Dose prediction for cervical cancer in radiotherapy based on the beam channel generative adversarial network.

Background: Existing deep learning methods, such as generative adversarial network (GAN) technology, face challenges when dealing with mixed datasets, which involve a combination of Intensity Modulated Radiotherapy (IMRT) and Volumetric Modulated Arc Therapy (VMAT). This issue significantly complicates the application of dose prediction in the field of radiotherapy. In this study, we propose a novel approach called beam channel GAN (Bc-GAN) to address the task of radiation dose prediction for mixed datasets. Bc-GAN introduces a dose prediction calculation method that requires less precision. By defining an approximate range for dose prediction, Bc-GAN limits the physical range of GAN prediction, resulting in more reasonable dose distribution predictions. Methods: We adopt a beam angle weighting method to determine the beam angle in the dose calculation. The dose of the beam with the highest weight is calculated using medical images and is then inputted into the artificial intelligence dose prediction model as the input channel. Additionally, we collect data from a total of 346 patients with Cervical Cancer (CC) for dataset. After cleaning the data, we exclude 51 cases with incomplete organ delineation, leaving us with 295 cases (IMRT: VMAT = 137:158) randomly divided into three sets: the training set, the validation set, and the test set, with proportions of 205:60:30, respectively. The assessment of model predictions was conducted via an analysis of dose distributions on the tomographic plane, dose volume histogram (DVH), and dosimetric parameters within the target zones and organs at risk (OAR). Results: After DVH analysis, minimal discrepancy was found between predicted and actual dose distributions in PTV and OAR. The predicted distribution aligned with clinical standards. Dosimetric parameters for PTV were generally lower in the predicted model, except for homogeneity index (HI) (0.238 ± 0.024, P = 0.017) and Dmax (53.599 ± 0.710 Gy, P = 1.8e-05). The prediction model varied in estimating doses for six organs. Specifically, small intestine showed higher V20 (67.92 ± 51.64 %, P = 0.019) and V30 (57.171 ± 1.213 %, P = 0.024) than manual planning. A similar trend was seen in colon's V30 (37.13 ± 61.14 %, P = 0.016). However, predicted bladder V30 (87.51 ± 41.44 %, P = 2.03e-16) was lower, indicating significant dosimetric differences. Conclusion: Overall, this study presents an innovative prediction method for CC in radiotherapy using the Bc-GAN model, addressing the challenges posed by different radiotherapy techniques. The proposed approach allows IMRT and VMAT in radiotherapy to be used as training sets, enabling the potential for large-scale engineering and commercialization applications of artificial intelligence (AI). The Bc-GAN-based prediction method for CC in radiotherapy not only reduces the amount of data needed for the training set but also expedites the model generation process. This approach can be applied to guide the development of clinical radiation therapy plans. Furthermore, future studies should consider extending the dose prediction method to encompass other types of tumors.

Integrating a deep neural network and Transformer architecture for the automatic segmentation and survival prediction in cervical cancer.

Background: Automated tumor segmentation and survival prediction are critical to clinical diagnosis and treatment. This study aimed to develop deep-learning models for automatic tumor segmentation and survival prediction in magnetic resonance imaging (MRI) of cervical cancer (CC) by combining deep neural networks and Transformer architecture. Methods: This study included 406 patients with CC, each with comprehensive clinical information and MRI scans. We randomly divided patients into training, validation, and independent test cohorts in a 6:2:2 ratio. During the model training, we employed two architecture types: one being a hybrid model combining convolutional neural network (CNN) and ransformer (CoTr) and one of pure CNNs. For survival prediction, the hybrid model combined tumor image features extracted by segmentation models with clinical information. The performance of the segmentation models was evaluated using the Dice similarity coefficient (DSC) and 95% Hausdorff distance (HD95). The performance of the survival models was assessed using the concordance index. Results: The CoTr model performed well in both contrast-enhanced T1-weighted (ceT1W) and T2-weighted (T2W) imaging segmentation tasks, with average DSCs of 0.827 and 0.820, respectively, which outperformed other the CNN models such as U-Net (DSC: 0.807 and 0.808), attention U-Net (DSC: 0.814 and 0.811), and V-Net (DSC: 0.805 and 0.807). For survival prediction, the proposed deep-learning model significantly outperformed traditional methods, yielding a concordance index of 0.732. Moreover, it effectively divided patients into low-risk and high-risk groups for disease progression (P<0.001). Conclusions: Combining Transformer architecture with a CNN can improve MRI tumor segmentation, and this deep-learning model excelled in the survival prediction of patients with CC as compared to traditional methods.

Using amide proton transfer-weighted magnetic resonance imaging (MRI) in peritumor tissue to predict parametrial infiltration of cervical cancer: a case-control study.

Background: Parametrial infiltration (PMI) is an important indicator for staging and treatment of cervical cancer (CC). The potential of amide proton transfer-weighted (APTw) parameters of peritumor tissue in predicting PMI is still uncertain. This study aims to explore whether the APTw parameters of peritumor tissue can improve diagnostic value of diffusion-weighted imaging (DWI) in magnetic resonance imaging (MRI). Methods: Eighty-one patients with pathologic analysis-confirmed CC were enrolled in this retrospective study. All patients underwent APTw MRI and DWI. The APTw values of tumor (APTw-t), APTw values in peritumor tissues (APTw-p) and apparent diffusion coefficient (ADC) values were independently reviewed by two radiologists to map the regions of interest and measure the corresponding values. Receiver operating characteristic curves were generated to evaluate the diagnostic performance of these quantitative parameters. Results: The study patients were divided into the PMI group (n=22) and non-PMI group (n=59). The APTw-t and APTw-p values (%) of PMI group were higher than those of the non-PMI group [3.71 (interquartile range, IQR, 3.60-3.98) and 2.75 (IQR, 2.68-2.77) vs. 3.33 (IQR, 3.24-3.60) and 1.98 (IQR, 1.82-2.36); P<0.001]. The ADC values of PMI group were lower than those of non-PMI group [0.88 (IQR, 0.83-0.94) ×10-3 vs. 0.95 (IQR, 0.88-1.04)×10-3 mm2/sec; P<0.001]. The area under the curve (AUC) of APTw-t, APTw-p and ADC value for PMI diagnosis were 0.810, 0.831 and 0.806 respectively. In addition, the AUC value (0.918) of APTw-p + ADC was optimal, with a sensitivity and specificity of 91.20% and 87.20% respectively. Conclusions: APTw in peritumor tissues, combined with ADC value can be used to efficiently distinguish PMI of CC.

Identification and validation of ferroptosis-related prognostic gene signature in patients with cervical cancer.

Background: Ferroptosis is an iron-dependent cell death, which is distinct from the other types of regulated cell death. Considerable studies have demonstrated that ferroptosis is involved in the biological process of various cancers. However, the role of ferroptosis in cervical cancer (CC) remains unclear. This study aims to explore the ferroptosis-related prognostic genes (FRPGs) expression profiles and their prognostic values in CC. Methods: The ferroptosis-related genes (FRGs) were obtained from The Cancer Genome Atlas (TCGA) and FerrDb databases. Core FRGs were determined by the Search Tool for the Retrieval of Interacting Genes (STRING) website. FRPGs were identified using univariate and multivariate Cox regressions, and the ferroptosis-related prognostic model was constructed. FRPGs were verified in clinical specimens. The relationship between FRPGs and tumor infiltrating immune cells were assessed through the CIBERSORT algorithm and the LM22 signature matrix. Bioinformatics functions of FRPGs were explored with the Database for Annotation, Visualization, and Integrated Discovery (DAVID). Results: Thirty-three significantly up-regulated and 28 down-regulated FRGs were screened from databases [P<0.05; false discovery rate (FDR) <0.05; and |log2 fold change (FC)| ≥2]. Twenty-four genes were found closely interacting with each other and regarded as hub genes (degree ≥3). Solute carrier family 2 member 1 (SLC2A1), carbonic anhydrases IX (CA9), and dual oxidase 1 (DUOX1) were identified as independent prognostic signatures for overall survival (OS) in a Cox regression. Time-dependent receiver operating characteristic (ROC) curves showed the predictive ability of the ferroptosis-related prognostic model, especially for 1-year OS [area under the curve (AUC) =0.76]. Consistent with the public data, our experiments demonstrated that the mRNA levels of SLC2A1 and DUOX1, and the protein levels of SLC2A1, DUOX1, and CA9 were significantly higher in the tumor tissues. Further analysis showed that there was a significant difference in the proportion of tumor infiltrating immune cells between the low- and high-risk group based on our prognostic model. The function enrichment of FRPGs was explored by applying Gene Ontology (GO) enrichment and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analyses. Conclusions: In this study, the features of FRPGs in CC were pictured. The results implicated that targeting ferroptosis may be a new reliable biomarker and an alternative therapy for CC.

High frequency of alpha7-HPV in Colombian Caribbean coast women: cervical cancer screening analysis.

BACKGROUND: Cervical cancer (CC) is a significant global public health concern, particularly in developing countries such as Colombia. The main risk factor involves high-risk HPV types (HR-HPV) infection, coupled with population-specific variables. The Caribbean region in Colombia lacks research on HR-HPV-type frequencies. Therefore, this study aims to establish the prevalence of type-specific HR-HPV and its association with sociodemographic factors among women undergoing cervical cytology screening. METHODS: A cross-sectional study involving voluntary women who provided informed consent and completed a questionnaire capturing sociodemographic, clinical, and sexual behavior information was conducted. All participants underwent cervical cytology and molecular analysis. Generic HPV detection employed three simultaneous PCRs (GP5+/6+, MY09/11, and PU1R/2 M), and positive samples were genotyped using the Optiplex HPV Genotyping kit. The analysis encompassed the 12 types of high-risk HPV (HR-HPV-16,-18,-31,-33,-35,-39,-45,-51,-52,-56,-58, and - 59). Frequencies were reported based on geographic subregions within the Córdoba department, and disparities were made between single and multiple infections. Sociodemographic and clinical variables were subjected to ordinal logistic regression, with statistical significance at a p-value < 0.05. The statistical analyses utilized STATA 14® and R-Core Team-software. RESULTS: We included 450 women, mean age 40 (SD±11.44). PCR analysis revealed 43% HPV-positive (n=192). GP5+/6+ detected the most positives at 26% (n=119), followed by PU1R/2 M at 22% (n = 100) and MY09/11 at 15% (n=69). Multiple infections occurred in 87.3% (n=142), primarily 2 to 4 types (47.37%, n=90). Dominant types were HPV-18 (15.6%, n=61), HPV-16 (14.9%, n=58), HPV-31 (13.0%, n = 51), and HPV-45 (11.5%, n=45). Logistic regression identified age above 60 as a risk for concurrent multiple types (OR=6.10; 95% CI 1.18-31.63). Menopause was protective (OR=0.31; 95% CI 0.11-0.89). CONCLUSIONS: Our study reveals a notable prevalence of multiple (2-4) high-risk HPV infections among adult women engaged in CC detection initiatives. Predominantly, α7 species constitute the prevalent HR-viral types, with the Medio Sinú subregion showing elevated prevalence. Menopausal status confers protection against diverse HR-HPV infections. Nevertheless, advancing age, particularly beyond 60 years, is linked to an increased susceptibility to simultaneous infections by multiple HPV-types.

Development and validation of a prognostic prediction model for cervical cancer patients treated with radical radiotherapy: a study based on TCGA database.

Background: Radiotherapy or concurrent chemoradiotherapy is the standard treatment for patients with locally advanced or inoperable cervical squamous cell carcinoma and endocervical adenocarcinoma (CESC). However, treatment failure for CESC patients treated with radical radiotherapy still occurs due to local recurrence and distant metastasis. The previous prediction models were focused on all CESC patients, neglecting the prognostic differences under different treatment modalities. Therefore, there is a pressing demand to explore novel biomarkers for the prognosis and sensitivity of radiotherapy in CESC patients treated with radical radiotherapy. As a single biomarker has limited effect in stratifying these patients, our objective was to identify radioresponse-related mRNAs to ameliorate forecast of the prognosis for CESC patients treated with radical radiotherapy. Methods: Sample data on CESC patients treated with radical radiotherapy were obtained from The Cancer Genome Atlas (TCGA) database. We randomly separated these patients into a training and test cohorts using a 1:1 ratio. Differential expression analysis was carried out to identify radioresponse-related mRNA sets that were significantly dysregulated between complete response (CR) and radiographic progressive disease (RPD) groups, and univariate Cox regression analyses, least absolute shrinkage and selection operator (LASSO) method and multivariate Cox regression were performed to identify the radioresponse-related signature in the training cohort. we adopted survival analysis to measure the predictive value of the radioresponse-related signature both in the test and entire cohorts. Moreover, we developed a novel nomogram to predict the overall survival (OS) of CESC patients treated with radical radiotherapy. In addition, immune infiltration analysis and Gene Set Enrichment Analysis (GSEA) were conducted to preliminarily explore possible mechanisms. Results: This study included a total of 92 CESC patients subjected to radical radiotherapy. We developed and verified a risk score model based on radioresponse-related mRNA. The radioresponse-related mRNA signature and International Federation of Gynecology and Obstetrics (FIGO) stage were served as independent prognostic factors for CESC patients treated with radical radiotherapy. Moreover, a nomogram integrating radioresponse-related mRNA signature with FIGO stage was established to perform better for predicting 1-, 3-, and 5-year survival rates. Mechanically, the low-risk group under the risk score of this model had a better survival status, and the distribution of CD4 T cells was potentially involved in the regulation of radiotherapy response in CESC, leading to a better survival outcome in the low-risk group. Conclusions: This study presents a new radioresponse-related mRNA signature that shows promising clinical efficacy in predicting the prognosis of CESC patients treated with radical radiotherapy.

Tobacco Smoke Condensate Induces Morphologic Changes in Human Papillomavirus-Positive Cervical Epithelial Cells Consistent with Epithelial to Mesenchymal Transition (EMT) with Activation of Receptor Tyrosine Kinases and Regulation of TGFB.

High-risk human papillomavirus (HR-HPV; HPV-16) and cigarette smoking are associated with cervical cancer (CC); however, the underlying mechanism(s) remain unclear. Additionally, the carcinogenic components of tobacco have been found in the cervical mucus of women smokers. Here, we determined the effects of cigarette smoke condensate (CSC; 3R4F) on human ectocervical cells (HPV-16 Ect/E6E7) exposed to CSC at various concentrations (10-6-100 µg/mL). We found CSC (10-3 or 10 µg/mL)-induced proliferation, enhanced migration, and histologic and electron microscopic changes consistent with EMT in ectocervical cells with a significant reduction in E-cadherin and an increase in the vimentin expression compared to controls at 72 h. There was increased phosphorylation of receptor tyrosine kinases (RTKs), including Eph receptors, FGFR, PDGFRA/B, and DDR2, with downstream Ras/MAPK/ERK1/2 activation and upregulation of common EMT-related genes, TGFB SNAI2, PDGFRB, and SMAD2. Our study demonstrated that CSC induces EMT in ectocervical cells with the upregulation of EMT-related genes, expression of protein biomarkers, and activation of RTKs that regulate TGFB expression, and other EMT-related genes. Understanding the molecular pathways and environmental factors that initiate EMT in ectocervical cells will help delineate molecular targets for intervention and define the role of EMT in the initiation and progression of cervical intraepithelial neoplasia and CC.

Knowledge, attitudes and practices of cervical cancer screening among female students enrolled in higher education institutions in Cabo Verde.

Cervical cancer (CC) is the fourth most common cancer among women in the world and the second in Africa. CC is the third most frequent cancer and the first cause of cancer-related death among women in Cabo Verde, with an estimated incidence of 17 cases per 100,000 women. The mortality rate is around 10.5% and represents one of the largest percentages of all types of cancer diagnosed in women in the country. The high mortality rate can be explained by the absence of a national screening programme and a lack of human and physical resources. This study aims to determine the level of knowledge, attitudes and practices on CC among undergraduate female students in Cabo Verde in 2020. Methods: A descriptive cross-sectional study, using a self-administered structured questionnaire, was conducted in six higher education institutions (HEI) in Cabo Verde between November and December 2020. A total of 618 female undergraduate students were recruited using a simple random sampling technique. Descriptive statistical data analysis was used to report the results. Results: The response rate was 96.6% (n = 618). Most of the participants, 90.6% (549), were single, with average age of 21.79 years (SD =±4). Although most of the participants had already heard about CC (94.6%), most students showed a low knowledge about this disease (86.2%). Moreover, only 9.1% reported having been screened for CC. Conclusion: Most undergraduate female students enrolled in HEI in Cabo Verde have poor knowledge and unfavourable attitudes toward CC. The level of knowledge is quite unsatisfactory. Within this context, the implementation of health policies focused on human papillomavirus education, prevention strategies, and CC screening is crucial.

Bioinformatics identification of characteristic genes of cervical cancer via an artificial neural network.

BACKGROUND: Artificial neural networks (ANNs) have been extensively used in the field of medicine. The present hypothesis-free study sought to use an ANN to identify the characteristic genes of cervical cancer (CC). METHODS: RNA sequencing profiles were obtained from the GSE7410, GSE9750, GSE63514, and GSE52903 datasets. The differentially expressed genes (DEGs) were identified and compared between the normal and CC tissues. An ANN analysis was conducted to obtain the random-forest tree and to examine differences in gene filtering. A neural network model was established using the characteristic genes of CC, while the verification accuracy of the model was examined by Cox regression. The differences in the immune infiltrating cells between the normal cervical and CC tissues were compared by CIBERSORT (an analytical tool can provide an estimation of the abundances of member cell types in a mixed cell population). RESULTS: Nine genes' characteristics for CC were identified: cyclin-dependent kinase inhibitor 2A (CDKN2A), chromosome 1 open reading frame 112 (C1orf112), helicase, lymphoid-specific (HELLS), mini-chromosome maintenance protein 5 (MCM5), mini-chromosome maintenance protein 2 (MCM2), kinetochore associated 1 (KNTC1), cysteine-rich secretory protein 3 (CRISP3), phytanoyl-CoA 2-hydroxylase interacting protein (PHYHIP), and cornulin (CRNN). CONCLUSIONS: ANN is a robust neural network model that can be used to potentially predict CC based on the gene score. It can provide novel insights into the pathogenesis and molecular mechanisms of CC.

Gold nanoparticles (AuNPs) decrease the viability of cervical cancer cells by inducing the BAX gene and activating antioxidant enzymes.

BACKGROUND: Cervical Cancer (CC), a leading cause of female mortality worldwide, demonstrates a direct association with high-risk human papillomavirus (HPV) infections. However, not all CC patients exhibit HPV infection, suggesting additional predisposing factors. Recently, disturbances in the oxidant-antioxidant balance have been implicated in CC development. This study explores the impact of gold nanoparticles (AuNPs) on the survival and antioxidant capacity of HeLa cells, aiming to contribute to novel CC therapy approaches. METHODS AND RESULTS: Synthesized and characterized AuNPs (25.5 nm, uniform distribution according to the DLS analysis) were administered to HeLa cells at varying concentrations. After 24 h, cell viability was assessed using the (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl-2 H-tetrazolium bromide) (MTT) assay. Real-time PCR measured expression levels of apoptosis-related genes (BCL2 associated X (BAX) and p53). Catalase and superoxide dismutase (SOD) activities, key antioxidant enzymes, were also evaluated post-AuNP treatment. AuNPs dose-dependently reduced HeLa cell viability, with an IC50 value of 113 µg/ml. BAX gene expression significantly increased, indicating pro-apoptotic effects. Moreover, enzyme activities significantly rose under AuNP influence. CONCLUSIONS: AuNPs demonstrated the potential to induce HeLa cell death by upregulating pro-apoptotic BAX gene expression and altering antioxidant system enzyme activities. These findings underscore the promise of AuNPs as a therapeutic avenue for CC, emphasizing their impact on crucial cellular processes involved in cancer progression.

Detection of Sialic Acid to Differentiate Cervical Cancer Cell Lines Using a Sambucus nigra Lectin Biosensor.

Pap smear screening is a widespread technique used to detect premalignant lesions of cervical cancer (CC); however, it lacks sensitivity, leading to identifying biomarkers that improve early diagnosis sensitivity. A characteristic of cancer is the aberrant sialylation that involves the abnormal expression of α2,6 sialic acid, a specific carbohydrate linked to glycoproteins and glycolipids on the cell surface, which has been reported in premalignant CC lesions. This work aimed to develop a method to differentiate CC cell lines and primary fibroblasts using a novel lectin-based biosensor to detect α2,6 sialic acid based on attenuated total reflectance Fourier transform infrared spectroscopy (ATR-FTIR) and chemometric. The biosensor was developed by conjugating gold nanoparticles (AuNPs) with 5 µg of Sambucus nigra (SNA) lectin as the biorecognition element. Sialic acid detection was associated with the signal amplification in the 1500-1350 cm-1 region observed by the surface-enhanced infrared absorption spectroscopy (SEIRA) effect from ATR-FTIR results. This region was further analyzed for the clustering of samples by applying principal component analysis (PCA) and confidence ellipses at a 95% interval. This work demonstrates the feasibility of employing SNA biosensors to discriminate between tumoral and non-tumoral cells, that have the potential for the early detection of premalignant lesions of CC.

Proteomic analysis of small extracellular vesicles unique to cervical cancer.

Background: Cervical cancer (CC) is the fourth most common cancer in females worldwide. Existing biomarkers for CC, such as squamous cell carcinoma antigens, show low specificity. Hence, a novel biomarker for the diagnosis of CC is required. Through proteomic analysis, this study aimed to distinguish between the small extracellular vesicle (sEV) protein profiles of healthy controls (HC) and CC sera and to identify potential sEV proteins that can serve as biomarkers for CC diagnosis. Methods: The number and size distribution of sEVs in HC and CC sera were measured using nanoparticle tracking analysis. Differential ultracentrifugation combined with size-exclusion chromatography was used to isolate and purify sEVs. Liquid chromatography-tandem mass spectrometry was used to identify and compare the protein profiles between patients with CC and HC. Differentially expressed extracellular vesicle (EV) proteins were validated using The Cancer Genome Atlas database. Results: The EV particle concentration in patients with CC was marginally higher than that in HC. Proteomic and functional protein analyses revealed a difference in the EV protein profiles between HC and CC and identified proteins that can serve as biomarkers for CC. Conclusions: This study provides insights into the potential of sEVs as less invasive biomarkers for CC diagnosis. Validation with a well-designed cohort should be performed to determine the clinical diagnostic value of specific protein markers for CC.

Knowledge on cervical cancer among Indian women in the state of Gujarat.

Women all around the world are affected by Cervical Cancer (CC). Nearly 5, 00,000 women were diagnosed with cervical cancer and more than 270,000 women die every year. Cervical Cancer is the second most typical form of Cancer in females worldwide. The aim of this study is to evaluate the effectiveness of an awareness programme on knowledge and attitude regarding CC among women. Quasi experimental research design was selected to evaluate the effectiveness of an awareness programme. Non-probability convenient sampling method was used to select 60 women from setting. Self-prepared multiple choice questionnaire was used to assess the knowledge level of women and 5 point likert scale (uni-dimensional scale for collecting opinion) was used to assess the attitude level of women. The Results were discussed by using mean, SD, paired "t" test and chi-square test. Data were collected & gathered. Knowledge levels were 2.87±1.50 and attitude level was 6.37±13.35 reported in the control group. But the knowledge and attitude levels in the experimental group were respectively 9.73±2.60 and 12.87±14.72. It concluded that the CC awareness program was successful in changing women's attitudes through knowledge.

Characteristics of vaginal microbiota in various cervical intraepithelial neoplasia: a cross-sectional study.

BACKGROUND: Precancerous lesions of cervical cancer exhibit characteristics indicative of natural progression. To prevent overtreatment of patients whose cervical intraepithelial neoplasia (CIN) in regression and to predict the onset of invasive cervical cancer at an early stage, we've identified the vaginal microbiome as a potential key factor, which is associated with both HPV infection and the various cervical intraepithelial neoplasia. This study aims to investigate the microbiome characteristics of patients with various cervical intraepithelial neoplasia. METHODS: Utilizing high-throughput 16S ribosomal RNA (16S rRNA) sequencing technology, a description of the characteristics and community composition of Vaginal Microbiota (VMB) was conducted among 692 Chinese women infected with the High-risk Human Papillomavirus (HR-HPV). RESULTS: As the grade of the lesions increased, the proportions of Lactobacillus and Pseudomonas demonstrated a significant declining trend, while the proportions of Gardnerella, Dialister, and Prevotella significantly increased. The diversity of the VMB was more significant in high-grade CIN. Furthermore, KEGG pathway enrichment analysis indicates that high-grade cervical intraepithelial neoplasia can inhibit various pathways, including those of phosphotransferase system, transcription factors, Fructose and mannose metabolism, amino sugar and nucleotide sugar metabolism, and galactose metabolism, which may contribute to the development of early cervical cancer symptoms. CONCLUSION: Patients with CIN exhibit a distinct vaginal microbial profile characterized by a decrease in Lactobacillus and Pseudomonas, and an increase in Gardnerella, Prevotella, and Dialister. The proliferation and diminution of these two types of microbial communities are interrelated, suggesting a mutual restraint and balance among them. Disruption of this regulatory balance could potentially lead to the onset of cervical lesions and carcinogenesis. Retrospectively registered: This study was approved by the Ethics Committee of the Beijing Chaoyang Hospital affiliated with the Capital Medical University (NO.2023-S-415).

The promoting effect and mechanism of Nrf2 on cell metastasis in cervical cancer.

BACKGROUND: Cervical cancer (CC) has poor prognosis and high mortality rate for its metastasis during the disease progression. Epithelial-mesenchymal transition (EMT) and anoikis are initial and pivotal steps during the metastatic process. Although higher levels of Nrf2 are associated with aggressive tumor behaviors in cervical cancer, the detailed mechanism of Nrf2 in cervical cancer metastasis, especially EMT and anoikis, remains unclear. METHODS: Immunohistochemistry (IHC) was used to examine Nrf2 expression in CC. Wound healing assay and transwell analysis were used to evaluate the migration ability of CC cells. Western blot, qTR-PCR and immunofluorescent staining were used to verify the expression level of Nrf2, the EMT associated markers and anoikis associated proteins. Flow cytometry assays and cell counting were used to detect the apoptosis of cervical cancer cells. The lung and lymph node metastatic mouse model were established for studies in vivo. The interaction between Nrf2 and Snail1 was confirmed by rescue-of-function assay. RESULTS: When compared with cervical cancer patients without lymph node metastasis, Nrf2 was highly expressed in patients with lymph node metastasis. And Nrf2 was proved to enhance the migration ability of HeLa and SiHa cells. In addition, Nrf2 was positively correlated with EMT processes and negatively associated with anoikis in cervical cancer. In vivo, a xenograft assay also showed that Nrf2 facilitated both pulmonary and lymphatic distant metastasis of cervical cancer. Rescue-of-function assay further revealed the mechanism that Nrf2 impacted the metastasis of CC through Snail1. CONCLUSION: Our fundings established Nrf2 plays a crucial role in the metastasis of cervical cancer by enhancing EMT and resistance to anoikis by promoting the expression of Snail1, with potential value as a therapeutic candidate.

miRNAs role in cervical cancer pathogenesis and targeted therapy: Signaling pathways interplay.

Cervical cancer (CC) is the primary cause of cancer deaths in underdeveloped countries. The persistence of infection with high-risk human papillomavirus (HPV) is a significant contributor to the development of CC. However, few women with morphologic HPV infection develop invasive illnesses, suggesting other mechanisms contribute to cervical carcinogenesis. MicroRNAs (miRNAs, miRs) are small chain nucleic acids that can regulate wide networks of cellular events. They can inhibit or degrade their target protein-encoding genes. They had the power to regulate CC's invasion, pathophysiology, angiogenesis, apoptosis, proliferation, and cell cycle phases. Further research is required, even though novel methods have been developed for employing miRNAs in the diagnosis, and treatment of CC. We'll go through some of the new findings about miRNAs and their function in CC below. The function of miRNAs in the development of CC and its treatment is one of these. Clinical uses of miRNAs in the analysis, prediction, and management of CC are also covered.

Relationship Between Expression of microRNA and Chemotherapy Resistance in Cervical Carcinoma.

Cervical cancer (CC), although being a potentially avoidable disease, is the second most often diagnose gynecological cancer, with at minimum 530,000 new instant reported each year, and optimism for CC remains poor. Nearly half of individuals with locally advanced cervical cancer have a poor pathological response to standard therapy. As a result, research into the molecular pathogenesis of cervical cancer and associated therapeutic targets is a must. MicroRNAs (miRNAs) are possible biomarkers in cervical cancer; elevations or reductions in many distinct miRNAs discovered in individuals with this illness indicate that miRNA could contain a function to play in the illness's pathogenesis. Nevertheless, little is known about their significance in detecting individuals who do not respond to traditional therapy. As a consequence, the intention of this study is to look at the relationship among the synthesis of miRNAs (miR 217 and miR-140-3p), which can be utilized as molecular biomarkers to predict pathological responses in cervical cancer patients after radiation and chemotherapy. Various analytical techniques were used to analyze the data, including quantitative real-time PCR (qRT-PCR), growth and apoptosis analysis, western blot analysis, luciferase reporter gene analysis, immunohistochemistry, and statistical analysis. The results show that such miRNAs participate a crucial responsibility in CC cell proliferation inhibition. They might be a new therapeutic target for microRNA-mediated cell proliferation inhibition in cervical cancer.

Reduced MHC Class I and II Expression in HPV-Negative vs. HPV-Positive Cervical Cancers.

Cervical cancer (CC) is the second most common cancer in women worldwide and the fourth leading cause of cancer-associated death in women. Although human papillomavirus (HPV) infection is associated with nearly all CC, it has recently become clear that HPV-negative (HPV-) CC represents a distinct disease phenotype with increased mortality. HPV-positive (HPV+) and HPV- CC demonstrate different molecular pathology, prognosis, and response to treatment. Furthermore, CC caused by HPV α9 types (HPV16-like) often have better outcomes than those caused by HPV α7 types (HPV18-like). This study systematically and comprehensively compared the expression of genes involved in major histocompatibility complex (MHC) class I and II presentation within CC caused by HPV α9 types, HPV α7 types, and HPV- CC. We observed increased expression of MHC class I and II classical and non-classical genes in HPV+ CC and overall higher expression of genes involved in their antigen loading and presentation apparatus as well as transcriptional regulation. Increased expression of MHC I-related genes differs from previous studies using cell culture models. These findings identify crucial differences between antigen presentation within the tumor immune microenvironments of HPV+ and HPV- CC, as well as modest differences between HPV α9 and α7 CC. These differences may contribute to the altered patient outcomes and responses to immunotherapy observed between these distinct cancers.

Cáncer de cérvix: una mirada práctica / Cervical cancer, a practical view

Resumen Introducción: El cáncer de cérvix (CC) es un problema de salud pública en países desarrollados y no desarrollados; esta patología tiene repercusiones socioeconómicas en mujeres en edad reproductiva. Objetivo: Describir las características sobre métodos de prevención, tamizaje, diagnóstico y tratamiento del cáncer de cérvix. Método: Se realizó una búsqueda bibliográfica exhaustiva en un período de seis años (2016-2021) en la base de datos de la Fundación Universitaria del Área Andina, utilizando motores de búsqueda como Dialnet, Science Direct, Medline, LIlacs, Scopus para revisar los conceptos generales sobre cáncer de cérvix. Resultados: El CC es el segundo cáncer más frecuente en Colombia, la principal etiología del cáncer de cérvix es el virus del papiloma humano (VPH), el cual es un virus prevenible mediante la adecuada educación e información y seguimiento a sus lesiones precancerosas. Conclusión: El CC es una patología con altas tasas de mortalidad, especialmente en países en vía de desarrollo y en las infecciones asociadas a VPH de alto riesgo, afectando principalmente a mujeres en edad reproductiva y estratos socioeconómicos bajos. Los principales pilares para el manejo de esta patología siguen siendo las estrategias de salud pública, como la vacunación y realización de las pruebas de tamizaje.

Abstract Introduction: Cervical cancer (CC) is a public health problem in both developed and undeveloped countries; besides it has socio-economic repercussions in women of reproductive age. Objective: To describe the characteristics of cervical cancer prevention, screening, diagnosis, and treatment methods. Method: An exhaustive bibliographic search was carried out within a period of 6 years (2016-2021) in the database of the Fundación Universitaria del Área Andina, using search engines such as Dialnet, Science Direct, Medline, Lilacs, and Scopus to review the concepts general information about cervical cancer. Results: The main etiology of cervical cancer is the human papillomavirus (HPV) which is a preventable virus through adequate education and information and follow-up of its precancerous lesions. It is the second most frequent cancer in Colombia. Conclusion: CC is a pathology that mainly affects women of reproductive age belonging to low socioeconomic strata. This type of cancer has high mortality rates, especially in developing countries and in high-risk HPV infections. Regarding the management of this pathology, public health strategies, such as vaccination and conducting screening tests continue being the fundamental pillars.