Treatment Of Cervical Cancer Research Articles

Beyond prevention: in silico designing a one-two punch novel therapeutic vaccine candidate against major oncoproteins of HPV 16, 18, 31, and 45 and subsequent cervical cancer

ABSTRACT The human papillomavirus (HPV) is the most prevalent viral sexually transmitted disease (STD). HPV 16, 18, 31 and 45 are most associated with the development of cervical cancer. Currently approved HPV vaccines are only preventive and have no therapeutic activity. With immunoinformatics approaches, we tried to design a novel vaccine against E6 and E7 oncoproteins of HPV 16, 18, 31 and 45 for the prevention and treatment of cervical cancer. The tertiary structure of the vaccine was modelled and validated. The vaccine was docked with TLR4 and TLR9 receptors, which have an undeniable anti-tumour immunity against cervical cancer. Molecular dynamic simulation indicates that the vaccine-TLR complexes were structurally stable. Immune stimulation and population coverage analysis results were much better than similar studies. Our new multi-epitope vaccine is the first HPV vaccine to target the E6 and E7 antigens of HPV 16, 18, 31 and 45. Also, this is the first study to target conserved regions of HPV and then merge the T and B cell epitopes as a regional epitope, which increases vaccine efficacy and reliability. We hope that the methodology of this study will even shed light on the design of vaccines against other viral STDs.

DeepCervix: enhancing cervical cancer detection through transfer learning with VGG-16 architecture

Cervical cancer remains a significant global health concern, emphasizing the urgent need for improved detection methods to ensure timely treatment. This research introduces a sophisticated methodology leveraging recent advances in medical imaging and deep learning algorithms to enhance the accuracy and efficiency of cervical cancer detection. The proposed approach comprises meticulous data preprocessing to ensure the integrity of input images, followed by the training of deep learning models including ResNet-50, AlexNet, and VGG-16, renowned for their performance in computer vision tasks. Evaluation metrics such as accuracy, precision, recall, and F1-score demonstrate the efficacy of the methodology, with an outstanding accuracy rate of 98% achieved. The model’s proficiency in accurately distinguishing healthy cervical tissue from cancerous tissue is underscored by precision, recall, and F1-score values. The primary strength of this deep learning-based approach lies in its potential for early detection, promising significant impact on cervical cancer diagnosis and treatment outcomes. This methodology contributes to advancements in medical imaging techniques, facilitating improved outcomes in cervical cancer detection and treatment.

Experiences of women living with cervical cancer in Ghana: challenges and coping strategies

BackgroundCervical cancer is a leading cause of morbidity and mortality among women globally. The condition is both preventable and treatable yet remains a leading cause of cancer death in Ghana. This study aims to explore the unique experiences of women living with cervical cancer with a focus on the challenges and coping strategies.MethodsThe study employed a qualitative approach with an exploratory, descriptive design. This study was conducted among women with cervical cancer aged 18 years and above who have been diagnosed with the disease for at least 3 months. A total of 16 participants were purposively sampled based on the eligibility criteria and individually interviewed using a semi-structured guide. The six-step technique for qualitative analysis by Braun and Clarke guided data analysis.ResultsMost participants resorted to self-medication, over-the-counter drugs and herbal preparations as a first line of defense against the disease. The presence of cervical cancer affected participants’ physical and mental well-being. Other challenges included financial burden and frequent equipment breakdowns which affected patients’ treatment. Participants adopted different coping strategies such as taking blood tonic, increased rest and sleep, spiritual prayers and recreational activities. Family members, friends, the church and health workers provided support in the area of finance, advice, meal preparation and house chores, prayers and counseling to participants.ConclusionsCervical cancer affects the quality of life of many women and their significant others. The condition puts a lot of financial burden on its victims and there is the need for a system to reduce the burden on patients. It is recommended that the treatment of cervical cancer should be covered by the National Health Insurance Scheme to ease the financial burden on patients. There is a need for expansion of access to cervical cancer treatment across the country to reduce patients’ burden and relieve the pressure on the few pieces of equipment at the current treatment centres.

Expression of variant isoforms of the tyrosine kinase SYK differentially regulates cervical cancer progression through PI3K/AKT pathway

Invasion and metastasis are the main reasons for the poor prognosis of patients with cervical cancer(CC). SYK is closely related to tumor development. However, the functions of its two isoforms, SYK (L) or SYK (S), are not fully understood to date. In this study, we investigated their biologic functions and possible prognostic values in CC. qRT-PCR was performed to detect the expression of SYK and two variant isoforms in cervical cancer tissues and cells. The association of SYK(L) and SYK(S) with Clinical pathological parameters were evaluated. The migration and invasion was detected by scratch assay and transwell. Western blot was conducted to measure the changes of epithelial mesenchymal transition (EMT)-related markers and PI3K/AKT signaling pathway proteins in cervical cancer cells. LY294002 (inhibitor of PI3K/AKT pathway) and IGF-1 (activator of PI3K/AKT pathway) were applied to evaluate the contribution of PI3K/AKT signaling pathway in cervical cancer cells. The expression of SYK(S) in cervical cancer tissues was significantly higher than that of SYK(L). SYK(L) and SYK(S) were correlated with muscular infiltration, SYK(L) high expression had a better prognosis, whereas SYK(S) high expression predicted a worse disease outcome. Cox multivariate regression analysis demonstrated that SYK(L) expression was an independent prognostic factor. SYK(L) significantly inhibited the proliferation, migration and invasion, while SYK(S) showed the opposite effects. LY294002 blocked SYK (L) knockdown-induced enhancement of migration and invasion as well as the expression EMT-related markers, whereas IGF-1 rescued the decreased migration, invasion and EMT induced by SYK (S) knockdown. The results suggest that SYK(L) and SYK(S) are involved in the progression of cervical cancer through PI3K/AKT signaling pathway, and may serve as potential targets for clinical treatment of advanced cervical cancer.

Ethanolic Fruit Extract of Piper retrofractum Induced Cell Cycle Arrest, Apoptosis, Increased Reactive Oxygen Species Production, and Mitochondrial Dysfunction in Human Cervical Cancer.

Cervical cancer remains a significant global health challenge, with high mortality rates and a pressing need for more effective therapeutic options. This study investigates the effects of an ethanolic extract from the fruit of Piper retrofractum (PR) on proliferation and apoptosis in cervical cancer cells. We evaluated the cytotoxicity of the crude ethanolic extract of PR using the sulforhodamine B and colony formation assay. ROS generation, apoptosis, and mitochondrial function were quantified via flow cytometry. The effects on cell migration was assessed using wound healing and Transwell migration assays. The PR extract exhibited a significant inhibitory effect on HeLa cell viability, leading to reduced cancer cell proliferation. The extract induced cell cycle arrest at the G0/G1 phase in a dose-dependent manner and decreased the proportion of cells in the G2/M phase at concentrations of 100 and 250 µg/mL. Additionally, treatment with the PR extract resulted in a marked increase in ROS production, disruption of mitochondrial function, and inhibition of cell migration. These findings suggest that the PR ethanolic fruit extract exerts substantial antiproliferative, antimigratory, and proapoptotic effects on HeLa cells. Consequently, the PR ethanolic fruit extract holds promise as a potential novel therapeutic agent for the treatment of cervical cancer.

DDR1 promotes metastasis of cervical cancer and downstream phosphorylation signal via binding GRB2

Cervical cancer is a leading cause of cancer-related death among women and its recurrence and metastasis poses challenges to treatment. Discoidin domain receptor 1 (DDR1) was associated with cellular migration and invasion in several types of cancers. However, its function in cervical cancer is still unclear. In this study, we found that DDR1 was significantly more expressed in cervical cancer samples than in normal tissues. SRY-Box transcription factor 2 (SOX2), a known oncogene in cervical cancer, showed a positive correlation with DDR1 and regulated DDR1 transcription, contributing to the elevated expression of DDR1 in cervical cancer. Regarding the function of DDR1 in cervical cancer, the overexpression of DDR1 caused an increase in the migration, invasion, and epithelial-mesenchymal transition (EMT) of cervical cancer cells. In contrast, cervical cancer cells with reduced DDR1 expression exhibited a lower migration rate, fewer invasive cells, and decreased levels of EMT markers. In vivo, mice injected with cervical cancer cells with overexpressed DDR1 showed more pulmonary metastasis and nodule number. Opposite results were found in mice injected with DDR1 silenced cervical cancer cells. Since DDR1 can cause phosphorylation of downstream targets, a phosphorylation omics was employed to reveal the downstream targets of DDR1, including eukaryotic translation initiation factor 4E binding protein 1 and EPH receptor A2. Furthermore, DDR1 bound directly with Src homology 2 domain of growth factor receptor bound protein 2 (GRB2) which mediated the function of DDR1 in the malignant behaviors of cervical cancer and the phosphorylation of downstream targets. In conclusion, DDR1 binds directly to GRB2 and then affects downstream phosphorylation signals, ultimately exacerbating the metastasis of cervical cancer cells. This work sheds light on the mechanism by which DDR1 functions in cervical cancer cells, providing therapeutic strategy for the treatment of cervical cancer.

Enlonstobart: First Approval.

Enlonstobart (Enshuxing®), a recombinant, fully humanised immunoglobulin G4 monoclonal antibody targeted against programmed cell death protein1 (PD-1), is being developed by the CSPC Pharmaceutical Group for the treatment of advanced cervical cancer and other solid tumours. Enlonstobart received its first approval (a conditional marketing authorisation) in June 2024, in China, for use in patients with recurrent or metastatic programmed cell death ligand1 (PD-L1)-positive cervical cancer who have failed previous platinum-containing chemotherapy. Phase III clinical evaluation of enlonstobart for use as first-line treatment (in combination with chemotherapy ± bevacizumab) in patients with recurrent or metastatic PD-L1-positive cervical cancer is also underway in China. Additionally, phase II clinical development of enlonstobart (as a part of combination therapy) for use against a range of other solid tumour types is continuing. This article summarises the milestones in the development of enlonstobart leading to this first approval for recurrent or metastatic cervical cancer.

A Comprehensive Review on Current and Future Treatments for Cervical Cancer

A Comprehensive Review on Current and Future Treatments for Cervical Cancer

Hematological changes in women with cervical cancer before and after cancer treatment: retrospective cohort study

Hematological changes is one of the most common complications occurred in cancer patients. Therefore, the current study aimed to assess the hematological toxicity of cervical cancer patients before and after the initiation of treatment. The retrospective cohort study was conducted from 2015 to 2022 at the University of Gondar Comprehensive Specialized Hospital. The hematological profile and sociodemographic and clinical data of the cervical cancer patients were collected using data extraction sheets. The Epidata version 3.1 and SPSS version 25 were used for data entry and analysis, respectively. Descriptive statistics were employed to summarize the data. To compare the median differences in hematological parameters before and after treatment, the Wilcoxon rank test was used. In addition, to assess the presence of an independent association between hematological abnormalities and the independent variables, logistic regression models were used. A p value less than 0.05 was considered to indicate statistical significance for all tests. In current study, the median (Interquartile range) of hemoglobin levels, white blood cell counts, and platelet counts, before treatment were 13.2 (12.1, 15) g/dl, 7.5 (5.8, 11.8) *109/L, and 330 (252, 383) *109/L, respectively. However, after treatment the median (Interquartile range) value of hemoglobin levels, white blood cell counts, and platelet counts were significantly lowered. On the other hand, red cell distribution width was significantly greater after treatment. At baseline, the magnitude of leucocytosis, anemia, and thrombocytosis were 27.9%, 24.6%, and 18.7%, respectively. After the treatment, anemia increased to 44.3%, but leucocytosis and thrombocytosis were replaced by leucopenia 18.3% and thrombocytopenia 17.8%, respectively. Hematological abnormalities such as anemia, leucopenia and thrombocytopenia were high after chemo-radiotherapy, and surgery. As the stage of cancer advances, the risk of developing anemia, leucocytosis, and thrombocytosis increased in 7.6, 6.9 and 9 times, respectively. Furthermore, being HIV patients and rural resident increased the risk of developing anemia about twofold. In conclusion hematological abnormalities were observed before and after cervical cancer treatment, with significance increment after chemo-radiotherapy and surgery. As the stage of cancer advances, the risk of developing hematological abnormalities increases. Therefore, routine monitoring of hematological changes before and after treatment and screening for major risk factors are important for improved patients’ management.

MiR-29a Downregulates PIK3CA Expression and Inhibits Cervical Cancer Cell Dynamics: A Comparative Clinical Analysis.

HPV/pap tests are widely used for cervical cancer screening, playing a crucial role in early diagnosis and guiding future treatment options. However, approximately 50% of cervical cancer patients are diagnosed at an advanced stage, which is associated with higher recurrence rates and poorer survival outcomes than early-stage diagnoses. This underscores the need for effective treatments for advanced-stage cervical cancer. Among the various oncogenes implicated in cancer, PIK3CA expression is known to cause cervical cancer, suggesting that inhibiting PIK3CA may impede cervical cancer progression. In this study, we transfected PIK3CA-overexpressing tumor cells (SiHa, C33A, and HeLa) with miR-29a, a microRNA extensively studied as a therapeutic candidate for oncogene suppression in various tumor types. We conducted RT-qPCR and Western blot analyses to assess changes in PIK3CA expression at the RNA and protein levels. Wound healing and cell migration assays were used to evaluate the effects of miR-29a on cell division and migration in HeLa cells. We confirmed a reduction in PIK3CA expression at both RNA and protein levels following miR-29a transfection. After transfecting miR-29a into HeLa cells, we observed a reduction in cell division and migration, as demonstrated by wound healing and cell migration assays. Additionally, we found that miR-29a binds to the 3'-UTR region of PIK3CA, leading to a reduction in its gene expression. Furthermore, we correlated the concentration of miR-29a in clinical histologic biopsy samples from cervical cancer patients with disease progression. These findings indicate that miR-29a can slow the progression of cervical cancer by targeting PIK3CA and potentially aid in its treatment. miR-29a shows promise as a therapeutic agent for inhibiting oncogene expression and controlling cervical cancer progression, especially in advanced-stage cases.

Cervical precancer screening using self-sampling, HPV DNA testing, and mobile colposcopy in a hard-to-reach community in Ghana: a pilot study

BackgroundThe World Health Organization has set ambitious goals to eliminate cervical cancer, necessitating evidence on increasing coverage and access to screening and treatment in high-burden areas. We implemented a pilot program to assess the feasibility of obtaining self-collected specimens for high-risk human papillomavirus (hr-HPV) testing in Nzulezo stilt village, a hard-to-reach community in Ghana, and inviting only hr-HPV-positive women to a central location for colposcopy and possible treatment. Subsequently, this study aimed to investigate the prevalence of hr-HPV infection and cervical lesions among the women and to explore factors potentially associated with hr-HPV infection among them.MethodsThis pilot community-based cross-sectional study utilized data from screening sessions held from 2 to 20 November 2021 with specimens collected by participants using Evalyn brushes. HPV DNA testing was performed using the Sansure MA-6000 platform, while visual inspection utilized the Enhanced Visual Assessment (EVA) mobile colposcope. Univariate and multivariable nominal logistic regression was employed to explore factors associated with hr-HPV positivity.ResultsAmong 100 women screened (mean age, 43.6 ± 14.5 years), the overall hr-HPV prevalence rate was 39.0% (95% CI, 29.4–49.3). The prevalence rates of hr-HPV genotypes were stratified as follows: HPV16–8.0% (95% CI, 3.5–15.2), HPV18–5.0% (95% CI, 1.6–11.2), and other genotype(s) – 31.0% (95% CI, 22.1–41.0). Single-genotype infections with HPV16 and HPV18 were found in 4.0% (95% CI, 1.1–9.9) and 3.0% (95% CI, 0.6–8.5) of women, respectively. Mixed infections were observed in 1.0% (95% CI, 0.0–5.4) for HPV16 + 18, 3.0% (95% CI, 0.6–8.5) for HPV16 + other type(s), and 1.0% (95% CI, 0.0–5.4) for HPV18 + other type(s). The prevalence of cervical lesions among hr-HPV-positive women screened via colposcopy was 11.4% (95% CI, 3.2–26.7). In the multivariable model, reliance on other sources for medical bill payment was associated with hr-HPV infection (aOR, 0.20; 95% CI, 0.04–0.93), whereas age was not (aOR, 1.02; 95% CI, 0.99–1.05).ConclusionsA high hr-HPV infection prevalence was recorded among the women. Utilizing technologies such as self-sampling, HPV DNA testing, and mobile colposcopy enables screening and treatment in remote and hard-to-reach communities where access to cervical cancer screening and treatment would otherwise be limited. Further research is warranted to assess the value and scalability of this approach in similar remote areas and its potential implementation in future programs.

Elevated ITGA3 expression serves as a novel prognostic biomarker and regulates tumor progression in cervical cancer

Patients with advanced and recurrent cervical cancer often lack satisfactory treatment outcomes. Thus, it is necessary to seek reliable biomarkers that provide the ability to identify the disease at an early stage and predict the patient prognosis, providing new strategies for the treatment of cervical cancer. The sequencing data of ITGA3 were retrieved from public datasets. Immune infiltration and sensitivity of potential immunotherapy and chemotherapy have been analyzed between two subgroups. Functional analysis was applied to excavate the related pathways of ITGA3 in cervical cancer. Furthermore, the impact of ITGA3 in tumor progression has been verified in vitro. The results revealed that the level of ITGA3 was upregulated in cervical cancer, and was positively correlated with worse prognosis. The tumor microenvironment of patients in the high-risk group was immunosuppressed. Patients in high-risk group may not benefit from immunotherapy, but be may be sensitive to several chemotherapy drugs. Notably, the angiogenesis, epithelial mesenchymal transition, and PI3K pathway were increased in high-risk group. Collectively, ITGA3 is a marker of poor prognosis and promotes tumor progression by regulating PI3K/AKT pathway in cervical cancer. Our results provide new insights for potential molecular targeted therapy and prognostic prediction of cervical cancer.

Automatic delineation of cervical cancer target volumes in small samples based on multi-decoder and semi-supervised learning and clinical application

Radiotherapy has been demonstrated to be one of the most significant treatments for cervical cancer, during which accurate and efficient delineation of target volumes is critical. To alleviate the data demand of deep learning and promote the establishment and promotion of auto-segmentation models in small and medium-sized oncology departments and single centres, we proposed an auto-segmentation algorithm to determine the cervical cancer target volume in small samples based on multi-decoder and semi-supervised learning (MDSSL), and we evaluated the accuracy via an independent test cohort. In this study, we retrospectively collected computed tomography (CT) datasets from 71 pelvic cervical cancer patients, and a 3:4 ratio was used for the training and testing sets. The clinical target volumes (CTVs) of the primary tumour area (CTV1) and pelvic lymph drainage area (CTV2) were delineated. For definitive radiotherapy (dRT), the primary gross target volume (GTVp) was simultaneously delineated. According to the data characteristics for small samples, the MDSSL network structure based on 3D U-Net was established to train the model by combining clinical anatomical information, which was compared with other segmentation methods, including supervised learning (SL) and transfer learning (TL). The dice similarity coefficient (DSC), 95% Hausdorff distance (HD95) and average surface distance (ASD) were used to evaluate the segmentation performance. The ability of the segmentation algorithm to improve the efficiency of online adaptive radiation therapy (ART) was assessed via geometric indicators and a subjective evaluation of radiation oncologists (ROs) in prospective clinical applications. Compared with the SL model and TL model, the proposed MDSSL model displayed the best DSC, HD95 and ASD overall, especially for the GTVp of dRT. We calculated the above geometric indicators in the range of the ground truth (head-foot direction). In the test set, the DSC, HD95 and ASD of the MDSSL model were 0.80/5.85 mm/0.95 mm for CTV1 of post-operative radiotherapy (pRT), 0.84/ 4.88 mm/0.73 mm for CTV2 of pRT, 0.84/6.58 mm/0.89 mm for GTVp of dRT, 0.85/5.36 mm/1.35 mm for CTV1 of dRT, and 0.84/4.09 mm/0.73 mm for CTV2 of dRT, respectively. In a prospective clinical study of online ART, the target volume modification time (MTime) was 3–5 min for dRT and 2–4 min for pRT, and the main duration of CTV1 modification was approximately 2 min. The introduction of the MDSSL method successfully improved the accuracy of auto-segmentation for the cervical cancer target volume in small samples, showed good consistency with RO delineation and satisfied clinical requirements. In this prospective online ART study, the application of the segmentation model was demonstrated to be useful for reducing the target volume delineation time and improving the efficiency of the online ART workflow, which can contribute to the development and promotion of cervical cancer online ART.

Brachytherapy for cervical cancer: from intracavitary to interstitial technique.

Cervical cancer is a common malignant tumor of female reproductive system. Radiation therapy is one of the main methods of cervical cancer treatment, of which brachytherapy is an essential and important part of radiation therapy for locally advanced cervical cancer. With the rapid development of imaging technologies such as computed tomography (CT) and magnetic resonance imaging (MRI), brachytherapy for cervical cancer has gradually developed from traditional two-dimensional image-guided technology to three-dimensional image-guided technology. And there are more and more treatment methods, including intracavitary brachytherapy, interstitial brachytherapy, and intracavitary combined interstitial implantation brachytherapy. We performed a PubMed search for introduce the application progress of intracavity, implantation, intracavity combined implantation brachytherapy and radioactive seed implantation, and discuss the dosimetric feasibility of internal and external fusion irradiation.

Lycopene induces antiproliferative effects through apoptosis, autophagy, and oxidative DNA damage in the HeLa cells

Background This study explores the role of apoptosis, autophagy, and oxidative DNA damage in influencing the cytotoxic impact of lycopene on HeLa cells. Material and methods Cell viability following exposure to varying lycopene concentrations was determined using an XTT assay. ELISA measured key cell death proteins (Bax, BCL-2, etc.), while immunofluorescence staining visualized LC3β (autophagy) and 8-oxo-dG (DNA damage). Results Lycopene significantly killed HeLa cells in a dose-dependent way (IC50 = 10 μM). Subsequent examinations conducted with the IC50 dose of lycopene demonstrated a notable elevation in the expression levels of apoptotic proteins, such as cleaved caspase 3, cleaved PARP, and Bax (p < 0.001). Additionally, treatment with this substance led to an increase in the levels of 8-oxo-dG (p < 0.001), a widely acknowledged biomarker indicative of oxidative DNA damage. Furthermore, a significant rise (p < 0.05) in LC3β protein levels, a well-established indicator of autophagy activation, was noted. Conclusion This study suggests lycopene’s potential to fight cervical cancer by triggering programmed cell death (apoptosis) and cellular self-digestion (autophagy). These findings highlight lycopene as a promising candidate for future cervical cancer treatments.

Cost-Effectiveness of Pembrolizumab as First-Line Treatment in Patients with Persistent, Recurrent, or Metastatic Cervical Cancer in the United States.

First-line treatment of persistent, recurrent, or metastatic (advanced) cervical cancer in patients who have a combined positive score (CPS) ≥ 1 with pembrolizumab + chemotherapy versus standard-of-care chemotherapy provides meaningful improvements in overall survival. We conducted a cost-effectiveness analysis from a US payer perspective. A societal perspective scenario was also considered, including productivity gains. The cost-effectiveness of pembrolizumab + chemotherapy versus chemotherapy was assessed using a state-transition model comprising the health states "pre-progression," "post-progression," and "death," with a 1-week cycle length and 50-year time horizon. Patient-level KEYNOTE-826 data informed the efficacy, safety, and health-related quality of life of pembrolizumab + chemotherapy versus chemotherapy at first-line and subsequent treatments. Real-world data were sought to cost subsequent treatments according to US clinical practice. Transition probabilities were derived from parametric survival models fit to time-to-progression, progression-free survival, and post-progression survival patient-level KEYNOTE-826 data. Sensitivity analyses explored the impact on outcomes from variables such as bevacizumab use. According to the state-transition model, pembrolizumab + chemotherapy extended mean life expectancy versus chemotherapy from 1.8 to 6.7 life-years. The mean gain of 4.9 life-years/patient was mostly caused by pembrolizumab delaying progression. Total discounted quality-adjusted life-years (QALY) were 5.0 and 1.3 per patient for pembrolizumab + chemotherapy and chemotherapy, respectively (mean gain: 3.7 QALY/patient). Pembrolizumab + chemotherapy had comparable safety outcomes to chemotherapy alone. Total costs incurred were US $320,247 (pembrolizumab + chemotherapy) versus US $105,446 (chemotherapy; mean incremental costs: US $214,801/patient). The incremental cost-effectiveness ratio of pembrolizumab + chemotherapy versus chemotherapy was US $58,446/QALY. Sensitivity analyses showed results were insensitive to bevacizumab use. Including productivity gains led to an incremental cost-effectiveness ratio of US $58,385 per QALY. Our model-based analysis suggests that first-line treatment of pembrolizumab + chemotherapy in advanced cervical cancer with a CPS ≥ 1 offers a substantial clinical benefit over standard-of-care chemotherapy alone and is cost-effective at a willingness-to-pay threshold of US $150,000. The approximate doubling of life-years and QALYs associated with pembrolizumab + chemotherapy represents a step improvement in the treatment of advanced cervical cancer. ClinicalTrials.gov Identification Number: NCT03635567.

Cisplatin-encapsulated TRAIL-engineered exosomes from human chorion-derived MSCs for targeted cervical cancer therapy

BackgroundCisplatin (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.MethodsHuman chorion-derived mesenchymal stem cells (hCD-MSCs) were isolated by adherent culture method. TRAIL-engineered hCD-MSCs (hCD-MSCsTRAIL) were constructed by lentivirus transfection, and its secreted Exo (hCD-MSCs-ExoTRAIL) were acquired by differential centrifugation and confirmed to overexpress TRAIL by western blotting. Next, nanoscale drug delivery systems (DDP & hCD-MSCs-ExoTRAIL) were fabricated by loading DDP into hCD-MSCs-ExoTRAIL 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-ExoTRAIL in vivo.ResultsCompared with hCD-MSCs-Exo, hCD-MSCs-ExoTRAIL weakened proliferation and enhanced apoptosis of cervical cancer cells. DDP & hCD-MSCs-ExoTRAIL were proved to retard cervical cancer cell proliferation and propel cell apoptosis more effectively than DDP or hCD-MSCs-ExoTRAIL alone in vitro. In cervical cancer-bearing mice, DDP & hCD-MSCs-ExoTRAIL 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-ExoTRAIL showed favorable biosafety in vivo.ConclusionsDDP & hCD-MSCs-ExoTRAIL nanoparticles exhibited great promise for cervical cancer treatment as an Exo-based chemo-gene combinational therapy in clinical practice.Graphical abstract

Cost-effectiveness analysis of atezolizumab plus bevacizumab and chemotherapy for the treatment of metastatic, persistent, or recurrent cervical cancer (BEATcc)

ABSTRACT Background The addition of atezolizumab to bevacizumab plus platinum regimen has demonstrated notable improvements in treating metastatic, persistent, or recurrent cervical cancer, but its cost-effectiveness requires further investigation. From a US payer perspective, we aimed to evaluate the cost-effectiveness of atezolizumab plus bevacizumab and chemotherapy vs. standard chemotherapy as a first-line treatment for metastatic, persistent, or recurrent cervical cancer. Methods A partitioned survival model based on the data from the BEATcc trial was used to calculate the incremental cost-effectiveness ratio (ICER), using cost and health utility information obtained from literature and publicly accessible databases. One-way and probabilistic sensitivity analyses were performed to evaluate the model’s responsiveness to variations in parameters. Results The addition of atezolizumab resulted in an additional 0.839 quality-adjusted life years (QALY) at an additional cost of $458,237, leading to an ICER of $545,943/QALY. One-way sensitivity analysis indicated that the cost of atezolizumab had the greatest impact on the ICER, followed by the utility value of progression-free survival (PFS) and follow-up costs. Probabilistic sensitivity analysis showed a 0% cost-effectiveness probability at the current willingness-to-pay (WTP) threshold of $150,000 per QALY. Conclusion Adding atezolizumab to chemotherapy is cost-prohibitive in the US and may not be cost-effective for patients.

Standard of care treatment for stage IVB cervical cancer: A systematic review and meta-analysis

Standard of care treatment for stage IVB cervical cancer: A systematic review and meta-analysis

Anlotinib plus penpulimab plus chemo-less therapy in first-line treatment for persistent, recurrent, or metastatic cervical cancer: A single-arm, phase II study (ALTN-AK105-II-06)

Anlotinib plus penpulimab plus chemo-less therapy in first-line treatment for persistent, recurrent, or metastatic cervical cancer: A single-arm, phase II study (ALTN-AK105-II-06)