Development Of Cervical Cancer Research Articles

Association of <i>VEGFA</i> gene rs2010963 polymorphism with cervical cancer and its progression

Background: Cervical cancer is the most common type of female genital malignancies. In Russia, its incidence is 17 to 19 cases per 100,000 of female population. Cervical cancer is characterized by high activity, rapid development of radio/chemoresistance and unfavorable prognosis. To assess the risk of recurrence, metastasis and choice of the optimal treatment strategy, factors related to the disease progression are under study. Vascular endothelial growth factor (VEGF) overexpression is related to tumor angiogenesis and poor outcome in various cancer types, including cervical cancer.
 Aim: To study an association between the rs2010963 polymorphism of the VEGFA gene and risk of development and progression of cervical cancer.
 Materials and methods: This case-control study included 120 women (aged 49 [42; 65] years) with cervical cancer stage I-II and 112 women without cervical or other types of cancer. Based on the results of histological examination, two subgroups were formed: the one with tumor emboli (TE+) in the tumor vasculature and surrounding tissues (n = 41, 34.17%) and the other without tumor emboli (TE-) (n = 79, 65.83%). The polymorphic DNA loci of the rs2010963 VEGFA gene were analyzed by real time polymerase chain reaction.
 Results: In the patients, cervical cancer has associated with the VEGFA gene allelic polymorphism rs2010963 (χ2 = 5.47; p = 0.021). The minor C allele increased risk of cervical cancer by 1.6-fold (odds ratio (ОR) 1.58, 95% confidence interval (CI) 1.08-2.31), and the ancestral G allele reduced the cervical cancer probability (ОR 0.63, 95% CI 0.43-0.93). The genotypes distribution in the dominant model (GG and GC + CC) confirmed the association of the rs2010963 VEGFA gene polymorphism with cervical cancer (χ2 = 4.73; p = 0.031), specifically, if there was a minor C allele in the genotype (GC + CC). We found that the association of the rs2010963 VEGFA gene polymorphism with TE in the tumor vessels and surrounding tissues was a predictor of unfavorable progression and metastasis of cervical cancer (χ2 = 3.94; р = 0.049). The minor C allele increased the risk of TE by 1.7-fold (ОR 1.72, 95% CI 1.004-2.98), whereas the ancestral G allele reduced this chance (ОR 0.58, 95% CI 0.34-0.996).
 Conclusion: The C allele of the rs2010963 polymorphism of the VEGFA gene is a risk factor for cervical cancer, as well as a risk factor for the development of tumor emboli.

Immediate histologic correlation in patients with different HPV genotypes and ages: a single center analysis in China

BackgroundHuman papillomavirus (HPV) has been confirmed as a major causative factor for malignant transformation of cervical epithelial cells and for the development of cervical intraepithelial neoplasia (CIN) and invasive cervical cancer. We carried out this study to investigate the association of different HPV genotypes and ages with immediate histological cervical lesions in opportunistic screening patients in a single center.MethodsA total of 1,661 samples with biopsy-confirmed histologic findings were collected from the gynecological clinic of our hospital between October 2017 and May 2020 for analysis. The distribution of single-type HPV genotypes in CIN of different severities and the age-dependent prevalence for single-type HPV infection were analyzed.ResultsIn both CIN2 and CIN3 group, HPV16, 58, 52, 33 and 31/18 were detected as top 5 high-risk human papillomavirus (hrHPV) types, which accounts for 89.25% and 88.54% of single HPV infection incidence respectively. Besides, not a single case of HPV45 was found in CIN2 and CIN3. HPV16 was the dominant genotype in both CIN2 and CIN3, accounted for 46.24% and 55.21%, respectively. The prevalence of HPV16 was the most frequent in all the age groups, except ≥ 65 years group in CIN3, and almost one in three HPV16-positive patients were diagnosed with high grade CIN. The peak of the incidence of CIN3 was observed at 25 ~ 34 years (33.68%), followed by 35 ~ 44 years (31.58%).ConclusionHigh grade CIN peak at 25 ~ 44 years, women of this age are recommended for normative screening if conditions permit. HPV16-positive patients should be given high priority in opportunistic screening, while the single-center data suggesting a low risk of CIN2/3 in HPV45-positive patients. For women ≥ 65 years old, patients infected with other HPV types should be also taken seriously. In general, HPV16, 58, 52, 33, 31 and 18 were the most common genotypes in CIN2/3, and a vaccine including these predominant genotypes might be of great significance for cervical cancer prevention in China.

In vitro activity of various Kenyan tea extracts against HeLa human cervical cancer cell line and molecular docking of tea catechins on high-risk HPV16E6 protein

Tea (Camellia sinensis) has been revealed to possess potential anticancer properties attributed to its catechin content. This study aimed to investigate the growth-inhibitory effects of various tea extracts on the HeLa cell line and molecular docking analysis of catechins on Human papillomavirus16 oncoprotein 6 (HPV16E6). Different catechins content in black, green, and purple tea were determined by using High-performance liquid chromatography (HPLC); molecular docking of four main catechins on HPV16E6 and in vitro antiproliferative activity and cell apoptosis assay were carried out. Molecular docking results suggested that the tea catechins have the potential to bind to the HPV16 E6 oncoprotein involved in cervical cancer development. The antiproliferative assay results indicated that purple tea had the highest inhibitory activity at both 24 h and 48 h, with IC50 values of 121.1 ± 3.25 μg/mL and 100.1 ± 3.76 μg/mL respectively, followed by green tea with 168.9 ± 12.59 μg/mL and 124.7 ± 3.53 μg/mL IC50 while black tea showed the least effectiveness with IC50 of 221 ± 19.35 μg/mL and 159.6 ± 2.33 μg/mL. DNA fragmentation, a characteristic of apoptosis, was observed in cells treated with the tea extracts. All three tea extracts demonstrated potential anti-cervical cancer activity bIy inhibiting cell proliferation and inducing apoptosis. The tea catechins showed promising interactions with the HPV16 E6 oncoprotein.

Progress in the Study of Significant Mutated Genes and Molecular Biological Factors in Cervical Tumors

Cervical cancer is the most prevalent gynecologic malignancy in developing countries, with incidence and mortality rates continuing to rise. Despite widespread research on cervical cancer, the specific mechanisms and synergistic factors underlying its occurrence remain unclear. In recent years, there has been a growing interest in the relationship between gene mutations and cervical cancer. Numerous studies have demonstrated that alterations in oncogenes, tumor suppressor genes, and related regulatory genes are closely associated with the development and progression of cervical cancer. The application of genome sequencing technology in malignant tumors has allowed for the identification of additional gene mutations in cervical cancer. By identifying significantly mutated genes, we can further target malignancy driver genes, which may be the key to uncovering the intrinsic mechanisms of sexual tumors. Therefore, a review of the current status of research on mutated genes in cervical cancer and factors associated with recurrence after treatment of early-stage cervical cancer can provide new insights for mechanistic studies, diagnosis, and targeted therapy of cervical cancer.

Selective applications of excisional surgical treatments of cervical precancers

Cervical precancers encompass high-grade squamous intraepithelial lesion and adenocarcinoma in situ. Treatment of precancerous lesions can reduce cervical cancer mortality and prevent the development of invasive cervical cancer. The choice of treatment regimen needs to follow the principle of individualization and should be based on a combination of factors, including the patient's age, fertility requirements, pregnancy status, pathological type, type of colposcopic transformation zone, patient's follow-up conditions, and the experience of the treating provider. This article presents an opinion regarding the appropriate indications for excisional surgery and total hysterectomy in the management of precancerous lesions of the cervix, with the aim of establishing standardized therapeutic approaches for the treatment of precancerous lesions of the cervix.

Erastin induces ferroptosis in cervical cancer cells via Nrf2/HO-1 signaling pathway.

Our research aims to assess the influence of erastin, a ferroptosis-inducing agent, on cervical cancer cells. Cervical cancer is a prevalent malignancy in females. Dysregulation of ferroptosis, a form of cell demise reliant on iron, is implicated in several cancers. The effect of erastin on HeLa and SiHa was detected by transwell assay, scratch test, and colony formation assay, while cell apoptosis was detected using flow cytometry. Cellular reactive oxygen species (ROS) generation was detected using the dichloro-dihydro-fluorescein diacetate assay. Sequencing analysis identified differentially expressed genes (DEGs), and Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) Enrichment analyses were employed to identify the target gene. Subsequently, the utilization of small interfering RNA (siRNA) was employed to suppress the targeted gene expression in HeLa cells, thereby effectively mitigating the impact of erastin on various cellular processes including invasion, colony formation, migration, and ROS generation. The findings indicate that erastin attenuates the viability of both HeLa cells (IC50 = 30.88µM) and SiHa cells (IC50 = 29.40µM). Treatment with erastin at 10µM inhibits the invasion, colony formation, and migration of both HeLa and SiHa cells within 24h. Ferrostatin-1 (1µM) notably alleviates the inhibitory effects of erastin of HeLa and SiHa cells. Upregulation of nuclear factor erythroid 2-related factor 2 (Nrf2) and its downstream target, heme oxygenase-1 (HO-1), was found in erastin-treated cells compared to the control group. When knocked down HO-1 in HeLa cells, effectively counteracting the effects of erastin on the invasion, colony formation, migration, and ROS production in HeLa cells. Our research demonstrates that erastin induces ferroptosis and the accumulation of ROS in cervical cancer cells by activating the Nrf2/HO-1 pathway, significantly reducing cell proliferation and motility. These findings propose a potential molecular mechanism of erastin-mediated cervical cancer development.

Cervical Cancer Stages, Human Papillomavirus Integration, and Malignant Genetic Mutations: Integrative Analysis of Datasets from Four Different Cohorts

Cervical cancer represents a significant global health concern, stemming from persistent infections with high-risk types of human papillomavirus (HPV). The understanding of cervical cancer’s clinical correlates, risk factors, molecular mechanisms, stages, and associated genetic mutations is important for early detection and improved treatment strategies. Through integrated analysis of clinical and molecular datasets, this study aims to identify key factors that are overlapping and distinct across four cohorts of different races and regions. Here, datasets from four distinct cohorts of patients from Uganda (N = 212), the United States of America (USA) (N = 228), China (N = 106), and Venezuela (N = 858) were examined to comprehensively explore the relationships between cervical cancer stages, HPV types (clades), productive HPV integration, and malignant genetic mutations. Cohort-specific findings included the occurrence frequencies of cervical cancer stages and grades. The majority of patients from the USA and China were diagnosed with stages I and II, while those from Uganda were diagnosed with stages II and III, reflecting levels of awareness and the availability of HPV vaccines and screening services. Conversely, cervical cancer and its stages were positively correlated with HPV types (clades), HPV integration, and risk-factor habits across the cohorts. Our findings indicate that the more common squamous cervical cancer can be potentially due to productive HPV16 (clade 9) integration. At the molecular level, pathways related to HPV infection, cancer-related conditions, and viral carcinogenesis were among the most significant pathways associated with mutated genes in cervical cancer (across cohorts). These findings collectively corroborate the prominent role of HPV infection and integration leading to genetic mutation and hence to the development of cervical cancer and its stages across patients of distinct races and regions.

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

BackgroundPrecancerous 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.MethodsUtilizing 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).ResultsAs 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.ConclusionPatients 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).

Correlation between the expression of p16/INK4a and Ki-67 proteins and the histopathological diagnostic in women infected by Human papillomavirus in the Agreste region of Pernambuco State, Brazil

Epidemiological studies have stated that cervical infection with high-risk human papillomavirus (HR-HPV) is a necessary but not sufficient cause in the development of cervical cancer. Cervical cancer is preceded by precursor lesions called cervical intraepithelial neoplasia (CIN), which are classified as CIN 1 (cervical intraepithelial neoplasia grade 1), CIN 2 (cervical intraepithelial neoplasia grade 2) and CIN 3 (cervical intraepithelial neoplasia grade 3). Markers such as p16/INK4a and Ki-67 have been studied with the aim of identifying lesions with a high risk of evolution. The objective of this study was to correlate the expression of the biomarkers p16INK4A and Ki-67 with histological diagnosis CIN 1, CIN 2, CIN 3 and cancer in HPV-infected cervical samples.The study involved conducting an analysis of 211 cases of women with histological confirmation to CIN 1, CIN 2, CIN 3 and cervical cancer. The immunohistochemical staining for the p16/INK4a and Ki-67 proteins was carried out through samples taken from the biopsies and waterproof containers that had representative tissues of the tumor. The expression of p16/INK4A was observed in 100% of the cases of cancer, 97.6% of the cases of NIC 3, 83.3% of the cases of NIC 2, as well as in 55.4% of the cases of NIC 1. In addition, the expression of Ki-67 was observed in 100% of the cases of cancer, 98.8% of the cases of NIC 3, 83.3% of the cases of NIC 2, as well as in 69.6% of the cases of NIC 1. The results obtained in this study make it possible to relate the expression of p16/INK4A and Ki-67 to the atypical histological findings found in the samples of patients infected with HPV.

The prevalence of HPV among 164,137 women in China exhibited some unique epidemiological characteristics

ObjectiveThe persistence of HPV infection is a significant etiological factor in the development of cervical cancer. The present study investigated the prevalence and genotype distribution of human papillomavirus (HPV) in a cohort of 164,137 unvaccinated women from Wenzhou, aiming to provide guidance for clinics in the cervical cancer screening and HPV vaccination strategies.MethodsThe present retrospective study included a total of 164,137 women, comprising 118,484 outpatients and 45,653 healthy female subjects recruited from 2015 to 2020. Cervical exfoliated cells were collected from these participants for subsequent DNA extraction. The extracted DNA samples were underwent analysis using a fluorescence in situ hybridization method, encompassing the detection of 27 HPV genotypes.ResultsThe overall prevalence of HPV was 17.35%; this corresponded to a prevalence of 19.10% in the outpatient group and 12.82% in the healthy female group. Among the outpatient group, the five most prevalent HPV genotypes were identified as HPV 52, 58, 16, 53, and 61. In the healthy female group, the five most common HPV genotypes were found to be HPV 52, 53, 58, 61, and 81. Additionally, it was estimated that the highest rate of HPV infection occurred among individuals aged between 10 and 19 years old (44.65%) and those aged between 60 and 69 years old (27.35%).ConclusionsThe prevalence of HPV in this region is substantial; therefore, it is imperative to implement scientifically sound and rational clinical interventions such as vaccination. Routine cervical screening should be performed to prevent the development of cervical intraepithelial neoplasia resulting from persistent infection with high-risk HPV, particularly in women with gynecological diseases and those over 60 years old.

Whole genome sequencing in high-grade cervical intraepithelial neoplasia patients from different ethnic groups in China.

Cervical cancer (CC) is the fourth most common cancer in women worldwide. It develops through precancerous lesions (cervical intraepithelial neoplasia (CIN), graded from low-grade (CIN1) to high-grade (CIN2-3)). It is well established that precancerous and cancerous cervical lesions are caused by a persistent infection with high-risk types of the human papilloma virus (hrHPV). To have a deeper understanding of the pathogenesis of CIN and CC, we systematically analyzed the landscape of genomic alterations and HPV integration profiles in high-grade CIN2/3. We performed deep whole genome sequencing on exfoliated cervical cells and matched peripheral blood samples from a cohort of 51 Chinese patients (of whom 35 were HPV+) with high-grade CIN from 3 ethnic groups and constructed strict integrated workflow of genomic analysis. In addition, the HPV types and integration breakpoints in the exfoliated cervical cells from these patients were examined. Genomic analysis identified 6 significantly mutated genes (SMGs), including CDKN2A, PIK3CB, FAM20A, RABEP1, TMPRSS2 and SS18L1, in 51 CIN2/3 samples. As none of them had previously been identified as SMGs in the Cancer Genome Atlas cervical squamous cell carcinoma and endocervical adenocarcinoma (TCGA-CESC) cohort, future studies with larger sample size of CINs may be needed to validate our findings. Mutational signature analysis showed that mutational signatures of CINs were dramatically different from CCs, highlighting their different mutational processes and etiologies. Moreover, non-silent somatic mutations were detected in all of the CIN2/3 samples, and 88% of these mutations occurred in genes that also mutated in CCs of TCGA cohort. CIN2 samples had significantly less non-silent mutations than CIN3 samples (P = .0006). Gene ontology and pathway level analysis revealed that functions of mutated genes were significantly associated with tumorigenesis, thus these genes may be involved in the development and progression of CC. HPV integration breakpoints occurred in 28.6% of the CIN2/3 samples with HPV infection. Integrations of common high risk HPV types in CCs, including HPV16, 52, 58 and 68, also occurred in the CIN samples. Our results lay the groundwork for a deeper understanding of the molecular mechanisms underlying the pathogenesis of CC and pave the way for new tools for screening, diagnosis and treatment of cervical precancerous and cancerous lesions.

Association between testosterone and cancers risk in women: a two-sample Mendelian randomization study

ObjectivePrevious observational studies have explored the correlation between testosterone and cancer risk. However, the causal association between testosterone and various cancer types in women remains inconclusive. The objective of this Mendelian randomization study is to evaluate the causal links between total testosterone (TT) and bioavailable testosterone (BT) with cancer risk in females.MethodsInitially, a rigorous quality control process was employed to identify suitable instrumental single nucleotide polymorphisms (SNPs) associated with the exposure under investigation that exhibited a significant association. The genetic causal relationship between female testosterone levels and the risk of developing cancers was examined through a two-sample Mendelian randomization. Various analytical methods, including inverse-variance weighted (IVW), MR-Egger, weighted median, simple mode, and weighted mode, were applied in the investigation. Key findings were primarily based on the results obtained via IVW (random effects), and sensitivity analyses were conducted to assess the reliability of the obtained results. Furthermore, maximum likelihood, penalized weighted median, and IVW (fixed effects) methods were utilized to further validate the robustness of the results.ResultsBased on the results of IVW analysis, our study indicated a positive causal relationship between BT and breast cancer (OR = 1.1407, 95%CI: 1.0627–1.2244, P = 0.0015) and endometrial cancer (OR = 1.4610, 95%CI: 1.2695–1.6813, P = 1.22E-06). Moreover, our findings also showed a positive causal association between TT and breast cancer (OR = 1.1764, 95%CI: 1.0846–1.2761, P = 0.0005), cervical cancer(OR = 1.0020, 95%CI: 1.0007–1.0032, P = 0.0077), and endometrial cancer(OR = 1.4124, 95%CI: 1.2083–1.6511, P = 0.0001). Additionally, our results demonstrated a negative causal relationship between BT and ovarian cancer (OR = 0.8649, 95%CI: 0.7750–0.9653, P = 0.0320). However, no causal relationship was found between BT, TT and other types of cancer (corrected P > 0.05).ConclusionsThis study elucidates the role of testosterone on the development of breast cancer, endometrial cancer, ovarian cancer, and cervical cancer. It also hints at a potential but fragile link between testosterone and bladder cancer, as well as thyroid cancer. Nonetheless, it's worth noting that no statistically significant relationship between testosterone and various other types of cancer in females was identified.

Efficacy and safety of Simiao decoction in the treatment of cervical HPV infection: A systematic review and meta-analysis of randomized clinical trials

BackgroundPersistent HPV infection can easily lead to the occurrence and development of cervical cancer and its precancerous lesions. Many studies have shown that Simiao Decoction may be effective in treating HPV infection, but the efficacy and safety of Simiao Decoction for HPV infection have never been systematically evaluated. PurposeTo evaluate the efficacy and safety of Simiao Decoction in the treatment of cervical HPV infection. Study designA systematic review and meta-analysis of all randomized clinical trials (RCTs) comparing Simiao Decoction versus conventional treatment. Materials and methodsSeven databases were searched from their inception until May 14, 2023. All the RCTs comparing the efficacy and safety of Simiao Decoction versus conventional treatment were selected. Analyses were performed using Review Manager 5.3. HPV negative conversion rate (NCR) was defined as the primary endpoint, and treatment response rate (TRR), and adverse reaction (AR) were defined as the secondary endpoints. The quality of each endpoint was assessed by The Grading of Recommendations, Assessment, Development and Evaluations (GRADE) system. ResultsTen RCTs recruiting 799 patients with HPV infection were included. The results showed that compared with conventional treatment, Simiao Decoction improved NCR (RR = 1.45, 95 % CI 1.31, 1.61, P < 0.00001), TRR (RR = 1.24, 95%CI 1.15, 1.33, P < 0.000 01), while it did not increase AR (RR = 0.79, 95%CI 0.46, 1.33, P = 0.37). Most results were robust and the quality of evidence was moderate. ConclusionSimiao Decoction is safer and more effective than conventional treatment for HPV infection. However, the efficacy and safety of Simiao Decoction should be further assessed by more high-quality RCTs with the outcome of HPV viral load and long-term follow-ups.

The Regulatory Role of Circular RNAs as miRNA Sponges in Cervical Cancer

Abstract: Cervical cancer is ranked as the fourth most frequently diagnosed cancer and the fourth leading cause of cancer-related deaths among females. Cervical cancer is a complex disease influenced by various genetic, epigenetic, and environmental factors. While treatment options such as radiotherapy, chemotherapy, and hormonal therapy exist, the prognosis remains poor due to high rates of distant and lymphatic metastasis. Recent research has shed light on the role of non-coding RNAs (ncRNAs) in cervical cancer development, with circular RNAs (circRNAs) emerging as a potentially significant regulator of cellular processes. Through targeting miRNAs/mRNAs, circRNAs can impact cell growth and invasion in cervical cancer cells, making them a promising biomarker for diagnosis and treatment. This review provides an overview of the functional roles of circRNAs in the context of cervical cancer.

The detection of high risk HPV genotypes by the PR-PCR method in the Republic of Serbia

Abstract Introduction The association between Human Papiloma Virus (HPV) positive cervical swabs and the development of cervical cancer has lead to extensive research. Studies employing the RT-PCR method for typization in the young women demographic worldwide. Based on their proven oncogenic potential 14 HPV types have been classified as carcinogenic (HPV16,18,31,33,35,39,45,51,52,56, 58,59,66,68). The imporatnce of HPV diagnostics is a result of the existing link between viral infection and relative risk of cervical cancer, while the detection complexity reflects the large variety of HPV genotypes. Methods The samples analyzed in our study were obtained from cervical swabs of women aged 19 to 25 years between the months of October and December 2022. All collected samples were routinely screened for high risk genotype positivity (HPV16 and 18). There were no other inclusion criteria, the samples used in the study were selected at random. After DNA isolation, genotype identification was done by L2 amplification for HPV 16, the L1 for HPV 18, E6 for HPV 35, 56 and 58, and E7 for HPV 31,33,39,45,51,52,59,66 and 68 genotypes, with specific primers and flourescently labelled probes. Results The results demonstrated that among the DNA positive individuals HPV genotype distribution was as follows: 50% (31,39,56); 40,90% HPV(52,59,68); 34,10% HPV16; 22,70% HPV(35, 58, 66); 15,90% HPV 18. Individually, by type, the highest prevalence was noted for the high risk genotype HPV 16 (34,1%), followed by HPV18 (15,90%). As for group clusters, HPV(31,39,56) were most frequent, followed by HPV(52,59,68). Conclusions Given the forementioned results of our study, the most prevalent HPV genotype in the Republic of Serbia among the women of pre-set demographic is HPV 16, which is in conconcurrence with epidemiological results for Eastern Europe. By comparative analysis of the HPV16 and 31 distribution, the results imply a similarity in sensitivity to infection. Key messages • The susceptibility of young adults to HPV infection entails a well-developed preventive medicine program is paramount, and not limited to this demographic. • RT-PCR offers in-depth insight into the distribution of risk of cancer to the screening team.

Reactive oxygen species within the vaginal space: An additional promoter of cervical intraepithelial neoplasia and uterine cervical cancer development?

Uterine cervical intraepithelial abnormalities and cancer development may also depend upon biological problems that arise as a result of complex molecular disturbances within the vaginal space, in addition to the widely known causative effect of human papillomavirus (HPV) infection. Chronic oxidative stress is a consequence of oxygen reduction in the vaginal space. Reactive oxygen species (ROS) and free radicals are yet unrecognizable causative agents and are probably very important factors for cervical intraepithelial neoplasia (CIN) and cancer development. The intermediate compounds of oxygen reduction on these metabolic pathways are superoxide anion (), hydrogen peroxide (H2O2), hydroxide ions (OH-), and hydroxyl radical (HO˙). Considering these points, the aim of this work was to summarize how these compounds can damage all molecules, including DNA, of vulnerable metaplastic cervical epithelium. Finally, in some women with a poor immune defense system, ROS alone or accompanied by a high-risk HPV type may promote all levels of CIN and cancer development.

Contributions of viral oncogenes of HPV-18 and hypoxia to oxidative stress and genetic damage in human keratinocytes

Infection with high-risk human papillomaviruses like HPV-16 and HPV-18 is highly associated with the development of cervical and other cancers. Malignant transformation requires viral oncoproteins E5, E6 and E7, which promote cell proliferation and increase DNA damage. Oxidative stress and hypoxia are also key factors in cervical malignant transformation. Increased levels of reactive species of oxygen (ROS) and nitrogen (RNS) are found in the hypoxic tumor microenvironment, promoting genetic instability and invasiveness. In this work, we studied the combined effect of E5, E6 and E7 and hypoxia in increasing oxidative stress and promoting DNA damage and nuclear architecture alterations. HaCaT cells containing HPV-18 viral oncogenes (HaCaT E5/E6/E7-18) showed higher ROS levels in normoxia and higher levels of RNS in hypoxia compared to HaCaT parental cells, as well as higher genetic damage in hypoxia as measured by γH2AX and comet assays. In hypoxia, HaCaT E5/E6/E7-18 increased its nuclear dry mass and both cell types displayed marked heterogeneity in nuclear dry mass distribution and increased nuclear foci. Our results show contributions of both viral oncogenes and hypoxia to oxidative stress, DNA damage and altered nuclear architecture, exemplifying how an altered microenvironment combines with oncogenic transformation to promote tumor progression.

Prevalence of Candida albicans in High-Risk Human Papillomavirus-Positive Women: A Study in Diyarbakır Province, Turkey.

The human papillomavirus (HPV) is a significant public health concern due to its association with the development of cervical cancer. Although inflammation caused by Candida spp. has been shown to facilitate oncogenesis, the interactions between HPV and Candida spp. remain unclear. This study aimed to determine the prevalence and genotype distribution of HR-HPV infection HR-HPV-positiveCandida albicans in HR-HPV-positive individuals in Diyarbakır province in Turkey. Cervical samples were taken from 350 participants aged 20-69 years who applied to Diyarbakır Gazi Yaşargil Training and Research Hospital, Gynecology and Obstetrics Clinic. For detection of HPV presence and HR-HPV genotyping, PCR/direct cycle sequencing was used. E6/E7 mRNA expression of HPV-16, -18, -31, -33, and -45 was determined by type-specific real-time NASBA assay (NucliSENS EasyQ(®)HPV v1.1). The presence of Candida albicans in cervical specimens of HR-HPV-positive women was investigated by RAPD-PCR and culture methods. Results. Of the 350 women who participated in the study, 24% were HPV positive and 10.5% were found to be HR-HPV positive. HR-HPV positivity was most frequently detected in the age range of 40-49 years. Among HR-HPV-positive women, C. albicans was found in 59.4%. Conclusion. The most frequent HR-HPV genotype was HPV16, followed by HPV31. Of women who tested positive for HR-HPV, C. albicans was discovered in 59.4%. C. albicans infection may occur when the immune system is weakened or the balance of the vaginal flora is disturbed, increasing tissue damage in the vaginal area and the risk of carcinogenesis of HR-HPV. Therefore, knowing the presence of Candida infection in HR-HPV-positive women is essential to plan the treatment and prevent the risk of secondary disease.

Evaluation of Long Non-coding RNA (LncRNA) in the Pathogenesis of Chemotherapy Resistance in Cervical Cancer: Diagnostic and Prognostic Approach.

Cervical cancer (CC), caused by human papillomavirus (HPV), is a leading cause of female malignancies worldwide. Therefore, understanding the underlying mechanisms of CC development and identifying novel therapeutic targets are significantly important. Cisplatin resistance is a significant challenge in the management of CC. Recent studies highlighted the critical role of long non-coding RNAs (lncRNAs) in modulation of cisplatin resistance. This comprehensive review aims to collect the current understanding roles of lncRNAs and their involvement in cisplatin resistance in CC by highlighting key processes of cancer progression, including apoptosis, proliferation, angiogenesis and epithelial-to-mesenchymal transition (EMT). We discussed the role of lncRNA in CC resistance to cisplatin through molecular pathways and examined gene expression changes. We also discussed treatment strategies and factors that reduce CC resistance to cisplatin by targeting them.

A study on the correlation between the prognosis of HPV infection and lesion recurrence after cervical conization.

Persistent human papillomavirus infection is an important factor in the development of cervical cancer, which is usually a long process evolving from the development of squamous intraepithelial lesions (SIL), also referred to as cervical intraepithelial neoplasia (CIN). Local treatment of advanced squamous intraepithelial lesions, also regarded as High-Grade Squamous Intraepithelial Lesion, may be effective in preventing cancer. To promptly identify high-risk patients with a tendency to recurrence. We retrospectively analyzed the clinical data of 300 patients with high-grade squamous intraepithelial lesions of the cervix admitted to the Second Affiliated Hospital of Dalian Medical University from 2019 to 2020 to investigate the relationship between recurrence of cervical lesions and postoperative regression of HPV infection, as well as other related risk factors. We found that the HPV-negative rates were 81.81, 85.71, and 90.91% at 6, 12, and 24 months, respectively, and the average lesion recurrence rate was 8.16%, with a median time to recurrence of 14 months in patients undergoing CKC for HSIL. The risk of cervical squamous intraepithelial lesions was highest in patients with HPV16. Patients over 61 years of age had the lowest postoperative HPV-negative rate. The conversion rate was significantly lower in patients with multiple HPV genotypes than in those with single HPV infection (p < 0.05). The probability of recurrence was higher in patients with the same HPV infection genotype before and after surgery than in patients with different infection genotypes before and after surgery (p < 0.05). Combined with the literature review, we believe that patients aged ≥50 years, with ≥3 pregnancies and births, a history of smoking, and consistent genotypes of preoperative and postoperative HPV infection in cervical conization have more HPV re-infection or persistent infection, and that these factors may be high-risk factors for lesion recurrence. For patients with possible potential high-risk factors, we need to carry out individualized follow-up and focused management, take timely and effective management measures, optimize the treatment plan, reduce the recurrence rate, prevent HSIL and cervical cancer, improve the quality of patient's survival, and improve the prognosis.