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1.
Arch Esp Urol ; 77(4): 397-404, 2024 May.
Artículo en Inglés | MEDLINE | ID: mdl-38840283

RESUMEN

OBJECTIVE: This study aimed to analyse the family resilience of patients with stress urinary incontinence (SUI) after cervical cancer surgery and its influencing factors. METHODS: Patients with cervical cancer postoperative SUI admitted to our hospital from May 2020, to May 2023, were retrospectively selected. They were divided into low-resilience group and high-resilience group in accordance with the Family Resilience Questionnaire (FaREQ). The general demographic data of the two groups were statistically analysed, and correlation and logistic regression analyses were performed. RESULTS: The FaREQ score of 222 patients was (93.61 ± 8.45). Amongst these patients, 21.62% scored less than 84 points, and 78.38% scored more than 84 points. Significant differences were found in the educational level, indwelling catheter time, family monthly income, religious belief, hope index, psychological resilience, family function and social support between the two groups (p < 0.05). A significant positive correlation was observed between family resilience and the above indicators (p < 0.05). The variance inflation coefficient values of educational level and indwelling catheter time were 15.764 and 43.766, and the tolerance values were 0.063 and 0.023, respectively. After removing them, family monthly income, religious belief, hope index, psychological resilience, family function and social support were the factors affecting the family resilience level of patients with SUI after cervical cancer surgery. CONCLUSIONS: The level of family resilience of patients with SUI after cervical cancer surgery is low. Many factors, such as family monthly income and religious belief, affect the level of resilience. Therefore, corresponding measures could be formulated in advance to improve the level of family resilience of such patients.


Asunto(s)
Complicaciones Posoperatorias , Resiliencia Psicológica , Incontinencia Urinaria de Esfuerzo , Neoplasias del Cuello Uterino , Humanos , Femenino , Estudios Retrospectivos , Neoplasias del Cuello Uterino/cirugía , Neoplasias del Cuello Uterino/psicología , Incontinencia Urinaria de Esfuerzo/psicología , Incontinencia Urinaria de Esfuerzo/cirugía , Persona de Mediana Edad , Complicaciones Posoperatorias/psicología , Complicaciones Posoperatorias/etiología , Familia/psicología , Adulto , Anciano
2.
Arch Esp Urol ; 77(4): 426-432, 2024 May.
Artículo en Inglés | MEDLINE | ID: mdl-38840287

RESUMEN

OBJECTIVE: This study aimed to analyse the effect of pelvic floor function exercises based on the enhanced recovery after surgery (ERAS) concept on lower urinary tract symptoms after radical hysterectomy for cervical cancer. METHODS: The retrospective study was conducted using clinical data of patients admitted to our hospital from January 2021 to December 2022 and underwent radical hysterectomy for cervical cancer. In accordance with the nursing method, the patients were divided into the routine group (conventional care) and the ERAS pelvic floor function exercise group, for which ERAS concept-based pelvic floor function exercises were carried out on the basis of the former group. The confounders between the two groups were matched by propensity score, and the scores of urination, pelvic floor muscle strength, lower urinary tract symptoms and quality of life (QoL) were compared between the two groups after matching. RESULTS: A total of 180 patients were included in the study, of whom 60 patients were identified after propensity score matching, consisting of 30 patients each in the ERAS and routine groups. The baseline characteristics of the two groups were balanced, and the difference was not statistically significant (p > 0.05). Compared with the routine group, the observation group showed significantly shorter first spontaneous urination time, greater first urination volume (p < 0.05), better pelvic floor muscle strength, considerably lower urinary tract symptoms and better QoL at discharge and 3 months after discharge (p < 0.05). CONCLUSIONS: Pelvic floor function exercises based on the ERAS concept can relieve lower urinary tract symptoms, accelerate urination and improve pelvic floor muscle strength and QoL after radical hysterectomy for cervical cancer.


Asunto(s)
Terapia por Ejercicio , Histerectomía , Síntomas del Sistema Urinario Inferior , Diafragma Pélvico , Complicaciones Posoperatorias , Neoplasias del Cuello Uterino , Humanos , Femenino , Estudios Retrospectivos , Neoplasias del Cuello Uterino/cirugía , Neoplasias del Cuello Uterino/rehabilitación , Histerectomía/efectos adversos , Persona de Mediana Edad , Terapia por Ejercicio/métodos , Síntomas del Sistema Urinario Inferior/etiología , Síntomas del Sistema Urinario Inferior/rehabilitación , Complicaciones Posoperatorias/prevención & control , Complicaciones Posoperatorias/etiología , Recuperación Mejorada Después de la Cirugía , Adulto , Estudios de Cohortes , Calidad de Vida
3.
J Med Virol ; 96(6): e29688, 2024 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-38847316

RESUMEN

To meet the screening goal of WHO's 90-70-90 strategy aimed at eliminating cervical cancer (CC) by 2030, clinical validation of human papillomavirus (HPV) assays is essential to provide accurate and valid results through fulfilling three criteria of the international validation guidelines (IVGs). Previously, the clinical accuracy of the AmpFire® HPV Screening 16/18/HR assay (AmpFire assay) was reported but reproducibility data are lacking. Here, we aim to evaluate the intra- and inter-laboratory reproducibility of the AmpFire assay. The reproducibility of the isothermal AmpFire assay was assessed using 556 cervical cell samples collected from women attending CC screening and biobanked in a Belgian HPV national reference center. This assay detects HPV16, HPV18, and 12 other high-risk HPV (hrHPV) types (31/33/35/39/45/51/52/56/58/59/66/68) in aggregate. Lower 95% confidence interval bound around the assay's reproducibility should exceed 87%, with κ ≥ 0.50. Additionally, a literature review of the assay's clinical performance was performed. The AmpFire assay showed an excellent intralaboratory (96.4%, 95% CI:94.5-97.8%, κ = 0.920) and interlaboratory (95.3%, 95% CI:93.2-96.9%, κ = 0.897) reproducibility. One study demonstrated noninferior sensitivity of a prototype AmpFire assay targeting 15 hrHPV types (including HPV53) to detect CIN2+. However, clinical specificity became similar to the comparator after removing HPV53 from analyses. The low-cost and easy-to-use AmpFire assay presents excellent reproducibility and-after removing HPV53 from the targeted types-fulfills also clinical accuracy requirements. Inclusion of HPV53, which is not recognized as carcinogenic, comprises clinical specificity of screening assays.


Asunto(s)
Infecciones por Papillomavirus , Neoplasias del Cuello Uterino , Humanos , Reproducibilidad de los Resultados , Infecciones por Papillomavirus/diagnóstico , Infecciones por Papillomavirus/virología , Femenino , Neoplasias del Cuello Uterino/diagnóstico , Neoplasias del Cuello Uterino/virología , Papillomaviridae/aislamiento & purificación , Bélgica , Detección Precoz del Cáncer/métodos , Detección Precoz del Cáncer/normas , Adulto , Sensibilidad y Especificidad , Persona de Mediana Edad , Técnicas de Diagnóstico Molecular/normas , Técnicas de Diagnóstico Molecular/métodos , Cuello del Útero/virología
4.
BMC Infect Dis ; 24(1): 558, 2024 Jun 04.
Artículo en Inglés | MEDLINE | ID: mdl-38834951

RESUMEN

In January 2020, a different cervical cancer screening program started in Germany. Women above the age of 35 are recommended to have a combined HPV and cytology swab every three years. Showing persistent high-risk human papillomavirus (hrHPV), cytologic negative cervical samples at baseline and after 12 months, patients are referred to colposcopy. Entailing considerable additional workload due to the required colposcopies, we analyzed the risk of high-grade cervical intraepithelial neoplasia (CIN 3) in cytologic negative and persistent hrHPV women according to their hrHPV genotypes.Methods In this single center retrospective study, patients with persistent hrHPV, cytology negative cervical samples from our certified Colposcopy Unit in 2020 and 2021 were analyzed. Patient demographics, hrHPV types, biopsy rates and histological reports were collected.Results During the study, 69 patients were enrolled. Most frequent hrHPV genotypes were: hrHPV other 72.5%; HPV 16, 20.3% and HPV 18, 7.2%. Colposcopy showed no or minor changes in 92.7% and major changes in 7.2%. CIN 3 was found in 7 patients (10.1%). Prevalence of CIN 3 by hrHPV genotypes was 27.3% for HPV16, 20.0% for HPV18 and 7.1% for HPVO. A statistically significant dependency between hrHPV and cervical intraepithelial neoplasia was demonstrated (p = 0.048).Conclusion Within this single center study of persistent hrHPV, cytologic negative samples, patients with HPV 16 were more likely to have high-grade disease compared to other hrHPV subtypes. Larger prospective randomized trials are needed to substantiate our results and obtain adjusted cervical cancer screening time intervals according to the hrHPV genotypes.


Asunto(s)
Colposcopía , Genotipo , Papillomaviridae , Infecciones por Papillomavirus , Displasia del Cuello del Útero , Neoplasias del Cuello Uterino , Humanos , Femenino , Estudios Retrospectivos , Infecciones por Papillomavirus/virología , Adulto , Persona de Mediana Edad , Neoplasias del Cuello Uterino/virología , Neoplasias del Cuello Uterino/patología , Displasia del Cuello del Útero/virología , Displasia del Cuello del Útero/patología , Displasia del Cuello del Útero/epidemiología , Papillomaviridae/genética , Papillomaviridae/aislamiento & purificación , Papillomaviridae/clasificación , Alemania/epidemiología , Anciano , Detección Precoz del Cáncer , Cuello del Útero/virología , Cuello del Útero/patología , Virus del Papiloma Humano
5.
BMC Womens Health ; 24(1): 322, 2024 Jun 04.
Artículo en Inglés | MEDLINE | ID: mdl-38834999

RESUMEN

BACKGROUND: Cervical cancer is one of the leading causes of death in women worldwide. The majority of the cases are found in developing countries. The increasing risk of cervical cancer prevalence and growing danger of death from cervical cancer and the high occurrence of human papillomavirus (HPV) infection in women who are HIV positive give us the ground to study the prevalence and associated risk factors. OBJECTIVE: The study aims to assess the prevalence of cervical cancer screening and associated risk factors among HIV-positive women attending the Adult ART clinic at the University of Gondar Hospital. METHODS: An institution-based cross-sectional study was conducted from March to August 2021, on adult HIV-positive women attending the Adult ART clinic at Gondar University Referral Hospital by phone calling patients per week for six months to complete a total of 2744 HIV-positive patients who were not screened for cervical cancer before. The data were collected using an interviewer-administered questionnaire. Bivariate and multivariable logistic regression analyses were used to determine the presence and the degree of association between dependent and independent variables. In the multivariable logistic analysis, a P-value of < 0.05 and odds ratio with a 95% confidence interval were considered to determine independent predictors for the prevalence of premalignant or malignant cervical lesions among HIV-positive patients. RESULT: This study assessed 915 HIV Positive women who were screened for cervical cancer via visual inspection with acetic acid (VIA) as the primary screening tool and found that 24.48% had positive VIA results. Those with VIA-positive cases pathology examination showed 72.4% had abnormal pathology reports (CIN 1/2/3-51.25%, 17.23% cancer & 3.9% CIS), strengthening the finding in many studies that suggest HIV-positive women have a high rate of premalignant lesions.


Asunto(s)
Infecciones por VIH , Lesiones Precancerosas , Neoplasias del Cuello Uterino , Humanos , Femenino , Etiopía/epidemiología , Estudios Transversales , Adulto , Neoplasias del Cuello Uterino/epidemiología , Prevalencia , Infecciones por VIH/epidemiología , Infecciones por VIH/complicaciones , Factores de Riesgo , Persona de Mediana Edad , Lesiones Precancerosas/epidemiología , Detección Precoz del Cáncer , Adulto Joven , Infecciones por Papillomavirus/epidemiología , Infecciones por Papillomavirus/complicaciones , Hospitales Universitarios , Derivación y Consulta/estadística & datos numéricos
6.
Front Immunol ; 15: 1391524, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38835778

RESUMEN

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.


Asunto(s)
Biomarcadores de Tumor , Inmunoterapia , Proteómica , Neoplasias del Cuello Uterino , Humanos , Femenino , Neoplasias del Cuello Uterino/terapia , Neoplasias del Cuello Uterino/inmunología , Neoplasias del Cuello Uterino/diagnóstico , Biomarcadores de Tumor/sangre , Proteómica/métodos , Pronóstico , Inmunoterapia/métodos , Persona de Mediana Edad , Adulto
7.
Front Immunol ; 15: 1411132, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38840928

RESUMEN

Background: Cervical cancer remains a significant gynecologic malignancy in both China and the United States, posing a substantial threat to women's lives and health due to its high morbidity and mortality rates. Altered energy metabolism and dysregulated mitochondrial function play crucial roles in the development, growth, metastasis, and recurrence of malignant tumors. In this study, we aimed to predict prognosis and assess efficacy of anti-tumor therapy in cervical cancer patients based on differential genes associated with mitochondrial metabolism. Methods: Transcriptomic data and clinical profiles of cervical cancer patients were retrieved from the TCGA and GEO databases. Differential gene-related cellular pathways were identified through GO, KEGG, and GSEA analyses. Prognostic indices were constructed using LASSO regression analysis. Immune cell infiltration was assessed using CIBERSORT and ssGSEA, and the correlation between immune checkpoint inhibitor genes and differential genes was examined. Tumor mutation load (TMB) and its association with prognostic indices were analyzed using nucleotide variant data from the TCGA database. Patient response to immunotherapy and sensitivity to antitumor drugs were determined using the TIDE algorithm and the oncoPredic algorithm, respectively. Results: A prognostic index based on metabolism-related differential genes was developed to predict the clinical outcome of cervical cancer patients, enabling their classification into two distinct subtypes. The prognostic index emerged as an independent risk factor for unfavorable prognosis. The high-index group exhibited a significantly worse overall prognosis, along with elevated tumor mutation burden (TMB), increased immune cell infiltration, and lower TIDE scores, indicating a potential benefit from immunotherapy. Conversely, the low-index group demonstrated increased sensitivity to metabolism-related antitumor agents, specifically multikinase inhibitors. Conclusion: The aim of this study was to develop a prognostic index based on differential genes associated with mitochondrial metabolism, which could be used to predict cervical cancer patients' prognoses. When combined with TIDE and TMB analyses, this prognostic index offers insights into the immune cell infiltration landscape, as well as the potential efficacy of immunotherapy and targeted therapy. Our analysis suggests that the Iron-Sulfur Cluster Assembly Enzyme (ISCU) gene holds promise as a biomarker for cervical cancer immunotherapy.


Asunto(s)
Biomarcadores de Tumor , Neoplasias del Cuello Uterino , Humanos , Neoplasias del Cuello Uterino/genética , Neoplasias del Cuello Uterino/inmunología , Neoplasias del Cuello Uterino/mortalidad , Femenino , Pronóstico , Biomarcadores de Tumor/genética , Linfocitos Infiltrantes de Tumor/inmunología , Linfocitos Infiltrantes de Tumor/metabolismo , Regulación Neoplásica de la Expresión Génica , Transcriptoma , Microambiente Tumoral/inmunología , Microambiente Tumoral/genética , Mitocondrias/metabolismo , Mitocondrias/genética , Metabolismo Energético/genética , Bases de Datos Genéticas , Persona de Mediana Edad , Mutación , Perfilación de la Expresión Génica
8.
Cancer Med ; 13(11): e7316, 2024 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-38828559

RESUMEN

OBJECTIVE: To assess the clinical values of extended human papillomavirus (HPV) genotyping in triage of high-risk HPV-positive women, focusing on the trade-off between cervical precancer detections and colposcopy referrals. METHODS: A bivariate random-effects model was used to estimate the diagnostic accuracy of primary HPV screening with following triage strategies to detect cervical precancers: (i) partial genotyping for HPV16/18 combined with cytological testing at atypical squamous cells of undetermined significance threshold (used as the comparator), (ii) genotyping for HPV16/18/58/52, (iii) genotyping for HPV16/18/58/52/33, (iv) genotyping for HPV16/18/58/33/31, (v) genotyping for HPV16/18/58/52/33/31, and (vi) genotyping for HPV16/18/58/52/33/31/39/51. Internal risk benchmarks for clinical management were used to evaluate the risk stratification of each triage strategy. RESULTS: A total of 16,982 women (mean age 46.1 years, range 17-69) were included in this analysis. For CIN3+ detection, triage with HPV16/18/58/33/31 genotyping achieved lower positivity (6.85% vs. 7.35%, p = 0.001), while maintaining similar sensitivity (91.35% vs. 96.42%, p = 0.32) and specificity (94.09% vs. 93.67%, p = 0.56) compared with the comparator strategy. Similar patterns were observed for CIN2+ detection. Women with a positive HPV16/18/58/33/31 genotyping test had high enough risk for CIN3+ for colposcopy referral, while the risk for women with a negative test was below the 1-year return decision threshold according to internal benchmarks. CONCLUSIONS: Our findings suggested extended HPV genotyping is of potential to be used as a triage technique integrated into HPV-based cervical cancer screening, leading to reduced need for colposcopy referral while maintaining similar disease detection and efficient risk stratification.


Asunto(s)
Detección Precoz del Cáncer , Genotipo , Infecciones por Papillomavirus , Triaje , Neoplasias del Cuello Uterino , Humanos , Femenino , Neoplasias del Cuello Uterino/virología , Neoplasias del Cuello Uterino/diagnóstico , Neoplasias del Cuello Uterino/epidemiología , Detección Precoz del Cáncer/métodos , Adulto , Infecciones por Papillomavirus/virología , Infecciones por Papillomavirus/diagnóstico , Infecciones por Papillomavirus/epidemiología , Persona de Mediana Edad , Triaje/métodos , China/epidemiología , Adolescente , Adulto Joven , Colposcopía , Papillomaviridae/genética , Papillomaviridae/aislamiento & purificación , Displasia del Cuello del Útero/virología , Displasia del Cuello del Útero/diagnóstico , Displasia del Cuello del Útero/epidemiología , Anciano , Papillomavirus Humano 18/genética , Papillomavirus Humano 18/aislamiento & purificación , Sensibilidad y Especificidad , Virus del Papiloma Humano
9.
BMC Complement Med Ther ; 24(1): 212, 2024 Jun 03.
Artículo en Inglés | MEDLINE | ID: mdl-38831394

RESUMEN

BACKGROUND: Cervical cancer is one of the most common gynecological malignancies. Previous studies have shown that the ethanol extract of Sophora moorcroftiana seeds (EESMS) possesses an antiproliferative effect on several tumors in vitro. Therefore, in this study, we assessed the impact of EESMS on human cervical carcinoma (HeLa) cell proliferation. METHODS: The proliferation and apoptotic effects of HeLa cells treated with EESMS were evaluated using 3-[4,5-dimethylthiazol-2-yl]-2,5 diphenyl tetrazolium bromide assay, dual acridine orange/ethidium bromide double staining, flow cytometry, and western blotting. Single-cell level atomic force microscopy (AFM) was conducted to detect the mechanical properties of HeLa cells, and proteomics and bioinformatics methods were used to elucidate the molecular mechanisms of EESMS. RESULTS: EESMS treatment inhibited HeLa cell proliferation by blocking the G0/G1 phase, increasing the expression of Caspase-3 and affecting its mechanical properties, and the EESMS indicated no significant inhibitory effect on mouse fibroblasts L929 cell line. In total, 218 differentially expressed proteins were identified using two-dimensional electrophoresis, and eight differentially expressed proteins were successfully identified using matrix-assisted laser desorption/ionization-time-of-flight mass spectrometry. The differentially expressed proteins were involved in various cellular and biological processes. CONCLUSION: This study provides a perspective on how cells change through biomechanics and a further theoretical foundation for the future application of Sophora moorcroftiana as a novel low-toxicity chemotherapy medication for treating human cervical cancer.


Asunto(s)
Proliferación Celular , Extractos Vegetales , Sophora , Neoplasias del Cuello Uterino , Humanos , Sophora/química , Células HeLa , Neoplasias del Cuello Uterino/tratamiento farmacológico , Femenino , Proliferación Celular/efectos de los fármacos , Extractos Vegetales/farmacología , Extractos Vegetales/química , Apoptosis/efectos de los fármacos , Antineoplásicos Fitogénicos/farmacología , Ratones , Etanol/química
10.
BMC Cancer ; 24(1): 678, 2024 Jun 03.
Artículo en Inglés | MEDLINE | ID: mdl-38831404

RESUMEN

BACKGROUND: Despite several preventative and control measures Ethiopia continues to see an increase in cervical cancer. Comprehensive evidence is very important to suggest ministry of health. Therefore, the aim of this study is to estimate the pooled violence of Precancerous Cervical Lesion and to identify associated factors among women living with HIV AIDS in Ethiopia. METHODS: From February 15, 2024 to March 17, 2024, systematic and methodical search of the literature was conducted using electronic databases such as PubMed, HINARI, Global Health, Scopus, EMBASE, Web of Science, African Journal online (AJOL), and Google Scholar. Quality appraisal was assessed based on Joanna Briggs Institute (JBI) critical appraisal checklist for analytical cross-sectional study using 9 criteria. The Cochrane Q and I2 test statistics were used to verify the heterogeneity of the studies. Using a fixed effect model, the pooled estimate prevalence of precancerous cervical lesion among women living with HIV was calculated. RESULTS: After reviewing 9,470 studies, 9 studies involving 2,910 women with HIV were included. The pooled estimate of precancerous cervical cancer among women living with HIV in Ethiopia was 15.34% (95% CI: 8.97, 21.72). Having history of sexual infection (POR = 3.12; 95% CI: 1.38, 7.05), having multiple sexual partner (POR = 3.14; 95% CI: 2.29, 4.30), and parity greater than two (POR = 4.97; 95% CI: 3.17, 7.78) were identified factors associated with precancerous cervical lesion. CONCLUSION: This study found that about one-six of HIV-positive women developed precancerous cervical lesion. According to this study, there was a substantial correlation between precancerous cervical lesion among HIV-positive women and having history of sexually transmitted infection, having multiple sexual partners, and being multipara. In order to reduce precancerous cervical lesion, FMOH, policy makers, and interested parties should pay particular attention to this issue.


Asunto(s)
Infecciones por VIH , Lesiones Precancerosas , Neoplasias del Cuello Uterino , Humanos , Femenino , Etiopía/epidemiología , Neoplasias del Cuello Uterino/epidemiología , Neoplasias del Cuello Uterino/virología , Infecciones por VIH/epidemiología , Infecciones por VIH/complicaciones , Lesiones Precancerosas/epidemiología , Lesiones Precancerosas/virología , Prevalencia , Factores de Riesgo , Estudios Transversales , Adulto
11.
BMC Infect Dis ; 24(1): 552, 2024 Jun 03.
Artículo en Inglés | MEDLINE | ID: mdl-38831406

RESUMEN

BACKGROUND: Persistent infections with high-risk human papillomavirus (hrHPV) can cause cervical squamous intraepithelial lesions (SIL) that may progress to cancer. The cervicovaginal microbiome (CVM) correlates with SIL, but the temporal composition of the CVM after hrHPV infections has not been fully clarified. METHODS: To determine the association between the CVM composition and infection outcome, we applied high-resolution microbiome profiling using the circular probe-based RNA sequencing technology on a longitudinal cohort of cervical smears obtained from 141 hrHPV DNA-positive women with normal cytology at first visit, of whom 51 were diagnosed by cytology with SIL six months later. RESULTS: Here we show that women with a microbial community characterized by low diversity and high Lactobacillus crispatus abundance at both visits exhibit low risk to SIL development, while women with a microbial community characterized by high diversity and Lactobacillus depletion at first visit have a higher risk of developing SIL. At the level of individual species, we observed that a high abundance for Gardnerella vaginalis and Atopobium vaginae at both visits associate with SIL outcomes. These species together with Dialister micraerophilus showed a moderate discriminatory power for hrHPV infection progression. CONCLUSIONS: Our results suggest that the CVM can potentially be used as a biomarker for cervical disease and SIL development after hrHPV infection diagnosis with implications on cervical cancer prevention strategies and treatment of SIL.


Asunto(s)
Cuello del Útero , Microbiota , Infecciones por Papillomavirus , Vagina , Humanos , Femenino , Estudios Longitudinales , Vagina/microbiología , Vagina/virología , Infecciones por Papillomavirus/virología , Infecciones por Papillomavirus/microbiología , Adulto , Cuello del Útero/microbiología , Cuello del Útero/virología , Persona de Mediana Edad , Papillomaviridae/genética , Papillomaviridae/aislamiento & purificación , Papillomaviridae/clasificación , Adulto Joven , Neoplasias del Cuello Uterino/virología , Neoplasias del Cuello Uterino/microbiología , Frotis Vaginal
12.
J Obstet Gynaecol ; 44(1): 2361858, 2024 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-38864403

RESUMEN

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.


Asunto(s)
Quimioradioterapia , Linfocitos , Terapia Neoadyuvante , Neutrófilos , Neoplasias del Cuello Uterino , Humanos , Femenino , Neoplasias del Cuello Uterino/terapia , Neoplasias del Cuello Uterino/sangre , Neoplasias del Cuello Uterino/mortalidad , Neoplasias del Cuello Uterino/patología , Persona de Mediana Edad , Estudios Retrospectivos , Quimioradioterapia/métodos , Adulto , Terapia Neoadyuvante/métodos , Plaquetas , Curva ROC , Recuento de Linfocitos , Anciano , Recuento de Plaquetas , Pronóstico , Valor Predictivo de las Pruebas , Estadificación de Neoplasias , Tasa de Supervivencia , Recuento de Leucocitos
13.
J Obstet Gynaecol ; 44(1): 2362420, 2024 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-38864525

RESUMEN

BACKGROUND: The aim of This study is to investigate the effects of Keratinocyte differentiation factor 1 (KDF1) on cervical cancer cells and the underlying mechanisms. METHODS: The Gene Expression Profiling Interactive Analysis database was used to analyse KDF1 expression in cervical cancer and paracancerous tissue samples. The correlation between the expression of KDF1 and clinicopathological features was also analysed. Cervical cancer cells (HeLa cells) with KDF1 overexpression or knockdown were constructed. Reverse transcription polymerase chain reaction was used to detect the mRNA expression of KDF1 in cervical cancer tissues and cells. In different treatment groups of cervical cancer cells, protein expression of KDF1, cell viability, invasion, and migration were subsequently confirmed by western blotting, CCK-8 assay, transwell assay, and wound healing assay, respectively. A PI3K inhibitor (LY294002) was used to detect the effect of KDF1 on the phosphoinositide 3-kinase (PI3K)/Protein Kinase B (AKT) pathway. RESULTS: KDF1 was highly expressed in cervical cancer tissues and cell lines (p < 0.01), and was significantly associated with poor prognosis (p < 0.05). Knockdown of KDF1 in HeLa cells resulted in a significant decrease in cell proliferation, migration, and invasion, as well as phosphorylated PI3K (P-PI3K) and p-AKT levels (p < 0.01). However, KDF1 overexpression activated the PI3K/AKT pathway and significantly enhanced the malignant biological behaviour of cervical cancer cells (p < 0.01). Additionally, the PI3K inhibitor reduced the proliferation, invasion, and migration of HeLa cells overexpressing KDF1 (p < 0.01). CONCLUSION: KDF1 enhances cervical cancer viability and migration by activating the PI3K/AKT pathway, and may serve as a therapeutic target for patients with cervical cancer.


Cervical cancer is the fourth most common cancer in women worldwide and the leading cause of cancer-related deaths. Keratinocyte differentiation factor 1 (KDF1) is a protein-coding gene containing an unknown functional domain (DUF4656).In the present study, we detected the expression of KDF1 in cervical cancer tissues and cells. Furthermore, we investigated the effects of KDF1 on the proliferation, invasion, and migration of cervical cancer cells and the downstream mechanisms of KDF1.KDF1 promotes cervical cancer cell proliferation, invasion, and migration by activating the PI3K/AKT pathway, and KDF1 may be a biomarker for the treatment of cervical cancer.


Asunto(s)
Movimiento Celular , Supervivencia Celular , Fosfatidilinositol 3-Quinasas , Proteínas Proto-Oncogénicas c-akt , Transducción de Señal , Neoplasias del Cuello Uterino , Humanos , Neoplasias del Cuello Uterino/genética , Neoplasias del Cuello Uterino/patología , Neoplasias del Cuello Uterino/metabolismo , Femenino , Proteínas Proto-Oncogénicas c-akt/metabolismo , Fosfatidilinositol 3-Quinasas/metabolismo , Células HeLa , Persona de Mediana Edad , Proliferación Celular/genética , Regulación Neoplásica de la Expresión Génica , Adulto , Invasividad Neoplásica , Línea Celular Tumoral
14.
Front Immunol ; 15: 1362904, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38855110

RESUMEN

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.


Asunto(s)
Receptor 2 Celular del Virus de la Hepatitis A , Inmunoterapia Adoptiva , Mesotelina , Receptores Quiméricos de Antígenos , Neoplasias del Cuello Uterino , Ensayos Antitumor por Modelo de Xenoinjerto , Humanos , Animales , Receptor 2 Celular del Virus de la Hepatitis A/metabolismo , Receptor 2 Celular del Virus de la Hepatitis A/genética , Femenino , Neoplasias del Cuello Uterino/inmunología , Neoplasias del Cuello Uterino/terapia , Neoplasias del Cuello Uterino/genética , Ratones , Inmunoterapia Adoptiva/métodos , Receptores Quiméricos de Antígenos/inmunología , Receptores Quiméricos de Antígenos/genética , Receptores Quiméricos de Antígenos/metabolismo , Linfocitos T/inmunología , Linfocitos T/metabolismo , Línea Celular Tumoral , Microambiente Tumoral/inmunología , Ratones SCID
15.
BMC Health Serv Res ; 24(1): 693, 2024 May 31.
Artículo en Inglés | MEDLINE | ID: mdl-38822370

RESUMEN

BACKGROUND: Cervical cancer patients in Colombia have a lower likelihood of survival compared to breast cancer patients. In 1993, Colombia enrolled citizens in one of two health insurance regimes (contributory-private insurance and subsidized- public insurance) with fewer benefits in the subsidized regime. In 2008, the Constitutional Court required the Colombian government to unify services of both regimes by 2012. This study evaluated the impact of this insurance change on cervical cancer mortality before and after 2012. METHODS: We accessed 24,491 cervical cancer mortality records for 2006-2020 from the vital statistics of Colombia's National Administrative Department of Statistics (DANE). We calculated crude mortality rates by health insurance type and departments (geopolitical division). Changes by department were analyzed by rate differences between 2006 and 2012 and 2013-2020, for each health insurance type. We analyzed trends using join-point regressions by health insurance and the two time-periods. RESULTS: The contributory regime (private insurance) exhibited a significant decline in cervical cancer mortality from 2006 to 2012, characterized by a noteworthy average annual percentage change (AAPC) of -3.27% (P = 0.02; 95% CI [-5.81, -0.65]), followed by a marginal non-significant increase from 2013 to 2020 (AAPC 0.08%; P = 0.92; 95% CI [-1.63, 1.82]). In the subsidized regime (public insurance), there is a non-significant decrease in mortality between 2006 and 2012 (AAPC - 0.29%; P = 0.76; 95% CI [-2.17, 1.62]), followed by a significant increase from 2013 to 2020 (AAPC of 2.28%; P < 0.001; 95% CI [1.21, 3.36]). Examining departments from 2013 to 2020 versus 2006 to 2012, the subsidized regime showed fewer cervical cancer-related deaths in 5 out of 32 departments, while 6 departments had higher mortality. In 21 departments, mortality rates remained similar between both regimes. CONCLUSION: Improvement of health benefits of the subsidized regime did not show a positive impact on cervical cancer mortality in women enrolled in this health insurance scheme, possibly due to unresolved administrative and socioeconomic barriers that hinder access to quality cancer screening and treatment.


Asunto(s)
Cobertura Universal del Seguro de Salud , Neoplasias del Cuello Uterino , Humanos , Colombia/epidemiología , Neoplasias del Cuello Uterino/mortalidad , Femenino , Persona de Mediana Edad , Adulto , Seguro de Salud/estadística & datos numéricos
16.
Sex Health ; 212024 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-38833543

RESUMEN

Background In mid-2022 Australia's National Cervical Screening Program made self-collection of a vaginal sample an option for screening for young women or people with a cervix aged 25 to 29 years for the first time. This study explored what young women thought about, and wanted to know about, self-collection, and what their future screening preferences are. Methods Young women (n =21), aged 24-29years, were recruited through social media. Semi-structured interviews explored screening history, screening preferences and thoughts about self-collection. Data were analysed using an a priori coding framework informed by the Theoretical Framework of Acceptability. Results Young women valued the addition of self-collection to the national cervical screening program, believing it to be less invasive and more convenient. However, they also valued the choice to opt for a clinician-collected specimen if preferred. Conclusions Self-collection is a valuable addition to the National Cervical Screening Program. This study suggests that continued efforts are needed to raise awareness of its availability, and improve understanding about its accuracy, the ease of collection, that you still need to engage with a primary healthcare service to access it and that you can still opt for a clinician-collected test.


Asunto(s)
Detección Precoz del Cáncer , Neoplasias del Cuello Uterino , Humanos , Femenino , Australia , Adulto , Neoplasias del Cuello Uterino/diagnóstico , Adulto Joven , Detección Precoz del Cáncer/métodos , Autocuidado , Manejo de Especímenes/métodos , Frotis Vaginal/estadística & datos numéricos , Aceptación de la Atención de Salud/estadística & datos numéricos , Conocimientos, Actitudes y Práctica en Salud
17.
J Am Coll Radiol ; 21(6S): S249-S267, 2024 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-38823948

RESUMEN

Cervical cancer is a common gynecological malignancy worldwide. Cervical cancer is staged based on the International Federation of Gynecology and Obstetrics (FIGO) classification system, which was revised in 2018 to incorporate radiologic and pathologic data. Imaging plays an important role in pretreatment assessment including initial staging and treatment response assessment of cervical cancer. Accurate determination of tumor size, local extension, and nodal and distant metastases is important for treatment selection and for prognostication. Although local recurrence can be diagnosed by physical examination, imaging plays a critical role in detection and follow-up of local and distant recurrence and subsequent treatment selection. The American College of Radiology Appropriateness Criteria are evidence-based guidelines for specific clinical conditions that are reviewed annually by a multidisciplinary expert panel. The guideline development and revision process support the systematic analysis of the medical literature from peer reviewed journals. Established methodology principles such as Grading of Recommendations Assessment, Development, and Evaluation or GRADE are adapted to evaluate the evidence. The RAND/UCLA Appropriateness Method User Manual provides the methodology to determine the appropriateness of imaging and treatment procedures for specific clinical scenarios. In those instances where peer reviewed literature is lacking or equivocal, experts may be the primary evidentiary source available to formulate a recommendation.


Asunto(s)
Sociedades Médicas , Neoplasias del Cuello Uterino , Humanos , Femenino , Neoplasias del Cuello Uterino/diagnóstico por imagen , Neoplasias del Cuello Uterino/patología , Estados Unidos , Invasividad Neoplásica , Estadificación de Neoplasias , Medicina Basada en la Evidencia
18.
PLoS One ; 19(6): e0302153, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38848414

RESUMEN

INTRODUCTION: Cervical cancer, a malignancy caused by infection with oncogenic human papillomavirus, disproportionally affects women from low resource settings. Persistence of human papillomavirus infection may mediate an association between tobacco use and cervical cancer. In limited resource settings, women from indigenous communities are often marginalized and do not benefit from evidence-based interventions to prevent tobacco use or cervical cancer due to the limited reach of mainstream healthcare services to these communities. This study determined the association between smoking and high-risk human papillomavirus infection among women from indigenous communities in western Botswana. METHODS: A cross-sectional study of women in indigenous communities was conducted between June and October 2022. Demographic, clinical and self-reported smoking data were collected. Cervical cytology and HPV DNA testing for high-risk human papillomavirus genotypes were performed. Multilevel multivariable logistic regression models were fit to evaluate the association between smoking and high-risk human papillomavirus infection while adjusting for potential confounders. RESULTS: A total of 171 participants with a median (interquartile range) age of 40 (31-50) years from three settlements and two villages were recruited for the study. Of these, 17% were current smokers, 32.8% were living with HIV and high-risk human papillomavirus DNA was detected in 32.8% of the cervical specimens. Women who were current smokers, were nearly twice as likely to have cervical high-risk human papillomavirus infection compared to non-smokers (Adjusted Odds Ratio (95% CI); 1.74(1.09, 2.79)) after controlling for confounders. CONCLUSION: These data underscore the need for effective tobacco control to help mitigate cervical cancer risk in this setting. These findings can help inform decisions about targeted cervical cancer prevention and tobacco cessation interventions for women from indigenous communities.


Asunto(s)
Infecciones por Papillomavirus , Fumar , Neoplasias del Cuello Uterino , Humanos , Femenino , Infecciones por Papillomavirus/epidemiología , Infecciones por Papillomavirus/virología , Botswana/epidemiología , Adulto , Persona de Mediana Edad , Estudios Transversales , Neoplasias del Cuello Uterino/virología , Neoplasias del Cuello Uterino/epidemiología , Neoplasias del Cuello Uterino/etiología , Neoplasias del Cuello Uterino/prevención & control , Pueblos Indígenas/estadística & datos numéricos , Papillomaviridae/aislamiento & purificación , Papillomaviridae/genética , Factores de Riesgo
19.
BMC Cancer ; 24(1): 702, 2024 Jun 07.
Artículo en Inglés | MEDLINE | ID: mdl-38849715

RESUMEN

BACKGROUND: Cervical cancer is the fourth most common cancer in women, with an estimated 342,000 deaths worldwide in 2020. Current standard of care in the UK for locally advanced cervical cancer is concurrent chemoradiotherapy with weekly cisplatin, yet 5-year overall survival rates are only 65% with a distant relapse rate of 50%. Inhibitors of Apoptosis Proteins (IAPs) are often overexpressed in cancer cells and associated with tumour progression and resistance to treatment. Tolinapant, developed by Astex Pharmaceuticals, is an IAP antagonist with an additional mechanism of action via down-regulation of NF-kB, an important regulator in cervical cancer. Preclinical studies performed using tolinapant in combination with cisplatin and radiotherapy showed inhibition of tumour growth and enhanced survival. There is therefore a strong rationale to combine tolinapant with chemoradiotherapy (CRT). METHODS: CRAIN is a phase Ib open-label, dose escalation study to characterise the safety, tolerability and initial evidence for clinical activity of tolinapant when administered in combination with cisplatin based CRT. Up to 42 patients with newly diagnosed cervix cancer will be recruited from six UK secondary care sites. The number of participants and the duration of the trial will depend on toxicities observed and dose escalation decisions, utilising a TiTE-CRM statistical design. Treatment will constist of standard of care CRT with 45 Gy external beam radiotherapy given in 25 daily fractions over 5 weeks with weekly cisplatin 40mg/m2. This is followed by brachytherapy for which common schedules will be 28 Gy in 4 fractions high-dose-rate or 34 Gy in 2 fractions pulsed-dose-rate. Tolinapant will be administered in fixed dose capsules taken orally daily for seven consecutive days as an outpatient on alternate weeks (weeks 1, 3, 5) during chemoradiation. Dose levels for tolinapant which will be assessed are: 60 mg; 90 mg (starting level); 120 mg; 150 mg; 180 mg. Escalation will be guided by emerging safety data and decisions by the Safety Review Committee. DISCUSSION: If this trial determines a recommended phase II dose and shows tolinapant to be safe and effective in combination with CRT, it would warrant future phase trials. Ultimately, we hope to provide a synergistic treatment option for these patients to improve outcome. TRIAL REGISTRATIONS: EudraCT Number: 2021-006555-34 (issued 30th November 2021); ISRCTN18574865 (registered 30th August 2022).


Asunto(s)
Quimioradioterapia , Neoplasias del Cuello Uterino , Humanos , Femenino , Neoplasias del Cuello Uterino/terapia , Neoplasias del Cuello Uterino/tratamiento farmacológico , Neoplasias del Cuello Uterino/patología , Quimioradioterapia/métodos , Reino Unido , Cisplatino/administración & dosificación , Cisplatino/uso terapéutico , Adulto
20.
BMC Womens Health ; 24(1): 332, 2024 Jun 07.
Artículo en Inglés | MEDLINE | ID: mdl-38849836

RESUMEN

OBJECTIVES: This study aims to analyze factors associated with positive surgical margins following cold knife conization (CKC) in patients with cervical high-grade squamous intraepithelial lesion (HSIL) and to develop a machine-learning-based risk prediction model. METHOD: We conducted a retrospective analysis of 3,343 patients who underwent CKC for HSIL at our institution. Logistic regression was employed to examine the relationship between demographic and pathological characteristics and the occurrence of positive surgical margins. Various machine learning methods were then applied to construct and evaluate the performance of the risk prediction model. RESULTS: The overall rate of positive surgical margins was 12.9%. Independent risk factors identified included glandular involvement (OR = 1.716, 95% CI: 1.345-2.189), transformation zone III (OR = 2.838, 95% CI: 2.258-3.568), HPV16/18 infection (OR = 2.863, 95% CI: 2.247-3.648), multiple HR-HPV infections (OR = 1.930, 95% CI: 1.537-2.425), TCT ≥ ASC-H (OR = 3.251, 95% CI: 2.584-4.091), and lesions covering ≥ 3 quadrants (OR = 3.264, 95% CI: 2.593-4.110). Logistic regression demonstrated the best prediction performance, with an accuracy of 74.7%, sensitivity of 76.7%, specificity of 74.4%, and AUC of 0.826. CONCLUSION: Independent risk factors for positive margins after CKC include HPV16/18 infection, multiple HR-HPV infections, glandular involvement, extensive lesion coverage, high TCT grades, and involvement of transformation zone III. The logistic regression model provides a robust and clinically valuable tool for predicting the risk of positive margins, guiding clinical decisions and patient management post-CKC.


Asunto(s)
Conización , Aprendizaje Automático , Márgenes de Escisión , Neoplasias del Cuello Uterino , Humanos , Femenino , Estudios Retrospectivos , Adulto , Conización/métodos , Persona de Mediana Edad , Neoplasias del Cuello Uterino/cirugía , Neoplasias del Cuello Uterino/patología , Lesiones Intraepiteliales Escamosas/patología , Lesiones Intraepiteliales Escamosas/cirugía , Factores de Riesgo , Lesiones Intraepiteliales Escamosas de Cuello Uterino/cirugía , Lesiones Intraepiteliales Escamosas de Cuello Uterino/patología , Displasia del Cuello del Útero/cirugía , Displasia del Cuello del Útero/patología , Infecciones por Papillomavirus/complicaciones , Anciano , Modelos Logísticos , Criocirugía/métodos , Adulto Joven
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