUC) of 0.74 (95 % CI: 0.6567-0.8306, P < 0.0001), indicating moderate diagnostic potential. Notably, the combined detection of hsa_circ_0008285 and CA_125 improved diagnostic specificity and sensitivity. Correlation analysis revealed that hsa_circ_0008285 upregulation was associated with tumor size, differentiation, and T stage. These findings suggest that hsa_circ_0008285 holds promise as a non-invasive biomarker for the diagnosis of OC, with potential applications in clinical practice.

Extraovarian dysgerminoma in a pregnant woman: an extremely rare finding

Extraovarian germ cell tumors are very rare and their occurrence during pregnancy is exceptional. In this case report an abdominal mass was shown by ultrasonography, during a routine monitoring of a 26-year-old pregnant woman. The patient was left under radiological control in the following months in order to bring the pregnancy to term. A few months after the delivery, the patient underwent surgery and a diagnosis of extraovarian (abdominal) dysgerminoma was made. To the best of our knowledge, there are only 3 other case reports describing an extra-gonadal dysgerminoma occurring during pregnancy. The aim of this study was to report an extremely rare tumor, whose management can be challenging first because this neoplasm has some differences from its ovarian and testicular counterparts. Furthermore, the occurrence during pregnancy makes the multidisciplinary approach mandatory since 3 distinct but not independent entities are involved (tumor, mother and fetus).

Borderline tumours of ovary and fertility preservation–Outcomes from a tertiary care center in India

Borderline ovarian tumors (BOT) are characterized by atypical epithelial proliferation without stromal invasion and majority are diagnosed in women of reproductive age group desirous of fertility preservation. A retrospective review of medical records of patients diagnosed with BOT and on regular follow up at the All India Institute of Medical Sciences New Delhi, during a nine-year study period from March 2014 to March 2023 was performed. Surgical treatment was classified as radical or fertility sparing surgery (FSS). Surgical staging was defined as complete, partial or un-staged. Median age of 91 women was 34 years. Follow up period ranged from 4 to 222 months (median 77 months). Among 68 premenopausal women, 31 (46 %) underwent radical surgery and FSS in 37 (54 %) cases. Median time to conception in 29 women with future fertility wishes was 13 months (range, 4 to38 m). Seven of 29 cases (29 %) required ovulation induction. The pregnancy rate was 82.7 % and live birth rate was 80 %. Eight cases (8.7 %) had a recurrence (7- un-staged, 1- partially staged) and median time to recur was 36 months. There was no significant difference in recurrence between cystectomy/oophorectomy. Ovary was the site of recurrence in all surgically salvaged cases except peritoneal cavity in 1 case with mortality. Relapse free survival at 5 and 10 years in FSS and radical surgery group were similar. FSS is a safe procedure and should be considered in young patients desirous of future fertility along with a comprehensive peritoneal staging. Reproductive outcomes are excellent.

Novel approaches for treatment of endometrial carcinoma

Endometrial cancer (EC) is common malignancy in women and its incidence is slowly on the rise. Accurate surgical staging, with aggressive cytoreduction when indicated, remains the most critical step in the treatment. Careful pathological evaluation and/or molecular risk stratification guides for proper systemic adjuvant radiotherapy ± chemotherapy. Recurrent and metastatic EC has dismal prognosis and palliative therapies (chemotherapy, hormonal therapy or radiation) forms the backbone of treatment. There is an unmet need of newer therapies to improve survival in such cases. A number of tyrosine kinase inhibitors are currently under evaluation. Recent data on therapeutic targeting of HER2 positive serous EC is exciting. Data on check point inhibitors particularly based on biomarker select population has raised hope for potentially effective treatment for women with high risk endometrial cancer .

Selinexor in patients with advanced and recurrent endometrial cancer

Selinexor is an oral inhibitor of the nuclear export protein called Exportin 1 (XPO1) with demonstrated antitumor activity in hematological and solid tumors. Selinexor, blocking XPO1, induces nuclear localization of tumor suppressor proteins (including p53, p73, BRCA1, and pRB), leading to the selective induction of apoptosis, and inhibition of DNA damage repair proteins. XPO1 overexpression is common in endometrial cancers. Phase I and II trials reported the antitumor activity of selinexor in patients with endometrial carcinoma. The preliminary results of the phase III Selinexor in ENDOmetrial Cancer (SIENDO/ENGOT-EN5/GOG-3055) trial supported the use of selinexor as maintenance therapy in advanced endometrial cancer patients achieving at least partial response after a minimum of 12 weeks of first-line platinum-based chemotherapy. Selinexor maintenance resulted in a (nonsignificant) 30% reduction in the risk of disease progression or death. Looking at the endometrial cancer molecular subgroup characterized by TP53 wild type, the antitumor activity of selinexor seemed more pronounced, resulting in approximately a 60% reduction in the risk of disease progression or death. The SIENDO and the XPORT-EC trials will clarify the benefits and risks of adding selinexor as a first-line chemotherapy maintenance treatment in all-comer and TP53 wild-type endometrial cancers. Preclinical data highlights the potential for selinexor to be synthetically lethal with PARP inhibitors and may also plan a role in overcoming acquired resistance to those therapies. Therefore, new possible combinations with PARP inhibitors and should be evaluated. Furthermore, the combination of selinexor plus immune checkpoint inhibitors deserves further investigation in clinical trials.

Integrated analysis of tumor mutation burden and immune infiltrates in endometrial cancer

To explore the prognostic value of tumor mutation burden (TMB) and its correlation with immune infiltrates in endometrial cancer. Transcriptome and somatic mutation profiles of Uterine Corpus Endometrial Carcinoma (UCEC) were downloaded from TCGA database. Somatic mutations were analyzed by "maftools" and visualized in waterfall plot. We calculated TMB of each patients and divided all patients into the high-TMB group and the low-TMB group by the median threshold. Survival analysis and Wilcoxon test were used to investigate the prognostic value of TMB and its association with clinical variables. Differentially expressed genes (DEGs) were identified in 2 TMN groups and functional analysis was performed to find out significant biological pathways. A TMB-related signature was conducted by multivariate analysis, receiver operating characteristic (ROC) curve was performed to predict accuracy of the model, meanwhile, a validation cohort from Fudan University Shanghai Cancer Center (FUSCC) was obtained to verify the signature. Then we estimated association between TMB and immune infiltrates by CIBERSORT algorithm and figured out prognostic immune cells of UCEC in TIMER database. Total 575 samples including 25 normal tissues and 552 tumor samples were enrolled from TCGA database. PTEN mutations accounted for the most and single nucleotide polymorphism and C>T transitions were most frequent forms of somatic mutations in UCEC. The low-TMB group possessed worse survival than the high-TMB group (P = 0.004). DEGs in 2 TMB groups were mostly enriched in adaptive immune response and immunoglobulin/immune receptor component. A TMB-related signature consisting of GFAP, EDN3, CXCR3, PLXNA4, SST presented good predictability with area under the curve (AUC) = 0.686. In FUSCC validation cohort, the high-risk group possessed worse survival outcome than the low-risk group (P = 0.015). Immune infiltrates was correlated to survival in UCEC and low TMB were associated with less immune infiltrates, which suggested poor immune response. TMB was not only related to overall survival but also immune infiltrates in UCEC. The TMB-related signature (GFAP, EDN3, CXCR3, PLXNA4, SST) had good predictability for overall survival in endometrial cancer. Our study might have some merits in elucidating potential mechanism of TMB and immune infiltrates in UCEC and providing guidance of immunotherapy for endometrial cancer.

Risk factors for omental metastasis and the effect of omentectomy on survival in type 2 endometrial cancer patients

To investigate the risk factors for occult omental metastasis and the effect of omentectomy on the survival of type 2 endometrial cancer (EC) patients. This study enrolled patients who were diagnosed with high-risk (grade 3, serous, clear cell, undifferentiated, carcinosarcoma, or mixed type) EC between 2000 and 2021 and underwent surgery in our center. Data from 482 patients were analyzed retrospectively. Omentectomy was performed in 405 (84.0%) patients. Omental metastases were detected in 61 (12.7%) patients. Eighteen (29.5%) of these metastases were occult. Adnexal involvement, malignant cytology, and peritoneal spread were independent risk factors for omental metastasis. The 5-year overall survival (OS) rate was 59.5% in patients who underwent omentectomy and 64.7% in those who did not (P = 0.558). In patients with and without omental metastases, the overall 5-year OS rates were 34.9% and 63.5%, respectively (P < 0.001). The 5-year OS rates of patients with a normal omentum, gross tumors, and occult metastases were 63.5%, 26.9%, and 52.5%, respectively (P < 0.001). Omental metastases is not uncommon in type II endometrial cancer; approximately one third of patients have occult metastases. Factors - positive cytology, adnexal involvement, and peritoneal involvement are associated with higher probability of omental metastases.

The prognostic value of FIGO staging defined by combining MRI and [18F]FDG PET/CT in patients with locally advanced cervical cancer

The last version of the FIGO classification recommended imaging tools to complete the clinical assessment of patients with cervical cancer. However, the preferable imaging approach is still unclear. We aimed to explore the prognostic power of Magnetic Resonance Imaging (MRI), contrast-enhanced Computed Tomography (ceCT), and [

Successful management of nongestational ovarian choriocarcinoma complicated with choriocarcinoma syndrome: A case report and a literature review

Nongestational ovarian choriocarcinoma (NGOC) accounts for <1% of ovarian germ cell tumors and may develop into the rare and fatal complication of choriocarcinoma syndrome. We reported a case of a 12-year-old girl with NGOC that metastasized to the lungs, retroperitoneal lymph nodes and brain. On day 2 of chemotherapy with actinomycin D and etoposide, choriocarcinoma syndrome developed due to a massive pulmonary hemorrhage, presenting as acute respiratory distress syndrome. The patient received mechanical ventilation and multimodal support and completed two cycles of an actinomycin D and etoposide regimen with intubation. After the patient's acute respiratory distress syndrome was under control, she received 9 cycles of more intensive chemotherapy regimens and achieved complete remission. An exploratory laparotomy with salpingo-oophorectomy confirmed ovarian choriocarcinoma. The patient remained disease-free at a 3-month follow-up visit. In conclusion, appropriate management consisting of multimodal support and timely, sequential and intensive chemotherapy is effective for NGOC complicated with choriocarcinoma syndrome. Stating with mild regimens would probably reduce the risk of choriocarcinoma syndrome, or at least lessen its severity. To our knowledge, we presented the first report of NGOC-related choriocarcinoma syndrome.

The prognostic role of peritoneal cytology in stage IA endometrial endometrioid carcinomas

Debates exist about the effects of peritoneal cytology and its treatment on the survival of early endometrial cancer. This study is to explore the prognostic role of peritoneal cytology and relevant therapy in patients with stage IA endometrial endometrioid carcinomas in a retrospective cohort study. From June 1, 2010, to June 1, 2017, in a teaching hospital, all the cases of pathologically confirmed stage IA endometrioid endometrial cancer were reviewed. Patients were followed up to February 1, 2019. The survival outcomes were compared among patients with negative peritoneal cytology, positive peritoneal cytology and no peritoneal cytology outcomes. In total, 1284 patients were included in the study, and 754 (58.7%) had peritoneal cytology evaluations with 22 (2.9%) of positive peritoneal cytology. After a median follow-up of 57.4 months, 1257 patients (97.9%) had definite survival outcomes. None of the patients with positive peritoneal cytology had recurrence or mortality. The appearance of positive peritoneal cytology had no impact on the disease-free, overall and cancer-specific overall survivals in univariate and multivariate analyses. No risk factors, including the adjuvant therapy, were found to be relevant with the appearance and survival in patients with positive peritoneal cytology. In patients with stage IA endometrial endometrioid carcinoma, the prevalence of positive peritoneal cytology was very low without know risk factor. Positive peritoneal cytology did not influence the survival outcomes of whole population, and adjuvant therapy did not influence the survival outcomes of patients with positive peritoneal cytology in such population. Mini Abstract The appearance of positive peritoneal cytology in stage IA endometrial endometrioid carcinomas had no clinical significance and need no adjuvant therapy.

Prognostic role of the peritoneal cancer index in ovarian cancer patients who undergo cytoreductive surgery: a meta-analysis

Advanced-stage ovarian cancer is usually associated with peritoneal carcinomatosis. This study evaluates the prognostic role of the Peritoneal Cancer Index (PCI) in predicting the survival of patients with ovarian cancer. A literature search was conducted in electronic databases (Google Scholar, PubMed, Ovid, and Science Direct) and study selection was based on precise eligibility criteria. Random-effects meta-analyses were performed to estimate survival with low and high PCI scores and to pool hazard ratios (HR) of survival between lower and higher PCI scores. A total of 20 studies (2588 patients) were included. Median follow-up was 39 months [95%CI: 25, 54]. Complete cytoreduction rate was 80% [95% CI: 73, 87]. The median PCI score was 11.3 [95% CI: 9.9, 12.7]. Median survival was 56.7 months [95% CI: 45.2, 68.2] with below and 28.8 months [95% CI: 23.0, 34.6] with above any PCI cutoff. Most studies used PCI cutoffs between 10 and 20. The median progression-free survival was 23.7 months [95% CI: 16.5, 30.8] with below and 11.9 months [95% CI: 5.9, 17.9] with above any PCI cutoff. 5-year survival rates were 61.3% [95% CI: 49.9, 72.8] with PCI10 cutoffs, 50.1% [95% CI: 39.0, 61.2] with PCI20 cutoffs. Pooled analysis of HRs showed that a higher PCI score was associated with worse survival in both univariate (HR 2.14 [95%CI: 1.63, 2.66]) and multivariate (HR 1.10 [95% CI: 1.02, 1.18]) analyses. In a set of studies that used varying PCI cutoffs, the PCI has been found to have a significant inverse association with the survival of patients with advanced ovarian cancer who underwent cytoreductive surgery.

RING finger protein 187 as a novel potential biomarker for predicting the prognosis of ovarian carcinoma in 2 cancer centers

RING finger protein 187 (RNF187) has been used to predict prognosis of several human carcinomas. However, the clinicopathologic and prognostic implication of RNF187 expression in ovarian carcinomas remains not to be evaluated. The aim of this study was to explore the clinicopathologic and the prognostic significance of RNF187 in patients with ovarian carcinomas. Expression levels of RNF187 protein were investigated by immunohistochemical staining based on tissue-microarray composed of 147 patients with ovarian carcinomas. Receiver operating characteristic curve analysis was used to select the ideal cut-off value of RNF187 expression in ovarian carcinoma, and then analyze the correlation between the status of RNF187 expression and various clinicopathologic variables by chi-square test. Univariate analysis was employed to investigate the association between clinicopathologic variables and prognosis of patients by Kaplan-Meier method. Multivariate analysis was performed to identify the independent prognostic factors by the Cox regression model. Our results demonstrated that high expression of RNF187 was significantly associated with late FIGO stage, high histologic grade and pN1 stage in ovarian carcinoma (P < 0.05). Univariate analysis uncovered patients with the high expression of RNF187 have the worse overall survival and disease-free survival (P < 0.05). More surprisingly, multivariate analysis determined that the RNF187 expression was served as an independent prognostic factor in ovarian carcinoma. The high expression of RNF187 might influence a more aggressive biological behavior in ovarian carcinoma. Therefore, RNF187 expression could be useful to act as a new independent prognostic biomarker for patients with ovarian carcinoma.

Characterization of HPV subtypes not covered by the nine-valent vaccine in patients with CIN 2-3 and cervical squamous cell carcinoma

As the second most common female malignant tumor, cervical cancer is also one of the most preventable and avoidable cancers. The World Health Organization has launched a global plan to accelerate the elimination of cervical cancer. Therefore, in the era of postvaccine, the role of HPV subtypes in cervical precancerous lesions and cervical cancer that are not covered by vaccine should be further discussed. The purpose of this study was to explore the role of HPV subtypes not covered by the nine-valent vaccine in high-grade cervical precancerous lesions and cervical cancer. A retrospective analysis was performed on the clinical data of 5220 patients with an HPV infection who were diagnosed and treated in the Department of Gynecology of Shanghai General Hospital between October 2016 and February 2020. In addition, the clinical characteristics of the biopsy results of 470 cases of cervical intraepithelial neoplasia (CIN) 2-3 and 205 cases of cervical squamous cell carcinoma were analyzed. Among patients with HPV subtype infection not covered by the nine-valent vaccine, univariate analysis showed that compared with patients with CIN 2-3, age ≥ 50, not using condom and TCT reported as ASC-H were risk factors for cervical squamous cell carcinoma (P < 0.05). The detection rates of HPV subtype not covered by the nine-valent vaccine in CIN 2-3 and cervical squamous cell carcinoma patients were 7.23% and 6.34%, respectively. In patients with CIN 2-3 and cervical squamous cell carcinoma, the infection rates of HPV subtype not covered by the nine-valent vaccine were 7.23% and 6.34%, respectively. With the increasing popularity of the vaccine, the infection rates of the corresponding HPV subtype decreased; however, HPV subtype infection not covered by the nine-valent vaccine should not be ignored.

Maternal age at first birth and uterine cancer risk: A comprehensive analysis using NHANES data (2003–2018)

Several reproductive factors, including parity and age at menarche, have been identified as risk factors for uterine cancers. However, the association between maternal age at first birth and uterine cancer remains conflicting. This cross-sectional study included females aged 20 years and older with at least one live birth across eight National Health and Nutrition Examination Survey (NHANES) cycles (2003-2018). We used design-adjusted logistic regression, with multiple imputation for missing data, to explore the association of age at first birth and uterine cancer. As a sensitivity analysis, the sample was restricted to post-menopausal females; logistic regression analyses were repeated. Among 7095 participants, 104 had uterine cancer. The adjusted odds ratio (aOR) for uterine cancer for participants with a first live birth at ≥25 years was 0.66 (95 % confidence interval (CI): 0.33-1.35) compared to those with a first birth at <20 years. For participants with a first birth between 20-24 years, the aOR was 0.93 (95 % CI: 0.51-1.69). Multiple imputation and sensitivity analyses yielded similar non-significant results. Our findings suggest no statistically significant association between maternal age at first live birth and uterine cancer, aligning with existing literature. Further research is needed to explore other reproductive factors and their role in uterine cancer risk.

Chemoradiotherapy treatment with gemcitabine improves renal function in locally advanced cervical cancer patients with renal dysfunction

Cervical cancer (CC) in Mexico is diagnosed mainly in locally advanced (LACC) and advanced (ACC) stages, where ureteral obstruction is more frequent. The standard treatment for this population is concurrent chemoradiotherapy (CCRT) with cisplatin, which is nephrotoxic and could lead to further deterioration of renal function in LACC patients with renal function decline. We aimed to evaluate the effect of CCRT with Gemcitabine on renal function in LACC patients. This retrospective study included LACC patients treated with CCRT with Gemcitabine as a radiosensitizer from February 2003 to December 2018. Data were collected from medical archives and electronic records. We assessed renal function before and after CCRT treatment and analyzed the patient's response to treatment and survival. 351 LACC patients treated were included and stratified into two groups: 198 with Glomerular Filtration Rate (GFR) ≥60ml/min (group A) and 153 with GFR<60ml/min (group B). An improvement in GFR was observed after CCRT in patients in group B, from 33 ml/min to 57.5 ml/min (p<0.001). Complete response was observed in 64.1% of patients in Group A and 43.8% in Group B (p<0.0001). Factors associated with increased risk of death included having a GFR of 15-29 ml/min (HR: 2.17; 1.08-4.35), having GFR<15 ml/min (HR: 3.08; 1.63-5.79), and receiving Boost treatment (HR: 2.09; 1.18-3.69). On the other hand, receiving brachytherapy is a positive predictor for OS (HR:0.51; 0.31-0.84). CCRT with gemcitabine is an appropriate treatment option for patients diagnosed with LACC who present impaired renal function due to the disease's obstructive nature or other comorbidities.

Vaginal intraepithelial neoplasia in patients after total hysterectomy

To investigate the incidence of vaginal intraepithelial neoplasia (VaIN) after total hysterectomy and, subsequently, optimize the follow-up strategy of patients after hysterectomy. This retrospective study was conducted on 8581 patients with benign gynecology disease who underwent total hysterectomy in our institution between January 2006 to December 2017, including 834 patients with cervical intraepithelial neoplasia (CIN) and 7747 patients without cervical lesions before hysterectomy. All patients underwent postoperative high-risk human papilloma virus (Hr-HPV) screening and liquid-based cytology test (LCT) as confirmatory tests. Colposcopies were performed if the results of the confirmatory tests were abnormal, and biopsies were performed depending on colposcopy images. The mean follow-up time was 33.8 ± 12.1 months. The relationship among VaIN, CIN, and confirmatory test results was investigated. VaIN was found in 81 patients after hysterectomy (incidence rate, 0.9%). The incidence rates of VaIN in patients with and without CIN history were significantly different (7.3%, 61/834, vs 0.3%, 20/7747; P < 0.05). Compared with patients without CIN history, those with CIN history were more likely to have abnormal LCT results in the postoperative follow-up, especially low-grade squamous intraepithelial lesions or worse (P < 0.001). Patients with high-grade squamous intraepithelial lesions in the LCT have a high VaIN incidence (patients with CIN history, 57.1%; patients without CIN history, 15.1%), and the 2 patients with squamous cell carcinoma or adenocarcinoma (SCC/AC) in the LCT had CIN and VaIN or worse after hysterectomy. The Hr-HPV infection rates after the hysterectomy of patients with and without CIN history were 18.8% (157/834) and 5.4% (419/7747), respectively. The incidences morbidities of VaIN in patients with persistent Hr-HPV infection and in those with and without CIN history were 35.7% and 12.0%, respectively, and were significantly higher than those in patients with negative Hr-HPV (patients with CIN history, 0.7%; patients without CIN history, 0.1%; P = 0.002). The incidence of VaIN in patients with CIN history with HPV-16 infection after hysterectomy was as high as 50%, but in patients without CIN history, the incidences of different Hr-HPV subtypes were not significantly different (P = 0.953). Patients with CIN history were more prone to VaIN and SCC after hysterectomy than were patients without CIN history. Patients should be screened thoroughly for cervical and vaginal lesions before hysterectomy. After hysterectomy, patients with CIN history should undergo lifetime annual LCT and HPV screening.

A rare case Of gastric cancer: Isolated vaginal metastasis

Gastric cancer is one of the most common cancers worldwide. The vast majority of gastric cancer is adenocarcinoma histologically. The majority of gastric cancer patients show distant metastasis at the time of diagnosis. Because they are diagnosed with metastatic disease, most often they are inoperable ovarian metastasis is a well-known metastasis of gastric cancer. Vaginal metastasis happens by the local spreading of ovarian or uterine metastasis. This study reports a gastric cancer case that presented with isolated vaginal metastasis in the absence of ovarian or uterine metastasis.

Hormone replacement therapy in endometrial cancer survivors: A retrospective cohort study on recurrence, survival, and quality of life

Endometrial cancer is the most common gynecologic malignancy in developed countries, often affecting postmenopausal women but also seen in younger patients. Standard treatment includes hysterectomy with bilateral salpingo-oophorectomy, which may lead to menopausal symptoms, especially in premenopausal women. The use of hormone replacement therapy (HRT) in survivors remains controversial due to concerns about stimulating cancer cells. This study aims to evaluate the impact of postoperative HRT on cancer recurrence, survival outcomes, and quality of life in endometrial cancer survivors. This retrospective cohort study analyzed 176 women -between August 2024 and May 2025- with histologically confirmed endometrial adenocarcinoma. Participants were categorized into HRT users (n = 91) and non-users (n = 85) with a median age of 58 and 62 years respectively. Demographic, clinical, and treatment data were compared. Survival analyses were conducted using Kaplan-Meier and Cox regression models. Quality of life was assessed using the MENQOL questionnaire. HRT use was associated with lower recurrence (HR=0.379, p = 0.002) and death hazard (HR=0.248, p = 0.039) rates. Mean recurrence-free survival was longer in the HRT group (53.14 vs 46.28 months, p < 0.001). Improvement in menopausal symptom scores was significantly higher in HRT users (MD= -2.03) compared to the control group (MD= -0.89). No significant increase in adverse cardiovascular or thromboembolic events was observed. Postoperative HRT appears safe and beneficial for selected endometrial cancer survivors, offering improved recurrence-free survival and better menopausal symptom control without increasing serious adverse events. Individualized assessment remains crucial, and further prospective trials are needed to confirm these findings.

Diagnostic accuracy of intraoperative frozen section in endometrial cancer: Correlation with final histopathology

Accurate intraoperative assessment of tumor characteristics for endometrial cancer, including histological type, grade, and depth of myometrial invasion (MI), is essential for determining the extent of surgery, particularly lymphadenectomy. This study aims to evaluate the concordance between intra-operative frozen section analysis (IFS) and final histopathology (FH) in endometrial cancer cases. This retrospective analysis included 100 patients who underwent laparoscopic staging surgery for endometrial carcinoma between March 2018 and September 2024. Data on histological type, tumor grade, MI, lymph node involvement, and cervical/adnexal metastases were extracted from medical records. The diagnostic accuracy of IFS was assessed by comparing findings with FH. Sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV), and Cohen's kappa (κ) statistics were used to determine agreement levels. IFS demonstrated high concordance with FH for malignancy detection (97%, κ = 0.56). Sensitivity, specificity, PPV, and NPV were 96.9%, 100%, 100%, and 40%, respectively. Tumor grading agreement was 78.2% (κ = 0.67), with the highest accuracy in Grade 3 tumors (sensitivity 85.0%, specificity 98.3%). MI assessment showed strong agreement (κ = 0.851) with 93.7% overall accuracy. Lymph node evaluation by IFS exhibited excellent agreement (κ = 0.942), with 98.3% accuracy. IFS is a reliable tool for intraoperative decision-making in endometrial cancer, particularly for malignancy detection, MI assessment, and lymph node evaluation. However, moderate concordance in tumor grading suggests caution in surgical decision-making based solely on IFS results. Future research should focus on optimizing frozen section protocols to improve diagnostic accuracy and streamline intraoperative management.

Evaluation and external validation of minor lymphatic pelvic pathway for distant metastases in cervical cancer patients treated with concurrent chemoradiotherapy

To evaluate and validate the minor lymphatic pathway for distant metastases in cervical cancer. This is a retrospective cohort of cervical cancer patients underwent curative concurrent chemoradiotherapy. We used original dataset from 1 university hospital and validation dataset from 3 university hospitals. Lymphadenopathy status in CT imaging was reviewed by radiologist in either the obturator and external iliac nodes (major pathway) or the internal iliac and presacral nodes (minor pathway). We then used Cox regression to adjust for all potential confounders, including paraaortic nodes, T stage, histology, age, total treatment time, total number of nodes, total short axis of nodes. 397 and 384 patients were in the original and validation datasets (median follow-up period, 59.5 month's). The minor pathway was independent prognostic factor in multivariable analysis [HR=2.64; 95%CI=1.07-6.55; P = 0.036] and [HR=14.84; 95%CI=3.15-70.01; P= 0.001] in original and validation datasets, respectively. Whereas, the major pathway was statistically non-significant. Further validation showed that the minor pathway had the highest HR for distant metastases with both the EMBRACE (HR=6.05; 95% CI=1.30-28.08; P = 0.022) and the FIGO 2018 (HR=7.43; 95% CI=2.94-18.78; P<0.001) in the original dataset. A similar result was found with the validation dataset: EMBRACE, HR=30.91; 95% CI=2.78-343.62; P = 0.005; and FIGO 2018, HR=42.41; 95% CI=8.83-203.60; P<0.001.This is the first clinical study to validate that the minor lymphatic pathway was predominantly associated with distant metastases in cervical cancer. This finding should be validated in larger cohort to further integrate in standard staging for prediction of distant metastases.