Pathogenesis Of Cervical Cancer Research Articles

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.

Untold story of human cervical cancers: HPV-negative cervical cancer

Cervical cancer is the fourth most common malignancy in women worldwide. Although infection from human papillomavirus (HPV) has been the leading cause of cervical cancer, HPV-negative cervical cancer accounts for approximately 3-8% of all cases. Previous research studies on cervical cancer have focused on HPV-positive cervical cancer due to its prevalence, resulting in HPV-negative cervical cancer receiving considerably less attention. As a result, HPV-negative cervical cancer is poorly understood. Its etiology remains elusive mainly due to limitations in research methodology such as lack of defined markers and model systems. Moreover, false HPV negativity can arise from inaccurate diagnostic methods, which also hinders the progress of research on HPV-negative cervical cancer. Since HPV-negative cervical cancer is associated with worse clinical features, greater attention is required to understand HPV-negative carcinoma. In this review, we provide a summary of knowledge gaps and current limitations of HPV-negative cervical cancer research based on current clinical statistics. We also discuss future directions for understanding the pathogenesis of HPV-independent cervical cancer.

Advances in Exosomes as Diagnostic and Therapeutic Biomarkers for Gynaecological Malignancies.

Simple SummaryThe three major gynaecological cancers are ovarian cancer, endometrial cancer, and cervical cancer, which endanger women’s health worldwide. Significant progress has been made in the study of exosomes, which have been proven to be an important form of intercellular communication, as well as an important carrier for the uptake, transport, and release of cargo. Exosomes may also be promising diagnostic or prognostic markers for gynaecologic malignancies, which may improve the level of treatment of gynaecologic malignancies. This article reviews the latest research progress and systematic knowledge of exosomes in gynaecological malignant tumours in recent years, in order to provide a new perspective for the treatment of gynaecological tumours and promote the clinical application of exosomes in gynaecological malignancies.Background: Exosomes are extracellular vesicles that can be released by practically all types of cells. They have a diameter of 30–150 nm. Exosomes control the exchange of materials and information between cells. This function is based on its special cargo-carrying and transporting functions, which can load a variety of useful components and guarantee their preservation. Recently, exosomes have been confirmed to play a significant role in the pathogenesis, diagnosis, treatment, and prognosis of gynaecological malignancies. Particularly, participation in liquid biopsy was studied extensively in gynaecological cancer, which holds the advantages of noninvasiveness and individualization. Literature Review: This article reviews the latest research progress of exosomes in gynaecological malignancies and discusses the involvement of humoral and cell-derived exosomes in the pathogenesis, progression, metastasis, drug resistance and treatment of ovarian cancer, cervical cancer, and endometrial cancer. Advances in the clinical application of exosomes in diagnostic technology, drug delivery, and overcoming tumour resistance are also presented. Conclusion: Exosomes are potentially diagnostic and prognostic biomarkers in gynaecological malignancies, and also provide new directions for the treatment of gynaecological tumours, showing great clinical potential.

Competing Endogenous RNA (ceRNA) Networks and Splicing Switches in Cervical Cancer: HPV Oncogenesis, Clinical Significance and Therapeutic Opportunities.

Cervical cancer (CC) is the primary cause of female cancer fatalities in low-middle-income countries (LMICs). Persistent infections from the human papillomavirus (HPV) can result in cervical cancer. However, numerous different factors influence the development and progression of cervical cancer. Transcriptomic knowledge of the mechanisms with which HPV causes cervical cancer pathogenesis is growing. Nonetheless, there is an existing gap hindering the development of therapeutic approaches and the improvement of patient outcomes. Alternative splicing allows for the production of numerous RNA transcripts and protein isoforms from a single gene, increasing the transcriptome and protein diversity in eukaryotes. Cancer cells exhibit astounding transcriptome modifications by expressing cancer-specific splicing isoforms. High-risk HPV uses cellular alternative splicing events to produce viral and host splice variants and proteins that drive cancer progression or contribute to distinct cancer hallmarks. Understanding how viruses utilize alternative splicing to drive pathogenesis and tumorigenesis is essential. Although research into the role of miRNAs in tumorigenesis is advancing, the function of other non-coding RNAs, including lncRNA and circRNA, has been understudied. Through their interaction with mRNA, non-coding RNAs form a network of competing endogenous RNAs (ceRNAs), which regulate gene expression and promote cervical cancer development and advancement. The dysregulated expression of non-coding RNAs is an understudied and tangled process that promotes cervical cancer development. This review will present the role of aberrant alternative splicing and immunosuppression events in HPV-mediated cervical tumorigenesis, and ceRNA network regulation in cervical cancer pathogenesis will also be discussed. Furthermore, the therapeutic potential of splicing disruptor drugs in cervical cancer will be deliberated.

ISG15 is associated with cervical cancer development.

Cervical cancer (CC) is a complex disease. Numerous factors contribute to the tumourigenesis and progression of CC neoplasms. The present study analysed transcriptomic differences and simulated tumour progression to explore the pathogenesis of CC. RNA sequencing was performed to analyse the transcriptomic differences among normal tissue (NC), paracarcinoma tissue (TP), and primary tumour tissue (TT). Pseudo-time analysis was performed to simulate tumour progression. Reverse transcription-quantitative PCR (RT-qPCR) and immunohistochemistry (IHC) were used to analyse the expression levels of ISG15 ubiquitin-like modifier (ISG15). Cell proliferation wound healing and Transwell assays were used to examine the effect of ISG15 inhibition and overexpression on HeLa cells. The RT-qPCR and IHC results indicated that ISG15 expression was significantly upregulated in TT. An increasing trend of ISG15 expression from NC to TP to TT was observed, which suggested that elevated ISG15 expression was closely associated with malignant evolution in CC tissues. HeLa cell experiments revealed that ISG15-small interfering RNA inhibited cell proliferation and invasion. The present study demonstrated that ISG15 was upregulated in CC and positively associated with the development of CC. ISG15 may act as an oncogene in the tumourigenesis of CC.

Exploration of shared gene signature with development of pre-eclampsia and cervical cancer.

Background: The relationship between pre-eclampsia (PE) and cervical cancer (CC) has drawn more attention recently, while little is known about the shared pathogenesis of CC and PE. In the present research, we aimed to generate the shared gene network as well as the prognostic model to reveal the development of CC and PE. Methods: The transcription data of CC and PE patients were obtained and enrolled into weighted gene co-expression network (WGCNA) analysis. Disease-specific modules in CC and PE were determined to discover the shared genes. The expression patterns of genes at protein level were examined by HPA database. Further, LASSO penalty regression and Cox analysis were applied to create a prognostic signature based on the shared genes, with survival curves and ROC plots employed to confirm the predictive capacity. To uncover the function roles and pathways involved in signature, gene set enrichment analysis (GSEA) was conducted. Finally, the immune infiltration status in CC was depicted using CIBERSORT algorithms. Results: WGCNA determined three hub modules between CC and PE. A total of 117 shared genes were obtained for CC and PE and mainly enriched in cell proliferation, regulation of cell development and neuron differentiation. Then, we created a robust prognostic model based on the 10 shared genes by performing stepwise Cox analyses. Our proposed model presented a favorable ability in prognosis forecast and was correlated with the infiltration of immunocytes including B cells, macrophages and T cells. GSEA disclosed that high-risk group was involved in cancer-related pathways. Conclusion: The present project identified the shared genes to uncover the pathogenesis of CC and PE and further proposed and validated a prognostic signature to accurately forecast the clinical outcomes of CC patients.

Research Status of HPV and Cervical Cancer

Cervical cancer is a worldwide malignant tumors in gynecology, which does great harm to women's health. The pathogenesis of cervical cancer is mainly related to the persistent infection of high-risk HPV virus. This paper mainly studies the relationship between HPV and cervical cancer, and finds that there is a close relationship between them. The significance of our study of this subject is that it is now clear that cervical cancer is transmitted through viruses and vectors, which is a great discovery. In this way, many years before the occurrence of cervical cancer, there is enough opportunity to find it and eliminate it, which is a very great contribution, so many patients who should have cervical cancer have been blocked, ensuring the health of women to a great extent.

Association of a genetic variant in the ATP-binding cassette sub-family B member 1 with risk of cervical cancer

BackgroundCervical cancer is one of the most prevalent cancers among women and is associated with high morbidity and mortality. Several factors are involved in the pathogenesis of cervical cancer including viral infections and/or genetic modifications that include single nucleotide polymorphisms (SNPs). MethodsWe aimed to investigate the association of genetic variants in ATP Binding Cassette Subfamily B Member 1 (ABCB1) (rs1128503) and Fc Gamma Receptor IIIa (FCGR3A) (rs396991) genes and susceptibility to cervical cancer in 263 individuals with or without this form of cancer. DNA samples were isolated and genotyped using a TaqMan based real-time (RT-) PCR method. ResultsThe rs1128503 was found to be associated with an increased risk of cervical cancer (recessive model: OR = 2.6, CI: 1.1–5.8, p = 0.02). whilst there was no association between the rs396991 and susceptibility to cervical cancer. ConclusionOur results showed that there is an association between the ABCB1 polymorphism and susceptibility for cervical cancer suggesting its potential as a risk stratification marker for cervical neoplasia.

Prognostic value of SOX9 in cervical cancer: Bioinformatics and experimental approaches.

Among gynecological cancers, cervical cancer is a common malignancy and remains the leading cause of cancer-related death for women. However, the exact molecular pathogenesis of cervical cancer is not known. Hence, understanding the molecular mechanisms underlying cervical cancer pathogenesis will aid in the development of effective treatment modalities. In this research, we attempted to discern candidate biomarkers for cervical cancer by using multiple bioinformatics approaches. First, we performed differential expression analysis based on cervical squamous cell carcinoma and endocervical adenocarcinoma data from The Cancer Genome Atlas database, then used differentially expressed genes for weighted gene co-expression network construction to find the most relevant gene module for cervical cancer. Next, the Gene Ontology and Kyoto Encyclopedia of Genes and Genomes enrichment analyses were performed on the module genes, followed by using protein–protein interaction network analysis and Cytoscape to find the key gene. Finally, we validated the key gene by using multiple online sites and experimental methods. Through weighted gene co-expression network analysis, we found the turquoise module was the highest correlated module with cervical cancer diagnosis. The biological process of the module genes focused on cell proliferation, cell adhesion, and protein binding processes, while the Kyoto Encyclopedia of Genes and Genomes pathway of the module significantly enriched pathways related to cancer and cell circle. Among the module genes, SOX9 was identified as the hub gene, and its expression was associated with cervical cancer prognosis. We found the expression of SOX9 correlates with cancer-associated fibroblast immune infiltration in immune cells by Timer2.0. Furthermore, cancer-associated fibroblast infiltration is linked to cervical cancer patients’ prognosis. Compared to those in normal adjacent, immunohistochemical and real-time quantitative polymerase chain reaction (qPCR) showed that the protein and mRNA expression of SOX9 in cervical cancer were higher. Therefore, the SOX9 gene acts as an oncogene in cervical cancer, interactive with immune infiltration of cancer-associated fibroblasts, thereby affecting the prognosis of patients with cervical cancer.

Phytocompounds from the Medicinal and Dietary Plants: Multi-target Agents for Cervical Cancer Prevention and Therapy.

Cervical cancer is the fourth leading cause of cancer death among women worldwide. Due to cervical cancer's high incidence and mortality, there is an unmet demand for effective diagnostic, therapeutic, and preventive agents. At present, the preferred treatment strategies for advanced metastatic cervical cancer include surgery, radiotherapy, and chemotherapy. However, cervical cancer is gradually developing resistance to chemotherapy, thereby reducing its efficacy. Over the last several decades, phytochemicals, a general term for compounds produced from plants, have gained attention for their role in preventing cervical cancer. This role in cervical cancer prevention has garnered attention on the medicinal properties of fruits and vegetables. Phytochemicals are currently being evaluated for their ability to block proteins involved in carcinogenesis and chemoresistance against cervical cancer. Chemoresistance to cancer drugs like cisplatin, doxorubicin, and 5-fluorouracil has become a significant limitation of drug-based chemotherapy. However, the combination of cisplatin with other phytochemicals has been identified as a promising alternative to subjugate cisplatin resistance. Phytochemicals are promising chemo-preventive and chemotherapeutic agents as they possess antioxidant, anti-inflammatory, and anti-proliferative potential against many cancers, including cervical cancer. Furthermore, the ability of the phytochemicals to modulate cellular signaling pathways through up and down regulation of various proteins has been claimed for their therapeutic potential. Phytochemicals also display a wide range of biological functions, including cell cycle arrest, apoptosis induction, inhibition of invasion, and migration in cervical cancer cells. Numerous studies have revealed the critical role of different signaling proteins and their signaling pathways in the pathogenesis of cervical cancer. Here, we review the ability of several dietary phytochemicals to alter carcinogenesis by modulating various molecular targets.

Long intergenic noncoding RNA LINC01287 drives the progression of cervical cancer via regulating miR-513a-5p/SERP1.

Cervical cancer is one of the most frequent types of cancer in women, which is characterized by high invasion and metastatic tendency in its advanced stage. Emerging evidence indicated that long non-coding RNAs (LncRNAs) are involved in the pathogenesis of cervical cancer. LINC01287 has been reported to play crucial regulatory roles in the pathogenesis and progression of multiple cancers. However, up until now, whether LINC01287 is associated with the initiation and development of cervical cancer remains largely unknown. In the present study, expression levels of LINC01287, miR-513a-5p and stress-associated endoplasmic reticulum protein 1 (SERP1) mRNA were quantified utilizing qRT-PCR. A series of functional experiments including CCK-8 assay, colony formation assay, transwell assay, flow cytometry, and tumor xenograft growth of cervical cancer cells were performed for studying the effects of LINC01287. The luciferase reporter assay, pull-down assay, and western blot were used to confirm the downstream targets of LINC01287 and miR-513a-5p. The results demonstrate that LINC01287 was highly expressed in cervical cancer tissue samples and cell lines. High LINC01287 predicts a poor prognosis for cervical cancer patients. Additional gain- and loss-of-function experiments demonstrated that silencing LINC01287 inhibited cervical cancer cells proliferation, colony formation, migration, apoptosis in vitro and retarded tumor growth and metastasis in vivo. Furthermore, the dual-luciferase reporter gene system and RNA pulldown assay validated that LINC01287 positively regulated SERP1 expressions by sponging miR-513a-5p, and LINC01287 inhibited cervical cancer progression by regulating miR-513a-5p/SERP1 axis. In conclusion, the current study first identified that LINC01287/miR-513a-5p/SERP1 axis played an important role in cervical cancer progression. LINC01287 might be a prognostic biomarker and a target for new therapies in patients with cervical cancer.

Pathogenesis of Hepatitis-B Virus-Related Hepatocellular Carcinoma and Human Papillomavirus-Associated Cervical Cancer

Cancer, which can be explained as malignant tumors and neoplasms, is one of the main factors of human mortality and greatly obstructs the extension global human life span. There are various human cancers induced by viruses. Hepatocellular carcinoma (HCC) and cervical cancer (CC) are two common cancers related to viruses. The pathogenesis of these carcinogenic viruses has been studied for a long period of time, and some progress has been made. Hepatitis B virus (HBV) infection functions as a promoter of hepatocellular carcinoma occurrence. The integration of HBV DNA into the host genome is one of the important factors of the development of hepatocellular carcinoma. Besides, miRNA plays an important part in HBV ampilification and the progression of HBV-related hepatocellular carcinoma. Another cancer-inducing virus, human papillomavirus (HPV) is highly related to cervical cancer, as the long-term chronic inflammation due to HPV infection can lead to the progression of cervical cancer. Apart from this, APOBECs also give rise to the progression of HPV-induced cervical cancer. This essay will estimate the pathogenesis of HBV-associated hepatocellular carcinoma, such as HBV DNA integration, microRNA. Meanwhile the pathogenesis of HPV-related cervical cancer, such as inflammation, APOBEC3, will also be noted.

Human papilloma virus vaccine: literature review

Inga Vasilevskytė1,2 1Vilniaus universitetas, Medicinos fakultetas, Vilnius, Lietuva 2Vilniaus universiteto ligoninė Santaros klinikos, Akušerijos ir ginekologijos katedra ABSTRACT The human papillomavirus (HPV) is one of the most common sexually transmitted infections, causing a variety of precancerous conditions and cancers in men and women. Cervical cancer is one of the most common forms of cancer that poses a risk to women’s health, and human papillomavirus infection is closely linked to the pathogenesis of cervical cancer. Every year in the world there are about 20 million people suffering from the human papillomavirus, and about 6 million become infected. However, despite a variety of preventive measures and treatments, such as HPV screening, preventive vaccines, surgery remains high worldwide. This review aims to systematically review the safety and efficacy of HPV vaccines in women and the indications and contraindications for immunization. Objective: To review the types of human papillomavirus, their effects on health, types of HPV vaccines, indications and contraindications for immunization, and the safety and efficacy of vaccines. Methods: The literature review was performed based on the scientific databases of PubMed, Medline, Web of Science of selected publications examining the prevalence of human papillomavirus, the types of HPV vaccines, their safety and efficacy, and the indications and contraindications for immunization. Systematic reviews and meta-analyzes no older than 10-15 years were included in the literature review. A total of 30 articles were reviewed, of which 9 were rejected. Conclusions: The analysis of the literature presents the epidemiology of HPV, the types of vaccines, their safety and efficacy, and indications and contraindications for vaccination. Keywords: Human papillomavirus, complications, HPV vaccine safety.

Cervical Cancer Prophylaxis-State-of-the-Art and Perspectives.

Background: Each year 604,127 new cases of cervical cancer (CC) are diagnosed, and 341,831 individuals die from the disease. It is the fourth most common cancer among women and the fourth most common cause of death from female cancers worldwide. The pathogenesis of CC is associated with human papillomavirus (HPV) infections and consists of several steps involving cell proliferation outside the human body’s control mechanisms. Strategies to prevent CC are based on screening and vaccination. Scope of the Review: The aim of this paper was to collect and analyze the available literature on the issue of CC prevention and the impact of the COVID-19 pandemic on its implementation. For this purpose, PubMed and Google Scholar databases were searched using keywords, such as “cervical cancer”; “HPV”; “prevention”; “prophylaxis”; “vaccination”; “screening” and “COVID-19” in different variations. Only articles published since 2018 were included in the study. Conclusions: Selected European countries have different CC prevention programs funded by national budgets. This translates into observed differences in the risk of death from CC (age-standardized rate Malta = 1.1, Poland = 5.9). COVID-19 pandemic due to disruption of CC screening may exacerbate these differences in the future. To improve the situation, new screening methods, such as p16/Ki67, HPV self-testing, and the use of artificial intelligence in colposcopic assessment, should be disseminated, as well as free HPV vaccination programs implemented in all countries. The search for new solutions is not without significance and entails ultra-sensitive screening tests for risk groups (mRNA E6/E7, SOX1/SOX14), HPV vaccines with shorter dosing schedules, and new therapeutic pathways using nanotheranostics.

Comparison of different blood biomarkers of cervical cancer patients with control subjects

Cervical cancer shows a high prevalence among Bangladeshi women. Reports indicated that oxidant-antioxidant balance plays a role in cervical cancer pathogenesis. Therefore, this study explores the change of different blood-derived enzymes, antioxidants, and biomarkers to understand the oxidative stress status of Bangladeshi cervical cancer patients. A clinician recruited the case and control participants for the study based on histopathologic reports. No significant difference was observed in the random blood glucose level, blood pressure, total cholesterol, triglycerides (TGs), HDL cholesterol, LDL cholesterol, and total protein levels in case participants compared to age and sex-matched control subjects. However, serum albumin, vitamins like alpha-tocopherol and ascorbic acid, antioxidant enzymes like SOD, and catalase levels significantly decreased in patients compared to controls. Other parameters, like, ALT, AST, ALP, phospholipid hydroperoxide, TBARS, protein carbonyl content, serum nitric oxide, cholesterol/phospholipid ratio (C/P) of erythrocyte and osmotic fragility were significantly increased in the case subjects compared to control. All of these reflect an oxidant-antioxidant imbalance in this setting. Thus, this study provides a detailed profile of the oxidant-antioxidant levels of the Bangladeshi cervical cancer patients, which revealed that the compromised antioxidant system in cervical cancer patients is associated with damage to various biomolecules and ultimately impairs cellular functions. J. Bangladesh Acad. Sci. 46(1); 117-128: June 2022

The Dysregulation of MicroRNAs in the Development of Cervical Pre-Cancer-An Update.

Globally in 2020, an estimated ~600,000 women were diagnosed with and 340,000 women died from cervical cancer. Compared to 2012, the number of cases increased by 7.5% and the number of deaths increased by 17%. MiRNAs are involved in multiple processes in the pathogenesis of cervical cancer. Dysregulation of miRNAs in the pre-stage of cervical cancer is the focus of this review. Here we summarize the dysregulated miRNAs in clinical samples from cervical pre-cancer patients and relate them to the early transformation process owing to human papillomavirus (HPV) infection in the cervical cells. When HPV infects the normal cervical cells, the DNA damage response is initiated with the involvement of HPV’s E1 and E2 proteins. Later, cell proliferation and cell death are affected by the E6 and E7 proteins. We find that the expressions of miRNAs in cervical pre-cancerous tissue revealed by different studies seldom agreed with each other. The discrepancy in sample types, samples’ HPV status, expression measurement, and methods for analysis contributed to the non-aligned results across studies. However, several miRNAs (miR-34a, miR-9, miR-21, miR-145, and miR-375) were found to be dysregulated across multiple studies. In addition, there are hints that the DNA damage response and cell growth response induced by HPV during the early transformation of the cervical cells are related to these miRNAs. Currently, no review articles analyse the relationship between the dysregulated miRNAs in cervical pre-cancerous tissue and their possible roles in the early processes involving HPV’s protein encoded by the early genes and DNA damage response during normal cell transformation. Our review provides insight on spotting miRNAs involved in the early pathogenic processes and pointing out their potential as biomarker targets of cervical pre-cancer.

Awareness of the link between HPV, cervical cancer, and HPV vaccination: An online survey among Polish women.

10538 Background: In 2019 cervical cancer (CC) was the 7th most common malignant neoplasm in Polish women. Its incidence has been declining over the years, nonetheless the 5-year survival rate is still significantly lower than the EU average. Vaccination against human papillomavirus (HPV) is not included in the mandatory immunization schedule in Poland and is not reimbursed yet. The aim of the study was to assess women's awareness of the risk factors of CC (including the role of HPV) and the possibility of cancer prevention through HPV vaccination. Methods: The questionnaire prepared by the study team was aimed at women and conducted online using social network sites. The single/multiple-choice questions included knowledge about CC, HPV and HPV vaccination. Statistical analyses were performed using MS Excel 2016 and Medistica pvalue.io 2021 software in general population and age- dependent subgroups. Results: The total number of 3262 women participated in the study. The age subgroups were: aged ≤ 18 years (group 1): 1090 (33.4%), aged 19-25 years (group 2): 1615 (49.5%) and > 25 years (group 3): 557 (17.1%). Overall 81.4% of the respondents correctly associated HPV as the key factor of CC, 85.0% believed that CC could be prevented and 80.0% had heard of HPV vaccination before. In the last two parameters a statistically significant difference in age subgroups was observed (p < 0.001). Only 21.2% of the total number of respondents were vaccinated (26.2%, 22.0% and 9.2% in age groups 1, 2 and 3 respectively, p < 0.001). In all studied populations the following factors had the greatest influence on the decision to get vaccinated: parents’ advice – 54.8%, pediatrician recommendation – 15.7%, possibility of free vaccination offered by municipality – 11.6%, teachers’ advice - 9.7%, gynecologist recommendation - 8.2%. The main reasons behind not getting vaccinated were: high price (63.0%) and disbelief in efficacy (41.5%); only 12.2% respondents were afraid of possible side effects. 65.0% of the unvaccinated respondents declared willingness to get vaccinated in the future (71.5%, 66.1% and 52.0% in age groups 1, 2 and 3 respectively p < 0.001), 28.5% of the respondents were not confident of their decision at the time of submitting answers. Conclusions: As oncogenic types of human papillomavirus play a vital role in pathogenesis of CC, the HPV vaccination and cytological screening together with awareness-raising campaigns should be considered the best strategy for the prevention of CC, its early detection and increase in survival rates. Vaccine willingness remains at high level especially among young women, however the effectiveness of vaccination should be emphasized and the HPV free vaccination programs should be introduced by the state. The educational role of gynecologists needs to be enhanced.

Human papillomavirus and cervical cancer: an insight highlighting pathogenesis and targeting strategies.

Cervical cancer is marked by the uncontrolled proliferation and division of cells making up the cervix. Because of its enormous population, Asia accounts for more than half of the cervical cancer cases and deaths in the world. Cervical cancer is the major cause of death from cancer in women in rural as well as urban areas in India. In most cases, persistent infection with highly infectious types of human papillomavirus (HPV) such as HPV 16 and 18 is believed to be the cause of the disease. The HPV virus is primarily reported to invade cervical epithelial cells and then goes through a non-viremic infection cycle under the influence of various potent viral oncogenic proteins, namely E6 and E7. Among several other risk factors, increased oxidative stress, hyperactivation of inflammatory pathways, and immunological factors play a key role in cervical cancer pathogenesis. Although, standardized screening services in developed countries have substantially reduced the prevalence of cervical cancer but there are numerous drawbacks to cytology-based screening. Advances in understanding the virology of the human papillomavirus have prompted the discovery of several novel biomarkers of different categories such as protein-based, DNA-based as well as stem cell-based markers. The incorporation of biomarker information will assist in recognizing efficacious therapy systems as well as improve the prognosis of cervical malignancy. The review discussed the role of HPV in the development of cervical cancer and its pathogenesis. Further, summarized the potential therapeutic biomarkers for the prevention and treatment of cervical cancer.

RETRACTED: Cervical cancer treatment of Co(II) coordination polymer through miR-9-5p-regulated BRCA1-OCT1-GADD45 pathways

Fresh Co(II) concluding coordination polymer based on {[Co(μ-ppda)(μ-pbmeix)]∙0.5pbmeix·H 2 O} n ( 1 ) was formed smoothly through the reaction of Co(II) salt with p -phenylenediacetic acid (H 2 ppda) under the conditions of N-donor co-ligand semirigid 1,4-bis(2-methylimidazol-1-ylmethyl)benzene (pbmeix) for cervical cancer therapy. In our biological research, we explored the pathogenesis of cervical cancer and provided new targets for cervical cancer treatment. In patients with cervical cancer and the cervical cancer rat model, the expression of Breast Cancer Susceptibility Protein-1 (BRCA1) was aberrantly upregulated. This phenomenon may play a role in the occurrence and development of cervical cancer. Then, bioinformatics prediction was conducted, and miR-9-5p was speculated as the up-regulator of BRCA1 in cervical cancer cells. The influence of miR-9-5p on the vascular endothelial growth factor and pigment epithelium-derived factor contents of cervical cancer lesions was determined via enzyme‐linked immunosorbent (ELISA) assay. Then, the proliferation of cervical cancer cells was determined via CCK-8 assay after miR-9-5p transfection. Finally, we proved that complex 1 is an excellent candidate for cervical cancer therapy through miR-9-5p-regulated BRCA1-OCT1-GADD45 pathways.

The Bethesda System for reporting cervical cytology.

The seminal observations of Dr. George Papanicolaou have grown, through the untiring efforts of many authors, into a universally accepted format of cytology reporting. This has helped immensely to improve the understanding of pathogenesis of cervical cancer. The insights into the complexity of interaction of the etiological and the host factors have further helped in reframing of the reporting system. The Bethesda System (TBS) stands out as a model of standardized reporting in cervicovaginal cytology. Apart from its reproducibility, it reflects the most current understanding of cervical cancer. The most important feature is its clinical relevance. Each category of this classification has clear clinical implications, which are based on solid evidence and worldwide consensus. Moreover, the authors have tried to keep it updated through continuous revisions, incorporating the technological and scientific advances. The component of specimen adequacy reflects the importance it has given to the quality assurance of the laboratory preparation. The minimization of categories, simple terminology, and the supporting image atlas – both in the print form and the web-based form, have made TBS an exemplary teaching-learning resource. The wide accessibility of TBS has been the most important factor in being adopted by a majority of pathology community all over the world.