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Purpose: The impact of the components of survivorship care plans on adherence to cancer screening guidelines among cancer survivors is limited. We examined the association of receipt of treatment summaries, follow-up instructions, and type of doctor providing survivorship care with adherence to breast cancer screening (BCS) and cervical cancer screening (CCS) guidelines in female cancer survivors., Methods: A cross-sectional analysis using Behavioral Risk Factor Surveillance System (BRFSS) data from 2014, 2016 and 2018 was conducted. BCS and CCS-eligible women were aged 40-74 and 30-64, respectively. BCS adherence was defined as a mammogram within 2 years and CCS adherence as a pap smear within 3 years or HPV test within 5 years. Univariate analysis with chi-square and multivariable logistic regression are reported., Results: 5,001 BCS and 3,014 CCS-eligible survivors were identified. In the BCS group, recipients of treatment summaries and follow-up instructions were significantly more adherent with BCS (84.1% vs. 77.4%; 83.4% vs. 74%, respectively, p < 0.001). In the CCS group, recipients of follow-up instructions were significantly more adherent with CCS (78.1% vs. 67.7%, p < 0.001). In both groups, there was no significant difference in BCS or CCS based on type of physician providing care (p = 0.087). On multivariate analysis, receipt of follow-up instructions was the only factor significantly associated with BCS (OR:2.81; 95%CI:1.76-4.49) and CCS (OR:3.14; 95%CI:1.88-5.23)., Conclusions: Follow-up instructions, as part of survivorship care plans, have the strongest association with BCS and CCS among female cancer survivors. Additional research should focus on improving the distribution of survivorship care plans, particularly follow-up instructions, as a method to increase BCS and CCS among cancer survivors., Competing Interests: Declarations Ethics approval This is an observational study with publicly available de-identified individual data and did not require approval from the Rutgers University Institutional Board Review. Competing interests The authors declare no competing interests. Disclaimers This research was presented as a poster at the 2023 ASCO Annual Meeting, held in Chicago, IL, June 2 to 6, 2023, and published as an abstract from the meeting., (© 2024. The Author(s).)

Purpose: Systemic immunity is essential for driving therapeutically induced antitumor immune responses, and the spleen may reflect alterations in systemic immunity. This study aimed to evaluate the predictive value of contrast-enhanced CT-based spleen radiomics for progression-free survival (PFS) in patients with locally advanced cervical cancer (LACC) who underwent definitive chemoradiotherapy (dCRT). Additionally, we investigated the role of spleen radiomics features and changes in spleen volume in assessing systemic immunity., Methods: This retrospective study included 257 patients with LACC who underwent dCRT. The patients were randomly divided into training and validation groups in a 7:3 ratio. Radiomic features were extracted from CT images obtained before and after dCRT. Radiomic scores (Radscore) were calculated using features selected through least absolute shrinkage and selection operator (LASSO) Cox regression. The percentage change in spleen volume was determined from measurements taken before and after treatment. Independent prognostic factors for PFS were identified through multivariate Cox regression analyses. Model performance was evaluated with the receiver operating characteristic (ROC) curve and the C-index. The Radscore cut-off value, determined from the ROC curve, was used to stratify patients into high- and low-risk survival groups. The Wilcoxon test was used to analyze differences in hematological parameters between different survival risk groups and between different spleen volume change groups. Spearman correlation analysis was used to explore the relationship between spleen volume change and hematological parameters., Results: Independent prognostic factors included FIGO stage, pre-treatment neutrophil-to-lymphocyte ratio (pre-NLR), spleen volume change, and Radscore. The radiomics-combined model demonstrated the best predictive performance for PFS in both the training group (AUC: 0.923, C-index: 0.884) and the validation group (AUC: 0.895, C-index: 0.834). Compared to the low-risk group, the high-risk group had higher pre-NLR (p = 0.0054) and post-NLR (p = 0.038). Additionally, compared to the decreased spleen volume group, the increased spleen volume group had lower post-NLR (p = 0.0059) and post-treatment platelet-to-lymphocyte ratio (p < 0.001)., Conclusion: Spleen radiomics combined with clinical features can effectively predict PFS in patients with LACC after dCRT. Furthermore, spleen radiomics features and changes in spleen volume can reflect alterations in systemic immunity., Competing Interests: Declarations Ethics approval and consent to participate Our retrospective study abided by the rules of medical ethics, and the Institutional Review Board (IRB) of Shandong Cancer Hospital approved this study. The number for the ethical statement was SDTHEC2024006159. All patients were informed before treatment, agreed to receive concurrent dCRT and signed informed consent forms. We protected patient privacy and excluded patient identification information from our analysis. Consent for publication Not applicable. Competing interests The authors declare no competing interests., (© 2024. The Author(s).)

Background: Despite being a widely used generic measure of health-related quality of life worldwide, there is limited evidence on the psychometric properties of the EuroQoL Five-dimensions five level (EQ-5D) among cervical cancer patients in Ethiopia., Objective: To evaluate psychometric properties of the Amharic version of EQ-5D among Ethiopian cervical cancer patients., Methods: A longitudinal survey of cervical cancer patients receiving treatment at two Ethiopian tertiary care facilities was conducted from March 2022 to July 2023. Participants completed the EQ-5D and the European Organization for Research and Therapy of Cancer (EORTC QLQ-C30) at baseline and after three months on treatment. Effect size and standardized response mean were used to assess responsiveness. Anchor-based and distribution-based methods were used to calculate the minimal clinically important difference (MCID). Minimal detectable change (MDC) ratios were computed at the individual and group levels. Statistical significance was determined at p < 0.05., Results: Three hundred seventy-one patients completed the survey at baseline and follow-up with a mean age of 49.72 (10.80) years. The majority (268,73%) of the patients had early-stage cancer. The EQ-5D index and EQ VAS scores respectively improved by 0.04 and 7.0 post-treatment.The physical domains of EORTC QLQ-C30 had showed high correlation with physical dimensions of EQ-5D (r > 0.6) and the instrument showed good discriminate validity between patients with different health states. The effect size ranged between - 0.12 and 0.60 for the EQ-5D index value and - 0.12 to 1.16 for the EQ VAS, indicating small to large responsiveness. The average (range) MCID value of the EQ-5D index was 0.10-0.15. The findings showed that MCID to MDC ratios at the group level were more clinically meaningful than the individual level., Conclusion: The EQ-5D effectively detected changes and discriminate patients with different levels of health. While group-level MCIDs were established in this study, further studies are recommended to prove its usefulness at the individual-level., Competing Interests: Declarations Ethics approval and consent to participate Ethical approval was obtained from the Ethics Review Board of the School of Pharmacy, Addis Ababa University (Ref. No.: ERB/SOP/405/14/2022) and permission was received from the study hospital. Written informed consent was obtained from patients. The study was conducted in accordance with the Declaration of Helsinki. Consent for publication Not applicable. Competing interests The authors declare no competing interests., (© 2024. The Author(s).)

Objective: To evaluate the efficacy and safety of pegylated recombinant human granulocyte colony stimulating factor (PEG-rhG-CSF) in preventing neutropenia during concurrent radiotherapy combined with weekly chemotherapy in patients with cervical cancer., Methods: From September 2019 to November 2020, 180 patients with cervical cancer who required concurrent chemoradiotherapy (CCRT) were enrolled in this study. The patients were randomly divided into the following three groups at a ratio of 1:1:1: Group A (PEG-rhG-CSF), Group B (PEG-rhG-CSF + rhG-CSF) and the control group (rhG-CSF). Cisplatin or carboplatin was administered weekly. The primary endpoint was the incidence of grade 3/4 neutropenia. The secondary endpoints were the incidence of febrile neutropenia (FN), delay of radiotherapy, chemotherapy dose reduction, rate of PFS at 2 years and 3 years, and incidence of adverse reactions., Results: Sixty patients were randomly assigned to each group. Two patients in Group B withdrew from the trial for personal reasons. The incidence of grade 1/2 neutropenia in the Control group was significantly lower than that in Group A and Group B (P < 0.001). However, the incidence of grade 3/4 neutropenia in the Control group was significantly greater than that in Group A and Group B (P < 0.001). There was no significant difference in the incidence of FN among the three groups (P = 0.771). The rate of platinum dose reduction in Group A (6.7%) and Group B (5.2%) was significantly lower than that in the Control group (30.0%) (P < 0.001). The delay rate of radiotherapy in Group A (10%) and Group B (13.8%) was obviously inferior to that in the Control group (31.7%) (P = 0.006). The 2-year PFS rates of Group A, Group B, and the Control group were 93.3%, 98.3%, and 91.7%, respectively, with no statistically significant difference (P = 0.270). The 3-year PFS rates were 89.8%, 94.1%, and 84.9%, respectively, with no statistically significant difference (P = 0.178). No treatment-related serious adverse events occurred in any of the patients., Conclusion: In Group A and Group B, The prophylactic application of PEG-rhG-CSF during conventional chemoradiotherapy combined with weekly chemotherapy for patients with cervical cancer can reduce the incidence of grade 3/4 neutropenia and does not increase the incidence of adverse reactions when compared to Control group., Trial Registration: chictr.org.cn, ChiCTR1900026309, registered 29 September 2019-prospectively registered., Competing Interests: Declarations Ethics approval and consent to participate This study was approved by the Medical Ethics Committee of the Affiliated Cancer Hospital of Zhengzhou University (No. 2019221). All patients signed informed consent forms. Consent for publication The study received written informed consent for publication by all patients. Competing interests The authors declare no competing interests., (© 2024. The Author(s).)

Locally advanced cervical carcinoma (LACC) remains a significant global health challenge owing to its high recurrence rates and poor outcomes, despite current treatments. This study aimed to develop a comprehensive risk stratification model for LACC by integrating Cox regression and competing risk analyses. This was done to improve clinical decision making. We analyzed data from 3428 patients with LACC registered in the Surveillance, Epidemiology, and End Results program and diagnosed them between 2010 and 2015. Cox regression and competing risk analyses were used to identify the prognostic factors. We constructed and validated nomograms for overall survival (OS) and disease-specific survival (DSS). Multivariate Cox regression identified key prognostic factors for OS, including advanced International Federation of Gynecology and Obstetrics stage, age, marital status, ethnicity, and tumor size. Notably, International Federation of Gynecology and Obstetrics stages IIIA, IIIB, and IVA had hazard ratios of 2.227, 2.451, and 4.852, respectively, significantly increasing the mortality risk compared to stage IB2. Ethnic disparities were evident, with African Americans facing a 39.8% higher risk than Caucasians did. Competing risk analyses confirmed the significance of these factors in DSS, particularly tumor size. Our nomogram demonstrated high predictive accuracy, with area under the curve values ranging from 0.706 to 0.784 for DSS and 0.717 to 0.781 for OS. Calibration plots and decision curve analyses further validated the clinical utility of this nomogram. We present effective nomograms for LACC risk stratification that incorporate multiple prognostic factors. These models provide a refined approach for individualized patient management and have the potential to significantly enhance therapeutic strategies for LACC., Competing Interests: The authors have no funding and conflicts of interest to disclose., (Copyright © 2024 the Author(s). Published by Wolters Kluwer Health, Inc.)

Background: Cisplatin (DDP) is an efficacious and widely applied chemotherapeutic drug for cervical cancer patients who are diagnosed as metastatic and inoperable, or desiring fertility preservation. Tumor necrosis factor (TNF)-related apoptosis inducing ligand (TRAIL) selectively triggers cancer cells apoptosis by binding to cognate death receptors (DR4 and DR5). Mesenchymal stem cells-derived exosomes (MSCs-Exo) have been regarded as ideal drug carriers on account of their nanoscale, low toxicity, low immunogenicity, high stability, biodegradability, and abundant sources., Methods: Human chorion-derived mesenchymal stem cells (hCD-MSCs) were isolated by adherent culture method. TRAIL-engineered hCD-MSCs (hCD-MSCs TRAIL ) were constructed by lentivirus transfection, and its secreted Exo (hCD-MSCs-Exo TRAIL ) were acquired by differential centrifugation and confirmed to overexpress TRAIL by western blotting. Next, nanoscale drug delivery systems (DDP & hCD-MSCs-Exo TRAIL ) were fabricated by loading DDP into hCD-MSCs-Exo TRAIL via electroporation. The CCK-8 assay and flow cytometry were conducted to explore the proliferation and apoptosis of cervical cancer cells (SiHa and HeLa), respectively. Cervical cancer-bearing nude mice were constructed to examine the antitumor activity and biosafety of DDP & hCD-MSCs-Exo TRAIL in vivo., Results: Compared with hCD-MSCs-Exo, hCD-MSCs-Exo TRAIL weakened proliferation and enhanced apoptosis of cervical cancer cells. DDP & hCD-MSCs-Exo TRAIL were proved to retard cervical cancer cell proliferation and propel cell apoptosis more effectively than DDP or hCD-MSCs-Exo TRAIL alone in vitro. In cervical cancer-bearing mice, DDP & hCD-MSCs-Exo TRAIL evidently hampered tumor growth, and its role in inducing apoptosis was mechanistically associated with JNK/p-c-Jun activation and survivin suppression. Moreover, DDP & hCD-MSCs-Exo TRAIL showed favorable biosafety in vivo., Conclusions: DDP & hCD-MSCs-Exo TRAIL nanoparticles exhibited great promise for cervical cancer treatment as an Exo-based chemo-gene combinational therapy in clinical practice., (© 2024. The Author(s).)

Background: Highly heterogeneity and inconsistency in terms of prognosis are widely identified for early-stage cervical cancer (esCC). Herein, we aim to investigate for an intuitional risk stratification model for better prognostication and decision-making in combination with clinical and pathological variables., Methods: We enrolled 2071 CC patients with preoperative biopsy-confirmed and clinically diagnosed with FIGO stage IA-IIA who received radical hysterectomy from 2013 to 2018. Patients were randomly assigned to the training set (n = 1450) and internal validation set (n = 621), in a ratio of 7:3. We used recursive partitioning analysis (RPA) to develop a risk stratification model and assessed the ability of discrimination and calibration of the RPA-derived model. The performances of the model were compared with the conventional FIGO 2018 and 9th edition T or N stage classifications., Results: RPA divided patients into four risk groups with distinct survival: 5-year OS for RPA I to IV were 98%, 95%, 85.5%, and 64.2%, respectively, in training cohort; and 99.5%, 93.2%, 85%, and 68.3% in internal validation cohort (log-rank p < 0.001). Calibration curves confirmed that the RPA-predicted survivals were in good agreement with the actual survivals. The RPA model outperformed the existing staging systems, with highest AUC for OS (training: 0.778 vs. 0.6-0.717; internal validation: 0.772 vs. 0.595-0.704; all p < 0.05), and C-index for OS (training: 0.768 vs. 0.598-0.707; internal validation: 0.741 vs. 0.583-0.676; all p < 0.05). Importantly, there were associations between RPA groups and the efficacy of treatment regimens. No obvious discrepancy was observed among different treatment modalities in RPA I (p = 0.922), whereas significant survival improvements were identified in patients who received adjuvant chemoradiotherapy in RPA II-IV (p value were 0.028, 0.036, and 0.024, respectively)., Conclusion: We presented a validated novel clinicopathological risk stratification signature for robust prognostication of esCC, which may be used for streamlining treatment strategies., (© 2024 The Author(s). Cancer Medicine published by John Wiley & Sons Ltd.)

Background: Concurrent chemoradiotherapy (CCRT) is used as the primary treatment modality for currently limited cervical cancer and lacks non-invasive quantitative parameters to assess clinical outcomes of treatment for cervical cancer treatment., Purpose: To develop nomograms based on clinical prognostic factors and apparent diffusion coefficient (ADC) in predicting downstaging and progression-free survival (PFS) after CCRT for cervical cancer., Material and Methods: X-tile was used to calculate the optimal threshold for ΔADC mean (%) for prognostic stratification. Kaplan-Meier curves were used to calculate the difference in PFS between high- and low-risk groups. Univariate and multivariate Cox proportional risk regression models were used to identify clinical and radiological risk factors for prognosis and construct a prognostic nomogram model., Results: ΔADC mean (%) was significantly correlated with tumor downstaging; the area under the receiver operating characteristic curve (AUC) was 0.868. X-tile showed that the optimal threshold for ΔADC mean (%) to diagnose prognosis was 40.8. Kaplan-Meier curves showed that the low-risk population in the training group had significantly longer PFS within 3 years ( P  < 0.001). Multivariate Cox regression showed that ΔADC (%) is independent risk factor for PFS. The C-index of ΔADC(%) predicting 3-year PFS in the training set is 0.761 and the C-index of the nomogram model is 0.862., Conclusion: ΔADC mean (%) is a non-invasive biomarker for predicting tumor downstaging in cervical cancer after CCRT. The nomograms based on ΔADC mean (%) predict PFS of patients with cervical cancer with moderate accuracy., Competing Interests: Declaration of conflicting interestsThe authors declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Background: Previous studies mainly concentrate on neoadjuvant chemotherapy (NACT) for delivery delay in FIGO Stage IB1-IIIB cervical cancer during pregnancy to prevent early preterm delivery while not affecting maternal outcome., Case: Here, we described two pregnant patients with FIGO Stage IIIC cervical cancer about their diagnosis, treatment, and outcome. Both patients underwent cesarean delivery, left enlarged lymph node dissection, and longitudinal monitoring by circulating tumor DNA. Our study suggested that pregnant patient was completely response to NACT, which was confirmed by ctDNA monitoring, followed by left pelvic enlarged lymph node dissection during cesarean section and adjuvant chemoradiotherapy postpartum. The infant grew normally, without any evidence of chemotherapy-related side effects after delivery., Conclusion: In pregnant women with advanced cervical cancer, longitudinal ctDNA monitoring might be able to evaluate maternal response to NACT and confirm if delivery delay to optimize fetal outcome would compacting the maternal outcomes or not. Cervical cancer may not transmit across the placental barrier and so it is safe for delayed delivery until fetal maturity in utero during pregnancy., (© 2024 The Author(s). Cancer Reports published by Wiley Periodicals LLC.)

Background/aim: Cervical cancer is the third leading cause of cancer-related death in women worldwide. Nearly all cases of cervical cancer are due to infection with human papillomavirus (HPV). Nowata110 has shown breakthrough therapeutic efficacy in phase II clinical study against plantar warts, with no reported side effects. This study evaluated the effectiveness of Nowarta110 in killing cultured HPV-transformed cancer cells and its anti-cancer effects in mice, using both vaginally engrafted and subcutaneously implanted animal cancer models., Materials and Methods: Nowata110 is a novel compound composed of colloidal silver and fig extract. The cytotoxic properties of Nowarta110 were evaluated on HPV-16 and HPV-18-transformed human cancer cells (ARPE-19/HPV-16 and HeLa cells, respectively). The therapeutic potential of Nowarta110 in vivo was evaluated following the engraftment of ME-180 epidermoid carcinoma cells in the mouse vagina or their subcutaneous implantation. Nowarta110 treatment was initiated when the tumor reached an approximate volume of 65 mm 3 Results: Our data showed that HPV16-expressing human retinal pigmented epithelial cells are susceptible to Nowarta110-induced cell death, with a reduction in cell viability observed at 1% Nowarta110 and a complete absence of viable cells at 5% Nowarta110. In HPV18-expressing HeLa cells, Nowarta110 caused significant and rapid cell death at a dose of 5%, whereas lower doses of 1% did not produce the same effects. The results from animal studies indicated that Nowarta110 effectively induced tumor regression in both the intravaginal and subcutaneous tumor models., Conclusion: Nowarta110 effectively induced cell death in HPV-16 and HPV-18-transformed human cancer cells. It also effectively induced tumor regression in mouse models with intravaginally engrafted or subcutaneously implanted cancer cells. Considering the high prevalence of HPV-induced cervical dysplasia and cancer and the lack of treatment, clinical studies to promote the implementation of Nowarta110 are warranted., (Copyright © 2024 International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.)

Cervical cancer, originating from the epithelial tissue of the uterine cervix, constitutes the most commonly diagnosed malignancy among women worldwide. The predominant etiological factor underpinning cervical carcinogenesis is persistent infection with high-risk human papillomavirus (HPV) genotypes, notably HPV-16 and HPV-18. Oncoproteins encoded by high-risk HPV interfere with multiple essential cellular signaling cascades. Specifically, E5, E6, and E7 proteins disrupt the signaling pathways like p53, retinoblastoma tumor suppressor protein (pRB), The phosphoinositide 3 kinase (PI3K)/Akt/mammalian target of rapamycin (mTOR), epidermal growth factor receptor (EGFR), mitogen-activated protein kinases (MAPK)/extracellular signal-regulated kinases (ERK), and Wnt/β-catenin, promoting HPV-mediated carcinogenesis. This dysregulation disrupts cell cycle control, apoptosis, and metastasis through modulation of microRNAs (miRNA) and key cellular processes. The novel therapeutic interventions for HPV prevention and detection are fundamental to patient management. RNA-based treatment modalities offer the potential for manipulating critical pathways involved in cervical carcinogenesis. RNA therapeutics offer novel approaches to drug development by targeting intracellular genetic elements inaccessible to conventional modalities. Additional advantages include rapid design, synthesis, and a reduced genotoxic profile compared to DNA-based therapies. Despite beneficial attributes, system stability and efficient delivery remain critical parameters. This study assessed the intricate relationship between HPV, cervical cancer, and various signaling pathways. The study explores miRNAs' diagnostic and therapeutic potential, mall interfering RNAs (siRNAs), and long non-coding RNAs (lncRNAs)in cervical cancer management. The review highlights the prospect of RNA-targeted therapies to modulate specific cancer signaling pathways. This approach offers a novel strategy for cervical cancer treatment through precise regulation of cancer signaling. Future research should concentrate on developing RNA-targeted interventions to improve cervical cancer treatment outcomes through increased therapeutic efficacy and specificity., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024. Published by Elsevier GmbH.)

Objective: Systemic immune, inflammatory, and nutritional indices are prognostic across multiple tumor sites. Comprehensive analysis of these markers in patients with locally advanced cervical cancer (LACC) treated with definitive (chemo)radiotherapy [(C)RT] is limited and may assist with future prognostication., Methods: For this retrospective cohort study, patients with LACC treated with definitive (C)RT were identified from a comprehensive cancer center's clinicopathological database. Pre-treatment indices were derived including systemic immune-inflammation index (SII), platelet lymphocyte ratio (PLR), neutrophil lymphocyte ratio (NLR), monocyte lymphocyte ratio (MLR), albumin to alkaline phosphatase ratio (AAPR) and prognostic nutritional index (PNI). Univariate analysis was performed for PFS and OS. ROC curves were analyzed to determine optimal cut points. PFS and OS were assessed by the Kaplan-Meier method and Log-Rank test. Multivariate analysis was performed using Cox regression., Results: 196 patients were identified: median follow-up 7 years (IQR 2-11). Higher SII (≤700 vs >700; p = 0.01), higher PLR (≤ 250 vs >250; p < 0.001) and higher NLR (≤ 5 vs >5; p = 0.003) were associated with worse PFS. Higher SII (≤700 vs >700: p = 0.02), higher PLR (≤ 250 vs >250: p < 0.001) and higher NLR (≤ 5 vs >5; p = 0.01) were associated with worse OS. On multivariate analysis, SII, NLR and PLR were independently associated with PFS. SII and PLR were independently associated with OS., Conclusions: SII and PLR were independently associated with PFS and OS in patients with LACC treated with definitive (C)RT. NLR was independently associated with PFS. High inflammatory state is associated with shorter survival suggesting this as a target for interventions if validated in future studies., Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: MK is a consultant for Helix Biopharma (outside the scope of this study). MK is an Editorial Board Member for Gynecologic Oncology and was not involved in the editorial review or the decision to publish this article. The other authors have no relevant financial or non-financial interests to disclose., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Objective: To assess the influence of geographies and race on the survival outcomes in patients diagnosed with cervical squamous cell carcinoma (CSCC) across three continents., Methods: This multicontinental retrospective study was conducted in 8 hospitals across Asia, Europe, and North America (NA). Clinicopathologic data of 595 patients with presumed early stages of CSCC, treated surgically, with curative intent was collected. Descriptive analysis and Cox regression models were produced., Results: A total of 595 patients, consisting of 445 (74.8 %) white, 75 (12.6 %) Blacks, and 75 (12.6 %) Asian patients were included. Geographical distribution comprised 69 % of patients from NA, 22 % from Europe, and 9 % from Asia. The median age at diagnosis was 46 years. The median overall survival (OS) and relapse-free survival (RFS) were 22.09 years and 21.19 years, respectively. Patient characteristics varied significantly across geographical regions, except for consensus tumor grade. Patients in Europe from middle-income countries with limited CC screening had a substantially higher risk of death than those in NA (HR, 1.79; 95 % CI, 1.13 to 2.79; p = 0.015). Patients from single center in Japan had higher risk of relapse than those from the four heterogeneous NA centers (sub-distribution hazard ratio, 2.19; 95 % CI, 1.22 to 3.95; p = 0.009), although OS did not differ significantly. Race remained statistically insignificant for survival outcomes across the three continents but seemed to influence survival outcomes in NA centers., Conclusion: Our study highlights impact of geographies and races on CSCC survival outcomes, emphasizing the need of considering these factors when developing targeted interventions against CSCC., Competing Interests: Declaration of competing interest The authors whose names are listed immediately below certify that they have NO affiliations with or involvement in any organization or entity with any financial interest (such as honoraria; educational grants; participation in speakers' bureaus; membership, employment, consultancies, stock ownership, or other equity interest; and expert testimony or patent-licensing arrangements), or non-financial interest (such as personal or professional relationships, affiliations, knowledge or beliefs) in the subject matter or materials discussed in this manuscript., (Copyright © 2024. Published by Elsevier Inc.)

Objective: The survival outcomes of Stage IIIC1 in FIGO 2018 showed significant heterogeneity and it seems unreasonable to administer a uniform treatment regimen for Stage IIIC1 patients. This study aimed to assess the survival outcomes among patients with locally advanced cervical cancer based on various lymph node statuses, T-stage classifications, and treatment modalities., Methods: This is a population-based cohort study utilizing the Surveillance, Epidemiology, and End Results Program from 2004 to 2018. Propensity score-based inverse probability of treatment weighting was used to achieve covariate balance. Women with locally advanced cervical cancer on different lymph node statuses who underwent radical hysterectomy + pelvic lymphadenectomy + chemoradiotherapy, chemoradiotherapy, or radiotherapy alone were examined. Trends, patient characteristics, and survival outcomes were compared across different treatment regimens., Results: Among 8777 patients analyzed, patients with early T-stage and married were identified as independent protective factors for cancer-specific survival regardless of lymph node status. The survival outcomes ranked in descending order as follows: T1N0>T2N0>T1N1 = T2N1>T3N0>T3N1. Therefore, the FIGO Stage IIIC1 was re-stratified into IIC (T1N1+T2N1) and IIIC1(T3N1). Patients who underwent radical hysterectomy combined with adjuvant therapy exhibited superior 5-year cancer-specific survival rates compared to those treated with chemoradiotherapy among IB3, IIA2, and IIC. The therapeutic efficacy of chemoradiotherapy surpassed that of radiotherapy alone in IIIA, IIIB, IIIC1(T3N1), and IVA patients., Conclusion: Restratification of Stage IIIC1 based on T-stage effectively discerns patients with divergent prognoses. Radical surgery + chemoradiotherapy is significantly associated with improved survival in early T-stage, regardless of lymph node status in locally advanced cervical cancer., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Objective: To evaluate the significance of response assessment with magnetic resonance imaging (MRI) during chemoradiotherapy (CRT) for outcomes of adenocarcinoma of the cervix., Methods: A retrospective analysis of 102 patients diagnosed with FIGO 1B3-IVa cervical adenocarcinoma was conducted. Patients underwent definitive CRT and brachytherapy. Mid-treatment MRI-assessments were used to evaluate tumor response during radiotherapy, focusing on tumor volume reduction rate (TVRR), which was defined as an optimal reduction rate from initial tumor volume for tumor progression. Locoregional recurrence (LRR), distant metastasis (DM), progression-free survival (PFS) and overall survival (OS) rates according to the tumor response were analyzed., Results: Forty-five (44.1 %) of 102 patients experienced tumor downstaging during CRT, with 72 (70.5 %) demonstrating a complete response on post-treatment MRI three months after radiotherapy. With a median follow-up of 35.5 months, the 3-year PFS and overall OS rates for all patients were 60.0 % and 84.0 %, respectively. LRR and DM rates at 3 years were 25.2 % and 23.3 %, respectively. Patients with TVRR≥81.8 % had significantly longer 3-year PFS (75.4 % vs. 36.2 %, P < 0.001) and OS (93.2 % vs. 69.0 %, P = 0.002) rates than the other patients with TVRR<81.8 %. LRR (10.6 % vs. 45.6 %, P = 0.003) and DM (14.6 % vs. 33.5 %, P = 0.008) rates at 3 years were significantly lower in TVRR≥81.8 % group compared to TVRR<81.8 % group. In the multivariate analysis, positive initial lymph node (hazard ratio [HR], 2.11; confidence interval [CI], 1.25-3.87; P = 0.02] and TVRR (HR, 0.42; CI, 0.19-0.93; P = 0.03) were significantly associated with PFS., Conclusion: Mid-treatment MRI assessment is crucial and higher rates of tumor volume reduction during radiotherapy indicates better prognosis for tumor recurrence and patient survival in cervical adenocarcinoma., Competing Interests: Declaration of competing interest The authors declare no financial or other interest that is relevant to this article., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Cervical cancer is among the most commonly diagnosed cancers in pregnancy and for some patients, abortion may be desired or recommended. The Dobbs v Jackson decision has the potential to limit choice while exacerbating disparities in cervical cancer care. We highlight the necessity of employing a reproductive justice framework to both clinical care and research for cervical cancer care in pregnancy to increase access to reproductive choice and to address inequities., Competing Interests: Declaration of competing interest The authors have no conflicts of interest related to this manuscript., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Objectives: This study aimed to investigate the influence of baseline sarcopenia and changes in body composition on survival during cervical cancer treatment., Methods: Patients diagnosed with stage IB1-IVB cervical cancer who underwent primary concurrent chemoradiation therapy (CCRT) between 2002 and 2022 were included. The exclusion criteria were prior radical hysterectomy, lack of pretreatment computed tomography (CT) imaging, or significant comorbidities. An artificial intelligence-based automatic segmentation program assessed body composition by analyzing CT images, defining L3 sarcopenia (L3 skeletal muscle index [SMI] <39cm 2 /m 2 ) and volumetric sarcopenia (volumetric SMI <180.4 cm 3 /m 3 ). Comparative and multivariate analyses identified the prognostic factors. The impact of body component changes during CCRT was explored., Results: Among 347 patients, there were 125 recurrences and 59 deaths (median follow-up, 50.5 months). Seven patients were excluded from the volumetric sarcopenia analysis because of incomplete baseline CT data, and 175 patients were included in the analysis of body composition changes. Patients with L3 sarcopenia had a lower 5-year progression-free survival (PFS) rate (55.6% vs. 66.2%, p = 0.027), while those with volumetric sarcopenia showed a poorer 5-year overall survival rate (76.5% vs. 85.1%, p = 0.036). Patients with total fat loss during CCRT had a worse 5-year PFS rate than those with total fat gain (61.9% vs. 73.8%, p = 0.029). Multivariate analyses revealed that total fat loss (adjusted hazard ratio [aHR], 2.172; 95% confidence interval [CI], 1.066-4.424; p = 0.033) was a significant factor for recurrence, whereas L3 sarcopenia was not. Volumetric sarcopenia increased the risk of death by 1.75-fold (aHR, 1.750; 95% CI, 1.012-3.025; p = 0.045)., Conclusions: Among patients with cervical cancer undergoing CCRT, initial volumetric sarcopenia and fat loss during treatment are survival risk factors. These findings suggest the potential importance of personalized supportive care, including tailored nutrition and exercise interventions., Competing Interests: Declaration of competing interest Soon Ho Yoon has stocks and stock options of MEDICAL IP. Other authors have no conflicts of interest., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Objective: To identify whether there is an association between body composition phenotypes and toxicity to chemoradiotherapy in women with cervical cancer., Methods: This is a prospective cohort study that included 330 adult patients with cervical cancer treated with chemoradiotherapy. Computed tomography images were used to assess skeletal muscle index (SMI) and radiodensity (SMD), total adipose tissue index, and visceral adipose tissue index. Chemoradiotherapy toxicity was assessed weekly, and toxicity-induced modification of treatment (TIMT) was considered as any severe adverse event resulting in treatment interruption, delay, or dose reduction., Results: Approximately 45% of the patients presented at least one unfavorable body composition parameter (lower SMI, lower SMD, higher total adipose tissue index, or higher visceral adipose tissue index), 23% had two conditions, and 3% had three conditions. The incidence of toxicity ≥ grade 3 and TIMT was 55% and 30%, respectively. For adverse events ≥ grade 3, lower SMI was the determining factor for worse outcomes when evaluated alone or combined with lower SMD and normal adiposity. All body composition phenotypes were associated with TIMT, increasing the risk when both conditions were present., Conclusions: Lower SMI was an independent factor for the higher number of adverse events, as it remained a risk factor when analyzed in isolation or in association with adipose tissue. Women with excess adipose tissue associated with lower muscle mass had a risk approximately 4 times higher of delaying or interrupting chemoradiotherapy. Furthermore, for the sum of unfavorable conditions, there was a progressive increase in the risk of TIMT., Competing Interests: Declaration of competing interest Gabriela Villaca Chaves reports financial support, administrative support, equipment, drugs, or supplies, and travel were provided by FAPERJ. If there are other authors, they declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this article., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Cervical cancer (CC) is the fourth most common cancer and the fourth leading cause of mortality in women worldwide. It is strongly associated with high-risk human papillomavirus infection. High-income countries that have implemented human papillomavirus (HPV) vaccination and screening programs have seen dramatic reductions in CC incidence, while developing countries where these programs are not available continue to experience high rates of CC deaths. In early-stage CC, the primary treatment is surgery or radiotherapy, whereas concurrent chemo-radiotherapy (CRT) remains the conventional approach in locally advanced stages until the upcoming approval of immunotherapy. The incorporation of immunotherapy in combination with chemotherapy (with or without bevacizumab) in first line and as monotherapy in second line after platinum-based chemotherapy, has significantly increased overall survival (OS) in recurrent or metastatic CC. The purpose of this guideline is to summarize the most relevant evidence in the diagnosis, treatment, and follow-up of CC and to provide evidence-based recommendations for clinical practice., (© 2024. The Author(s).)

The European Society of Gynaecological Oncology, the European Society of Human Reproduction and Embryology, and the European Society for Gynaecological Endoscopy jointly developed clinically relevant and evidence-based guidelines focusing on key aspects of fertility-sparing strategies and follow-up of patients with cervical cancers, ovarian cancers, and borderline ovarian tumours. The developmental process of these guidelines is based on a systematic literature review and critical appraisal involving an international multidisciplinary development group consisting of 25 experts from relevant disciplines (ie, gynaecological oncology, oncofertility, reproductive surgery, endoscopy, imaging, conservative surgery, medical oncology, and histopathology). Before publication, the guidelines were reviewed by 121 independent international practitioners in cancer care delivery and patient representatives. The guidelines comprehensively cover oncological aspects of fertility-sparing strategies during the initial management, optimisation of fertility results and infertility management, and the patient's desire for future pregnancy and beyond., Competing Interests: Declaration of interests PM reports having had an advisory role or received speaker's honoraria (paid to him or to his institution) from GlaxoSmithKline, AstraZeneca, and ImmunoGen. GS reports grants or contracts from MSD, consulting fees from Tesaro Bio Italy and Johnson and Johnson, and payment or honoraria from Clovis Oncology Italy. NRA-R reports grants or contracts from Grail (paid to the institution). FFi reports honoraria from Theramex and Organon, and support for attending and travelling to meetings from Organon, Merck-Serono, and Theramex (paid to the institution). SB reports honoraria from MSD; support for attending and travelling to meetings from Hologic, MSD, and Pfizer; and honoraria for participation on a data safety monitoring board or advisory board from Hologic. CR-J reports payment for lectures (paid to the institution) from Organon and Novartis, speakers bureau (paid to the institution) from Gédéon Richter and Roche, and for manuscript writing (paid to the institution) from Roche. All other authors declare no competing interests., (Copyright © Elsevier Ltd. All rights reserved, including those for text and data mining, AI training, and similar technologies.)

Background: Sexual health is an important survivorship issue in cervical cancer. We assessed patient-reported sexual health outcomes and correlations with oncologist-assessed vaginal toxicity (VT)., Methods: This was a prospective, cross-sectional study of stage IB-IVA cervical cancer patients treated with definitive chemoradiation, who completed a socio-demographic questionnaire and the following patient-reported-outcomes (PROs): Female Sexual Function Index (FSFI), Female Sexual Distress Scale-Revised (FSDS-R), Menopause Rating Scale (MRS), Hospital Anxiety and Depression Scale (HADS). VT was assessed using the CTCAE v4.0. Sociodemographic, clinical data, PROs and VT were summarized using descriptive statistics; correlations were evaluated using linear regression analyses., Results: Between August 2018 and April 2022, 73 patients were analyzed. Median age was 49 (range 25-81), 57.5% had vaginal involvement at diagnosis and 76.9% were partnered. Sexual dysfunction (FSFI score ≤ 26), sexual distress (FSDS-R ≥ 11), severe menopausal symptoms (MRS ≥ 17), anxiety (HAD-Anxiety >7) and depression (HAS-Depression >7) were reported in 86.3%, 54.5%, 36.2%, 46.6% and 24.7%, respectively. Grade 2+ VT was reported in 27.4%. No significant associations were found between PROs and VT. On multivariable analysis, non-partnered status, use of hormone replacement therapy, and International Commission on Radiation Units and Measurements - rectovaginal dose (ICRU-RV) >65Gy were associated with worse sexual health (p < 0.005)., Conclusion: Cervical cancer patients self-report high rates of sexual distress, dysfunction and menopause symptoms. Discordance between oncologist-assessed VT and PROs highlights the importance of evaluating the patient's experience. Proactive treatment of menopausal symptoms and attention to radiotherapy doses to the vagina should be considered., Competing Interests: Declaration of competing interest Dr. Kathy Han was on the Astra Zeneca Cervical Cancer Radiation Oncology and Merck Gynaecological Cancer Advisory Board. All the other co-authors report no conflict of interest., (Crown Copyright © 2024. Published by Elsevier Inc. All rights reserved.)

Purpose: This study sought to determine the predictive and prognostic value of clinicopathological parameters and neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR), and hemoglobin (Hgb) level in predicting recurrence patterns and locoregional relapse-free survival (LRFS) and distant metastasis-free survival (DMFS) in cervical cancer patients receiving definitive chemoradiotherapy (ChRT)., Methods: This study included 261 cervical cancer patients treated with ChRT. The primary endpoints were the predictors of local recurrence (LR) and distant metastasis (DM), whereas the secondary endpoints were LRFS and DMFS. The association of survival with potential prognostic factors was analyzed using Cox regression analysis, and the predictors of LR and DM were identified using logistic regression analysis., Results: The median follow-up time was 10.9 years. Recurrences occurred in 132 patients (50.6%) within a median of 11.2 months after definitive ChRT. NLR and PLR values were significantly higher in patients with LR and DM than in those without, with no significant differences in Hgb levels in patients with or without LR and DM. In the multivariable logistic regression analysis, lymph node metastasis, elevated NLR, and low Hgb level were significantly correlated with LR and DM. In the multivariable analysis, large tumor size, presence of lymph node metastasis, and elevated NLR were the independent predictors for poor LRFS and DMFS, and Hgb level was an additional prognostic factor for DMFS., Conclusion: Hematological markers, particularly NLR and Hgb, may serve as cost-effective and readily accessible indicators for predicting recurrence and survival in cervical cancer patients, contributing to their practical use in routine assessments., (© 2024. The Author(s).)

Introduction: We present the rare case of an 18-year-old patient with a Dicer-1 mutation-associated sarcoma of the cervix uteri., Case: The patient presented with irregular vaginal bleeding in July 2022. The clinical examination showed an exophytic tumor of the cervix, uterus and ovaries were normal in sonogram. The tumor of the cervix was resected, followed by a diagnostic hysteroscopy and abrasion of the uterine cervix and cavity. Hysteroscopy showed normal findings of the cervix and uterus. After diagnosis of a highly malignant Dicer-1 mutation-associated sarcoma of the cervix, cryopreservation of oocytes was realized. Based on the principle of obtaining maximum oncological safety while preserving fertility in this 18-year-old patient, we recommended chemotherapy rather than radiation with its far severe implications on the patient´s reproductive organs. 4 cycles of chemotherapy consisting of doxorubicin and ifosfamide were applied until December 2022. After re-staging in December 2022 via CT scan and MRI, the abdomen and pelvis as well as control hysteroscopy and abrasion were unremarkable. Until now, the patient is tumor free., Discussion: Primary sarcomas of the cervix are very rare. Recent literature hints towards a distinct DICER-1 sarcoma entity characterized by specific mutational clusters. Limited follow-up data suggested that DICER1-mutant tumors might exhibit a less aggressive clinical course than DICER1-wild-type tumors., Conclusion: Decision-making in case of rare histological entities with sparse recommendations in the literature poses a challenge to the treating physician. Treatment strategies should consider oncological safety as well as options of preserving fertility. Gonadotoxic potential of different strategies should be taken into consideration and discussed in detail with the affected patient., (© 2024. The Author(s).)

Purpose: The purpose of this study was to evaluate the efficacy of recombinant human superoxide dismutase (rhSOD) enemas in radiation-induced acute rectal injury (RARI) in patients with locally advanced cervical cancer., Methods and Materials: In this phase 3, randomized, open-label trial (NCT04819685) conducted across 14 medical centers in China from June 2021 to August 2023, all patients received concurrent chemoradiation therapy (CCRT). The experimental group was treated with a rhSOD enema during chemoradiation therapy, and the control group had no enema. The Common Terminology Criteria for Adverse Events (version 5.0) was used to evaluate radiation therapy-induced side effects. Endoscopic appearance was assessed using the Vienna Rectoscopy Score. The primary endpoint in the acute phase was the occurrence rate and duration of grade ≥1 (≥G1) diarrhea during CCRT. Secondary endpoints included the occurrence rate and duration of ≥G2 and ≥G3 diarrhea, ≥G1 and ≥G2 diarrhea lasting at least 3 days, and damage to the rectal mucosa due to radiation therapy measured by endoscopy., Results: Two hundred and eighty-three patients were randomly divided into the experimental (n = 141) or control group (n = 142). The mean number of ≥G1 and ≥G2 diarrhea days were significantly lower in the experimental group than in the control group (3.5 and 0.8 days vs 14.8 and 4.5 days, respectively; P < .001). The incidence of ≥G2 diarrhea decreased from 53.6% to 24.1% when rhSOD enemas were used. Use of antidiarrheals was lower in the experimental group (36.2% vs 55.7%, P < .001). Three patients felt intolerable or abdominal pain after rhSOD enema. RARI grades in the experimental group tended to be lower than those in the control group (P = .061). Logistic regression analysis revealed that rhSOD enema was associated with a lower occurrence rate of ≥G1/2 diarrhea for at least 3 days (P < .001)., Conclusions: The results of this study suggest that rhSOD enema is safe and significantly reduces the incidence, severity, and duration of RARI, protecting the rectal mucosa., (Copyright © 2024 The Author(s). Published by Elsevier Inc. All rights reserved.)

Background: The comprehensive treatment mode of combining concurrent chemoradiotherapy (CCRT) with adjuvant chemotherapy (AC) is a commonly used mainstream model in the clinical practice of locally advanced cervical cancer (LACC). However, the necessity for AC after CCRT lacks sufficient evidence-based medical support. This study constructs a predictive model for the survival time dependence of CCRT ± AC for LACC based on the 2018 International Federation of Gynecology and Obstetrics (FIGO) staging with internal validation, the prognosis was assessed with intensity-modulated radiotherapy (IMRT) and concurrent cisplatin, and provides guidance for future stratified treatment. Materials and Methods: The retrospective analysis included 482 patients with LACC who CCRT from January 2016 to January 2023. Patients who used the 2009 FIGO staging were all standardized for the 2018 FIGO staging. The 482 patients with LACC were divided into a training set ( n = 290) and a validation set ( n = 192) at a ratio of 6:4. COX multivariate regression model and LASSO regression were used to screen for independent prognostic factors affecting progression-free survival (PFS) and overall survival (OS), and a nomogram clinical prediction model was constructed based on these factors. Evaluate the effectiveness of the model through the receiver operating characteristic curve, calibration curve, decision curve, risk heat map, and survival curves for risk stratification. Results: The PFS and OS independent prognostic risk factors affecting the 2018 FIGO staging of LACC during CCRT were validated to be similar to the 2009 FIGO staging prediction model reported in previous literature. In the training cohort, area under the curve (AUC) values at 1, 3, and 5 years were 0.941, 0.882, and 0.885 for PFS, and 0.946, 0.946, and 0.969 for OS, respectively. When applied to a test cohort, the model also showed accurate prediction result (AUC at 1, 3, and 5 years were 0.869, 0.891, and 0.899 for PFS, and 0.891, 0.941 and 0.878 for OS, respectively). Subgroup analysis suggests that patients with LACC, adenocarcinoma, stage IVA, pelvic lymph node metastasis, pretreatment hemoglobin ≤100 g/l and residual tumor diameter >2 cm, who received CCRT in the 2018 FIGO stage, may benefit more from adjuvant chemtherapy. Conclusions: Based on the 2018 FIGO staging, a nomogram prediction model for PFS and OS in patients with LACC undergoing CCRT was developed. The model, established by combining weighted clinical and pathological factors, can provide more personalized treatment predictions in clinical practice. For patients with high-risk factors such as residual tumor diameter > 2 cm after CCRT for LACC, AC may bring benefits.

The aim of the study is to evaluate the treatment patterns, time to start treatment, and healthcare resources utilization (HCRU) of cervical cancer (CC) patients within the Brazilian public health system (SUS). This is an observational retrospective study using SUS administrative database (DATASUS). Data from January-2014 to December-2020 was gathered from patients with the ICD-10 C53 codes. From 2014 to 2020, 206,861 women were included, among whom 90,073 (43.5%) had stage information. Of staged patients, 60.7% (54,719) had advanced disease (stages III and IV) and the most performed treatments were chemoradiotherapy (CRT) (41.6%), surgery + CRT (19.1%), radiotherapy (RT) only (16.8%) and chemotherapy (CT) only (13.3%). The proportion of patients submitted to CT in advanced stages was higher than in non-advanced stages (I and II), in contrast to RT, which was more frequent in stage I than stage IV. Median time to initiate treatment surpassed two months in approximately 30% of the cases, regardless of stage. Conization was the most performed surgical procedure. The hospitalization rate per patient per month for stage IV was twice as high as stage I (0.05 [95%CI 0.05-0.05] and 0.11 [0.11-0.11], respectively). The same trend was observed for outpatient visits (0.54 [95%CI 0.53-0.55] and 0.96 [0.93-0.98], respectively). This study demonstrated a high proportion of advanced CC at diagnosis in Brazil. The treatment pattern showed that chemoradiotherapy was the most frequent regimen overall and the use of chemotherapy and HCRU increased with staging. These results could provide information to improve public policies towards access to prevention, diagnosis, and treatment of CC in Brazil., Competing Interests: I have read the journal’s policy and the authors of this manuscript have the following competing interests: TMFC, MACSM, PMB, MACR, MN, LPLG and CPM are employees of Merck Sharp Dohme Farmacêutica Ltda, Sao Paulo, Brazil, who may own stock and/or hold stock options in Merck & Co., Inc., Rahway, NJ, USA. ANR is a scientific medical consultant who was paid by MSD Brazil. PCP and ACS were employees of IQVIA Brazil, which was contracted by MSD Brazil to conduct the study., (Copyright: © 2024 Campuzano et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Objective: To describe the treatment outcomes of locally advanced cervical cancer managed with neoadjuvant chemotherapy (NACT) plus radical surgery at a gynecology oncology center in Ethiopia., Methods: This was a retrospective descriptive study of management of locally advanced cervical cancer (LACC) at St. Paul's Hospital Millennium Medical College (Ethiopia) over 5 years. Data were collected by reviewing patient records. Data were analyzed using SPSS version 23. Simple descriptive analysis was employed to analyze clinical, histologic, and treatment outcomes of LACC managed with NACT+ radical surgery. Frequency and proportions were used to present the results' significance., Results: A total of 98 patients were analyzed. One-third (31.6%) of cervical cancer patients with locally advanced disease were operable after neoadjuvant chemotherapy. Out of this, nodal metastasis was found in 2 patients (all pelvic lymph node metastasis). Disease recurrence within 2 years was 3% (1 recurrence within 6-12 months and 2 recurrences at 12-24 months)., Conclusion: This study supports utilization of NACT plus radical surgery for locally advanced cervical cancer, where chemoradiation is not readily available. Our findings imply that this treatment modality is a life-saving alternative treatment in a low-income setting, which is often married by shortage or unavailability of radiotherapy at the needed time before disease progression ensues., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2024 Birara et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Cervical cancer remains a leading cause of cancer-related mortality among women worldwide, particularly in underdeveloped nations. Despite advances in standard therapies, patients with recurrent metastatic cervical cancer face a poor prognosis and limited treatment options. This study aims to evaluate the efficacy and safety of emerging therapeutic approaches in managing this challenging condition, including immunotherapy, targeted medicines, and chemotherapy. Our review of recent literature and clinical trials highlights the significant progress made in the systematic treatment of metastatic cervical cancer. While each treatment modality has its strengths and limitations, the collective data suggest a trend towards improved patient outcomes with the adoption of these novel therapies. However, the heterogeneity of patient responses underscores the need for personalised treatment strategies. In conclusion, improvements in medical technology and the adoption of tailored treatment approaches have led to promising advancements in the management of recurrent metastatic cervical cancer. To further enhance patient care, there is an urgent need for more extensive clinical trial data and the development of more efficient personalised treatment plans. This study aims to contribute to this effort by comprehensively analysing current therapeutic strategies and identifying areas for future research.

Objective: This study aims to develop and validate a predictive model that integrates clinical features, MRI radiomics, and nutritional-inflammatory biomarkers to forecast progression-free survival (PFS) in cervical cancer (CC) patients undergoing concurrent chemoradiotherapy (CCRT). The goal is to identify high-risk patients and guide personalized treatment., Methods: We performed a retrospective analysis of 188 patients from two centers, divided into training (132) and validation (56) sets. Clinical data, systemic inflammatory markers, and immune-nutritional indices were collected. Radiomic features from three MRI sequences were extracted and selected for predictive value. We developed and evaluated five models incorporating clinical features, nutritional-inflammatory indicators, and radiomics using C-index. The best-performing model was used to create a nomogram, which was validated through ROC curves, calibration plots, and decision curve analysis (DCA)., Results: Model 5, which integrates clinical features, Systemic Immune-Inflammation Index (SII), Prognostic Nutritional Index (PNI), and MRI radiomics, showed the highest performance. It achieved a C-index of 0.833 (95% CI: 0.792-0.874) in the training set and 0.789 (95% CI: 0.679-0.899) in the validation set. The nomogram derived from Model 5 effectively stratified patients into risk groups, with AUCs of 0.833, 0.941, and 0.973 for 1-year, 3-year, and 5-year PFS in the training set, and 0.812, 0.940, and 0.944 in the validation set., Conclusions: The integrated model combining clinical features, nutritional-inflammatory biomarkers, and radiomics offers a robust tool for predicting PFS in CC patients undergoing CCRT. The nomogram provides precise predictions, supporting its application in personalized patient management., (© 2024. The Author(s).)

Background: Locally advanced cervical cancer is treated with chemoradiotherapy (standard of care), but many patients still relapse and die from metastatic disease. We investigated chemoradiotherapy with or without induction chemotherapy to determine whether induction chemotherapy improves both progression-free survival and overall survival., Methods: The INTERLACE trial was a multicentre, randomised phase 3 trial done at 32 medical centres in Brazil, India, Italy, Mexico, and the UK. Adults (aged ≥18 years) with locally advanced cervical cancer (FIGO 2008 stage IB1 disease with nodal involvement, or stage IB2, IIA, IIB, IIIB, or IVA disease) were randomly assigned (1:1), by minimisation, using a central electronic system, to standard cisplatin-based chemoradiotherapy (once-a-week intravenous cisplatin 40 mg/m 2 for 5 weeks with 45·0-50·4 Gy external beam radiotherapy delivered in 20-28 fractions plus brachytherapy to achieve a minimum total 2 Gy equivalent dose of 78-86 Gy) alone or induction chemotherapy (once-a-week intravenous carboplatin area under the receiver operator curve 2 and paclitaxel 80 mg/m 2 for 6 weeks) followed by standard cisplatin-based chemoradiotherapy. Stratification factors were recruiting site, stage, nodal status, three-dimensional conformal radiotherapy or intensity modulated radiotherapy, age, tumour size, and histology (squamous vs non-squamous). Primary endpoints were progression-free survival and overall survival within the intention-to-treat population. This trial is registered with ClinicalTrials.gov, NCT01566240, and EUDRACT, 2011-001300-35., Findings: Between Nov 8, 2012, and Nov 17, 2022, 500 eligible patients were enrolled and randomly assigned to the chemoradiotherapy alone group (n=250) or the induction chemotherapy with chemoradiotherapy group. Of 500 patients, 354 (70%) had stage IIB disease and 56 (11%) stage IIIB disease. Pelvic lymph nodes were positive in 215 (43%) patients. 230 (92%) patients who received induction chemotherapy had at least five cycles. Median interval between induction chemotherapy and chemoradiotherapy was 7 days. Four or more cycles of cisplatin were given to 212 (85%) participants in the induction chemotherapy with chemoradiotherapy group and to 224 (90%) of participants in the chemoradiotherapy alone group. 462 (92%) participants received external beam radiotherapy and brachytherapy with a median overall treatment time of 45 days. After a median follow-up of 67 months, 5-year progression-free survival rates were 72% in the induction chemotherapy with chemoradiotherapy group and 64% in the chemoradiotherapy alone group with a hazard ratio (HR) of 0·65 (95% CI 0·46-0·91, p=0·013). 5-year overall survival rates were 80% in the induction chemotherapy with chemoradiotherapy group and 72% in the chemoradiotherapy alone group, with an HR of 0·60 (95% CI 0·40-0·91, p=0·015). Grade 3 or greater adverse events were reported in 147 (59%) of 250 individuals in the induction chemotherapy with chemoradiotherapy group versus 120 (48%) of 250 individuals in the chemoradiotherapy alone group., Interpretation: Short-course induction chemotherapy followed by chemoradiotherapy significantly improves survival of patients with locally advanced cervical cancer., Funding: Cancer Research UK and University College London-University College London Hospitals Biomedical Research Centre., Competing Interests: Declaration of interests GE reports consulting fees from MSD and Eisai; payment or honoraria from Eisai and GSK; support for attending meeting from MSD; and participation on Data Safety Monitoring Board or Advisory Board for GSK, MSD, and Eisai, outside the submitted work. JAL reports grants from AstraZeneca and Merck/MSD; consulting fees from AstraZeneca, Clovis Oncology, GSK, Artios Pharma, Merck/MSD, VBL Therapeutics, Bristol Myers Squibb, Nuvation, Immagene, Incyte, Immunogen/AbbVie, and Novocure; payment or honoraria from AstraZeneca, MSD/Merck, Clovis Oncology, and GSK; participation on Data Safety Monitoring Board or Advisory Board for Mersana and SutroBio; and leadership role on the European Society for Medical Oncology's Clinical Practice Guidelines—Gynaecological Cancer—until December, 2023, past Vice President role for the European Society of Gynaecological Oncology, until 2021, and Chair for National Ovarian Cancer Audit Committee, outside the submitted work. MM reports payment or honoraria from MSD, Eisai, GSK, Roche, and Medscape; support for attending meetings or travel from Daiichi Sanko; and past role as a Chair of Cervical Cancer Research Network (until September 2021), outside the submitted work. AM reports participation on data safety monitoring board or advisory board for Cannariabio (on an ovarian cancer trial, since 2023) and executive committee member role with the Gynecologic Cancer Intergroup (since 2024), outside the submitted work. AH reports honoraria for educational activities from AbbVie, Almirall, Boehringer Ingelheim, Clovis Oncology, Ipsen, Takeda, AstraZeneca, Daiichi Sankyo, Merck Serono, MSD, UCB, Kyowa Kirin, Servier, Sobi, Pfizer, and Roche, outside the submitted work. All other authors declare no competing interests., (Copyright © 2024 The Author(s). Published by Elsevier Ltd. This is an Open Access article under the CC BY 4.0 license. Published by Elsevier Ltd.. All rights reserved.)

Background: The 5-year survival rates for breast and cervical cancers in Ghana are low in comparison to rates in developed countries. This striking disparity is attributed to numerous factors, including limited access and navigability to appropriate services. A one-time cross-sectional, hospital-based survey was performed by the University of Utah in collaboration with Ghana Health Services (GHS) and Health Facilities Regulatory Agency (HeFRA) from November, 2020 to October, 2021 so as to determine existing hospital-based breast and cervical cancer care services capacity and their geographic availability nationwide. This related information remains dynamic in nature and time. The current project employs a public-academic implementation science and research configuration to explore and develop a real-time interface (RTIF) showing the availability of breast and cervical cancer care services at hospital facilities in-country so as to anchor up-to-date data products for the government, private-sector, and patient-centric consumption., Methods and Analysis: Multiple methods will be employed to achieve the study objectives between December 2023 to November 2024. The first three objectives shall focus on contextual, needs, and feasibility assessments guided by the domains and constructs within the updated Consolidated Framework for Implementation Research (CFIR) during coding and thematic qualitative analysis. Using purposive sampling, breast and cervical cancer care service stakeholders shall be identified for individual in-depth interviews. The fourth objective will involve creating the RTIF prototype and piloting it in the Eastern Region of Ghana. The final and fifth objective shall employ the systems usability scale (SUS) amongst ten randomly selected individual stakeholders to assess the technical functionality of the interface. A nationwide scale-up shall follow this., Competing Interests: The authors declare that this research could evolve into a self-sustaining project by exploring and leveraging viable start-up opportunities. They affirm that this competing interest has not influenced the design, execution, or interpretation of the study., (Copyright: © 2024 Sutherland et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Background: Breast, cervical, and ovarian cancers are among the top ten global cancers, affecting women, with age-standardized rates per 100,000 being 47.8 for breast, 13.3 for cervical, and 6.6 for ovarian cancer. The journey from cancer symptoms, through diagnosis and treatment, to survivorship, presents numerous challenges. These challenges encompass physical, psychological, and social aspects, significantly impacting patients' quality of life. It is crucial for research to explore not only the challenges faced by patients but also the strategies they employ to cope with these obstacles., Methods: This study employed a cross-sectional qualitative approach. Twenty respondents, aged between 15 and 45 years and had been diagnosed with a reproductive cancer (breast, ovarian, or cervical), and were either undergoing treatment or had completed treatment within one year of the study period were purposively selected. Respondents were interviewed using a semi-structured interview guide. A thematic analysis was conducted on twenty in-depth interviews (IDIs) to understand the challenges and support systems for cancer patients., Results: The study identified two principal themes: the challenges faced by patients and the available support systems. The findings are based on patient narratives regarding the obstacles encountered during diagnosis, treatment, and follow-up, along with the mitigation strategies employed. Patients reported a range of challenges, categorized into financial and non-financial. Prominent among the non-financial challenges were psychological distress, body image issues, reduced sexual drive, and overall health deterioration. Support was primarily found through personal relationships and religious or spiritual beliefs., Conclusion: The research highlights the extensive psychological and social effects of cancer and it's treatment. The study revealed the intertwined nature of financial difficulties and non-financial challenges, emphasizing the importance of social support, including religious, family, healthcare, and peer support. The findings suggest that a comprehensive, multidisciplinary management plan which encompasses both medical and supportive care is required to enhance patient well-being., (© 2024. The Author(s).)

A platinum-based concurrent chemoradiotherapy (CCRT) is the standard treatment for refractory cervical cancer (CC). However, the recurrence of disease and the occurrence of metastasis remain prevalent. We observed the long-term efficacy and safety of bevacizumab combined with neoadjuvant chemotherapy (NACT) and CCRT in refractory CC. A total of 62 patients with refractory CC were enrolled in this study from January 2016 to December 2019. The NACT regimen included bevacizumab (7.5 mg/kg), docetaxel (75 mg/m2), and cisplatin (75 mg/m2), administered tri-weekly for 2 cycles. The CCRT regimen included bevacizumab (7.5 mg/kg) and cisplatin (75 mg/m2), administered tri-weekly for 2 cycles. A dose of 45-50 Gy was prescribed for external beam radiotherapy (EBRT), while 30-35 Gy in 4-5 fractions was prescribed for brachytherapy (BT). Among the patients, 21 patients (33.9%) were at stages IIB-IIIB, 8 patients (12.9%) were at stage IIIC1, 19 patients (30.6%) were at stage IIIC2, and 14 patients (22.6%) were at stage IVB. Pelvic, para-aortic, supraclavicular, and inguinal lymph node metastases were discovered in 41 patients (66.1%). The median follow-up was 49.8 months (12.3-82.7 months). The median tumor volumes pre-treatment, after NACT, and before BT were 84.64 ± 53.15 cm3, 1.64 ± 13.15 cm3, and 0 ± 1.5 cm3, respectively. Complete clinical response (cCR) rates after NACT and EBRT were 35.5% and 66.1%, respectively. Four years after the diagnosis, the overall survival (OS) rate was 78.6%, the local region-free survival (LRFS) rate was 91.3%, the disease-free survival (DFS) rate was 70.6%, and the distant metastasis-free survival (DMFS) rate was 81.4%. A total of 29 patients (46.8%) experienced grade 3/4 hematological toxicity, 3 patients (4.8%) experienced grade 3 gastrointestinal toxicities, and none experienced grade 5 adverse events. Bevacizumab combined with NACT and CCRT significantly improved cCR and OS in refractory CC with acceptable toxicity.

In this comprehensive review supported by clinical examples, the authors explore the topic of cervical cancer in pregnancy, with emphasis on potential pre-cancer progression, the possibility of coexisting preinvasive and invasive disease, and neoadjuvant chemotherapy. This manuscript addresses the challenges of managing cervical cancer in pregnant women with a pregnancy-preserving approach, including the importance of screening, the timing of surgery, and the impact of pregnancy on the course of the disease. The first case study illustrates the potential for a benign cervical lesion to transform into a malignant one during pregnancy and the possible coexistence of preinvasive lesions together with early-stage cervical cancer. It also questions the rationale behind the non-treatment of pregnant patients initially diagnosed with CIN 2/3 during pregnancy. The second presented clinical example shows the histologically confirmed response to neoadjuvant chemotherapy, resulting in a radiologically diagnosed FIGO stage IIA1 being downgraded to adenocarcinoma in situ in the histology report after surgery performed six weeks postpartum. The treatment of cervical cancer, which is becoming increasingly prevalent among pregnant women, and the necessity for an individualized diagnostic and therapeutic approach represent significant challenges for contemporary medicine. Discrepancies in therapeutic options proposed among centers within the same region lead to the conclusion that there is a need for centralization and unification of evidence-based management in referral centers with both high-level oncological and perinatal care.

Background and Aims: Cervical cancer (CC) is a common cancer among women, often treated with Doxorubicin (Doxo). Research is underway to explore the use of oncolytic virus (OV) therapy as a means to improve drug efficacy and enhance the immune system's tumor-fighting capabilities. Hence, our study purposes to evaluate the therapeutic potential of Newcastle disease virus (NDV) in increasing the antitumor efficacy of Doxo in mouse models of CC., Methods and Materials: TC1 cells were administered to C57BL/6 mice (Female) in a range of 6 to 8 weeks age (n = 40) to induce tumor growth. After tumor development, four treatment groups of mice were formed. Treatment were performed through NDV, Doxo, and a combination of both in three groups of treatment twice in a one-week intervention manner, while the control group treated with PBS. Following the last treatment, half of these mice were subjected to euthanize due to the immune-response assessment, and the other half were followed up till they died naturally in a certain period of time., Results: Mice that underwent the combined treatment showed significantly improved survival rates and slower tumor progression in comparison with the control group. This combined treatment substantially elevated nitric oxide (NO) and lactate dehydrogenase (LDH) levels in the splenocytes cultures of mice bearing cervical tumors. Furthermore, combination therapy resulted in a notable elevation in TNF-α, IL-12, and IFN-γ, secretion alongside a reduction in the release of TGF-β and IL-4 within the splenocytes in counter with the treatment of just NDV or Doxo., Conclusion: According to the findings of this study, it seems that utilizing NDV can improve the effectiveness of Doxo in a mouse model of CC, suggesting it can serve as an adjunct therapy alongside chemotherapy., (© 2024. The Author(s).)

Cervical cancer (CC), one of the most prevalent and detrimental gynaecologic cancers, evolves through genetic and epigenetic alterations resulting in the promotion of oncogenic activity and dysfunction of tumour-suppressing mechanisms. Despite medical advancement, the prognosis for advanced-stage patients remains extremely low due to high recurrence rates and resistance to existing treatments. Thereby, the search for potential prognostic biomarkers is heightened to unravel new modalities of CC pathogenesis and to develop novel anti-cancer therapies. Epitranscriptomic modifications, reversible epigenetic RNA modifications, regulate various biological processes by deciding RNA fate to mediating RNA interactions. This narrative review provides insight into the cellular and molecular roles of endogenous RNA-editing proteins and their associated epitranscriptomic modifications, especially N 6 -methyladenosine (m 6 A), 5-methylcytosine (m 5 C) and N 1 -methyladenosine (m 1 A), in governing the development, progression and metastasis of CC. We discussed the in-depth epitranscriptomic mechanisms underlying the regulation of over 50 RNAs responsible for tumorigenesis, proliferation, migration, invasion, survival, autophagy, stemness, epithelial-mesenchymal transition, metabolism (glucose, lipid, glutamate and glutamine), resistance (drug and radiation), angiogenesis and recurrence of CC. Additionally, we provided a concise overview of the therapeutic potential of targeting the altered expression of endogenous RNA-editing proteins and aberrant deposition of RNA modifications on both coding and non-coding RNAs in CC.

Objectives: To examine the benefits of extended-field chemoradiation with simultaneous integrated boost to positive lymph nodes, followed by image-guided adaptive brachytherapy in patients with cervical cancer with para-aortic metastasis., Methods: This retrospective cohort study enrolled 143 patients diagnosed between January 2011 and July 2023 at a single center. Survival and recurrence were evaluated using the Kaplan-Meier method and log-rank test. Cox regression was employed to identify prognostic factors and adjust for confounding factors. Patients were then stratified according to neoadjuvant chemotherapy, and its impact on survival outcomes was evaluated., Results: A total of 129 patients completed the entire treatment course. The 5-year overall survival rate was 57.6%, and the para-aortic failure rate was 6.8% after a median follow-up of 61 months (95% CI 49 to 82 months). Multivariate analysis indicated that neoadjuvant chemotherapy, larger primary tumor or pelvic/para-aortic lymph nodes, and lower hemoglobin nadir (for widespread metastasis-free survival only) predicted poorer survival. After propensity score matching, the 5-year para-aortic recurrence-free, widespread metastasis-free, and overall survival rates were 92.2% vs 92.8% (p=0.85), 50.8% vs 72.1% (p=0.007), and 47.5% vs 65.5% (p=0.037), respectively, in groups receiving neoadjuvant chemotherapy or not. Sixteen patients (12.4%) experienced grade 3-4 late toxicities. Patients who received neoadjuvant chemotherapy had a significantly higher incidence of grade 3-4 anemia and neutropenia than those who did not (45.2% vs 26.7% and 38.1% vs 21.8%, respectively), if including another 14 patients who discontinued treatment due to acute vomiting., Conclusion: Chemoradiation with simultaneous integrated boost to positive lymph nodes demonstrates favorable outcomes and acceptable late toxicities in para-aortic metastatic cervical cancer. Neoadjuvant chemotherapy has been shown to adversely affect outcomes, and acute vomiting is a major cause of treatment abortion., Competing Interests: Competing interests: None declared., (© IGCS and ESGO 2024. No commercial re-use. See rights and permissions. Published by BMJ.)

Background: Cervical squamous cell carcinoma (CSCC) is a prevalent gynecological malignancy worldwide. Current treatments for CSCC can impact fertility and cause long-term complications, underscoring the need for new therapeutic strategies. Oncolytic virotherapy has emerged as a promising option for cancer treatment. Previous research has demonstrated the oncolytic activity of the coxsackievirus B3 strain 2035 A (CVB3/2035A) against various tumor types. This study aims to evaluate the clinical viability of CVB3/2035A for CSCC treatment, focusing on its oncolytic effect in patient-derived CSCC organoids., Methods: The oncolytic effects of CVB3/2035A were investigated using human CSCC cell lines in vitro and mouse xenograft models in vivo. Preliminary tests for tumor-selectivity were conducted on patient-derived CSCC tissue samples and compared to normal cervical tissues ex vivo. Three patient-derived CSCC organoid lines were developed and treated with CVB3/2035A alone and in combination with paclitaxel. Both cytotoxicity and virus replication were evaluated in vitro., Results: CVB3/2035A exhibited significant cytotoxic effects in human CSCC cell lines and xenograft mouse models. The virus selectively induced oncolysis in patient-derived CSCC tissue samples while sparing normal cervical tissues ex vivo. In patient-derived CSCC organoids, which retained the immunohistological characteristics of the original tumors, CVB3/2035A also demonstrated significant cytotoxic effects and efficient replication, as evidenced by increased viral titers and presence of viral nucleic acids and proteins. Notably, the combination of CVB3/2035A and paclitaxel resulted in enhanced cytotoxicity and viral replication., Conclusions: CVB3/2035A showed oncolytic activity in CSCC cell lines, xenografts, and patient-derived tissue cultures and organoids. Furthermore, the virus exhibited synergistic anti-tumor effects with paclitaxel against CSCC. These results suggest CVB3/2035A could serve as an alternative or adjunct to current CSCC chemotherapy regimens., (© 2024. The Author(s).)

Purpose: This phase I/II trial (ChiCTR2000032879) assessed the safety and efficacy of toripalimab combined with chemoradiotherapy for locally advanced cervical squamous cell carcinoma., Methods and Materials: Twenty-two patients, regardless of their programmed death ligand-1 (PD-L1) status, received toripalimab combined with concurrent chemoradiotherapy (CCRT). CCRT included cisplatin (40 mg/m 2 , once weekly for 5 weeks), radiotherapy (45-50.4 Gy/25-28 Fx, 5 fractions weekly), followed by brachytherapy (24-30 Gy/3-5 Fx) and toripalimab (240 mg, intravenous) on days 1, 22 and 43 during CCRT. The primary endpoints were safety and 2-year progression-free survival (PFS). The secondary endpoints included 2-year local control (LC), local regional control and overall survival (OS)., Results: All patients successfully completed CCRT and toripalimab treatment. Grade III and higher adverse events (AEs) were observed in 11 patients (11/22, 50%), and no patient experienced grade V AEs. The objective response rate (ORR) was 100%. At the data cutoff (June 30, 2023), the median follow-up was 31.8 months (9.5 to 37.8 months). The 2-year PFS rate was 81.8%. The 2-year LC and local regional control rates were both 95.5%, and the 2-year OS rate was 90.9%., Conclusions: Toripalimab combined with CCRT achieved good tolerance and showed promising anti-tumor effects in patients with locally advanced cervical cancer., (© 2024. The Author(s).)

Radiotherapy and surgery are the two pivotal curative treatments for cervical cancer. Although cervical cancer is relatively sensitive to chemotherapy, chemotherapy is not included in the curative treatment of cervical cancer and has a role in limited medical conditions. Chemotherapy used to treat cervical cancer can be divided into four categories: (1) preceding chemotherapy (neoadjuvant chemotherapy) to augment the effects of radical therapy (surgery or radiation therapy), (2) chemotherapy administered concurrently with radiation therapy, and (3) adjuvant chemotherapy administered after radical therapy. In addition, (4) chemotherapy is used to prolong survival and alleviate symptoms in patients who cannot be radically cured. Recently, molecular targeted agents, angiogenesis inhibitors, and immune checkpoint inhibitors have been incorporated into existing chemotherapy regimens. This review summarizes these trends along with the history of chemotherapy for cervical cancer., (© 2024 Japan Society of Obstetrics and Gynecology.)

Objective: Immunotherapy has led to changes in cervical cancer guidelines. Therefore, additional biomarkers to identify the ideal patient who would experience the most benefit may be important., Methods: We retrospectively collected 208 patients with R/M CC and recorded clinicopathologic information, peripheral blood markers and treatments to analyze the prognostic factors of clinical outcomes. Response rate comparison, univariate, and multivariate analyses were performed to assess the efficacy of different factors., Results: A total of 43.27% patients achieved objective responses, including 18 with complete response and 72 with partial response. Patients receiving first-line immunotherapy had much higher objective response rate (ORR) than the remaining patients (53.8% vs. 34.8%, p = 0.006). CRP >3 ECOG ≥1 and recurrence in 6 months predicted shorter progression free survival (PFS). CRP >3, GLU >6.1 independently predicted unfavorable overall survival (OS). Compared with no antiangiogenic therapy, previous antiangiogenic therapy reduced the median OS by nearly 14 months. Immunotherapy rechallenge was still effective after first immunotherapy failure, and combined with dual-immunotherapy or bevacizumab combined with chemoradiotherapy resulted in a 60.00% or 62.50% ORR, respectively. Patients with squamous cell carcinoma, with stable disease or objective response in the first immunotherapy or without chemotherapy in second immunotherapy had favorable clinical outcome., Conclusion: The baseline CRP levels in serum was an independent factor for PFS and OS of R/M CC patients treated with immunotherapy, and previous antiangiogenic therapy was associated with poor OS. Patients still show response to immunotherapy rechallenge and combined treatment with bevacizumab or candonilimab showed higher response rate than anti-PD-1 after immunotherapy failure., (© 2024 The Author(s). Cancer Medicine published by John Wiley & Sons Ltd.)

Introduction: Cervical cancer remains one of the most common gynecologic malignancies worldwide. A disproportionate burden of cases occurs in developing countries due to inadequate screening and treatment. Even among patients adequately treated, in the presence of locally advanced or recurrent disease, outcomes tend to be poor. The introduction of biologic therapy into treatment has increased overall survival; however, a considerable opportunity still exists to improve current standards in treatment. Biologics have shown antitumor activity in multiple tumor types and are actively being pursued for the management of cervical cancer., Areas Covered: In this article, we will discuss the historical evolution of biologic therapy in cervical cancer including use of angiogenesis inhibitors, immune checkpoint inhibitors, antibody-drug conjugates, and vaccines. We will review how these therapies have been integrated into current treatment recommendations and discuss ongoing investigations intended to improve clinical outcomes. We also postulate on persistent gaps in care., Expert Opinion: Biologic therapies have had a tremendous impact on our current approach to managing cervical cancer. We anticipate that significant more research and development will be committed to the continued investigation of biologics in cervical cancer in an effort to improve a historically difficult to treat malignancy.

Endocervical gastric-type adenocarcinoma (GAS) is an aggressive type of endocervical mucinous adenocarcinoma characterized as being unrelated to human papillomavirus (HPV) and resistant to chemo/radiotherapy. In this study, we investigated the histology, immunohistochemistry patterns, and molecular characteristics in a large cohort of GAS (n = 62). Histologically, the majority of GAS cases exhibited a distinct morphology resembling gastric glands, although 2 exceptional cases exhibited HPV-associated adenocarcinoma morphology while retaining the characteristic histology of GAS at the invasive front. By immunohistochemistry, Claudin18.2 emerged as a highly sensitive and specific marker for GAS. Additionally, the strong expression of Claudin18.2 in patients with GAS indicated the potential of anti-Claudin18.2 therapy in the treatment of GAS. Other immunohistochemistry markers, including Muc6, p16, p53, Pax8, ER, and PR, may provide additional diagnostic clues for GAS. Quantitative methylation analysis revealed that the overexpression of Claudin18.2 in GAS was governed by the hypomethylation of the CLDN18.2 promoter CpG islands. To further elucidate the pathogenic mechanisms of GAS and its relationship with gastric adenocarcinoma, we performed whole exome sequencing on 11 GAS and 9 gastric adenocarcinomas. TP53, CDKN2A, STK11, and TTN emerged as the most frequently mutated genes in GAS. Mutations in these genes primarily affected cell growth, cell cycle regulation, senescence, and apoptosis. Intriguingly, these top mutated genes in GAS were also commonly mutated in gastric and pancreaticobiliary adenocarcinomas. Regarding germline variants, we identified a probably pathogenic variant in SPINK1, a gene linked to hereditary pancreatic cancer syndrome, in one GAS sample. This finding suggests a potential pathogenic link between pancreatic cancers and GAS. Overall, GAS exhibits molecular characteristics that resemble those observed in gastric and pancreaticobiliary adenocarcinomas, thereby lending support to the aggressive nature of GAS compared with HPV-associated adenocarcinoma., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

Objective: To investigate the associations between apparent diffusion coefficient (ADC) values extracted from three different region of interest (ROI) position approaches and programmed cell death ligand-1 (PD-L1) expression, and evaluate the performance of the nomogram established based on ADC values and clinicopathological parameters in predicting PD-L1 expression in cervical cancer (CC) patients., Methods: Through retrospective recruitment, a training cohort of 683 CC patients was created, and a validation cohort of 332 CC patients was prospectively recruited. ROIs were delineated using three different methods to measure the mean ADC (ADC mean ), single-section ADC (ADC ss ), and the minimum ADC of tumors (ADC min ). Logistic regression was employed to identify independent factors related to PD-L1 expression. A nomogram was drawn based on ADC values combined with clinicopathological features, its discrimination and calibration performances were estimated using the area under the curve (AUC) of receiver operating characteristic and calibration curve. The clinical benefits were evaluated by decision curve analysis., Results: The ADC min independently correlated with PD-L1 expression. The nomogram constructed with ADC min and other independent clinicopathological-related factors: FIGO staging, pathological grade, parametrial invasion, and lymph node status demonstrated excellent diagnostic performance (AUC = 0.912 and 0.903, respectively), good calibration capacities, and greater net benefits compared to the clinicopathological model in both the training and validation cohorts., Conclusion: ADC min independently correlated PD-L1 expression, and the nomogram established with ADC min and clinicopathological independent prognostic factors had a strong predictive performance for PD-L1 expression, thereby serving as a promising tool for selecting cases eligible for immunotherapy., Clinical Relevance Statement: The minimum ADC can serve as a reliable imaging biomarker related to PD-L1 expression; the established nomogram combines the minimum ADC and clinicopathological factors that can assist clinical immunotherapy decisions., (© 2024. The Author(s), under exclusive licence to European Society of Radiology.)

While several treatment choices exist for cervical cancer, such as surgical therapy, chemotherapy, and radiotherapy, some patients will still show poor prognosis. HPV infection is a principal factor for cervical cancer development, from early inflammation to proliferation, angiogenesis, and neoplastic growth. While HPV T-cell responses exist, the tumor seems to evade the immune system upon its tolerance. The latter suggests the existence of a confluent tumor microenvironment responsible for the evasion tactics employed by the neoplasm. Therefore, novel biomarkers governing prognosis and treatment planning must be developed, with several studies tackling the significance of the tumor microenvironment in the genesis, development, proliferation, and overall response of cervical cancer during neoplastic processes. This review aims to analyze and contemplate the characteristics of the tumor microenvironment and its role in prognosis, progression, evasion, and invasion, including therapeutic outcome and overall survival., (©The Author(s) 2024. Open Access. This article is licensed under a Creative Commons CC-BY International License.)

The microbiota in the female genital tract is an intricate assembly of diverse aerobic, anaerobic, and microaerophilic microorganisms, which share the space within the reproductive tract and engage in complex interactions. Microbiome dysbiosis may disrupt the symbiotic relationship between the host and microorganisms and play a pivotal role in the pathogenesis of various diseases, including its involvement in the establishment of human papillomavirus (HPV)-associated cervical cancer (CC). Interventions to restore microbiota homeostasis (e.g., probiotics) and bacterial-vector HPV therapeutic vaccines have been reported to be potentially effective in clearing HPV infection and ameliorating cytological abnormalities. In this review, we place emphasis on elucidating the alterations within the cervical-vaginal microbiota as well as the intratumoral microbiota in the context of high-risk HPV (HR-HPV) infection and its subsequent progression to cervical intraepithelial neoplasia/CC. Furthermore, we explore the mechanisms by which these microbial communities exert potential pathogenic or protective effects, including modulating genital inflammation and immune responses, affecting HR-HPV oncogene expression and oncoprotein production, regulating oxidative stress and deoxyribonucleic acid (DNA) damage, and inducing metabolic rewiring. Lastly, we summarize the latest evidence in human trials regarding the efficacy of probiotics, prebiotics and probiotic-vector HPV therapeutic vaccines. This review aims to foster a deeper understanding of the role of the microbiota in HR-HPV infection-related cervix cancer development, and further provide a theoretical basis for the development of preventive and therapeutic strategies based on microbial modulation., Competing Interests: Declaration of Competing Interest The authors report there are no competing interests to declare. Figures were created with BioRender software, ©biorender.com., (Copyright © 2024 The Authors. Published by Elsevier GmbH.. All rights reserved.)

Introduction: To develop and validate a T2-weighted magnetic resonance imaging (MRI)-based radiomic signature associated with disease-free survival (DFS) in locally advanced cervical cancer., Materials and Methods: The study comprised a training dataset of 132 patients (93 Norwegian; 39 The Cancer Imaging Archive (TCIA) and an independent validation Canadian dataset of 199 patients with FIGO stage IB-IVA cervical cancer treated with chemoradiation. Radiomic features were extracted using PyRadiomics. A radiomic signature was developed based on a multivariable radiomic prognostic model for DFS built using the training dataset, with minimal redundancy maximum relevancy feature selection method. Univariate and multivariable Cox regression analyses were then conducted to examine the association of the derived radiomic signature with DFS., Results: A radiomic signature was prognostic for DFS in the training cohort (Norwegian hazard ratio [HR] 5.54, p = 0.002; TCIA HR 3.59, p = 0.04). The radiomic signature remained independently associated with DFS (HR 3.70, p = 0.004) when adjusted for stage and tumor volume. The radiomic signature was also prognostic for DFS in the validation cohort, both on univariate analysis (HR 2.22, p = 0.003), and multivariable analysis adjusted for stage and tumor volume (HR 1.84, p = 0.04). The 4-year DFS rates of patients with radiomic signature score > 0 vs ≤ 0 were 48.2 % vs 87.9 %, and 56.4 % vs 80.8 % for training and validation cohorts respectively., Conclusion: An MRI-based radiomic signature can be used as a prognostic biomarker for DFS in patients with locally advanced cervical cancer undergoing chemoradiation., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Authors. Published by Elsevier B.V. All rights reserved.)

Objective: This study explored patients and providers' perspectives on therapeutic vaccines for cervical cancer and assessed barriers and facilitators., Methods: Qualitative semi-structured in-depth interviews were conducted with patients who had cervical dysplasia, or a past or current cervical cancer diagnosis and providers who provided care to patients with cervical abnormalities or cervical cancer. Data were analyzed using thematic analysis in NVivo., Results: A total of 28 in-depth interviews were conducted with patients (N = 15) and providers (N = 13). Participants in both groups expressed enthusiasm for the prospect of a therapeutic vaccine for cervical cancer and were encouraged by less invasive treatment opportunities. Perceived patient barriers included concerns about side effects, eligibility criteria, costs, transportation, and logistical obstacles. Providers echoed these concerns, highlighted additional structural barriers such as racism and limited availability of culturally sensitive educational aids, and underscored the need for provider training on this topic., Conclusion: Our results reinforce the need for future multi-level interventions discussing vaccine efficacy, durability, and safety, as well as addressing factors such as awareness, knowledge, and beliefs., Practice Implications: Our findings can contribute to the development of provider and patient-centered tools that promote therapeutic vaccine acceptance., Competing Interests: Declaration of Competing Interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Anna Giuliano reports a relationship with Merck & Co Inc that includes: board membership and consulting or advisory. Dr. Giuliano’s institution has received funds to support HPV-related research. No other authors have conflicts of interest to report related to this paper. All authors attest that they meet the ICMJE criteria for authorship., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Objective: This study sought to explore the efficiency of para-aortic and pelvic lymphadenectomy in the treatment of locally advanced cervical cancer (LACC) with pelvic lymph node (PLN) metastasis., Methods: A total of 171 LACC patients with imaging-confirmed pelvic lymph node metastasis were included in this study. These patients were divided into two groups: the surgical staging group, comprising 58 patients who had received para-aortic and pelvic lymphadenectomy (surgical staging) along with concurrent chemoradiation therapy (CCRT), and the imaging staging group, comprising 113 patients who had received only CCRT. The two groups' progression-free survival (PFS), overall survival (OS) and treatment-related complications were compared., Results: The surgical staging group started radiotherapy 10.2 days (range 9-12 days) later than the imaging staging group. The overall incidence of lymphatic cysts was 9.30%. In the surgical staging group, para-aortic lymph node metastasis was identified in 34.48% (20/58) of patients, while pathology-negative PLN was observed in 12.07% (7/58). Over a median follow-up period of 52 months, no significant differences in PFS and OS rates were found between the two groups (p > 0.05). Subgroup analysis of patients with lymph node diameters of ≥ 1.5 cm revealed a five-year PFS rate of 75.0% and an OS rate of 80.0% in the surgical staging group, compared to 41.5% and 50.1% in the imaging staging group, respectively, showing statistically significant differences (p = 0.022, HR:0.34 [0.13, 0.90] and p = 0.038, HR: 0.34 [0.12,0.94], respectively for PFS and OS). Additionally, in patients with two or more metastatic lymph nodes, the five-year PFS and OS rates were 69.2% and 73.1% in the surgical staging group, versus 41.0% and 48.4% in the imaging staging group, with these differences also being statistically significant (p = 0.025, HR: 0.41[0.19,0.93] and p = 0.046, HR: 0.42[0.18,0.98], respectively)., Conclusion: Performing surgical staging before CCRT is safe and delivers accurate lymph node details crucial for tailoring radiotherapy. This approach merits further investigation, particularly in women with pelvic lymph nodes measuring 1.5 cm or more in diameter or patients with two or more imaging-positive PLNs., (© 2024. The Author(s).)