Pathogenesis Of Cervical Cancer Research Articles

The role of proteomics in the modern diagnosis of cervical cancer

Cervical cancer is a leading global health problem and the second most common form of cancer in women living in developing countries. Despite the available methods of diagnosis and treatment, cervical cancer is still the cause of a large number of deaths among vulnerable groups of the female population, which makes further research relevant. The aim of this study was to summarize new technological developments and scientific information about proteomics, which will allow for deepening the understanding of the pathogenesis of cervical cancer and developing new methods of diagnosis and treatment of this pathology. Recent achievements in the field of analytical research methods and bioinformatics provide a wide range of alternatives in the field of proteomic research. To date, proteomic analysis can be performed on almost any biological sample (tumor tissue, blood, urine, saliva, vaginal secretions). Each type of biological sample represents a potential source of diagnostic and prognostic biomarkers, as well as potential targets for therapy. The main limitation of proteomic studies aimed at finding potential biomarkers of the disease is the high variability of the results depending on the specific laboratory. There is variability in concentrations and even in the type of biomarker identified, even though research teams are working with the same samples.

The Regulatory Functions and the Mechanisms of Long Non-Coding RNAs in Cervical Cancer.

Cervical cancer is one of the leading causes of death in gynecology cancer worldwide. High-risk human papillomaviruses (HPVs) are the major etiological agents for cervical cancer. Still, other factors also contribute to cervical cancer development because these cancers commonly arise decades after initial exposure to HPV. So far, the molecular mechanisms underlying the pathogenesis of cervical cancer are still quite limited, and a knowledge gap needs to be filled to help develop novel strategies that will ultimately facilitate the development of therapies and improve cervical cancer patient outcomes. Long non-coding RNAs (lncRNAs) have been increasingly shown to be involved in gene regulation, and the relevant role of lncRNAs in cervical cancer has recently been investigated. In this review, we summarize the recent progress in ascertaining the biological functions of lncRNAs in cervical cancer from the perspective of cervical cancer proliferation, invasion, and metastasis. In addition, we provide the current state of knowledge by discussing the molecular mechanisms underlying the regulation and emerging role of lncRNAs in the pathogenesis of cervical cancer. Comprehensive and deeper insights into lncRNA-mediated alterations and interactions in cellular events will help develop novel strategies to treat patients with cervical cancer.

Pap Smear Collection and Preparation: Key Points

Cytology is the science of study of cells. It is derived from the Greek word “cytos” which means cells. The cells of the cervicovaginal epithelium are continuously evolving. The mature cells reach the surface and are then exfoliated. Initially, these exfoliated cells were collected from the posterior fornix, which showed cells from endocervix, ectocervix, and the vaginal epithelium. Hence, it was known as the exfoliative vaginal cytology. But now, the cells are taken directly by scraping the ecto and the endocervix. A variety of sampling devices are available in the market. The basic aim is to augment sampling of the complete transformation zone (TZ) as well as the squamocolumnar junction (SCJ) and cause least possible trauma to the cervical and endocervical epithelium during its use. The SCJ is of crucial significance for cervical cancer pathogenesis. Most of the precancerous changes take place within the TZ and at the SCJ. Hence, the collection of cells from this area is of utmost importance. The reliability of cervical cytology for the detection of precancerous lesions also strongly depends on immediate wet fixation of the smear. Therefore, the gynecologists or the paramedics who perform the conventional Pap smears must not only be trained in the art of cell collection and smearing of the material onto the glass slides but also learn immediate wet fixation of the cervical cells. Liquid-based preparations have made all these steps relatively easy for them as the design of the Cervex brush is such that it mostly ensures the sampling of the complete TZ and the SCJ. Pre-fixation of cells occurs in the vial containing a weak fixative and the transfer of cells onto the glass slide is standardized by the automated stations designed for this purpose. This chapter gives an in depth description of the prerequisites and precautions while collecting and preparing a Pap smear with different devices, especially for settings where conventional smears are still the norm. Instructions for women undergoing Pap smear and the medical personnel who conduct this test are also highlighted.

Significance of Altered Fatty Acid Transporter Expressions in Uterine Cervical Cancer and Its Precursor Lesions.

High-risk human papilloma virus (HR HPV) infection is a major factor leading to the development of uterine cervical cancer. Data suggest that alterations in lipid metabolism are related to the pathogenesis of cervical cancer. Specifically, the uptake of exogenous fatty acids and their intracellular storage in lipid droplets enables cancer cells to survive and adapt to the changing tumor environment. We compared the immunohistochemical expression of fatty acid transport protein 4 (FATP4), and cluster of differentiation 36/fatty acid translocase (CD36/FAT) in normal cervical epithelium, low-grade squamous intraepithelial lesion (LSIL), high-grade squamous intraepithelial lesion (HSIL), and squamous cell carcinoma (SCC) tissues of the uterine cervix. We also investigated the clinicopathological implications of these fatty acid transporters in SCC. Compared with that in normal cervical tissues, the expression of FATP4 was lower in LSIL (p=0.002), HSIL (p=0.006), and SCC (p=0.001). In contrast, CD36 expression was higher in SCC tissues than in normal cervical tissues (p<0.001). In normal cervical tissues, HR HPV-infected lesions exhibited a decrease in FATP4 (p<0.001) and an increase of CD36 (p=0.134), compared to those that were not infected with HR HPV. High CD36 expression was associated with a shorter recurrence-free survival (p<0.001). However, high FATP4 levels showed no significant correlation with the clinicopathological parameters of SCC. Altered expression levels of FATP4 and CD36 are unique features that might be related to HR HPV infection and promote tumorigenesis and progression of cervical cancer.

Overexpression of Ubiquilin4 is associated with poor prognosis in patients with cervical cancer.

BACKGROUNDUbiquilins (UBQLNs) are important factors for cell proteostasis maintenance. UBQLNs are involved in the modulation of the cell cycle, as well as in apoptosis, membrane receptors regulation, DNA repair, epithelial-mesenchymal transition, and miRNA activities. They also affect the selection of double-strand break repair pathways. Abnormal UBQLNs expression can lead to many diseases, including cancer. Studies have found that the expression of Ubiquilin4 (UBQLN4) is associated with the development of several tumor types. However, the association between UBQLN4 and cervical cancer has not been examined yet.AIMTo investigate the expression of UBQLN4 in cervical cancer and to evaluate its correlation with disease prognosis.METHODSImmunohistochemistry was performed to examine the expression of UBQLN4 in 117 cervical cancer tissues and 32 matching pericervical tissues. Paired t-test (two-tailed) was used to compare the differences between groups. We collected patients’ clinical characteristics, including age, histological grade, pathologic type, lymph node metastasis, and FIGO stage (2018) and compared them by chi-square test. All patients were followed for 5.5 to 6.8 years. Kaplan-Meier method and log-rank test were used to compare the differences in the overall survival (OS) and progression-free survival (PFS) among the different groups.RESULTSOverexpression of UBQLN4 was observed in 70.9% (83/117) of all cervical cancer tissues and in 15.6% (5/32) of the paired parauterine tissues. The expression of UBQLN4 was associated with lymph node metastasis, poor differentiation, and advanced stage, but the difference was not significant. Kaplan-Meier and log-rank test results suggested the high expression of UBQLN4 was associated with short OS and PFS. Regardless of UBQLN4 expression, the patient age and FIGO stage were also associated with disease prognosis. The statistically significant variables obtained from univariate the Kaplan-Meier analysis were subjected to Cox multivariate survival regression analysis, which showed that, in addition to the FIGO stage and age, UBQLN4 was also an independent prognostic marker for OS and PFS (P = 0.011 and P = 0.024, respectively).CONCLUSIONThe overexpression of UBQLN4 was associated with poor prognosis in cervical cancer. Our study proposed a novel prognostic factor and improved the existing understanding of the pathogenesis of cervical cancer.

Detection of Host Cell Gene/HPV DNA Methylation Markers: A Promising Triage Approach for Cervical Cancer

Cervical cancer is the most prevalent gynecologic malignancy, especially in women of low- and middle-income countries (LMICs). With a better understanding of the etiology and pathogenesis of cervical cancer, it has been well accepted that this type of cancer can be prevented and treated via early screening. Due to its higher sensitivity than cytology to identify precursor lesions of cervical cancer, detection of high-risk human papillomavirus (HR-HPV) DNA has been implemented as the primary screening approach. However, a high referral rate for colposcopy after HR-HPV DNA detection due to its low specificity in HR-HPV screening often leads to overtreatment and thus increases the healthcare burden. Emerging evidence has demonstrated that detection of host cell gene and/or HPV DNA methylation represents a promising approach for the early triage of cervical cancer in HR-HPV-positive women owing to its convenience and comparable performance to cytology, particularly in LMICs with limited healthcare resources. While numerous potential markers involving DNA methylation of host cell genes and the HPV genome have been identified thus far, it is crucial to define which genes or panels involving host and/or HPV are feasible and appropriate for large-scale screening and triage. An ideal approach for screening and triage of CIN/ICC requires high sensitivity and adequate specificity and is suitable for self-sampling and inexpensive to allow population-based screening, particularly in LMICs. In this review, we summarize the markers of host cell gene/HR-HPV DNA methylation and discuss their triage performance and feasibility for high-grade precancerous cervical intraepithelial neoplasia or worse (CIN2+ and CIN3+) in HR-HPV-positive women.

Knowledge, Attitude, and Practice on Cervical Cancer and HPV Vaccination among Medical Students in Jakarta, Indonesia: A Cross-Sectional Study

BACKGROUND: Cervical cancer is the second-most common cancer in Indonesian women. While the cervical cancer screening has been integrated in Indonesian primary health-care facilities, the HPV vaccination has not yet become a national program. AIM: The objective of this research was to measure the knowledge, attitude, and behavior of medical students in Jakarta toward cervical cancer and its prevention. The result of this study could be implemented to develop a more comprehensive national educational program and public health policy. METHODS: We conducted a cross-sectional study on medical students at 10 different universities in Jakarta, Indonesia. Student’s knowledge, attitude, and behavior were collected through a self-administered online questionnaire consist of a total of 27 questions concerning cervical cancer epidemiology, pathogenesis, screening, diagnosis, and prevention. RESULTS: A total of 2159 medical students participated in this study. More than half (55%) of the students obtained satisfactory knowledge score. The students’ knowledge regarding HPV vaccination was low. However, 87.2% of them agreed to get the HPV vaccination. Only 7.0% had participated in cervical cancer screening program and only 16.8% had received HPV vaccination. Female gender, second or third year of study, and three universities had better odds to have good practice score. CONCLUSION: The knowledge and attitude score did not reflect on student’s practice on cervical cancer and its prevention. Effort to increase the awareness toward cervical cancer should be endorsed through university curriculum and public health policy.

Systematic Survey of the Regulatory Networks of the Long Noncoding RNA BANCR in Cervical Cancer Cells.

Long noncoding RNAs (lncRNAs) are increasingly recognized as functional regulators of human cancers. BRAF-activated noncoding RNA (BANCR), an oncogenic lncRNA, has a carcinogenic effect on many types of cancers. However, the clinical significance and molecular mechanisms of BANCR in cervical cancer are still unclear. Here, we generated BANCR knockout cell lines via CRISPR/Cas9 editing and revealed that BANCR plays roles in the apoptosis, proliferation, and migration of HeLa cells. A quantitative proteomics strategy was employed to globally identify BANCR-regulated proteins in HeLa cells. In total, we identified 569 differentially expressed proteins (DEPs) upon knockout of BANCR in HeLa cells. Bioinformatic analysis revealed that these DEPs were involved in diverse cellular pathways. Functional studies revealed that BANCR exerts its effects on the proliferation and apoptosis of HeLa cells through the regulation of cAMP-responsive element binding protein 1 (CREB1) expression. Mechanistically, BANCR could inhibit the expression of miR-582-5p, and CREB1 is a direct target of miR-582-5p; therefore, BANCR may exert its function by regulating CREB1 expression via targeting miR-582-5p in cervical cancer cells. Collectively, this study established a proteome-wide BANCR regulatory network, which provides novel insight into the molecular pathogenesis of cervical cancer and can serve as a basis for the development of targeted therapies.

Inhibition of LDHA suppresses cell proliferation and increases mitochondrial apoptosis via the JNK signaling pathway in cervical cancer cells.

The Warburg effect or aerobic glycolysis is a hallmark of cancer. Lactate dehydrogenase (LDH), which catalyzes conversion of pyruvate into lactate, serves a critical role during Warburg effect. LDH A chain (LDHA), a member of the LDH family, is upregulated in multiple types of cancer and serves a vital role in tumor growth and progression. However, its expression and function in cervical cancer has not been characterized. The present study evaluated LDHA expression in The Cancer Genome Atlas database and found that LDHA was upregulated in cervical cancer compared with normal tissue. To clarify the role of LDHA in cervical cancer HeLa and SiHa cells, lentiviral shRNA was used to stably knockdown LDHA and oxamate, a small-molecule inhibitor of LDHA, was used to inhibit the activity of LDHA. Glucose uptake assay, lactate production measurement and ATP detection assay demonstrated LDHA inhibition notably decreased glucose consumption, lactate production and ATP levels in both HeLa and SiHa cells. Furthermore, the effect of LDHA inhibition on cell proliferation, cell cycle and apoptosis was investigated by MTT, BrdU incorporation, colony formation assay, flow cytometry and western blotting; LDHA knockdown or oxamate treatment led to decreased cell proliferation and increased apoptosis. Inhibition of LDHA induced G2/M cell cycle arrest and activated the mitochondrial apoptosis pathway. Mechanistically, the JNK signaling pathway was key for LDHA inhibition-mediated cell cycle arrest and apoptosis. Collectively, these results indicated that LDHA was involved in cervical cancer pathogenesis and may be a promising therapeutic target for treatment.

The association of telomere maintenance and TERT expression with susceptibility to human papillomavirus infection in cervical epithelium.

The role of telomerase reverse transcriptase (TERT) induction and telomere maintenance in carcinogenesis including cervical cancer (CC) pathogenesis has been well established. However, it remains unclear whether they affect infection of high-risk human papillomavirus (hrHPV), an initiating event for CC development. Similarly, genetic variants at the TERT locus are shown to be associated with susceptibility to CC, but it is unclear whether these SNPs modify the risk for cervical HPV infection. Here we show that in CC-derived HeLa cells, TERT overexpression inhibits, while its depletion upregulates expression of Syndecan-1 (SDC-1), a key component for HPV entry receptors. The TCGA cohort of CC analyses reveals an inverse correlation between TERT and SDC-1 expression (R = -0.23, P = 0.001). We further recruited 1330 females (520 non-HPV and 810 hrHPV-infected) without CC or high-grade cervicalintraepithelial neoplasia to analyze telomeres in cervical epithelial cells and SNPs at rs2736098, rs2736100 and rs2736108, previously identified TERT SNPs for CC risk. Non-infected females exhibited age-related telomere shortening in cervical epithelial cells and their telomeres were significantly longer than those in hrHPV-infected group (1.31 ± 0.62 vs 1.19 ± 0.48, P < 0.001). There were no differences in rs2736098 and rs2736100 genotypes, but non-infected individuals had significantly a higher C-allele frequency (associated with higher TERT expression) while lower T-allele levels at rs2736108 compared with those in the hrHPV group (P = 0.020). Collectively, appropriate telomere maintenance and TERT expression in normal cervical cells may prevent CC by modulating hrHPV infection predisposition, although they are required for CC development and progression.

The Role of Chlamydia Trachomatis in the Pathogenesis of Cervical Cancer.

Chlamydia trachomatis (CT) is an obligate intracellular, Gram-negative bacterium that causes a variety of infections in both humans and animals. It is the causative agent of one of the most common sexually transmitted infections (STIs) with sequelae such as pelvic inflammatory disease, ectopic pregnancy, and infertility. Furthermore, Chlamydia infections have been epidemiologically linked to cervical cancer (CC) in patients with human papillomavirus (HPV) coinfection. However, a molecular mechanism linking Chlamydia to CC is yet to be established, and we still do not know if more aggressive diagnosis and treatment of Chlamydia could possibly lead to lower incidences of CC and associated mortality. Since CC is a leading cause of death among women worldwide, and HPV infection alone is insufficient to cause cancer, our goal was to determine the link between Chlamydia, HPV, and CC. This literature review aimed to understand the pathologic model of CC and how Chlamydia might induce or promote carcinogenesis alone or alongside HPV. In addition, we compared multiple studies attempting to associate Chlamydial infection with CC in different populations and aimed to determine whether there is an epidemiological correlation or not.

Correlation between vaginal microbiota and different progression stages of cervical cancer.

The process from high-risk human papillomavirus (HR-HPV) infection to cervical cancer is a continuous and long-term process, but the pathogenesis of the whole process is not completely clear. Here, 59 Chinese women were engaged in this study, and divided into five groups: normal healthy group, HR-HPV infections group, low-grade intraepithelial neoplasia (LSIL) group, high-SIL(HSIL) group, and cervical cancer group. With the occurrence of HR-HPV infection and the development of cervical lesions, the diversity of vaginal microbiota species was increased, and the relative abundance of Lactobacillus (L.), the dominant bacteria in maintaining vaginal microecological balance, was decreased gradually. In contrast, the abundance of Actinobacteria in the four disease groups was significantly higher than that in normal group. Furthermore L. iners may be related to the serious progression of cervical cancer. After analyzing the whole process, we found that Gardnerella(G.), Atopobium(A.) and Dialister(D.) have important effects on both persistent HR-HPV infection and the pathogenesis of cervical cancer. In addition, PICRUSt2 and KEGG results showed that the KEGG pathways enriched by the predicted genes of vaginal microbiota in cancer group included metabolic diseases, endocrine system and immune systems when compared with that in normal group. These findings may provide insights into the pathogenesis of cervical cancer, and help to improve the early detection and prevention of cervical precancerous lesions.

Analiza varijabilnosti L1 gena humanog papiloma virusa tipa 16 u našoj populaciji

Introduction: Human papilloma viruses (HPV) have been identified as a major etiological factor in the pathogenesis of cervical cancer. High-risk type HPV16 has the greatest medical significance. Based on differences in the nucleotide sequence of the type 16 genome, the existence of 16 variants of this type with different geographical distribution has been shown. Aim: Examination of the nucleotide sequence variability of the L1 gene presented in HPV16 variants in our territory. Material and methods: The paper includes 37 sequences of HPV16 L1 genes taken from the database of the Institute of Microbiology and Immunology of the Faculty of Medicine, University of Belgrade. The sequences were compared with the reference sequences of the HPV16 variants and the construction of the phylogenetic tree was done using the MEGA (Molecular Evolutionary Genetics Analysis, version X) software package. Results: Out of the 37 HPV16 L1 analyzed gene sequences, 23 were grouped with European variants. Other isolates were grouped with non-European HPV16 variants. The nucleotide distance was less than 1%, that is, at the level of subvariants. Conclusion: The results of this study indicate that the European variants of the HPV16 virus are the most common in our population, but they also indicate the presence of non-European variants. Further analysis is necessary in order to monitor the circulation of HPV16 variants in our population.

The Importance of Tumor Necrosis Factor-α-Induced Protein-8 Like-2 in the Pathogenesis of Cervical Cancer and Preeclampsia via Regulation of Cell Invasion.

Tumor necrosis factor-α-induced protein-8 like-2 (TIPE2) as a novel negative immune regulator plays an important role in several human diseases. However, its influences in cervical cancer and preeclampsia (PE) remain unclear. This study aims to explore the important role of TIPE2 in cervical cancer and PE via regulating cell invasion. TIPE2 expression in the cervical cancer tissues or the placenta of PE patients was detected. Human cervical cancer cell lines and trophoblasts were transfected with adenovirus expressing human TIPE2 and green fluorescent protein (GFP) (Ad-TIPE2), or the control adenovirus expressing GFP (Ad-GFP). Xenograft models were also constructed on nude mice, aiming to clarify how TIPE2 affects in vivo growth of cervical cancer cells. TIPE2 was down-regulated in the tumor tissues or placenta of patients with cervical cancer or PE. As a result, CaSKi and Hela cells in the Ad-TIPE2 group had decreased migration and invasion, with significant up-regulations of TIPE2 and E-cadherin, but down-regulations of β-catenin and N-cadherin. Ad-TIPE2 decreased the volume and weight of xenograft tumors in the nude mice, with the down-regulation of Ki67. The quantity of cells (HTR8/SVneo and JEG3 cells) transfected with Ad-TIPE2 had increased, with up-regulations of TIPE2, matrix metalloproteinase (MMP)-2 and MMP-9. TIPE2 overexpression could reduce the invasion and migration of cervical cancer cells via inhibiting the epithelial-mesenchymal transition (EMT) process, and promote trophocyte invasion via upregulating the expression of MMPs, and it may be used as a potential therapeutic target for cervical cancer and PE.

Role of lncRNA Alterations in Cervical Oncogenesis

Objectives: Human Papillomavirus (HPV) is the main contributor to the development of cervical cancer. This study aimed to investigate the biological significance of changes in the expression of lncRNAs induced by HPV oncoproteins in cervical oncogenesis mechanisms. Methods: We performed a review using online databases. The alterations were associated with some molecular and/or cellular characteristics that could be involved in the pathogenesis of cervical cancer. The molecular targets of the RNAs were identified using the Gene Expression Profiling Interactive Analysis (GEPIA) bioinformatics sites/tools, GeneCards®, OMIM, and Lnc2Cancer 3.0. Results: Sixty-one altered lncRNAs were identified. The alterations contribute to the higher staging of cervical cancer and a worse prognosis. These lncRNAs can act by competing for miRNAs for response elements, influencing the regulation of target genes and, ultimately, participating in the cancer regulation process and exhibit multiple biological functions, such as chromatin modification, transcription, translation, splicing, and epigenetic regulation. Conclusion: Changes in lncRNA expression have been associated with the onset, progression, and prognosis of cervical cancer. These changes can contribute to several features of cervical oncogenesis, and their identification has the potential to provide new biomarkers and therapeutic targets for the treatment of this cancer. Keywords: Cervical cancer, HPV Human Papillomavirus, Long Noncoding, Oncogenesis, RNA

Abstract PO-238: Implementing a culturally-appropriate biospecimen collection protocol during the COVID-19 pandemic to address cervical cancer disparities among Native American women

Abstract Background: Native American women experience twice the rate and mortality of cervical cancer compared to non-Hispanic white women. This cervical cancer disparity is primarily attributed to a lack of screening and unequal access to healthcare. While infection with high-risk HPV genotypes is a well-established risk factor for cervical cancer, there are likely other factors within the local microenvironment that contribute to cervical carcinogenesis. Therefore, the goal of the pilot project is to address the role of the vaginal microbiome (VMB) and inflammation in cervical cancer pathogenesis among Native American women. In 2019, we partnered with the Native Americans for Community Action (NACA) clinic to implement a culturally-appropriate biospecimen protocol. Unfortunately, the COVID-19 pandemic caused NACA and many clinics nation-wide to limit in-patient services or transition to 100% telehealth. As such, preventative care such as breast and cervical cancer screenings were not conducted during the annual well women's exam. Another hurdle in our pilot project included the resignation of the trained nurse in consenting, enrollment, collection and storage at NACA. Therefore, we needed to quickly adapt to accommodate the clinic's COVID-19 restrictions and train a new nurse on the biospecimen collection protocol. Methods: Adjustments to the protocol included vaginal self-collection rather than physician collection of samples. We also provided new clinic staff a “virtual in-service training” to review all required documents (recruitment, consenting, sample collection, gift cards, specimen storage, etc.). Recruitment was slow during the early stage of the COVID-19 vaccine roll out. Therefore, we developed culturally tailored recruitment flyers that were distributed over social media. In addition, we developed a culturally appropriate video on the significance of the well women's exam through collaboration with the NACA clinic and researchers at the partnership for Native American Cancer Prevention (NACP) that will be disseminated in the upcoming weeks. All amendments were approved by the clinic leadership and appropriate institutional review boards (IRBs). Results: As COVID-19 restrictions lifted, the NACA staff was prepared to immediately begin recruitment. Thus far, the NACA staff successfully enrolled (n=25) participants since March 2020 with survey data entered into REDCap. With continued recruitment efforts and launch of the video, we aim to have at least 50% of participants enrolled by Fall 2021. Survey data analyses are in-progress with expected completion by Spring 2022. Conclusion: In summary, the continued efforts by the NACA staff and research team resulted in successful recruitment for the pilot study during the COVID-19 pandemic. This study will set the foundation to evaluate the role of the VMB and HPV-mediated cancer in Native American women. Citation Format: Skyler Bordeaux, Elisa Martinez, Pawel Laniewski, Natalie Metz, Verity Quioz, Donna Peace, Gregory Caporaso, Melissa Herbst-Kralovetz, Naomi Lee. Implementing a culturally-appropriate biospecimen collection protocol during the COVID-19 pandemic to address cervical cancer disparities among Native American women [abstract]. In: Proceedings of the AACR Virtual Conference: 14th AACR Conference on the Science of Cancer Health Disparities in Racial/Ethnic Minorities and the Medically Underserved; 2021 Oct 6-8. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2022;31(1 Suppl):Abstract nr PO-238.

Взаимодействие вируса Эпштейна — Барр и вируса папилломы человека в канцерогенезе шейки матки. Возможности профилактики

Objective of the Review: To comprehensively analyse the potential role of Epstein-Barr virus (EBV) in development of cervical cancer. Key Points. Human papilloma virus (HPV) is a key causative factor of cervical cancer. However, there are a lot of data collected over the last two decades demonstrating that EBV has a role to play in this process; still, its contribution to development of cervical cancer has been studied poorly. This review describes the real-time published data on EBV and HPV co-infection in the genesis of cervical cancer, and the potential role of EBV in gynaecological cancer progression. Conclusion. EBV has an important role in the genesis and progression of some human malignancies including lymphoid tumours (both В- and Т-cell cancer) and carcinoma (nasopharyngeal and gastric cancer). The available data are indicative of potential cause-effect relations between EBV and cervical cancer pathogenesis. A frequent EBV and HPV co-infection in cervical cancer witnesses possible cancer-causing interaction between the two viruses. Thus, more in-depth studies are needed to find out the mechanisms underlying the EBV and HPV synergism and its clinical effects. Taking into account successful cervical cancer prevention with HPV vaccine and possible future EBV vaccination, the carcinogenesis mechanisms should be studied more thoroughly in order to improve the prevention of oncological diseases. Keywords: oncology, Epstein-Barr virus, human papilloma virus, co-infection, cervical cancer.

Quantitative proteomic analysis of cervical cancer based on TMT-labeled quantitative proteomics

Cervical cancer is the second most common gynecological malignancy, which immensely threatens the well-being of women. However, the pathogenesis of cervical cancer is still unclear. Using tandem mass tags-labeled quantitative proteomic technology and bioinformatics tools, we analyzed the exfoliated cervical cells from the normal and cervical cancer groups to establish a cancer-specific protein profile, thereby identifying key proteins related to cervical oncogenesis. When compared with the normal group, a total of 351 differentially expressed proteins were identified in the cervical cancer group, including 247 up-regulated and 104 down-regulated proteins. Gene ontology function annotation revealed that the differentially expressed proteins were mainly involved in the single-multicellular organism process, multicellular organismal process, and negative regulation of biological process. These proteins were discerned to play a role in the extracellular membrane-bounded organelle, exosome of cell components, protein binding, structural molecule activity, and enzyme binding of molecular functions. The results of Kyoto Encyclopedia of Genes and Genomes signaling pathway enrichment proved that these differentially expressed proteins were mainly involved in PI3K − Akt, ECM-receptor interaction, complement and coagulation cascades, and other signaling pathways. Particularly, peroxiredoxin-2 may be involved in cervical tumor oncogenesis through inhibition of apoptosis signaling. SignificanceIn this study, we determined that the proteins of the cervical cancer group exhibited qualitative and quantitative changes, and a total of 351 differentially expressed proteins were identified. The functions and signaling pathways of these differentially expressed proteins have laid a theoretical foundation for elucidating the molecular mechanism of cervical cancer.

Molecular characterization of high-risk humanpapillomavirus genotypes in women with or without cervical lesions at VIA/VILI in Kara, Togo

Persistent infection with high-risk (HR) papillomavirus (HPV) genotypes plays a central role in the pathogenesis of invasive cervical cancer. This study aimed to determine the prevalence and distribution of HR-HPV among women with or without cervical lesions at VIA/VILI in Togo. Cervical samples were collected from 238 women with or without cervical lesions at VIA / VILI and[c3] DNA [c4]was extracted and analyzed by real-time multiplex PCR. Logistic regression analysis was used to determined risk factors associated with HPV infection.inPietro Annigoni Biomolecular Research Center (CERBA / LABIOGENE) in Burkina Faso. The age of the women ranged from 17 to 61 years old, and most were married (73.5%). The prevalence of HRHPV was 35.71% and this was higher in the age range 35-39 years. The six most common genotypes were HPV 31 (18.7%), HPV 52 (13.82%), HPV 68 (13.01%), HPV 66 (9.76%), HPV 58 (8.13%) and HPV 56 (8.13%). Genotypes HPV 18 (4.07%) and HPV 16 (0.81%) were less frequent.[c5] Married or living with a partner was associated with HPV infection (OR=2,17, IC [1.20-3.91], p<0,009). This study allowed characterizing for the first time in Togo, HR-HPV genotypes. This will help mapping-HR-HPV genotypes circulating in West Africa.

Clinical and demographic characteristics of cervical cancer patients presenting at Parirenyatwa Hospital, Zimbabwe.

Cervical cancer is the leading cause of cancer deaths in women in Africa, predominately due to late diagnosis. This study aims to identify risk factors, potential prognostic indicators, and optimal treatment modalities for Zimbabwean cervical cancer patients. Medical records for 1063 cervical cancer patients were reviewed for sociodemographic, clinical, treatment, and response data. All data were analysed using SPSS version 25. More than half of the cohort was pre-menopausal (63%) with low (2%) history of cervical cancer screening. Schistosoma ova were observed in 2.4% of the tumour specimens. More than 50% were diagnosed at stage 3 and later, with a high frequency of comorbidities (~68%). This study highlights a need for improving screening education and uptake in Zimbabwe. Moreover, the current data provides a dataset for understanding cervical cancer pathogenesis and treatment responses in an African cohort.