OBJECTIVE: To report the results of a multicenter cohort of preoperative brachytherapy (PBT) for treatment of early-stage cervical cancer (ESCC).
METHODS: A retrospective analysis was conducted among five French comprehensive cancer centers on behalf of the SFRO Brachytherapy Group to examine the outcome of patients with ESCC who received PBT between 2001 and 2019 because of adverse prognostic factors (tumor size >2 cm, presence of lymphovascular invasion, adenocarcinoma).Brachytherapy was followed 4-8 weeks later by surgery. Local relapse free, distant metastasis-free survival, disease-free, and overall survival and adverse effects were examined. Uni- and multivariate analyses were conducted looking for oncological prognostic factors.
RESULTS: A total of 451 patients were identified, with a mean tumor size of 24.7 mm. Adenocarcinoma accounted for 43.5% of cases, and lympho-vascular space invasion (LVSI) was present in 15.7%. A complete histological response was observed in 69.6%. With a mean follow-up of 75.4 months, DFS, LRFS, and OS rates at five years were 88% [95% CI (84-91), 98% [95% CI (96-99), and 92% [95% CI (87-95)], respectively. At the last follow-up, 8.2% of patients had died, including 31 (6.8%) from cervical cancer. Severe side effects range from 1.1% to 2%. At multivariate analysis, adenocarcinoma histological type, tumor size ≥2 cm, and the presence of residual tumors were prognosticators for DFS and DMFS.
CONCLUSIONS: PBT shows excellent oncological outcomes in this cohort of patients with adverse histoprognostic factors. Favorable survival rates and low complications rates were observed, supporting this strategy in the management of ESCC.

OBJECTIVE: To report the outcome of SLN staging in the SENTIX international prospective trial of SLN biopsy in patients with cervical cancer with an intensive ultrastaging protocol and central quality control and to evaluate how the intensity of pathological assessment correlates with metastatic detection rate in SLNs.
METHODS: Eligible were patients with stages T1a1/LVSI+ to T1b2 (<4 cm, ≤2 cm for fertility sparing), common tumor types, no suspicious lymph nodes on imaging, and bilateral SLN detection. SLNs were examined intraoperatively and processed by an intensive protocol for ultrastaging (paraffin blocks sectioned completely in 150-μm intervals/levels). SLNs from each site were submitted for central quality control.
RESULTS: In the SENTIX SLN study, 647 out of 733 enrolled patients underwent SLN ultrastaging, identifying 12.5% (81/647) with node positive, N1 cases. Intraoperative detection revealed metastases in 56.8% (46/81) of these cases, categorized into macrometastases (83.7%), micrometastases (26.3%), and isolated tumor cells (9.1%). Ultrastaging identified additional metastatic involvement in 43.2% (35/81) of patients, with detailed sectioning revealing metastases (MAC/MIC) at first level in 20 cases (24.7%), at levels 2-4 in 9 cases (11.1%), and at level ≥5 in 6 cases (7.4%).
CONCLUSIONS: SLN ultrastaging detects additional 43% of N1 (MAC/MIC) in patients with negative LNs by imaging and intraoperative pathological assessment. The detection rate of positive SLN correlates with the intensity (number of levels) of ultrastaging. Examination of four levels from paraffin blocks, which detects >90% of patients with N1, is a reasonable compromise for an international standard for ultrastaging.
BACKGROUND: NCT02494063 (ClinicalTrials.gov).

OBJECTIVE: This study aimed to systematically examine the relationship between polycystic ovary syndrome and ovarian, endometrial, and cervical cancers using the National Inpatient Sample (NIS) database.
METHODS: We utilized the International Classification of Diseases (ICD-10) system to identify relevant codes from the NIS database (2016-2019). Univariate and multivariable regression analyses (adjusted age, race, hospital region, hospital teaching status, income Zip score, smoking, alcohol use, and hormonal replacement therapy) were conducted to evaluate association between PCOS and gynecologic cancers. Results were summarized as odds ratio (OR) with 95% confidence intervals (CI).
RESULTS: Overall, 15,024,965 patients were analyzed, of whom 56,183 and 14,968,782 patients were diagnosed with and without PCOS, respectively. Among the patients diagnosed with gynecologic cancers (n = 91,599), there were 286 with PCOS and 91,313 without PCOS. Univariate analysis revealed that PCOS was significantly associated with higher risk of endometrial cancer (OR = 1.39, 95 % CI [1.18-1.63], p < 0.0001), but lower risk of ovarian cancer (OR = 0.55, 95 % CI [0.45-0.67], p < 0.0001) and cervical cancer (OR = 0.68, 95 % CI [0.51-0.91], p = 0.009). In contrast, after Bonferroni correction, multivariable analysis depicted that PCOS remained significantly associated with higher risk of endometrial cancer (OR = 3.90, 95 % CI [4.32-4.59], p < 0.0001). There was no significant correlation between PCOS and risk of ovarian cancer (OR = 1.09, 95 % CI [0.89-1.34], p = 0.409) and cervical cancer (OR = 0.83, 95 % CI [0.62-1.11], p = 0.218).
CONCLUSIONS: This first-ever NIS analysis showed that patients with PCOS exhibited unique gynecologic cancer risk profiles, with higher risk for endometrial cancer, and no significant risk for ovarian or cervical cancers.

A consensus regarding subsequent therapeutic strategies for patients with platinum- and poly (ADP-ribose) polymerase inhibitor (PARPi)-resistant ovarian cancer is lacking. These patients typically receive non-platinum-based chemotherapy; however, survival outcomes remain poor. Compared with chemotherapy alone, combination therapy with novel target agents can provide additional benefits to these patients. Oregovomab, an investigational murine monoclonal antibody against CA-125, has shown promising efficacy in a phase II study in patients with recurrent ovarian cancer. Herein, we described the rationale and design of OPERA/KGOG 3065/APGOT-OV6, a multicenter, investigator-initiated, two-cohort, single-arm phase II trial, aimed at examining the efficacy of oregovomab plus non-platinum-based chemotherapy in patients with PARPi/platinum-resistant ovarian cancer. The primary end point was the objective response rate, according to RECIST 1.1.Clinical Trial Registration: NCT05407584 (ClinicalTrials.gov).
OPERA/KGOG 3065/APGOT-OV6 is a promising phase II studies that test new drug (oregovomab) on the patients with poly (ADP-ribose) polymerase inhibitor (PARPi)/platinum-resistant epithelial ovarian cancer. PARPis have changed the treatment landscape of ovarian cancer in a relatively short time. PARPi/platinum-resistant epithelial ovarian cancer refer to a subtype of recurrent epithelial cancer of ovarian, tubal or peritoneal origin who experienced disease progression despite treatment with a PARPi or platinum-based chemotherapy drugs. Although various new drugs have been tested to improve the treatment response in resistant patients, a consensus regarding the international standard of treatment is yet to be established, despite the poor survival outcomes of these patients. OPERA/KGOG 3065/APGOT-OV6 has been designed to add oregovomab, a murine monoclonal antibody to cancer antigen-125 (CA-125), to non-platinum chemotherapy (pegylated liposomal doxorubicin or paclitaxel) for patients with ovarian cancer determined as PARPi/platinum-resistant and ineligible for bevacizumab treatment. The results of this study will aid in developing effective treatment strategies for patients with PARPi/platinum-resistant ovarian cancer.

The aim of the present study was to explore the effects of dexmedetomidine (DEX) combined with ketorolac on postoperative patient-controlled analgesia (PCA), the balance of Th1/Th2 and the level of vascular endothelial growth factor (VEGF) in patients with cervical cancer following laparoscopic radical surgery. A total of 70 women with cervical cancer undergoing laparoscopic radical hysterectomy were enrolled in the study to randomly receive postoperative dexmedetomidine combined with ketorolac analgesia (DK group) and postoperative sufentanil analgesia (SUF group). The primary outcomes were the serum levels of interleukin-4 (IL-4), interferon-γ (IFN-γ) and VEGF, and the IFN-γ/IL-4 ratio 30 min before induction (T0), and 24 and 48 h after surgery. Secondary outcomes included numerical rating scale scores at 0 h (T0), 4 h (T1), 12 h (T2), 24 h (T3) and 48 h (T4) postoperatively, cumulative times of rescue analgesia, as well as the incidence of postoperative side effects within 48 h from surgery. Patients in the DK group reported similar analgesic effects as patients in the SUF group at T2, T3 and T4, and the incidence of postoperative nausea and vomiting was significantly lower in the DK group. In the DK group, the serum concentration of IFN-γ and IFN-γ/IL-4 ratio at 24 and 48 h after surgery were higher compared with those in the SUF group. Conversely, the serum concentrations of IL-4 at 24 h after surgery and VEGF at 24 and 48 h after surgery were significantly lower. The results indicated that the combination of DEX and ketorolac for PCA significantly improved postoperative pain and decreased the serum level of VEGF, which are associated with tumor angiogenesis. In addition, it maintained the homeostasis of postoperative immune dysfunction of patients with cervical cancer by shifting the balance between type 1 T helper cells and type 2 T helper cell (Th1/Th2 balance) to Th1 (registration no. ChiCTR1900027979; December 7, 2019).

BACKGROUND: Cervical cancer is the fourth most frequent cancer among women, with 90% of cervical cancer-related deaths occurring in low- and middle-income countries like Cameroon. Visual inspection with acetic acid is often used in low-resource settings to screen for cervical cancer; however, its accuracy can be limited. To address this issue, the Swiss Federal Institute of Technology Lausanne and the University Hospitals of Geneva are collaborating to develop an automated smartphone-based image classifier that serves as a computer aided diagnosis tool for cancerous lesions. The primary objective of this study is to explore the acceptability and perspectives of women in Dschang regarding the usage of a screening tool for cervical cancer relying on artificial intelligence. A secondary objective is to understand the preferred form and type of information women would like to receive regarding this artificial intelligence-based screening tool.
METHODS: A qualitative methodology was employed to gain better insight into the women\'s perspectives. Participants, aged between 30 and 49 were invited from both rural and urban regions and semi-structured interviews using a pre-tested interview guide were conducted. The focus groups were divided on the basis of level of education, as well as HPV status. The interviews were audio-recorded, transcribed, and coded using the ATLAS.ti software.
RESULTS: A total of 32 participants took part in the six focus groups, and 38% of participants had a primary level of education. The perspectives identified were classified using an adapted version of the Technology Acceptance Model. Key factors influencing the acceptability of artificial intelligence include privacy concerns, perceived usefulness, and trust in the competence of providers, accuracy of the tool as well as the potential negative impact of smartphones.
CONCLUSIONS: The results suggest that an artificial intelligence-based screening tool for cervical cancer is mostly acceptable to the women in Dschang. By ensuring patient confidentiality and by providing clear explanations, acceptance can be fostered in the community and uptake of cervical cancer screening can be improved.
BACKGROUND: Ethical Cantonal Board of Geneva, Switzerland (CCER, N°2017-0110 and CER-amendment n°4) and Cameroonian National Ethics Committee for Human Health Research (N°2022/12/1518/CE/CNERSH/SP). NCT: 03757299.
Globally, cervical cancer is the fourth most frequent cancer among women. However, 90% of all deaths caused by cervical cancer occur in low-and middle-income countries. Methods traditionally used in settings like Cameroon to detect cervical cancer unfortunately lack accuracy. Therefore, researchers at the Swiss Federal Institute of Technology Lausanne and the University Hospitals of Geneva are developing an artificial intelligence-based computer aided diagnosis tool to detect pre-cancerous lesions using a smartphone application. The aim of this study was to explore the acceptability and perspectives regarding an AI-based tool for cervical cancer screening for women in Dschang, a city in the west of Cameroon. A qualitative methodology was conducted with six focus groups and a total of 32 participants. The main concerns highlighted by the study are related to privacy, trust in the ability of the healthcare providers, accuracy of the tool as well as the potential negative impact of smartphones. In conclusion, our results show that a computer aided diagnosis tool using artificial intelligence is mostly acceptable to women in Dschang, as long as their confidentiality is preserved, and they are provided with clear explanations beforehand.

Cervical cancer (CC) is a prevalent gynecological cancer worldwide that significantly impacts the quality of life and the physical and mental well-being of women. However, there have been limited studies utilizing Mendelian randomization (MR) analysis to investigate the connection between immune cells and CC. This study is to investigate the causal effects of immune traits on CC and non-neoplastic conditions of the cervix. The GWAS data for 731 immunophenotypes and six GWAS data for CC from the FinnGen database were downloaded. Subsequently, a two-sample MR analysis was conducted using the MR Egger, Weighted median, Inverse variance weighted (IVW), Simple mode, and Weighted mode methods. Our study has identified the potential causal effects of immune traits on inflammatory diseases of the cervix, other noninflammatory disorders of the cervix uteri, carcinoma in situ of cervix uteri, adenocarcinomas of cervix, squamous cell neoplasms and carcinoma of cervix, as well as malignant neoplasm of the cervix uteri, with the respective numbers being 8, 6, 11, 8, 23, and 12, respectively. A strong correlation between classic monocytes and various cervical diseases was revealed. Furthermore, we discovered that B cells expressing BAFF-R have the ability to impede the advancement of malignant CC, specifically squamous cell neoplasms and carcinoma of cervix. Our study has demonstrated a significant association between immune traits and both CC and non-neoplastic conditions of the cervix through two-sample Mendelian randomization, providing valuable insights for future clinical research.

BACKGROUND: The endometrium remains a difficult tissue for the analysis of microbiota, mainly due to the low bacterial presence and the sampling procedures. Among its pathologies, endometrial cancer has not yet been completely investigated for its relationship with microbiota composition. In this work, we report on possible correlations between endometrial microbiota dysbiosis and endometrial cancer.
METHODS: Women with endometrial cancer at various stages of tumor progression were enrolled together with women with a benign polymyomatous uterus as the control. Analyses were performed using biopsies collected at two specific endometrial sites during the surgery. This study adopted two approaches: the absolute quantification of the bacterial load, using droplet digital PCR (ddPCR), and the analysis of the bacterial composition, using a deep metabarcoding NGS procedure.
RESULTS: ddPCR provided the first-ever assessment of the absolute quantification of bacterial DNA in the endometrium, confirming a generally low microbial abundance. Metabarcoding analysis revealed a different microbiota distribution in the two endometrial sites, regardless of pathology, accompanied by an overall higher prevalence of pathogenic bacterial genera in cancerous tissues.
CONCLUSIONS: These results pave the way for future studies aimed at identifying potential biomarkers and gaining a deeper understanding of the role of bacteria associated with tumors.

Background and Objectives: Our aim was to perform a retrospective analysis of the volume of cervical screening tests, the number of patients treated with an excision method, and the incidence of invasive and non-invasive cervical during a pandemic and pre-pandemic period of 24 months. Materials and Methods: The study compared 404 patients who underwent cervical cone biopsy for cervical cancer. The study examined patients\' specimens based on histopathological characteristics and categorized cervical lesions based on pap smear. Results: There was a statistically significant age difference between the two study periods. The mean difference was 32 years before the pandemic and 35 years during the pandemic (p-value > 0.05). The biggest patient loss ratio identified by age group was in the 50-59-year group, with a 14.53% loss in the pre-pandemic period and a 9.1% loss in the pandemic period. In the pandemic period, patients from rural areas presented in the clinical trial with a lower rate of 39.52% (83 patients) vs. 60.47% (127 patients) in urban areas. A higher percentage of patients experiencing cervicorrhagia as a clinical manifestation in the pandemic period vs. the pre-pandemic period, with an increase in more severe lesions in the pandemic period, had a statistical significance of 8% more newly diagnosed compared to the pre-pandemic period. Conclusions: The addressability of the patients during the COVID period was not affected in a drastic way in our study. We encountered a decrease in appointments in the age group of 50-59 years and a decrease in patients with rural residence. In our study, we found an increase in cervical bleeding as a reason for consultation in the pandemic period with a higher lesion degree, both on a pap smear and on a cervical biopsy.

Raf Kinase Inhibitor Protein (RKIP) is recognized as a bona fide tumor suppressor gene, and its diminished expression or loss is associated with the progression and poor prognosis of various solid tumors. It exerts multifaceted roles in carcinogenesis by modulating diverse intracellular signaling pathways, including those governed by HER receptors such as MAPK. Given the significance of HER receptor overexpression in numerous tumor types, we investigated the potential oncogenic relationship between RKIP and HER receptors in solid tumors. Through a comprehensive in silico analysis of 30 TCGA PanCancer Atlas studies encompassing solid tumors (10,719 samples), we uncovered compelling evidence of an inverse correlation between RKIP and EGFR expression in solid tumors observed in 25 out of 30 studies. Conversely, a predominantly positive association was noted for the other HER receptors (ERBB2, ERBB3, and ERBB4). In particular, cervical cancer (CC) emerged as a tumor type exhibiting a robust inverse association between RKIP and EGFR expression, a finding that was further validated in a cohort of 202 patient samples. Subsequent in vitro experiments involving pharmacological and genetic modulation of EGFR and RKIP showed that RKIP depletion led to significant upregulation of EGFR mRNA levels and induction of EGFR phosphorylation. Conversely, EGFR overactivation decreased RKIP expression in CC cell lines. Additionally, we identified a common molecular signature among patients depicting low RKIP and high EGFR expression and demonstrated the prognostic value of this inverse correlation in CC patients. In conclusion, our findings reveal an inverse association between RKIP and EGFR expression across various solid tumors, shedding new light on the underlying molecular mechanisms contributing to the aggressive phenotype associated with RKIP and EGFR in cervical cancer.