RESUMEN
BACKGROUND: Cervical cancer, primarily caused by HPV infection, remains a global health concern. Current treatments face challenges including drug resistance and toxicity. This study investigates combining E5-siRNA with chemotherapy drugs, Oxaliplatin and Ifosfamide, to enhance treatment efficacy in HPV-16 positive cervical cancer cells, targeting E5 oncoprotein to overcome limitations of existing therapies. METHODS: The CaSki cervical cancer cell line was transfected with E5-siRNA, and subsequently treated with Oxaliplatin/Ifosfamide. Quantitative real-time PCR was employed to assess the expression of related genes including p53, MMP2, Nanog, and Caspases. Cell apoptosis, cell cycle progression, and cell viability were evaluated using Annexin V/PI staining, DAPI staining, and MTT test, respectively. Furthermore, stemness ability was determined through a colony formation assay, and cell motility was assessed by wound healing assay. RESULTS: E5-siRNA transfection significantly reduced E5 mRNA expression in CaSki cells compared to the control group. The MTT assay revealed that monotherapy with E5-siRNA, Oxaliplatin, or Ifosfamide had moderate effects on cell viability. However, combination therapy showed synergistic effects, reducing the IC50 of Oxaliplatin from 11.42 × 10-8 M (45.36 µg/ml) to 6.71 × 10-8 M (26.66 µg/ml) and Ifosfamide from 12.52 × 10-5 M (32.7 µg/ml) to 8.206 × 10-5 M (21.43 µg/ml). Flow cytometry analysis demonstrated a significant increase in apoptosis for combination treatments, with apoptosis rates rising from 11.02 % (Oxaliplatin alone) and 16.98 % (Ifosfamide alone) to 24.8 % (Oxaliplatin + E5-siRNA) and 34.9 % (Ifosfamide + E5-siRNA). The sub-G1 cell population increased from 15.7 % (Oxaliplatin alone) and 18 % (Ifosfamide alone) to 21.9 % (Oxaliplatin + E5-siRNA) and 27.1 % (Ifosfamide + E5-siRNA), indicating cell cycle arrest. The colony formation assay revealed a substantial decrease in the number of colonies following combination treatment. qRT-PCR analysis showed decreased expression of stemness-related genes CD44 and Nanog, and migration-related genes MMP2 and CXCL8 in the combination groups. Apoptosis-related genes Casp-3, Casp-9, and pP53 showed increased expression following combination therapy, while BAX expression increased and BCL2 expression decreased relative to the control. CONCLUSION: The study demonstrates that combining E5-siRNA with Oxaliplatin or Ifosfamide enhances the efficacy of chemotherapy in HPV-16 positive cervical cancer cells. This synergistic approach effectively targets multiple aspects of cancer cell behavior, including proliferation, apoptosis, migration, and stemness. The findings suggest that this combination strategy could potentially allow for lower chemotherapy doses, thereby reducing toxicity while maintaining therapeutic efficacy. This research provides valuable insights into targeting HPV E5 as a complementary approach to existing therapies focused on E6 and E7 oncoproteins, opening new avenues for combination therapies in cervical cancer treatment.
Asunto(s)
Apoptosis , Papillomavirus Humano 16 , Ifosfamida , Oxaliplatino , ARN Interferente Pequeño , Neoplasias del Cuello Uterino , Humanos , Neoplasias del Cuello Uterino/tratamiento farmacológico , Neoplasias del Cuello Uterino/genética , Neoplasias del Cuello Uterino/virología , Oxaliplatino/farmacología , Femenino , ARN Interferente Pequeño/genética , Línea Celular Tumoral , Ifosfamida/farmacología , Apoptosis/efectos de los fármacos , Papillomavirus Humano 16/genética , Infecciones por Papillomavirus/tratamiento farmacológico , Infecciones por Papillomavirus/genética , Infecciones por Papillomavirus/virología , Supervivencia Celular/efectos de los fármacos , Proteínas Oncogénicas Virales/genética , Movimiento Celular/efectos de los fármacos , Proliferación Celular/efectos de los fármacos , Antineoplásicos/farmacología , Regulación Neoplásica de la Expresión Génica/efectos de los fármacosRESUMEN
Radiotherapy as a mainstay of in-depth cervical cancer (CC) treatment suffers from its radioresistance. Radiodynamic therapy (RDT) effectively reverses radio-resistance by generating reactive oxygen species (ROS) with deep tissue penetration. However, the photosensitizers stimulated by X-ray have high toxicity and energy attenuation. Therefore, X-ray responsive diselenide-bridged mesoporous silica nanoparticles (DMSNs) are designed, loading X-ray-activated photosensitizer acridine orange (AO) for spot blasting RDT like Trojan-horse against radio-resistance cervical cancer (R-CC). DMSNs can encapsulate a large amount of AO, in the tumor microenvironment (TME), which has a high concentration of hydrogen peroxide, X-ray radiation triggers the cleavage of diselenide bonds, leading to the degradation of DMSNs and the consequent release of AO directly at the tumor site. On the one hand, it solves the problems of rapid drug clearance, adverse distribution, and side effects caused by simple AO treatment. On the other hand, it fully utilizes the advantages of highly penetrating X-ray responsive RDT to enhance radiotherapy sensitivity. This approach results in ROS-induced mitochondria damage, inhibition of DNA damage repair, cell cycle arrest and promotion of cancer cell apoptosis in R-CC. The X-ray responsive DMSNs@AO hold considerable potential in overcoming obstacles for advanced RDT in the treatment of R-CC.
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Nanopartículas , Dióxido de Silicio , Humanos , Animales , Rayos X , Nanopartículas/química , Femenino , Dióxido de Silicio/química , Ratones , Neoplasias del Cuello Uterino/terapia , Neoplasias del Cuello Uterino/tratamiento farmacológico , Neoplasias del Cuello Uterino/patología , Especies Reactivas de Oxígeno/metabolismo , Fármacos Fotosensibilizantes/farmacología , Fármacos Fotosensibilizantes/uso terapéutico , Tolerancia a Radiación/efectos de los fármacos , Microambiente Tumoral/efectos de los fármacos , Ratones Desnudos , Células HeLa , Ratones Endogámicos BALB C , Apoptosis/efectos de los fármacos , Línea Celular TumoralRESUMEN
Objective To evaluate cervical cancer screening with primary human papillomavirus (HPV) testing in Mozambique, a country with one of the highest burdens of cervical cancer globally. Methods Women aged 3049 years were prospectively enrolled and offered primary HPV testing using either self- collected or provider- collected specimens. Patients who tested positive for HPV underwent visual assessment for treatment using visual inspection with acetic acid to determine eligibility for thermal ablation. If ineligible, they were referred for excision with a loop electrosurgical excision procedure, for cold knife conization, or for cervical biopsy if malignancy was suspected. Results Between January 2020 and January 2023, 9014 patients underwent cervical cancer screening. Median age was 37 years (range 3049) and 4122 women (45.7%) were patients living with HIV. Most (n=8792, 97.5%) chose self- collection. The HPV positivity rate was 31.1% overall and 39.5% among patients living with HIV. Of the 2805 HPV- positive patients, 2588 (92.3%) returned for all steps of their diagnostic work- up and treatment, including ablation (n=2383, 92.1%), loop electrosurgical excision procedure (n=169, 6.5%), and cold knife conization (n=5, 0.2%). Thirty- one patients (1.2%) were diagnosed with cancer and referred to gynecologic oncology. Conclusion It is feasible to perform cervical cancer screening with primary HPV testing and follow- up in low- resource settings. Participants preferred self- collection, and the majority of screen- positive patients completed all steps of their diagnostic work- up and treatment. Our findings provide important information for further implementation and scale- up of cervical cancer screening and treatment services as part of the WHO global strategy for the elimination of cervical cancer.
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Humanos , Adulto , Persona de Mediana Edad , Infecciones por VIH/diagnóstico , Displasia del Cuello del Útero , Neoplasias del Cuello Uterino/cirugía , Neoplasias del Cuello Uterino/diagnóstico , Neoplasias del Cuello Uterino/prevención & control , Infecciones por Papillomavirus/diagnóstico , Neoplasias del Cuello Uterino , Detección Precoz del Cáncer/métodos , MozambiqueRESUMEN
AIM: A retrospective audit from a urological center focused on urological fistulas that directly connect with the treatment of gynecological malignancy. Ureteroarterial fistulas, i.e., pathological communication between the ureter and the artery, are discussed in more detail. MATERIALS AND METHODS: Over a period of ten years, from 2011 to 2020, a group of 47 patients with a diagnosis of urinary fistula was retrospectively evaluated. These patients, with a history of treatment for gynecological malignancy, were sent to our clinic from local and non-regional departments in the Czech Republic. We found three cases of ureteroarterial fistula in the presented analysis that focused on urological toxicity of oncogynecological treatment. RESULTS: Within the mentioned period of ten years, we recorded 64 cases of urinary fistulas, and 47 patients (73.4%) were directly related to oncogynecological treatment. In the group with gynecological tumors, we found three patients (6.4%) with a diagnosis of ureteroarterial fistula, two of whom died directly related to this complication (exsanguination). These patients were treated for cervical cancer. All of them underwent radiotherapy during the treatment. CONCLUSION: Ureteroarterial fistulas are the most severe complications that can occur in medicine. This work confirms that we have encountered these cases even recently. Management is highly demanding for patients affected in this way and requires multidisciplinary cooperation. Endovascular intervention methods can control bleeding in emergency situations with non-surgical approaches. However, they are usually the first step towards a definitive surgical solution.
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Fístula Urinaria , Fístula Vascular , Humanos , Femenino , Fístula Urinaria/etiología , Estudios Retrospectivos , Fístula Vascular/etiología , Enfermedades Ureterales/etiología , Persona de Mediana Edad , Anciano , Neoplasias de los Genitales Femeninos/radioterapia , Neoplasias del Cuello Uterino , AdultoAsunto(s)
Planificación de la Radioterapia Asistida por Computador , Radioterapia de Intensidad Modulada , Neoplasias del Cuello Uterino , Humanos , Neoplasias del Cuello Uterino/radioterapia , Femenino , Radioterapia de Intensidad Modulada/métodos , Planificación de la Radioterapia Asistida por Computador/métodos , Dosificación RadioterapéuticaAsunto(s)
Dosificación Radioterapéutica , Planificación de la Radioterapia Asistida por Computador , Radioterapia de Intensidad Modulada , Neoplasias del Cuello Uterino , Humanos , Neoplasias del Cuello Uterino/radioterapia , Femenino , Radioterapia de Intensidad Modulada/métodos , Planificación de la Radioterapia Asistida por Computador/métodosRESUMEN
Despite widespread cervical cancer (CC) screening programs, low participation has led to high morbidity and mortality rates, especially in developing countries. Because early-stage CC often has no symptoms, a non-invasive and convenient diagnostic method is needed to improve disease detection. In this study, we developed a new approach for differentiating both CC and cervical intraepithelial neoplasia (CIN)2/3, a precancerous lesion, from healthy individuals by exploring CC fatty acid metabolic reprogramming. Analysis of public datasets suggested that various fatty acid metabolizing enzymes were expressed at higher levels in CC tissues than in normal tissues. Correspondingly, 11 free fatty acids (FFAs) showed significantly different serum levels in CC patient samples compared with healthy donor samples. Nine of these 11 FFAs also displayed significant alterations in CIN2/3 patients. We then generated diagnostic models using combinations of these FFAs, with the optimal model including stearic and dihomo-γ-linolenic acids. Receiver operating characteristic curve analyses suggested that this diagnostic model could detect CC and CIN2/3 more accurately than using serum squamous cell carcinoma antigen level. In addition, the diagnostic model using FFAs was able to detect patients regardless of clinical stage or histological type. Overall, the serum FFA diagnostic model developed in this study could be a powerful new tool for the non-invasive early detection of CC and CIN2/3.
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Ácidos Esteáricos , Displasia del Cuello del Útero , Neoplasias del Cuello Uterino , Humanos , Femenino , Displasia del Cuello del Útero/diagnóstico , Displasia del Cuello del Útero/sangre , Neoplasias del Cuello Uterino/sangre , Neoplasias del Cuello Uterino/diagnóstico , Ácidos Esteáricos/sangre , Adulto , Ácido 8,11,14-Eicosatrienoico/sangre , Persona de Mediana Edad , Biomarcadores de Tumor/sangre , Curva ROCRESUMEN
Cervical cancer screening programs in Australia have been developed to detect early precancerous changes in women with a cervix aged between 25 and 74. Yet, many barriers remain to the uptake of cervical screening. Barriers include a lack of culturally appropriate service provision, physical access, poor health literacy, emotional difficulties, socio-economic disadvantage and not having access to a female service provider. In remote and very remote areas of Australia, additional barriers experienced by Aboriginal or Torres Strait Islander peoples include a distrust of healthcare providers and a lack of services, resulting in a much higher rate of diagnosis and death from cervical cancer. General practice nurses (GPNs) are well placed to conduct cervical screening tests (CSTs) after they have undertaken additional education and practical training. GPNs' increase in scope of practice is beneficial to general practice as it helps to remove some barriers to cervical screening. In addition, GPNs conducting CSTs reduce GP workload and burnout and increase teamwork. GPNs working in metropolitan clinics have greater access to training facilities, whereas those working in rural and remote clinics are required to travel potentially long distances to complete practical assessments. This highlights the need for training to be made available in rural and remote areas. The aim of this forum paper is therefore to generate further discussion on the need for training programs to be made available in rural and remote areas to aid the upskilling of GPNs.
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Detección Precoz del Cáncer , Neoplasias del Cuello Uterino , Adulto , Anciano , Femenino , Humanos , Persona de Mediana Edad , Australia , Detección Precoz del Cáncer/métodos , Medicina General/métodos , Tamizaje Masivo/métodos , Neoplasias del Cuello Uterino/diagnóstico , Aborigenas Australianos e Isleños del Estrecho de TorresRESUMEN
BACKGROUND: Desmoglein-2 (DSG2) has been reported to play pivotal roles in various diseases. However, its roles in cervical cancer (CC) remain insufficiently elucidated. Here, we aimed to comprehensively explore the functional mechanisms of DSG2 in CC using bioinformatics and experimental methods. METHODS: Several online databases, including Gene Expression Profiling Interactive Analysis (GEPIA), ONCOMINE, LinkedOmics, MetaScape, Human protein atlas (HPA), OMICS and single-cell RNA sequencing (scRNA-seq) data were used to explore the expression, prognosis, gene mutations, and potential signaling pathway of DSG2 in CC. Quantitative real-time PCR (qRT-PCR) and western blotting were used to measure DSG2 expression in collected samples. Experimental assays were conducted to verify the effects of dysregulated DSG2 on cervical cell lines in vitro. RESULTS: Bioinformatic analyses revealed that DSG2 was significantly up-regulated in CC compared to normal cervical tissues at both mRNA and protein levels. Elevated DSG2 levels were also associated with poor prognosis and clinical parameters (e.g., cancer stages, tumor grade, nodal metastasis status, etc.). DSG2 expression was predominantly observed in epithelial cells, increasing with disease progression on a single-cell resolution. Additionally, up-regulation of DSG2 significantly enhanced tumor purity by reducing the infiltration of immune cells (e.g., B cells, T cells, NK cells, etc.). Over-expression of DSG2 was further validated in collected CC samples at both mRNA and protein levels. Knockdown of DSG2 markedly reduced the proliferation and invasion of CC cell lines in vitro. CONCLUSIONS: In summary, elevated levels of DSG2 were significantly associated with poor prognosis and diminished immune infiltration in CC. Thus, DSG2 may serve as a potential therapeutic and diagnostic biomarker for CC.
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Desmogleína 2 , Regulación Neoplásica de la Expresión Génica , Regulación hacia Arriba , Neoplasias del Cuello Uterino , Desmogleína 2/genética , Desmogleína 2/metabolismo , Humanos , Neoplasias del Cuello Uterino/patología , Neoplasias del Cuello Uterino/genética , Neoplasias del Cuello Uterino/inmunología , Femenino , Proliferación Celular , Linfocitos Infiltrantes de Tumor/inmunología , Linfocitos Infiltrantes de Tumor/patología , Pronóstico , Biomarcadores de Tumor/genética , Biomarcadores de Tumor/metabolismo , Línea Celular TumoralRESUMEN
Importance: To inform the design and implementation of targeted interventions to reduce the future burden of human papillomavirus (HPV)-related cancers in Texas, it is necessary to examine the county and health service region (HSR) levels of (1) the proportion of children and teenagers aged 9 to 17 years who initiated and were up to date for HPV vaccination series and (2) HPV-related cancer incidence rates (IRs). Objective: To evaluate temporal trends and geospatial patterns of HPV vaccination initiation and up-to-date status as well as HPV-related cancer rates at county and HSR levels in Texas. Design, Setting, and Participants: This population-based cross-sectional study used data from the Texas Immunization Registry, the National Cancer Institute's Surveillance, Epidemiology, and End Results Program database, and Texas Department of State Health Services annual population counts from 2006 to 2022. The analysis of HPV vaccination rates was conducted among children and teenagers aged 9 to 17 years; the analysis of HPV-related cancer rates was conducted among adults aged 20 years and older. Data were extracted between June and July 2023 and statistical analysis was performed from February to April 2024. Main Outcomes and Measures: HPV vaccination initiation and up-to-date status rates and HPV-related cancer IR at county and HSR levels. Results: A total of 32â¯270â¯243 children and teenagers (65.8% female individuals and 34.2% male individuals) and 22â¯490â¯105 individuals aged 20 years and older (50.7% female individuals and 49.3% male individuals) were included. The mean 2021 to 2022 county-level HPV vaccination series initiation estimates ranged from 6.3% to 69.1% for female and from 7.0% to 77.6% for male children and teenagers aged 9 to 17 years. County-level vaccination up-to-date estimates were generally lower compared with those of initiation estimates and ranged from 1.6% to 30.4% for female and from 2.1% to 34.8% for male children and teenagers. The pattern of HPV vaccination rates stratified by sex were similar across counties and HSRs. The age-adjusted annual HPV-related cancer IR by county for years 2016 to 2020 ranged from 0 to 154.2 per 100â¯000 for female individuals and from 0 to 60.1 per 100â¯000 for male individuals. The counties located in North Texas, HSRs 2/3 and 4/5N, had lower HPV vaccination rates and higher IRs of HPV-related cancers for both female and male individuals compared with other regions. Conclusions and Relevance: In this study, the incidence of HPV-related cancers varied widely across the counties and HSRs of Texas. More counties in North Texas, HSRs 2/3 and 4/5N, had higher IRs of HPV-related cancers and a lower proportion of HPV vaccination rates than counties in other regions. Designing and implementing targeted interventions to increase uptake and completion of HPV vaccination series across counties with low HPV vaccination rates may help to reduce future the burden of HPV-related cancers.
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Infecciones por Papillomavirus , Vacunas contra Papillomavirus , Humanos , Adolescente , Femenino , Vacunas contra Papillomavirus/administración & dosificación , Texas/epidemiología , Niño , Infecciones por Papillomavirus/prevención & control , Infecciones por Papillomavirus/epidemiología , Masculino , Estudios Transversales , Adulto , Incidencia , Adulto Joven , Vacunación/estadística & datos numéricos , Neoplasias del Cuello Uterino/prevención & control , Neoplasias del Cuello Uterino/epidemiología , Neoplasias del Cuello Uterino/virología , Virus del Papiloma HumanoRESUMEN
Cervical cancer screening in Brazil is opportunistic, based on cytology and offered for women aged 25-64 years, with low coverage (30%) and 70% of cancer diagnoses done in advanced stages, without impact on mortality. The current study reports 5-year first-round results of a population-based DNA-HPV testing screening program in a Brazilian city, which intended to be a model for transition to a more efficient program. Program flowchart is simple and current, indicating repetition of a negative test after five years. The first-round (October 2017-September 2022) screened 20,551 women by DNA-HPV testing with 58.7% coverage and 99.4% compliance with the program's targeted age range. Coverage increases to 77.8% when excluding the 'pandemic period'. The DNA-HPV testing was 87.2% negative with 6.2% colposcopy referrals and 84.8% colposcopies performed. A total of 258 high-grade precursor lesions and 29 cervical cancers (mean age = 41.4 years, 83% Stage I) were detected. As a reference, 41,387 cytology tests from the previous program (2012-2016) detected 36 cervical cancers (mean age = 52.0 years, p = 0.0005), with 67% in advanced stages (p < 0.0001). Organizing cervical cancer screening using DNA-HPV testing demonstrated good coverage, high age and colposcopy compliance, and detection of more precancerous lesions and cervical cancers 10 years in advance.
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Detección Precoz del Cáncer , Infecciones por Papillomavirus , Neoplasias del Cuello Uterino , Humanos , Femenino , Neoplasias del Cuello Uterino/diagnóstico , Neoplasias del Cuello Uterino/virología , Neoplasias del Cuello Uterino/patología , Neoplasias del Cuello Uterino/epidemiología , Persona de Mediana Edad , Adulto , Detección Precoz del Cáncer/métodos , Infecciones por Papillomavirus/diagnóstico , Infecciones por Papillomavirus/virología , Brasil/epidemiología , ADN Viral/genética , Colposcopía , Tamizaje Masivo/métodos , Papillomaviridae/genética , Papillomaviridae/aislamiento & purificación , Prevalencia , AncianoRESUMEN
While HC2 and GP5+/6+ PCR-EIA were pivotal in test validation of new HPV assays, they represent the first generation of comparator tests based upon technologies that are not in widespread use anymore. In the current guideline, criteria for second-generation comparator tests are presented that include more detailed resolution of HPV genotypes. Second-generation comparator tests should preferentially target only the 12 genotypes classified as carcinogenic (IARC-group I), and show consistent non-inferior sensitivity for CIN2+ and CIN3+ and specificity for ≤CIN1 compared to one of the first-generations comparators, in at least three validation studies using benchmarks of 0.95 for relative sensitivity and 0.98 for relative specificity. Validation should take into account used storage media and other sample handling procedures. Meta-analyses were conducted to identify the assays that fulfill these stringent criteria. Four tests fulfilled the new criteria: (1) RealTime High-Risk HPV Test (Abbott), (2) Cobas-4800 HPV test (Roche Molecular System), (3) Onclarity HPV Assay (BD Diagnostics), and (4) Anyplex II HPV HR Detection (Seegene), each evaluated in three to six studies. Whereas the four assays target 14 carcinogenic genotypes, the first two identify separately HPV16 and 18, the third assay identifies five types separately and the fourth identifies all the types separately.
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Detección Precoz del Cáncer , Papillomaviridae , Infecciones por Papillomavirus , Sensibilidad y Especificidad , Neoplasias del Cuello Uterino , Femenino , Humanos , ADN Viral/genética , Detección Precoz del Cáncer/métodos , Genotipo , Pruebas de ADN del Papillomavirus Humano/métodos , Pruebas de ADN del Papillomavirus Humano/normas , Técnicas de Diagnóstico Molecular/métodos , Técnicas de Diagnóstico Molecular/normas , Papillomaviridae/genética , Papillomaviridae/clasificación , Papillomaviridae/aislamiento & purificación , Infecciones por Papillomavirus/diagnóstico , Infecciones por Papillomavirus/virología , Neoplasias del Cuello Uterino/diagnóstico , Neoplasias del Cuello Uterino/virologíaRESUMEN
Background: Cervical cancer (CC) is the fourth most common malignancy among women globally and serves as the main cause of cancer-related deaths among women in developing countries. The early symptoms of CC are often not apparent, with diagnoses typically made at advanced stages, which lead to poor clinical prognoses. In recent years, numerous studies have shown that there is a close relationship between mast cells (MCs) and tumor development. However, research on the role MCs played in CC is still very limited at that time. Thus, the study conducted a single-cell multi-omics analysis on human CC cells, aiming to explore the mechanisms by which MCs interact with the tumor microenvironment in CC. The goal was to provide a scientific basis for the prevention, diagnosis, and treatment of CC, with the hope of improving patients' prognoses and quality of life. Method: The present study acquired single-cell RNA sequencing data from ten CC tumor samples in the ArrayExpress database. Slingshot and AUCcell were utilized to infer and assess the differentiation trajectory and cell plasticity of MCs subpopulations. Differential expression analysis of MCs subpopulations in CC was performed, employing Gene Ontology, gene set enrichment analysis, and gene set variation analysis. CellChat software package was applied to predict cell communication between MCs subpopulations and CC cells. Cellular functional experiments validated the functionality of TNFRSF12A in HeLa and Caski cell lines. Additionally, a risk scoring model was constructed to evaluate the differences in clinical features, prognosis, immune infiltration, immune checkpoint, and functional enrichment across various risk scores. Copy number variation levels were computed using inference of copy number variations. Result: The obtained 93,524 high-quality cells were classified into ten cell types, including T_NK cells, endothelial cells, fibroblasts, smooth muscle cells, epithelial cells, B cells, plasma cells, MCs, neutrophils, and myeloid cells. Furthermore, a total of 1,392 MCs were subdivided into seven subpopulations: C0 CTSG+ MCs, C1 CALR+ MCs, C2 ALOX5+ MCs, C3 ANXA2+ MCs, C4 MGP+ MCs, C5 IL32+ MCs, and C6 ADGRL4+ MCs. Notably, the C2 subpopulation showed close associations with tumor-related MCs, with Slingshot results indicating that C2 subpopulation resided at the intermediate-to-late stage of differentiation, potentially representing a crucial transition point in the benign-to-malignant transformation of CC. CNVscore and bulk analysis results further confirmed the transforming state of the C2 subpopulation. CellChat analysis revealed TNFRSF12A as a key receptor involved in the actions of C2 ALOX5+ MCs. Moreover, in vitro experiments indicated that downregulating the TNFRSF12A gene may partially inhibit the development of CC. Additionally, a prognosis model and immune infiltration analysis based on the marker genes of the C2 subpopulation provided valuable guidance for patient prognosis and clinical intervention strategies. Conclusions: We first identified the transformative tumor-associated MCs subpopulation C2 ALOX5+ MCs within CC, which was at a critical stage of tumor differentiation and impacted the progression of CC. In vitro experiments confirmed the inhibitory effect of knocking down the TNFRSF12A gene on the development of CC. The prognostic model constructed based on the C2 ALOX5+MCs subset demonstrated excellent predictive value. These findings offer a fresh perspective for clinical decision-making in CC.
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Araquidonato 5-Lipooxigenasa , Progresión de la Enfermedad , Mastocitos , Análisis de la Célula Individual , Microambiente Tumoral , Neoplasias del Cuello Uterino , Humanos , Mastocitos/inmunología , Mastocitos/metabolismo , Neoplasias del Cuello Uterino/genética , Neoplasias del Cuello Uterino/inmunología , Neoplasias del Cuello Uterino/patología , Femenino , Análisis de la Célula Individual/métodos , Microambiente Tumoral/inmunología , Microambiente Tumoral/genética , Araquidonato 5-Lipooxigenasa/genética , Araquidonato 5-Lipooxigenasa/metabolismo , Regulación Neoplásica de la Expresión Génica , Análisis de Secuencia de ARN , Biomarcadores de Tumor/genéticaRESUMEN
Background: Microbial community dynamics have been involved in numerous diseases, including cancer. The diversity of intertumoral microbiota in human papillomavirus independent endocervical adenocarcinoma (HPVI ECA) is not well-characterized. Objective: Our objective is to delineate the intratumoral microbiota profile in HPVI ECA and investigate its potential influence on oncogenesis. Methods: We analyzed 45 HPVI ECA cases, comprising 36 gastric-type ECA (GEA) and 9 clear cell carcinomas (CCC). We compared the microbial composition within cancerous and adjacent noncancerous tissue samples using 5R-16S ribosomal DNA sequencing. Further, we investigated the correlation between specific microbes and clinical-pathological metrics as well as patient outcomes. Results: Our findings demonstrate notable differences in the microbial spectra between cancerous and adjacent noncancerous tissues. Amongst HPVI ECA subtypes, GEAs exhibit more microbial variations compared to CCCs. Using the Random Forest algorithm, we identified two distinct microbial signatures that could act as predictive biomarkers for HPVI ECA and differentiate between GEA and CCC. Varied microbial abundances was related to clinical characteristics of HPVI ECA patients. In addition, high levels of Micrococcus and low levels of unknown genus75 from the Comamonadaceae family were associated with poorer outcomes in HPVI ECA patients. Similarly, an abundance of Microbacterium correlated with reduced overall survival (OS), and a high presence of Streptococcaceae family microbes was linked to reduced recurrence-free survival (RFS) in GEA patients. Intriguingly, a high abundance of Micrococcus was also associated with a worse OS in GEA patients. Conclusion: The study reveals distinct microbial signatures in HPVI ECA, which have potential as biomarkers for disease prognosis. The correlation between these tumor-associated microbiota features and clinicopathological characteristics underscores the possibility of microbiome-based interventions. Our research provides a foundation for more in-depth studies into the cervical microbiome's role in HPVI ECA.
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Adenocarcinoma , Microbiota , Neoplasias del Cuello Uterino , Humanos , Femenino , Neoplasias del Cuello Uterino/microbiología , Neoplasias del Cuello Uterino/virología , Neoplasias del Cuello Uterino/diagnóstico , Microbiota/genética , Adenocarcinoma/microbiología , Adenocarcinoma/virología , Pronóstico , Persona de Mediana Edad , Adulto , ARN Ribosómico 16S/genética , Anciano , Papillomaviridae/genética , Papillomaviridae/aislamiento & purificación , Bacterias/clasificación , Bacterias/aislamiento & purificación , Bacterias/genética , Infecciones por Papillomavirus/virología , Infecciones por Papillomavirus/microbiología , Infecciones por Papillomavirus/complicaciones , Infecciones por Papillomavirus/diagnósticoRESUMEN
Background: Vaginal microbiota is involved in human papillomavirus (HPV) infection and cervical cancer (CC) progression, and the specific changes in vaginal microbial composition during this process remains uncertain. Objective: This study aimed to observe the changes in the specific composition of vaginal microorganisms in different cervical lesions and identify biomarkers at different stages of lesions. Methods: In this study we used the illumina high-throughput gene sequencing technology to determine the V4 region of 16SrRNA and observed the vaginal microbial composition in different cervical lesions. Results: The vaginal microbiota of patients with high-risk HPV infection and cervical lesions is significantly different from that of the normal population, but there is no significant difference in the richness of vaginal microbes. The diversity of vaginal species in CC patients is higher than that in high-risk HPV infection or CIN patients. The main manifestation is an increase in the diversity of vaginal microbes, a decrease in the relative abundance of cyanobacteria and Lactobacillus, and an increase in the relative abundance of dialister, peptonephila and other miscellaneous bacteria. There are characteristic vaginal biomarker in normal women, high risk HPV patients and CC patients. In detail, the biomarker in the normal group was varibaculum, the biomarker in the high-risk HPV group was saccharopolyspora, the biomarker of the CC group was the Proteobacteria, Corynebacterium, Coprococcus, Peptococcus and Ruminococcus. Conclusions: The study indicated that the compositions of vaginal microbes in different cervical lesions is different. The vaginal microbial composition has a certain diagnostic effect on healthy women, patients with high-risk HPV infection and cervical lesions. These microbes may serve as potential biomarkers for CC. It also provided an effective way for the treatment of HPV infections and cervical lesions.
Asunto(s)
Bacterias , Microbiota , Infecciones por Papillomavirus , ARN Ribosómico 16S , Neoplasias del Cuello Uterino , Vagina , Humanos , Femenino , Vagina/microbiología , Vagina/virología , Infecciones por Papillomavirus/virología , Neoplasias del Cuello Uterino/virología , Neoplasias del Cuello Uterino/microbiología , Adulto , ARN Ribosómico 16S/genética , Bacterias/clasificación , Bacterias/aislamiento & purificación , Bacterias/genética , Persona de Mediana Edad , Secuenciación de Nucleótidos de Alto Rendimiento , Papillomaviridae/genética , Papillomaviridae/aislamiento & purificación , Adulto Joven , Cuello del Útero/virología , Cuello del Útero/microbiología , Cuello del Útero/patologíaRESUMEN
Objectives: This study assessed the change in cervical cancer screening attendance across 10 years and identified the associated factors. Methods: Data from the European Health Interview Surveys in Hungary (2009, 2014, 2019) were analyzed with multivariate and multiple logistic regressions. Results: The analysis involved 4,850 participants, revealing a significant (p < 0.001) increase in screening attendance from 69% to 77% over 10 years. Factors significantly associated with higher attendance rates included a higher education level (tertiary level AOR = 2.51 [2.03-3.09]), being in a relationship (AOR = 1.59 [1.39-1.83]), the belief that one can do much for one's health (OR = 1.26 [1.05-1.52]), and the absence of chronic health problems (AOR = 1.56 [1.33-1.84]). Lower screening odds were significantly correlated with worse self-perceived health status (AOR = 0.65 [0.52-0.81]) and less frequent doctor (AOR = 0.64 [0.54-0.76]) and specialist visits (AOR = 0.46 [0.39-0.53]). Conclusion: Enhancing cervical cancer screening rates requires tailored public health strategies, particularly targeting individuals with lower education and poor health perceptions. Public health initiatives and enhanced collaboration among healthcare professionals are required to further increase participation rates, particularly among the identified groups.
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Detección Precoz del Cáncer , Neoplasias del Cuello Uterino , Humanos , Neoplasias del Cuello Uterino/diagnóstico , Femenino , Hungría , Detección Precoz del Cáncer/estadística & datos numéricos , Persona de Mediana Edad , Adulto , Aceptación de la Atención de Salud/estadística & datos numéricos , Anciano , Encuestas Epidemiológicas , Tamizaje Masivo/estadística & datos numéricosRESUMEN
Background: In the general population, primary human papillomavirus (HPV) testing is advocated for cervical cancer (CC) screening. HPV E6/E7 mRNA (Aptima HPV, AHPV) assays have garnered considerable traction due to their higher specificity when compared with HPV DNA assays. Here, we investigated age-specific primary AHPV screening assays and different triage strategies versus cytology to identify the best approach. Methods: Between April 2018 and December 2021, we recruited female participants from 34 communities across Liaoning province and Qingdao City, China. Primary cervical screening protocols included liquid-based cytology (LBC) and AHPV assays, with females positive for any assays undergoing colposcopy. Genotyping (AHPV-GT) was conducted on all HPV-positive samples. Our primary outcomes were the identification of age-specific detection rates, colposcopy referral rates, and sensitivity and specificity values for high-grade squamous intraepithelial lesions or worse (HSIL+). AHPV and different triage strategy performances were also examined across different age cohorts. Results: Our investigation included 9911 eligible females. Age-specific abnormal cytology rates were in the 6.1%-8.0% range, and were highest in 45-54-year olds. When compared with 35-44-or 45-54-year olds, HPV prevalence was highest in 55-64-year olds (12.2% or 11.6% vs.14.1%, P = 0.048 and P = 0.002, respectively). In 35-44-year olds, AHPV sensitivity for detecting HSIL+ was 96.6 (95% confidence interval [CI]: 89.7-100) - significantly higher than LBC sensitivity (65.5 [95% CI: 48.3-82.8], P < 0.001). When compared with LBC, HSIL+ detection rates by AHPV-GT using reflex LBC triage increased by 31.5% (9.6 vs. 7.3), and colposcopy referral rates decreased by 16.4% (5.1% vs. 6.1%). In 45-54-year olds, HSIL+ detection rates for AHPV-GT using reflex LBC triage were lower than LBC rates (6.2 vs. 6.6). In 55-64-year olds, AHPV sensitivity (97.2 [95% CI: 91.7-100.0]) was higher than LBC sensitivity (66.7 [95% CI: 50.0-80.6], P = 0.003). The area under the curve (AUC) value was not significantly different between AHPV-GT with reflex LBC triage and LBC (0.845 [95% CI: 0.771-0.920] vs. 0.812 [95% CI: 0.734-0.891], P = 0.236). Conclusions: Primary AHPV screening using different triage strategies were different across different age cohorts. Thus, AHPV may be an appropriate primary screening method for 35-44 and 55-64 year old females, while AHPV-GT with reflex LBC triage may be more apt for 35-44 year old females.
Asunto(s)
Detección Precoz del Cáncer , Infecciones por Papillomavirus , Sensibilidad y Especificidad , Triaje , Neoplasias del Cuello Uterino , Humanos , Femenino , Neoplasias del Cuello Uterino/diagnóstico , Neoplasias del Cuello Uterino/virología , Persona de Mediana Edad , China/epidemiología , Adulto , Detección Precoz del Cáncer/métodos , Infecciones por Papillomavirus/diagnóstico , Infecciones por Papillomavirus/virología , Triaje/métodos , Anciano , Factores de Edad , Colposcopía , Papillomaviridae/genética , Papillomaviridae/aislamiento & purificación , ARN Mensajero/genética , Proteínas Oncogénicas Virales/genética , Adulto Joven , Genotipo , Tamizaje Masivo/métodos , Virus del Papiloma Humano , CitologíaRESUMEN
BACKGROUND: Human papillomavirus (HPV) is known as a common agent of sexually transmitted infections and cervical cancer. One of the most effective ways for parents to protect their children from HPV is by ensuring they receive vaccinations. AIM: To determine the percentage of parents who intend to vaccinate their children against HPV and associated factors. METHOD: A cross-sectional study was conducted on 365 parents who had children attending high school in Ha Tinh province, Vietnam, from April to May 2023, using stratified and random sampling methods. Data were collected by a self-administered questionnaire designed based on previous studies and the domains of the Theory of Planned Behavior and Health Belief Model. A multivariable logistic regression was performed to determine the association between several factors and vaccination status. RESULT: A total of 365 participants took part in the study. The rate of parents intending to vaccinate their children against HPV was 55.9%. Knowledge about the HPV disease and vaccine (all P < .05) and the attitude of parents (P < .001) were determined as the motivation factors that affect the intention to vaccinate children against HPV. CONCLUSION: Many parents still do not have the intention to vaccinate children against HPV. Health education communication should focus on the motivation factors, not only to improve the parents' knowledge and perspective but also to increase the coverage of the vaccine to prevent cancers caused by HPV.
Background: Human papillomavirus (HPV) is known as a common agent of sexually transmitted infections and cervical cancer. One of the most effective ways for parents to protect their children from HPV is by ensuring they receive vaccinations. Aim: To determine the percentage of parents who intend to vaccinate their children against HPV and associated factors. Method: A cross-sectional study was conducted on 365 parents who had children attending high school in Ha Tinh province, Vietnam in 2023, using stratified and random sampling methods. The data was collected by a self-administered questionnaire designed based on the previous studies, and domains of Theory of Planned Behavior and Health Belief Model. A multivariable logistic regression was performed to determine the association between several factors and vaccination status. Result: 365 participants took part in the study. The rate of parents intending to vaccinate their children against HPV was 55.9%. Knowledge about the HPV disease and vaccine (all P < .05), and the attitude of parents (P < .001) were determined as the motivation factors that affect the intention to vaccinate children against HPV. Conclusion: Many parents still don't have the intention to vaccinate children against HPV. Health education communication should focus on the motivation factors, not only to improve the parents' knowledge and perspective but also to increase the coverage of the vaccine to prevent cancers caused by HPV.
Asunto(s)
Conocimientos, Actitudes y Práctica en Salud , Intención , Infecciones por Papillomavirus , Vacunas contra Papillomavirus , Padres , Humanos , Estudios Transversales , Femenino , Vietnam , Padres/psicología , Masculino , Vacunas contra Papillomavirus/administración & dosificación , Infecciones por Papillomavirus/prevención & control , Adulto , Estudiantes/psicología , Estudiantes/estadística & datos numéricos , Encuestas y Cuestionarios , Vacunación/psicología , Vacunación/estadística & datos numéricos , Adolescente , Neoplasias del Cuello Uterino/prevención & control , Neoplasias del Cuello Uterino/virología , Persona de Mediana Edad , Virus del Papiloma HumanoRESUMEN
BACKGROUND: Previous studies underscore the crucial link between awareness and timely cervical cancer screening and treatment, particularly among women of reproductive age. Yet, insights remain limited when it comes to women living with HIV in Addis Ababa. This study examined the knowledge and practices of these women regarding cervical cancer screening and treatment, illuminating the factors that both enable and hinder their uptake. METHODS: This cross-sectional study took place in six public hospitals in Addis Ababa, Ethiopia, involving 578 women with HIV. The recruitment spanned 10 months, from January 1st to October 31st, 2021. Trained clinicians utilized the Open Data Kit for data collection, ensuring real-time submission to the server. Statistical analysis was performed using SPSS version 25, employing descriptive and inferential statistics. The logistic regression model identified predictors of outcome variables, and open-ended questions were thematically narrated for qualitative insights. RESULTS: A notable 51.2% of women with HIV exhibited inadequate knowledge regarding cervical cancer prevention and control programs. Furthermore, a substantial 68.5% had never undergone cervical examination, citing reasons such as considering themselves healthy (49.6%), perceiving the examination as painful (28.4%), and feeling shy to undergo screening (23.3%). Notably, participants with non-formal education were 70% less likely to possess knowledge about cervical cancer prevention and control (AOR = 0.30; 95% CI = 0.13-0.71). Income emerged as an independent predictor for both knowledge and practice in women's approach to cervical cancer prevention and control (P < 0.05). Additionally, occupation and duration of HIV diagnosis independently predicted practice, even after adjusting for confounding factors. CONCLUSION: Half of the participating HIV-positive women lacked adequate awareness about cervical cancer prevention and control, underscoring the urgent need for comprehensive awareness initiatives tailored to this population. Relevant ministries, health care providers, and advocacy groups must collaborate to implement targeted education programs, utilizing diverse channels like community outreach, health care settings, and media campaigns.