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1.
BMJ Case Rep ; 17(7)2024 Jul 08.
Article de Anglais | MEDLINE | ID: mdl-38977317
2.
Pan Afr Med J ; 47: 151, 2024.
Article de Anglais | MEDLINE | ID: mdl-38974700

RÉSUMÉ

Introduction: in Senegal, cervical cancer is the leading cause of cancers among women. This study estimated the costs associated with cervical cancer screening and treatment for precancerous lesions from the health system perspective. Methods: we estimated costs for screening, diagnostics, and treatment. We conducted a cross-sectional study in seven regions with primary data collected from 50 health facilities. Data collection included structured questionnaires, with secondary data from the Ministry of Health and other sources. A mixed-methods approach combined ingredients-based costing and financial expenditures to estimate direct medical and non-medical costs. All costs are reported in 2019 USD. Results: average costs were $3.71 for visual inspection with acetic acid, $16.49 for Pap smear, and $46.65 for human papillomavirus deoxyribonucleic acid (HPV DNA) testing. Screening cost drivers were clinical exam supplies and clinical equipment for visual inspection with acetic acid, offsite processing of specimens for Pap smear, and lab equipment costs for HPV DNA procedure. The average cost of diagnosis via colposcopy alone was $25.73, and colposcopy with biopsy/endocervical curettage was $74.96. The average cost of treatment followed by one visit for pre-cancerous lesions was $195.24 for loop electrosurgical excision, $47.35 for cryotherapy, and $32.35 for thermal ablation. Clinical equipment and lab costs were the largest contributors to colposcopy and endocervical curettage/biopsy expenses. Clinical equipment made up the largest portion of cryotherapy, loop electrosurgical excision, and thermoablation costs. Conclusion: this study is the first to estimate the costs of HPV screening and treatment in Senegal, which can be used to inform decision-making on cervical cancer investments.


Sujet(s)
Colposcopie , Dépistage précoce du cancer , Dépistage de masse , Test de Papanicolaou , Tumeurs du col de l'utérus , Frottis vaginaux , Humains , Tumeurs du col de l'utérus/diagnostic , Tumeurs du col de l'utérus/économie , Tumeurs du col de l'utérus/thérapie , Femelle , Sénégal , Études transversales , Dépistage précoce du cancer/économie , Test de Papanicolaou/économie , Frottis vaginaux/économie , Dépistage de masse/économie , Dépistage de masse/méthodes , Colposcopie/économie , Coûts des soins de santé/statistiques et données numériques , Infections à papillomavirus/diagnostic , Infections à papillomavirus/économie , Enquêtes et questionnaires , Tests de détection de l'ADN du virus du papillome humain/économie , Acide acétique , États précancéreux/diagnostic , États précancéreux/économie , États précancéreux/thérapie , Biopsie/économie
3.
Chin Clin Oncol ; 13(3): 35, 2024 Jun.
Article de Anglais | MEDLINE | ID: mdl-38984488

RÉSUMÉ

BACKGROUND: Cancers that metastasize to the skin are rare, especially cervical squamous cell carcinoma to the skin. Here, we have reported clinical analysis of patients with cervical squamous cell carcinoma metastasize to skin, to obtain a general understanding of this malignancy for clinicians. METHODS: A retrospective analysis of patients with skin metastasis from cervical squamous cell carcinoma was conducted, focusing on clinical manifestations, histopathology, diagnosis, treatment, and prognosis. RESULTS: The average age of onset for the six patients with skin metastasis from cervical squamous cell carcinoma was 55.17±17.08 years, with four cases presenting as solitary lesions and two cases as multiple lesions. Treatment strategies included local excision for isolated lesions, chemotherapy, radiotherapy, or targeted therapy based on the extent of skin involvement, and immunotherapy was proved to have promising results in our cases. Among the six patients, three have passed away with a diagnosis-to-death time of approximately 5-6 months, while three patients are alive, with survival times ranging from 30 to 72 months. CONCLUSIONS: Skin metastasis from cervical squamous cell carcinoma is rare and often accompanies recurrent metastases to other visceral sites, necessitating early and accurate diagnosis. For isolated metastatic lesions, early detection followed by wide excision surgery and adjuvant radiotherapy can yield favorable outcomes. However, in cases of multiple skin metastases or concurrent metastases to multiple organs, treatment is challenging with a poor prognosis. Nevertheless, with advancements in medicine, combination chemotherapy, immunotherapy, and targeted therapy can effectively prolong survival, offering new hope for patients with skin metastasis from cervical cancer.


Sujet(s)
Carcinome épidermoïde , Tumeurs cutanées , Tumeurs du col de l'utérus , Humains , Femelle , Tumeurs cutanées/thérapie , Tumeurs cutanées/anatomopathologie , Carcinome épidermoïde/thérapie , Carcinome épidermoïde/secondaire , Tumeurs du col de l'utérus/thérapie , Tumeurs du col de l'utérus/anatomopathologie , Adulte d'âge moyen , Études rétrospectives , Adulte , Sujet âgé , Pronostic
4.
Support Care Cancer ; 32(8): 503, 2024 Jul 10.
Article de Anglais | MEDLINE | ID: mdl-38985342

RÉSUMÉ

INTRODUCTION: Cervical cancer (CC) and its treatments impact various dimensions of quality of life (QoL), including physical, psychological, and sexual functioning. Sexual health, a crucial QoL aspect, is often compromised, highlighting the necessity for open sexual communication. MATERIALS AND METHODS: This study involved 60 women diagnosed with stage IIb-IIIa CC. The 36-Item Short Form Survey (SF-36) was used to measure physical and psychological components of QoL, the Female Sexual Function Index-6 (FSFI-6) to assess its sexual component, and the Sexual Communication Self-Efficacy Scale (SCSES) to diagnose communication confidence. Self-administered questions gauged patient-provider sexual communication. The results include quotes from participants, providing additional insight. RESULTS: Sexual communication self-efficacy and patient-provider communication correlated significantly with QoL components. Only 23.33% discussed sexual issues with their doctors. Participants' experiences highlighted the impact of cancer on sexuality and the need for tailored support. DISCUSSION: Post-diagnosis psychosexual changes emphasize the importance of communication in renegotiating sexual identity and needs. Effective communication is associated with improved QoL, highlighting the role of healthcare professionals in addressing psychosexual issues. Integrating PLISSIT and BETTER models provides a comprehensive approach to sexual communication in the cancer context. CONCLUSION: The study demonstrates the importance of sexual communication self-efficacy in QoL of CC patients and highlights the need for healthcare professionals to include sexual communication education in cancer care.


Sujet(s)
Communication , Qualité de vie , Auto-efficacité , Tumeurs du col de l'utérus , Humains , Femelle , Tumeurs du col de l'utérus/psychologie , Tumeurs du col de l'utérus/thérapie , Adulte d'âge moyen , Adulte , Comportement sexuel/psychologie , Enquêtes et questionnaires , Sujet âgé , Relations médecin-patient , Santé sexuelle
6.
Biomed Environ Sci ; 37(6): 565-580, 2024 Jun 20.
Article de Anglais | MEDLINE | ID: mdl-38988108

RÉSUMÉ

Objective: Genomic alterations and potential neoantigens for cervical cancer immunotherapy were identified in a cohort of Chinese patients with cervical squamous cell carcinoma (CSCC). Methods: Whole-exome sequencing was used to identify genomic alterations and potential neoantigens for CSCC immunotherapy. RNA Sequencing was performed to analyze neoantigen expression. Results: Systematic bioinformatics analysis showed that C>T/G>A transitions/transversions were dominant in CSCCs. Missense mutations were the most frequent types of somatic mutation in the coding sequence regions. Mutational signature analysis detected signature 2, signature 6, and signature 7 in CSCC samples. PIK3CA, FBXW7, and BICRA were identified as potential driver genes, with BICRA as a newly reported gene. Genomic variation profiling identified 4,960 potential neoantigens, of which 114 were listed in two neoantigen-related databases. Conclusion: The present findings contribute to our understanding of the genomic characteristics of CSCC and provide a foundation for the development of new biotechnology methods for individualized immunotherapy in CSCC.


Sujet(s)
Carcinome épidermoïde , Immunothérapie , Tumeurs du col de l'utérus , Humains , Femelle , Tumeurs du col de l'utérus/génétique , Tumeurs du col de l'utérus/thérapie , Tumeurs du col de l'utérus/immunologie , Carcinome épidermoïde/génétique , Carcinome épidermoïde/thérapie , Carcinome épidermoïde/immunologie , Études de cohortes , Antigènes néoplasiques/génétique , Antigènes néoplasiques/immunologie , Adulte d'âge moyen , , Chine , Mutation , Adulte , Génomique , Peuples d'Asie de l'Est
7.
BMC Health Serv Res ; 24(1): 792, 2024 Jul 09.
Article de Anglais | MEDLINE | ID: mdl-38982430

RÉSUMÉ

BACKGROUND: Recently-updated global guidelines for cervical cancer screening incorporated new technologies-most significantly, the inclusion of HPV DNA detection as a primary screening test-but leave many implementation decisions at countries' discretion. We sought to develop recommendations for Malawi as a test case since it has the second-highest cervical cancer burden globally and high HIV prevalence. We incorporated updated epidemiologic data, the full range of ablation methods recommended, and a more nuanced representation of how HIV status intersects with cervical cancer risk and exposure to screening to model outcomes of different approaches to screening. METHODS: Using a Markov model, we estimate the relative health outcomes and costs of different approaches to cervical cancer screening among Malawian women. The model was parameterized using published data, and focused on comparing "triage" approaches-i.e., lesion treatment (cryotherapy or thermocoagulation) at differing frequencies and varying by HIV status. Health outcomes were quality-adjusted life years (QALYs) and deaths averted. The model was built using TreeAge Pro software. RESULTS: Thermocoagulation was more cost-effective than cryotherapy at all screening frequencies. Screening women once per decade would avert substantially more deaths than screening only once per lifetime, at relatively little additional cost. Moreover, at this frequency, it would be advisable to ensure that all women who screen positive receive treatment (rather than investing in further increases in screening frequency): for a similar gain in QALYs, it would cost more than four times as much to implement once-per-5 years screening with only 50% of women treated versus once-per-decade screening with 100% of women treated. Stratified screening schedules by HIV status was found to be an optimal approach. CONCLUSIONS: These results add new evidence about cost-effective approaches to cervical cancer screening in low-income countries. At relatively infrequent screening intervals, if resources are limited, it would be more cost-effective to invest in scaling up thermocoagulation for treatment before increasing the recommended screening frequency. In Malawi or countries in a similar stage of the HIV epidemic, a stratified approach that prioritizes more frequent screening for women living with HIV may be more cost-effective than population-wide recommendations that are HIV status neutral.


Sujet(s)
Analyse coût-bénéfice , Dépistage précoce du cancer , Chaines de Markov , Années de vie ajustées sur la qualité , Tumeurs du col de l'utérus , Humains , Femelle , Malawi/épidémiologie , Tumeurs du col de l'utérus/diagnostic , Tumeurs du col de l'utérus/thérapie , Tumeurs du col de l'utérus/économie , Dépistage précoce du cancer/économie , Dépistage précoce du cancer/méthodes , Adulte , Adulte d'âge moyen , Infections à VIH/diagnostic , Infections à VIH/épidémiologie , Cryothérapie/économie , Dépistage de masse/économie , Dépistage de masse/méthodes
8.
Medicina (Kaunas) ; 60(6)2024 May 26.
Article de Anglais | MEDLINE | ID: mdl-38929488

RÉSUMÉ

Background and Objectives: Cervical cancer is the fourth most frequent type of neoplasia in women. It is most commonly caused by the persistent infection with high-risk strands of human papillomavirus (hrHPV). Its incidence increases rapidly from age 25 when routine HPV screening starts and then decreases at the age of 45. This reflects both the diagnosis of prevalent cases at first-time screening and the likely peak of HPV exposure in early adulthood. For early stages, the treatment offers the possibility of fertility preservation.. However, in more advanced stages, the treatment is restricted to concomitant chemo-radiotherapy, combined, in very selected cases with surgical intervention. After the neoadjuvant treatment, an imagistic re-evaluation of the patients is carried out to analyze if the stage of the disease remained the same or suffered a downstaging. Lymph node downstaging following neoadjuvant treatment is regarded as an indubitable prognostic factor for predicting disease recurrence and survival in patients with advanced cervical cancer. This study aims to ascertain the important survival role of radiotherapy in the downstaging of the disease and of lymphadenectomy in the control of lymph node invasion for patients with advanced-stage cervical cancer. Material and Methods: We describe the outcome of patients with cervical cancer in stage IIIC1 FIGO treated at Bucharest Oncological Institute. All patients received radiotherapy and two-thirds received concomitant chemotherapy. A surgical intervention consisting of type C radical hysterectomy with radical pelvic lymphadenectomy was performed six to eight weeks after the end of the neoadjuvant treatment. Results: The McNemar test demonstrated the regression of lymphadenopathies after neoadjuvant treatment-p: <0.001. However, the persistence of adenopathies was not related to the dose of irradiation (p: 0.61), the number of sessions of radiotherapy (p: 0.80), or the chemotherapy (p: 0.44). Also, there were no significant differences between the adenopathies reported by imagistic methods and those identified during surgical intervention-p: 0.62. The overall survival evaluated using Kaplan-Meier curves is dependent on the post-radiotherapy FIGO stage-p: 0.002 and on the lymph node status evaluated during surgical intervention-p: 0.04. The risk factors associated with an increased risk of death were represented by a low preoperative hemoglobin level (p: 0.003) and by the advanced FIGO stage determined during surgical intervention (p-value: 0.006 for stage IIIA and 0.01 for stage IIIC1). In the multivariate Cox model, the independent predictor of survival was the preoperative hemoglobin level (p: 0.004, HR 0.535, CI: 0.347 to 0.823). Out of a total of 33 patients with neoadjuvant treatment, 22 survived until the end of the study, all 33 responded to the treatment in varying degrees, but in 3 of them, tumor cells were found in the lymph nodes during the intraoperative histopathological examination. Conclusions: For advanced cervical cancer patients, radical surgery after neoadjuvant treatment may be associated with a better survival rate. Further research is needed to identify all the causes that lead to the persistence of adenopathies in certain patients, to decrease the FIGO stage after surgical intervention, and, therefore, to lower the risk of death. Also, it is mandatory to correctly evaluate and treat the anemia, as it seems to be an independent predictor factor for mortality.


Sujet(s)
Traitement néoadjuvant , Stadification tumorale , Tumeurs du col de l'utérus , Humains , Femelle , Tumeurs du col de l'utérus/anatomopathologie , Tumeurs du col de l'utérus/thérapie , Tumeurs du col de l'utérus/mortalité , Traitement néoadjuvant/méthodes , Adulte , Adulte d'âge moyen , Lymphadénectomie , Noeuds lymphatiques/anatomopathologie , Hystérectomie , Métastase lymphatique , Sujet âgé
9.
BMC Womens Health ; 24(1): 365, 2024 Jun 22.
Article de Anglais | MEDLINE | ID: mdl-38909186

RÉSUMÉ

BACKGROUND: This study aimed to evaluate the outcomes of patients diagnosed with stage IB2/IIA2 cervical squamous cell carcinoma who underwent neoadjuvant chemotherapy (NACT) prior to radical hysterectomy compared to those who did not receive NACT before surgery. MATERIALS AND METHODS: This is a multicenter study including data of 6 gynecological oncology departments. The study is approved from one of the institution's local ethics committee. Patients were stratified into two cohorts based on the receipt of NACT preceding their surgical intervention. Clinico-pathological factors and progression-free survival were analyzed. RESULTS: Totally 87 patients were included. Lymphovascular space invasion (LVSI) was observed as 40% in the group receiving NACT, while it was 66.1% in the group not receiving NACT (p = 0.036). Deep stromal invasion (> 50%) was 56% in the group receiving NACT and 84.8% in the group not receiving NACT (p = 0.001). In the univariate analysis, application of NACT is statistically significant among the factors that would be associated with disease-free survival. Consequently, a multivariate analysis was conducted for progression-free survival, incorporating factors such as the depth of stromal invasion, the presence of LVSI, and the administration of NACT. Of these, only the administration of NACT emerged as an independent predictor associated with decreased progression-free survival. (RR:5.88; 95% CI: 1.63-21.25; p = 0.07). CONCLUSIONS: NACT shouldn't be used routinely in patients with stage IB2/IIA2 cervical cancer before radical surgery. Presented as oral presentation at National Congress of Gynaecological Oncology & National Congress of Cervical Pathologies and Colposcopy (2022/ TURKEY).


Sujet(s)
Carcinome épidermoïde , Hystérectomie , Traitement néoadjuvant , Stadification tumorale , Tumeurs du col de l'utérus , Humains , Femelle , Tumeurs du col de l'utérus/anatomopathologie , Tumeurs du col de l'utérus/chirurgie , Tumeurs du col de l'utérus/thérapie , Tumeurs du col de l'utérus/traitement médicamenteux , Traitement néoadjuvant/méthodes , Traitement néoadjuvant/statistiques et données numériques , Adulte d'âge moyen , Carcinome épidermoïde/chirurgie , Carcinome épidermoïde/thérapie , Carcinome épidermoïde/traitement médicamenteux , Carcinome épidermoïde/anatomopathologie , Hystérectomie/méthodes , Hystérectomie/statistiques et données numériques , Adulte , Traitement médicamenteux adjuvant/méthodes , Traitement médicamenteux adjuvant/statistiques et données numériques , Sujet âgé , Études rétrospectives , Survie sans rechute
10.
In Vivo ; 38(4): 1973-1983, 2024.
Article de Anglais | MEDLINE | ID: mdl-38936897

RÉSUMÉ

BACKGROUND/AIM: Distinguishing ovarian metastasis of usual-type endocervical adenocarcinoma (UEA) from primary ovarian tumors is often challenging because of several overlapping features. This study aimed to investigate the clinicopathological characteristics and outcomes of patients with metastatic ovarian UEA. PATIENTS AND METHODS: Clinicopathological information was collected from eight patients with metastatic ovarian UEA. Immunostaining was also performed. RESULTS: Most patients presented with adnexal masses that were suspected to be primary ovarian tumors. All examined cases showed block p16 positivity in paired primary and metastatic tumors. Five patients who completed post-operative chemotherapy or concurrent chemoradiotherapy (CCRT) did not experience recurrence. In contrast, one patient who refused further treatment after the first CCRT cycle experienced ovarian and peritoneal metastases. One patient with isolated ovarian metastasis left untreated and developed peritoneal metastasis during follow-up. CONCLUSION: Patients with UEA who received proper management for ovarian metastases showed favorable outcomes. Given that ovarian metastatic UEA can mimic primary ovarian borderline tumor or carcinoma of the mucinous or endometrioid type, pathologists should be aware of this unusual but distinctive morphology to avoid misdiagnosis and inappropriate treatment.


Sujet(s)
Carcinome endométrioïde , Tumeurs de l'ovaire , Tumeurs du col de l'utérus , Humains , Femelle , Tumeurs de l'ovaire/anatomopathologie , Tumeurs de l'ovaire/diagnostic , Adulte d'âge moyen , Tumeurs du col de l'utérus/anatomopathologie , Tumeurs du col de l'utérus/diagnostic , Tumeurs du col de l'utérus/thérapie , Tumeurs du col de l'utérus/virologie , Adulte , Diagnostic différentiel , Carcinome endométrioïde/anatomopathologie , Carcinome endométrioïde/diagnostic , Carcinome endométrioïde/thérapie , Adénocarcinome mucineux/secondaire , Adénocarcinome mucineux/thérapie , Adénocarcinome mucineux/diagnostic , Adénocarcinome mucineux/anatomopathologie , Infections à papillomavirus/anatomopathologie , Infections à papillomavirus/complications , Infections à papillomavirus/virologie , Infections à papillomavirus/diagnostic , Sujet âgé , Adénocarcinome/virologie , Adénocarcinome/secondaire , Adénocarcinome/diagnostic , Adénocarcinome/anatomopathologie , Adénocarcinome/thérapie , Papillomaviridae/isolement et purification , Métastase tumorale , Virus des Papillomavirus humains
11.
ACS Nano ; 18(26): 16516-16529, 2024 Jul 02.
Article de Anglais | MEDLINE | ID: mdl-38912600

RÉSUMÉ

Activated guided irradiation by X-ray (AGuIX) nanoparticles are gadolinium-based agents that have the dual benefit of mimicking the effects of a magnetic resonance imaging (MRI) contrast agent used in a clinical routine and enhancing the radiotherapeutic activity of conventional X-rays (for cancer treatment). This "theragnostic" action is explained on the one hand by the paramagnetic properties of gadolinium and on the other hand by the generation of high densities of secondary radiation following the interaction of ionizing radiation and high-Z atoms, which leads to enhanced radiation dose deposits within the tumors where the nanoparticles accumulate. Here, we report the results of a phase I trial that aimed to assess the safety and determine the optimal dose of AGuIX nanoparticles in combination with chemoradiation and brachytherapy in patients with locally advanced cervical cancer. AGuIX nanoparticles were administered intravenously and appropriately accumulated within tumors on a dose-dependent manner, as assessed by T1-weighted MRI, with a rapid urinary clearance of uncaught nanoparticles. We show that the observed tumor accumulation of the compounds can support precise delineation of functional target volumes at the time of brachytherapy based on gadolinium enhancement. AGuIX nanoparticles combined with chemoradiation appeared well tolerated among the 12 patients treated, with no dose-limiting toxicity observed. Treatment yielded excellent local control, with all patients achieving complete remission of the primary tumor. One patient had a distant tumor recurrence. These results demonstrate the clinical feasibility of using theranostic nanoparticles to augment the accuracy of MRI-based treatments while focally enhancing the radiation activity in tumors.


Sujet(s)
Gadolinium , Imagerie par résonance magnétique , Nanoparticules , Tumeurs du col de l'utérus , Gadolinium/composition chimique , Humains , Tumeurs du col de l'utérus/imagerie diagnostique , Tumeurs du col de l'utérus/traitement médicamenteux , Tumeurs du col de l'utérus/thérapie , Tumeurs du col de l'utérus/anatomopathologie , Femelle , Nanoparticules/composition chimique , Adulte d'âge moyen , Curiethérapie , Produits de contraste/composition chimique , Rayons X , Adulte , Sujet âgé , Chimioradiothérapie
12.
Front Immunol ; 15: 1362904, 2024.
Article de Anglais | MEDLINE | ID: mdl-38855110

RÉSUMÉ

Introduction: Chimeric antigen receptor (CAR) T cell therapy has transformed the treatment of hematological malignancies. However, its efficacy in solid tumors is limited by the immunosuppressive tumor microenvironment that compromises CAR T cell antitumor function in clinical settings. To overcome this challenge, researchers have investigated the potential of inhibiting specific immune checkpoint receptors, including A2aR (Adenosine A2 Receptor) and Tim3 (T cell immunoglobulin and mucin domain-containing protein 3), to enhance CAR T cell function. In this study, we evaluated the impact of genetic targeting of Tim3 and A2a receptors on the antitumor function of human mesothelin-specific CAR T cells (MSLN-CAR) in vitro and in vivo. Methods: Second-generation anti-mesothelin CAR T cells were produced using standard cellular and molecular techniques. A2aR-knockdown and/or Tim3- knockdown anti-mesothelin-CAR T cells were generated using shRNA-mediated gene silencing. The antitumor function of CAR T cells was evaluated by measuring cytokine production, proliferation, and cytotoxicity in vitro through coculture with cervical cancer cells (HeLa cell line). To evaluate in vivo antitumor efficacy of manufactured CAR T cells, tumor growth and mouse survival were monitored in a human cervical cancer xenograft model. Results: In vitro experiments demonstrated that knockdown of A2aR alone or in combination with Tim3 significantly improved CAR T cell proliferation, cytokine production, and cytotoxicity in presence of tumor cells in an antigen-specific manner. Furthermore, in the humanized xenograft model, both double knockdown CAR T cells and control CAR T cells could effectively control tumor growth. However, single knockdown CAR T cells were associated with reduced survival in mice. Conclusion: These findings highlight the potential of concomitant genetic targeting of Tim3 and A2a receptors to augment the efficacy of CAR T cell therapy in solid tumors. Nevertheless, caution should be exercised in light of our observation of decreased survival in mice treated with single knockdown MSLN-CAR T cells, emphasizing the need for careful efficacy considerations.


Sujet(s)
Récepteur cellulaire-2 du virus de l'hépatite A , Immunothérapie adoptive , Mésothéline , Récepteurs chimériques pour l'antigène , Tumeurs du col de l'utérus , Tests d'activité antitumorale sur modèle de xénogreffe , Humains , Animaux , Récepteur cellulaire-2 du virus de l'hépatite A/métabolisme , Récepteur cellulaire-2 du virus de l'hépatite A/génétique , Femelle , Tumeurs du col de l'utérus/immunologie , Tumeurs du col de l'utérus/thérapie , Tumeurs du col de l'utérus/génétique , Souris , Immunothérapie adoptive/méthodes , Récepteurs chimériques pour l'antigène/immunologie , Récepteurs chimériques pour l'antigène/génétique , Récepteurs chimériques pour l'antigène/métabolisme , Lymphocytes T/immunologie , Lymphocytes T/métabolisme , Lignée cellulaire tumorale , Microenvironnement tumoral/immunologie , Souris SCID
13.
J Transl Med ; 22(1): 575, 2024 Jun 17.
Article de Anglais | MEDLINE | ID: mdl-38886729

RÉSUMÉ

The vaginal microbiome is an immune defense against reproductive diseases and can serve as an important biomarker for cervical cancer. However, the intrinsic relationship between the recurrence and the vaginal microbiome in patients with cervical cancer before and after concurrent chemoradiotherapy is poorly understood. Here, we analyzed 125 vaginal microbial profiles from a patient cohort of stage IB-IVB cervical cancer using 16S metagenomic sequencing and deciphered the microbial composition and functional characteristics of the recurrent and non-recurrent both before and after chemoradiotherapy. We demonstrated that the abundance of beneficial bacteria and stability of the microbial community in the vagina decreased in the recurrence group, implying the unique characteristics of the vaginal microbiome for recurrent cervical cancer. Moreover, using machine learning, we identified Lactobacillus iners as the most important biomarker, combined with age and other biomarkers (such as Ndongobacter massiliensis, Corynebacterium pyruviciproducens ATCC BAA-1742, and Prevotella buccalis), and could predict cancer recurrence phenotype before chemoradiotherapy. This study prospectively employed rigorous bioinformatics analysis and highlights the critical role of vaginal microbiota in post-treatment cervical cancer recurrence, identifying promising biomarkers with prognostic significance in the context of concurrent chemoradiotherapy for cervical cancer. The role of L. iners in determining chemoradiation resistance in cervical cancer warrants further detailed investigation. Our results expand our understanding of cervical cancer recurrence and help develop better strategies for prognosis prediction and personalized therapy.


Sujet(s)
Chimioradiothérapie , Lactobacillus , Microbiote , Récidive tumorale locale , Tumeurs du col de l'utérus , Vagin , Humains , Femelle , Tumeurs du col de l'utérus/microbiologie , Tumeurs du col de l'utérus/thérapie , Tumeurs du col de l'utérus/anatomopathologie , Vagin/microbiologie , Récidive tumorale locale/microbiologie , Adulte d'âge moyen , Adulte , Sujet âgé , Apprentissage machine
14.
Int J Nanomedicine ; 19: 5837-5858, 2024.
Article de Anglais | MEDLINE | ID: mdl-38887692

RÉSUMÉ

Purpose: Phototherapy, known for its high selectivity, few side effects, strong controllability, and synergistic enhancement of combined treatments, is widely used in treating diseases like cervical cancer. Methods: In this study, hollow mesoporous manganese dioxide was used as a carrier to construct positively charged, poly(allylamine hydrochloride)-modified nanoparticles (NPs). The NP was efficiently loaded with the photosensitizer indocyanine green (ICG) via the addition of hydrogen phosphate ions to produce a counterion aggregation effect. HeLa cell membrane encapsulation was performed to achieve the final M-HMnO2@ICG NP. In this structure, the HMnO2 carrier responsively degrades to release ICG in the tumor microenvironment, self-generates O2 for sensitization to ICG-mediated photodynamic therapy (PDT), and consumes GSH to expand the oxidative stress therapeutic effect [chemodynamic therapy (CDT) + PDT]. The ICG accumulated in tumor tissues exerts a synergistic PDT/photothermal therapy (PTT) effect through single laser irradiation, improving efficiency and reducing side effects. The cell membrane encapsulation increases nanomedicine accumulation in tumor tissues and confers an immune evasion ability. In addition, high local temperatures induced by PTT can enhance CDT. These properties of the NP enable full achievement of PTT/PDT/CDT and targeted effects. Results: Mn2+ can serve as a magnetic resonance imaging agent to guide therapy, and ICG can be used for photothermal and fluorescence imaging. After its intravenous injection, M-HMnO2@ICG accumulated effectively at mouse tumor sites; the optimal timing of in-vivo laser treatment could be verified by near-infrared fluorescence, magnetic resonance, and photothermal imaging. The M-HMnO2@ICG NPs had the best antitumor effects among treatment groups under near-infrared light conditions, and showed good biocompatibility. Conclusion: In this study, we designed a nano-biomimetic delivery system that improves hypoxia, responds to the tumor microenvironment, and efficiently loads ICG. It provides a new economical and convenient strategy for synergistic phototherapy and CDT for cervical cancer.


Sujet(s)
Vert indocyanine , Composés du manganèse , Imagerie multimodale , Nanoparticules , Photothérapie dynamique , Photosensibilisants , Microenvironnement tumoral , Tumeurs du col de l'utérus , Tumeurs du col de l'utérus/thérapie , Tumeurs du col de l'utérus/imagerie diagnostique , Tumeurs du col de l'utérus/traitement médicamenteux , Femelle , Microenvironnement tumoral/effets des médicaments et des substances chimiques , Humains , Vert indocyanine/composition chimique , Vert indocyanine/pharmacologie , Photothérapie dynamique/méthodes , Animaux , Cellules HeLa , Photosensibilisants/pharmacologie , Photosensibilisants/composition chimique , Nanoparticules/composition chimique , Composés du manganèse/composition chimique , Composés du manganèse/pharmacologie , Souris , Imagerie multimodale/méthodes , Thérapie photothermique/méthodes , Oxydes/composition chimique , Oxydes/pharmacologie , Souris de lignée BALB C , Polyamines/composition chimique , Polyamines/pharmacologie , Imagerie par résonance magnétique/méthodes
15.
Front Immunol ; 15: 1391524, 2024.
Article de Anglais | MEDLINE | ID: mdl-38835778

RÉSUMÉ

Background: Cervical cancer (CC) poses a global health challenge, with a particularly poor prognosis in cases of recurrence, metastasis, or advanced stages. A single biomarker is inadequate to predict CC prognosis or identify CC patients likely to benefit from immunotherapy, presumably owing to tumor complexity and heterogeneity. Methods: Using advanced Olink proteomics, we analyzed 92 oncology-related proteins in plasma from CC patients receiving immunotherapy, based upon the comparison of protein expression levels of pre-therapy with those of therapy-Cycle 6 in the partial response (PR) group and progressive disease (PD) group, respectively. Results: 55 proteins were identified to exhibit differential expression trends across pre-therapy and post-therapy in both PR and PD groups. Enriched GO terms and KEGG pathways were associated with vital oncological and immunological processes. A logistic regression model, using 5 proteins (ITGB5, TGF-α, TLR3, WIF-1, and ERBB3) with highest AUC values, demonstrated good predictive performance for prognosis of CC patients undergoing immunotherapy and showed potential across different cancer types. The effectiveness of these proteins in prognosis prediction was further validated using TCGA-CESC datasets. A negative correlation and previously unidentified roles of WIF-1 in CC immunotherapy was also first determined. Conclusion: Our findings reveal multi-biomarker profiles effectively predicting CC prognosis and identifying patients benefitting most from immunotherapy, especially for those with limited treatment options and traditionally poor prognosis, paving the way for personalized immunotherapeutic treatments and improved clinical strategies.


Sujet(s)
Marqueurs biologiques tumoraux , Immunothérapie , Protéomique , Tumeurs du col de l'utérus , Humains , Femelle , Tumeurs du col de l'utérus/thérapie , Tumeurs du col de l'utérus/immunologie , Tumeurs du col de l'utérus/diagnostic , Marqueurs biologiques tumoraux/sang , Protéomique/méthodes , Pronostic , Immunothérapie/méthodes , Adulte d'âge moyen , Adulte
16.
J Obstet Gynaecol ; 44(1): 2361858, 2024 Dec.
Article de Anglais | MEDLINE | ID: mdl-38864403

RÉSUMÉ

BACKGROUND: Cervical cancer ranks as the second most fatal tumour globally among females. Neutrophil-to-lymphocyte ratio (NLR) and platelet-to-lymphocyte ratio (PLR) have been widely applied to the diagnosis of cancers. METHODS: The clinicopathologic data of 180 patients with stage IB2-IIB cervical cancer who underwent radical concurrent chemoradiotherapy from January 2018 to December 2019 were retrospectively analysed. Receiver operating characteristic (ROC) curves were plotted to analyse the optimal cut-off values of NLR and PLR for predicting the therapeutic effects of concurrent chemoradiotherapy. The associations of PLR and other clinicopathological factors with 1-year survival rates were explored through univariate analysis and multivariate Cox regression analysis, respectively. RESULTS: NLR was significantly associated with the therapeutic effects of neoadjuvant therapy, with the optimal cut-off value of 2.89, area under the ROC curve (AUC) of 0.848 (95% confidence interval [CI]: 0.712-0.896), sensitivity of 0.892 (95% CI: 0.856-0.923) and specificity of 0.564 (95% CI: 0.512-0.592). PLR had a significant association with the therapeutic effects of neoadjuvant therapy, with the optimal cut-off value of 134.27, AUC of 0.766 (95% CI: 0.724-0.861), sensitivity of 0.874 (95% CI: 0.843-0.905) and specificity of 0.534 (95% CI: 0.512-0.556). Lymphatic metastasis ([95% CI: 1.435-5.461], [95% CI: 1.336-4.281], depth of invasion ([95% CI: 1.281-3.546], [95% CI: 1.183-3.359]) and tumour size ([95% CI: 1.129-3.451], [95% CI: 1.129-3.451]) were independent factors influencing the overall survival and disease-free survival (DFS) of patients with cervical cancer. NLR (95%CI: 1.256-4.039) and PLR (95%CI:1.281-3.546) were also independent factors affecting DFS. CONCLUSION: NLR and PLR in the peripheral blood before treatment may predict DFS of patients with stage IB2-IIB cervical cancer.


The clinicopathologic data of 180 patients with stage IB2-IIB cervical cancer who underwent radical concurrent chemoradiotherapy were retrospectively analysed. Receiver operating characteristic curves showed that neutrophil-to-lymphocyte ratio (NLR) and platelet-to-lymphocyte ratio (PLR) were significantly associated with the therapeutic effects of neoadjuvant therapy. Univariate and multivariate regression analysis revealed that lymphatic metastasis, depth of invasion and tumour size were independent factors influencing the overall survival and disease-free survival (DFS) of patients with cervical cancer. NLR and PLR in the peripheral blood before treatment may predict the DFS of patients with stage IB2-IIB cervical cancer.


Sujet(s)
Chimioradiothérapie , Lymphocytes , Traitement néoadjuvant , Granulocytes neutrophiles , Tumeurs du col de l'utérus , Humains , Femelle , Tumeurs du col de l'utérus/thérapie , Tumeurs du col de l'utérus/sang , Tumeurs du col de l'utérus/mortalité , Tumeurs du col de l'utérus/anatomopathologie , Adulte d'âge moyen , Études rétrospectives , Chimioradiothérapie/méthodes , Adulte , Traitement néoadjuvant/méthodes , Plaquettes , Courbe ROC , Numération des lymphocytes , Sujet âgé , Numération des plaquettes , Pronostic , Valeur prédictive des tests , Stadification tumorale , Taux de survie , Numération des leucocytes
17.
Med ; 5(6): 487-489, 2024 Jun 14.
Article de Anglais | MEDLINE | ID: mdl-38878765

RÉSUMÉ

In locally advanced cervical cancer (LACC), the benefit of PD-1 blockade was unknown. In KEYNOTE-A18, Lorusso et al.1 compared the efficacy and safety of adding pembrolizumab to chemoradiation in LACC and demonstrated favorable outcomes. Given multiple approved indications of pembrolizumab in cervical cancer, strategies for optimal integration into management will be needed to maximize overall survival.


Sujet(s)
Anticorps monoclonaux humanisés , Chimioradiothérapie , Tumeurs du col de l'utérus , Humains , Tumeurs du col de l'utérus/thérapie , Tumeurs du col de l'utérus/traitement médicamenteux , Tumeurs du col de l'utérus/anatomopathologie , Femelle , Anticorps monoclonaux humanisés/usage thérapeutique , Chimioradiothérapie/méthodes , Immunothérapie/méthodes , Inhibiteurs de points de contrôle immunitaires/usage thérapeutique , Inhibiteurs de points de contrôle immunitaires/pharmacologie , Essais contrôlés randomisés comme sujet
18.
Anticancer Res ; 44(7): 3077-3086, 2024 Jul.
Article de Anglais | MEDLINE | ID: mdl-38925822

RÉSUMÉ

BACKGROUND/AIM: This study evaluated the association between programmed cell death-ligand 1 (PD-L1) and prognosis in patients with cervical cancer treated with postoperative radiation and the impact of neoadjuvant chemotherapy (NAC) on this association. PATIENTS AND METHODS: Immunohistochemical analysis was performed on biopsy specimens from 42 patients who did not receive NAC and from paired samples before (biopsies) and after (resected tissues) chemotherapy from 46 patients who received NAC to determine the association of PD-L1 with radiotherapy outcomes. RESULTS: In the non-NAC group, patients with ≥10% PD-L1-expressing tumor cells prior to treatment had better recurrence-free survival (RFS) than those with <10% PD-L1-expressing tumor cells (p=0.001). In the NAC group, RFS was significantly lower (p=0.005) in the group with a ≥5% reduction of PD-L1 expression in tumor cells after chemotherapy than in those with <5% reduction. In multivariate analysis, only PD-L1 expression (non-NAC group) and the change in PD-L1 expression (NAC group) were associated with RFS. CONCLUSION: Low PD-L1 expression in a cervical tumor prior to treatment was identified as a risk factor for a poor outcome after postoperative radiotherapy. Furthermore, NAC induces an immunological shift that reduces PD-L1 levels in tumor cells, thereby negatively impacting treatment outcomes.


Sujet(s)
Antigène CD274 , Traitement néoadjuvant , Tumeurs du col de l'utérus , Humains , Tumeurs du col de l'utérus/immunologie , Tumeurs du col de l'utérus/anatomopathologie , Tumeurs du col de l'utérus/thérapie , Tumeurs du col de l'utérus/radiothérapie , Tumeurs du col de l'utérus/métabolisme , Femelle , Adulte d'âge moyen , Antigène CD274/métabolisme , Adulte , Sujet âgé , Pronostic , Résultat thérapeutique , Marqueurs biologiques tumoraux/métabolisme , Survie sans rechute
19.
Gynecol Oncol ; 186: 199-203, 2024 Jul.
Article de Anglais | MEDLINE | ID: mdl-38833852

RÉSUMÉ

BACKGROUND: Patients may use crowdfunding to solicit donations, typically from multiple small donors using internet-based means, to offset the financial toxicity of cancer care. OBJECTIVE: To describe crowdfunding campaigns by gynecologic cancer patients and to compare campaign characteristics and needs expressed between patients with cervical, uterine, and ovarian cancer. STUDY DESIGN: We queried the public crowdfunding forum GoFundMe.com for "cervical cancer," "uterine cancer," and "ovarian cancer." The first 200 consecutive posts for each cancer type fundraising within the United States were analyzed. Data on campaign goals and needs expressed were manually extracted. Descriptive statistics and bivariate analyses were performed. RESULTS: Among the 600 fundraising pages, the median campaign goal was $10,000 [IQR $5000-$23,000]. Campaigns raised a median of 28.6% of their goal with only 8.7% of campaigns reaching their goal after a median of 54 days online. On average, ovarian cancer campaigns had higher monetary goals, more donors, and larger donation amounts than cervical cancer campaigns and raised more money than both cervical and uterine cancer campaigns. Campaigns were fundraising to support medical costs (80-85%) followed by lost wages (36-56%) or living expenses (27-41%). Cervical cancer campaigns reported need for non-medical costs more frequently than uterine or ovarian cancer campaigns. States without Medicaid expansions (31% of the national population) were over-represented among cervical cancer and uterine cancer, but not ovarian cancer campaigns. CONCLUSIONS: Crowdfunding pages reveal patients fundraising for out-of-pocket costs in the thousands of dollars and a wide range of unmet financial needs based on cancer type.


Sujet(s)
Collecte de fonds , Tumeurs de l'appareil génital féminin , Humains , Femelle , Collecte de fonds/économie , Tumeurs de l'appareil génital féminin/économie , Tumeurs de l'appareil génital féminin/thérapie , États-Unis , Externalisation ouverte/économie , Tumeurs du col de l'utérus/économie , Tumeurs du col de l'utérus/thérapie , Tumeurs de l'ovaire/économie , Tumeurs de l'ovaire/thérapie
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