Development Of Cervical Lesions Research Articles

Vaginal micro-environment disorder promotes malignant prognosis of low-grade cervical intraepithelial neoplasia: a prospective community cohort study in Shanxi Province, China.

Emerging evidence suggests that vaginal micro-environment disorder is closely related to the development of cervical lesions. Low-grade cervical intraepithelial neoplasia (CIN1), as an early stage of cervical lesions, exhibits a high risk of progressing to high-grade lesions or even cervical cancer. However, the effect of vaginal micro-environment on the malignant prognosis of CIN1 remains uncertain. A total of 504 patients diagnosed with CIN1 by pathology, who were from the population-based cohorts established in Shanxi Province, China, were enrolled and followed up for 2years. Micro-environmental factors such as vaginal pH, cleanliness, hydrogen peroxide (H2O2), β-glucuronidase (GUSB), leucocyte esterase (LE), and sialidase (SNA) were detected to evaluate their effect on the malignant prognosis of CIN1. Abnormal vaginal pH (HR = 1.472, 95%CI 1.071-2.022), cleanliness (HR = 1.446, 95%CI 1.067-1.960), H2O2 (HR = 1.525, 95%CI 1.155-2.013), GUSB (HR = 1.739, 95%CI 1.235-2.448), LE (HR = 1.434, 95%CI 1.038-1.981), and SNA (HR = 1.411, 95%CI 1.065-1.870) could promote a higher incidence of CIN1 malignant prognosis, and the combined effects of these micro-environmental factors resulted in a nearly twofold increased risk (HR = 2.492, 95%CI 1.773-3.504) compared to any single factor alone, especially under the high-risk human papillomavirus (HR-HPV) infection. Notably, the cumulative incidence of malignant prognosis for CIN1 gradually increased during the early follow-up period, reaching its peak at approximately 8months, and then stabilizing. Vaginal micro-environment disorder could promote CIN1 malignant prognosis, particularly in HR-HPV-infected women. Taking micro-environmental factors as the breakthrough, our study provides a feasible vision for preventing early stage cervical lesions.

High-Risk HPV Cervical Lesion Potential Correlations Mining over Large-Scale Knowledge Graphs

Lesion prediction, a very important aspect of cancer disease prediction, is an important marker for patients before they become cancerous. Currently, traditional machine learning methods are gradually applied in disease prediction based on patient vital signs data. Accurate prediction requires a large amount and high quality of data, however, the difficulty in obtaining and incompleteness of electronic medical record (EMR) data leads to certain difficulties in disease prediction by traditional machine learning methods. Secondly, there are many factors that contribute to the development of cervical lesions, some risk factors are directly related to it while others are indirectly related to them. In addition, risk factors have an interactive effect on the development of cervical lesions; it does not occur in isolation, a large-scale knowledge graph is constructed base on the close relationships among risk factors in the literature, and new potential key risk factors are mined based on common risk factors through a subgraph mining method. Then lesion prediction algorithm is proposed to predict the likelihood of lesions in patients base on the set of key risk factors. Experimental results show that the circumvents the problems of large number of missing values in EMR data and discovered key risk factors that are easily ignored but have better prediction effect. Therefore, The method had better accuracy in predicting cervical lesions.

Prevalence of high-risk human papillomavirus infection and genotype distribution among Kazakhstani women with abnormal cervical cytology

Aim This study aimed to identify the prevalence and distribution of high-risk human papillomavirus (HR-HPV) types among Kazakhstani women with abnormal cervical cytology. Methods A cross-sectional study was performed from May 2019 to June 2020. Cervical samples were collected from women in the different regions of Kazakhstan. Results A total of 316 patients’ samples were analysed for HR-HPV using real-time multiplex PCR. Cervical cytology abnormalities were reported according to the Bethesda classification. HPV detection by cytology showed a statistically significant association with HPV status and the number of HPV infection types (p < .05). Among women with abnormal cervical cytology, 62.4% were positive for HPV infection of those 79.4% had low-grade squamous intraepithelial lesions (LSIL), and 20.6% had high-grade squamous intraepithelial lesions (HSIL). Among patients with LSIL, 77.4% had HPV16 and 58.8% were infected with HPV18. Among patients with HSIL, 41.2% had HPV18 and 22.6% – HPV16. Conclusions There is a high prevalence of HR-HPV types among Kazakhstani women with abnormal cervical cytology. The most identified types were HPV16, 18, 31, 33 and 52. There is an emergency need to implement an HPV vaccination program to prevent cervical lesion development.

HPV positivity status in males is related to the acquisition of HPV infection in females in heterosexual couples

PurposeFew studies have focused on the impact of human papillomavirus (HPV) positivity in male partners on female HPV infection and cervical lesions. The purpose of this study was to evaluate the impact of the HPV infection status of husbands on wives’ cervical HPV infection and lesions.MethodsWe surveyed 251 monogamous couples who attended the outpatient department of Fujian Maternity and Child Health Hospital from 2013 to 2021. HPV type analysis was performed on exfoliated cells of the females’ cervix and males’ urethra by the PCR-reverse dot blot method. We analyzed the prevalence and consistency of HPV types in 251 couples. Subsequently, the risk of HPV infection in females with HPV-positive male partners was analyzed. SPSS version 26 (IBM, Chicago, USA) was used for statistical analysis.ResultsIn 251 couples, the most commonly detected high-risk HPV (HR-HPV) genotypes were 52, 51, 16, and 58 for males and 16, 52, 18, and 58 for females. Wives with HPV-positive husbands had higher infection rates for most HR-HPV genotypes. HR-HPV positivity in husbands was a risk factor for the development of cervical lesions in wives (OR = 2.250, P = 0.014). Both single-type (OR = 2.085, P = 0.040) and multiple-type (OR = 2.751, P = 0.036) infection in husbands will contributed to an increased risk of non-HR-HPV infection and cervical lesions in wives.ConclusionHusbands’ HPV positivity increases the burden of non-HR-HPV infection and increases the risk of cervical lesions developing in wives. It is hoped to provide a reference value for cervical cancer prevention in females and HPV vaccination in males.

Cervicovaginal microbiota disorder combined with the change of cytosine phosphate guanine motif- tolllike receptor 9 axis was associated with cervical cancerization.

Convincing studies demonstrated that cervicovaginal microbiota disorder and toll-like receptor 9 (TLR9) high expression were related to cervical carcinogenesis. However, the effects of cervicovaginal microbiota integration TLR9 in cervical cancerization are unclear. Based on the biological basis that unmethylated cytosine-phosphate-guanine (CpG) motifs of bacteria could activate TLR9, we explored the effects of cervicovaginal microbiota disorder and CpG motif-TLR9 axis change in cervical carcinogenesis. A total of 341 participants, including 124 normal cervical (NC), 90 low-grade cervical intraepithelial neoplasia (CIN1), 78 high-grade cervical intraepithelial neoplasia (CIN2/3) and 49 squamous cervical cancer (SCC), diagnosed by pathology were enrolled in the study. Here, metagenomic shotgun sequencing was used to reveal cervicovaginal microbiota characteristics, and TLR9 protein was detected by western blotting. Our results showed that the diversity of cervicovaginal microbiota gradually increased along with the poor development of cervical lesions, showing the abundance of Lactobacillus crispatus and Lactobacillus iners decreased, while the abundance of pathogenic bacteria gradually increased. The level of TLR9 expression was gradually increased with cervicovaginal microbiota diversity increasing, the abundance of Lactobacillus decreasing, and we found a positive correlation dependency relationship (r = 0.384, P = 0.002) between TLR9 and GTCGTT motif content. Stratified analysis based on HPV16 infection, we found that the characteristics of cervicovaginal microbiota and increased TLR9 expression were also closely related to HPV16 infection. Cervicovaginal microbiota dysbiosis might lead to the CpG motif increased, which was closely associated with TLR9 high expression, and ultimately might promote the progression of cervical lesions.

Human papillomavirus positivity and cervical lesions in relation to HIV infection: a comparative assessment in the Cameroonian female population.

Cervical lesions, induced by high-risk oncogenic human papillomavirus (HR-HPV), in the context of HIV remains a global health challenge. We determined the effect of HR-HPV on the development of cervical lesions in women with and without HIV infection. A cross-sectional analytical study was conducted among 257 women living in Cameroon. HIV serology, HR-HPV genotyping and cervico-vaginal smear (CVS) were performed for all participants; among those declared HIV positive, plasma HIV viral load and CD4 count were measured. Statistical analyses were performed using Graph Pad version 6.0; P#x003C;0.05 was considered statistically significant. The mean age of the participants in our study was 37±6.5 years. According to HIV serology, 184 (71.59%) were HIV-positive vs. 73 (28.40%) HIV-negative. Among the HIV-positive women, the median CD4 count was 438 [IQR: 317-597] cells/mm3 and the median viremia was #x003C;40 [IQR: #x003C;40-2318] copies/ml. After successful genotyping, the prevalence of HR-HPV was 36.32% (73/201), with a significantly higher proportion in HIV-infected individuals (41.98% (55/131) vs. 25.71% (18/70); P=0.02; OR=2.1). The overall rate of cervical lesions was 23.34% (60/257), with a non-significantly higher proportion in HIV-infected participants (25.00% (46/184) vs. 19.17% (14/73); P=0.31). Relevantly, the presence of HR-HPV was significantly associated with cervical lesions (P#x003C;0.0001; OR=5.07), with a higher odds of cervical lesion in HIV-positive individuals (P#x003C;0.0001 and OR=5.67) compared to HIV-negative individuals (P=0.03 and OR=3.83). Although oncogenic HPV appears to be an independent factor in the development of cervical lesions, this study reveals higher odds of cervical lesions among HIV/HPV co-infection than in HPV infection alone.

ADCY7 mRNA Is a Novel Biomarker in HPV Infection and Cervical High-Grade Squamous Lesions or Higher

The effect of cervical cancer immunotherapy is limited. Combination therapy will be a new direction for cervical cancer. Thus, it is essential to discover a novel and available predictive biomarker to stratify patients who may benefit from immunotherapy for cervical cancer. In this study, 563 participants were enrolled. Adenylate cyclase 7 (ADCY7) mRNA was detected by real-time quantitative PCR (qPCR) with cervical cytology specimens. The relationship between ADCY7 and cervical intraepithelial neoplasia in grade 2 and higher (CIN2+) was analyzed, and the optimal cut-off values of the relative expression of ADCY7 mRNA to predict CIN2+ were calculated. In addition, the clinical significance of ADCY7 in cervical cancer was determined by the Kaplan-Meier Cox regression based on the TCGA database. The mean ADCY7 mRNA expression increased significantly with cervical lesion development, especially compared with CIN2+ (p < 0.05). Moreover, the expression of ADCY7 increased significantly in high-risk human papillomavirus (HR-HPV) infection but not in HPV-A5/6 species. The area under the receiver operating characteristic curve (AUC) of ADCY7 was 0.897, and an optimal cut-off was 0.435. Furthermore, ADCY7 had the highest OR (OR= 8.589; 95% CI (2.281-22.339)) for detecting CIN 2+, followed by HPV genotyping, TCT, and age (OR = 4.487, OR = 2.071, and OR = 1.345; 95% CI (1.156-10.518), (0.370-8.137), and (0.171-4.694), respectively). Moreover, this study indicated that higher ADCY7 levels could be a suitable predictor for poor prognosis in cervical cancer due to immune cell infiltration. A new auxiliary predictor of CIN2+ in cervical cytology specimens is ADCY7 ≥ 0.435. Furthermore, it may be a promising prognosis predictor and potential immunotherapy target for the combined treatment of cervical cancer and possibly further block HR-HPV persistent infection.

PSGL-1 is a novel tumor microenvironment prognostic biomarker with cervical high-grade squamous lesions and more.

Macrophages secrete many cytokines and chemokines, which can provoke either an anti-tumor or pro-tumor immune response. P-selectin glycoprotein ligand-1 (PSGL-1) is expressed in macrophages and plays a vital role in synergizing for a more robust anti-tumor response. However, there are few studies about PSGL-1 expression status and clinical value of biological function in cervical cancer. In this study, 565 participants were enrolled. PSGL-1 mRNA was detected by real-time quantitative PCR (qPCR) with cervical cytology specimens. The relationship between PSGL-1 and cervical intraepithelial neoplasia in two grades and more (CIN2+) was analyzed, and the optimal cut-off values of PSGL-1 to predict CIN2+ were calculated. In addition, the clinical significance of PSGL-1 in cervical cancer was determined by Kaplan-Meier Cox regression based on the database. The mean PSGL-1 increased significantly with cervical lesion development, especially compared with CIN2+ (p<0.05). Moreover, the expression of PSGL-1 increased significantly in HPV-16/18 positive and HPV-18 positive, but not in HPV-16 positive and other HR-HPV positive. And then, it demonstrated that the area under the receiver operating characteristic curve (AUC) of PSGL-1 was 0.820, and an optimal cut-off 0.245. Furthermore, the PSGL-1 had the highest odds ratio and highest OR (OR= 8.707; 95% CI (.371-19.321)) for the detection of CIN 2+. In addition, our result also indicated that higher PSGL-1 expression was significantly related to a better prognosis in cervical cancer due to immune cell infiltration. PSGL-1≥0.245 in cervical cytology specimens is a new auxiliary biomarker of CIN2+, and it may be a promising prognosis predictor and potential immunotherapy target linked with immune infiltration of cervical cancer.

FEATURES OF THE CERVICAL AREA STRUCTURE OF PERMANENT TEETH OF DIFFERENT GROUPS

According to the findings of various authors, almost 100% of the world's population suffers from dental caries. Carious lesions of the cervical area of the teeth attract special attention since their localization does not provide for the early detection of the pathological process, and the features of the microbiocenosis of the oral cavity and the structural features of the enamel-cementum-dentine junction are significant risk factors for the development and progression of cervical caries. The aim of the study is to research different options of the cervical area structure of teeth of different groups and to find out the frequency of their occurrence. Material and methods. We determined the ratio of the hard tissues – enamel, cementum and dentin – in the cervical area of 320 permanent teeth of the maxilla and mandible (10 teeth each of 11-18, 21-28, 31-38 and 41-48), which were removed due to clinical indications in their vestibular, oral (palatal/lingual), medial and distal contact surfaces. Results. Four options of the hard tissue ratio in the cervical region of the tooth were identified: lack of contact between enamel and cementum and the presence of zones of open dentin; contact of the enamel margin with the cementum; enamel overlapping cementum; cementum overlapping enamel. Each of the specified options occurs with different frequency on the vestibular, oral, medial and distal contact surfaces of teeth of different groups. Among all examined tooth surfaces, 2% have a zone of exposed dentin in the cervical area, 4% have the enamel in the cervical area covered with a layer of cementum, 47% of the surfaces have variants of contact of enamel margin with cementum and overlapping of cementum with a layer of enamel. Further study of the characteristics of the ratio of the hard tissues of the tooth in the cervical area will allow to find out the etiological factors of the development of cervical lesions and offer new and improved methods of their prevention, diagnosis and treatment.

Prevalence of HPV infection and cervical intraepithelial lesions in HIV positive and negative women in the city of Florianopolis

Introduction: The human papillomavirus (HPV) is the most common sexually transmitted infection among women. The HPV of high oncogenic risk, associated with other factors, presents a risk of progressing to a precancerous lesion of the uterus and even cancer. Such an evolution is related to the persistence of the infection and other factors, mainly those that interfere with women’s immunity. The immunosuppression caused by HIV infection is an important factor for viral persistence and the onset of these lesions. Objectives: To compare the prevalence of HPV infection and cervical intraepithelial lesions in HIV-positive and negative women and describe the possible associated risk factors. Methods: The sample consisted of 50 HIV positive women (study group) and 50 HIV negative women (control group) recruited from the public health system of Florianópolis from January to April 2022. Cervical samples were collected for cytological analysis and for the detection of high-risk oncogenic HPV DNA by polymerase chain reaction (PCR). Categorical variables were compared using the chi-square test, with a significance level set at 5% Results: HPV infection was more prevalent in the control group; however, HIV positive women presented higher frequency of intraepithelial lesions diagnosed on cytology. Factors such as higher number of sexual partners, depression and smoking were more frequent in the group of HIV positive women. CD4 T cells lower than 200 cells/mm3 was associated with a higher number of altered Pap smears and a positive HPV DNA test. The use of combination antiretroviral therapy and undetectable viral load were associated with more frequent normal cytology and undetected HPV DNA. Conclusion: The prevalence of cervical intraepithelial lesions in HIV-infected women is higher than among women without the infection. The presence of HIV infection was the most important risk factor associated with the development of cervical lesions.

HnRNP E1 Regulates HPV16 Oncogene Expression and Inhibits Cervical Cancerization.

hnRNP E1 (heterogeneous nuclear ribonucleoprotein E1) is an important RNA-binding protein (RBPs) that plays a vital role in tumor development. Human papillomavirus 16 (HPV16) contains numerous sites that can bind to RNA/DNA and may be modified by multiple RBPs, which contribute to HPV gene expression and HPV-associated cancer development. However, the effects of hnRNP E1 on HPV16 oncogenes in the development of cervical lesions remain unclear. A total of 816 participants with different grades of cervical lesions were enrolled in a community-based cohort established in Shanxi Province, China. The Gene Expression Omnibus (GEO) and The Cancer Genome Atlas (TCGA) databases were used to analyze the association between hnRNP E1 mRNA expression and cervical lesions. Cells with up_ and down_regulated hnRNP E1 were established. hnRNP E1 functions were evaluated using cell counting kit-8, flow cytometry analyses, and chromatin immunoprecipitation sequencing. Our results showed that hnRNP E1 expression was linearly dependent on the severity of the cervical lesions. Low expression of HPV16 E2, high expression of E6, and a low ratio of E2 to E6 could increase the risk of cervical lesions. hnRNP E1 expression was correlated with HPV16 oncogene expression. hnRNP E1-relevant genes were involved in the dopaminergic synapses, Wnt signaling pathway, gnRH secretion, and mTOR signaling pathway. hnRNP E1 significantly inhibited cell proliferation, induced apoptosis, arrested the cell cycle at the G0/G1 stage, and decreased HPV16 E6 expression. Our results indicate that hnRNP E1 could downregulate HPV16 E6 oncogene expression and inhibit cervical cancerization, which sheds new light on preventing the carcinogenicity of HPV across a range of diseases by regulating RNA-binding proteins.

Current data on the efficacy of prophylactic HPV vaccination in the primary prevention of cervical lesions.

A review of current knowledge on the efficacy of HPV (human papillomavirus) HPV vaccination against pre-cancers and cervical cancer. HPV infection is probably the most common sexually transmitted disease and the cause of approximately 5% of all human cancers. Currently, three prophylactic vaccines against HPV infection are on the market: bivalent Cervarix, quadrivalent Gardasil (formerly Silgard) and nonavalent Gardasil9. The Czech Republic is one of the countries with a national vaccination program where HPV vaccination is covered by health insurance for girls and boys aged 13-14 years. Extensive scientific data on the efficacy of the vaccines clearly demonstrate significant efficacy against the development of cervical pre-cancers for all three vaccines. According to a high-certainty evidence of the Cochrane database, the efficacy of HPV vaccines against cervical intraepithelial neoplasia grade 2 or 3 associated with HPV 16, 18 compared with placebo in girls and women aged 15-26 is 99%. There is also moderate-certainty evidence that HPV vaccines reduce the risk of adenocarcinoma in situ for approximately 90% for the same population. Initial data also demonstrate a direct impact on reducing the incidence of invasive cervical cancer in vaccinated individuals. In addition, quadrivalent and nonavalent vaccines are highly effective in preventing genital warts. All three available prophylactic vaccines show high efficacy in preventing the development of cervical lesions. Efficacy is highest against lesions caused by vaccine genotypes and the highest efficacy is achieved in the HPV naive population.

Correlation between Vaginal Microecological Status and Prognosis of CIN Patients with High-Risk HPV Infection.

Many microorganisms live in the vagina of healthy women. They interact with and compete with the microenvironment in the female vagina to form a dynamic balance of the microenvironment in the female vagina. However, imbalanced vaginal microecology can lead to vaginal resistance to pathogenic microorganisms. Poor capacity can cause women to develop infections of the reproductive tract. This article analyzes the vaginal microecological status of women with high-risk HPV infection for more than 6 months and healthy women and explores the risk factors that cause long-term high-risk HPV infection for timely detection and regulation of possible vaginal microecological imbalance in women with high-risk HPV infection for more than 6 months to prevent further development of cervical lesions in such patients. This article covers women with a sexual life history who attended the gynecology department of a hospital from January 2020 to September 2021. There were 280 patients in the experimental group: positive high-risk HPV; and there were 140 patients in the control group: negative high-risk HPV test. The correlation between vaginal microecology of CIN patients and patient prognosis according to the subject's vaginal microecology test results and prognosis of various levels of cervical lesions was analyzed. The experiment proved that the detection rate of normal vaginal microecology in the experimental group was 12.14% (34/280) compared with the detection rate of 29.29% (41/140) in the control group, and there was a trend of decrease, and the difference was statistically significant (χ2 = 17.23, P < 0.05). The detection rate of vaginal BV in the experimental group was 10.36% (29/280) compared with the detection rate of 5.0% (7/140) in the control group, and the difference was statistically significant (χ2 = 5.19, P < 0.05). This indicates that women with high-risk HPV infections for 6 months or longer have a higher incidence of vaginal microecological imbalances than healthy individuals and aggressive vaginal microecological screening. It is necessary to carry out the program. Detect and treat possible abnormal conditions in time to prevent the further onset of the disease.

IL-10 and TNF-α genes polymorphisms and the development of cervical lesions and cervical adenocarcinoma: a case-control study.

Cytokines have an important role in the progression of cervical lesions and/or adenocarcinoma. We investigated whether polymorphisms at the promoter regions of the IL-10 -1082 (A&gt; G, rs1800896) and TNF-α -308 (G&gt;A, rs1800629) genes were associated with susceptibility to progression of cervical dysplasia and adenocarcinoma. The study consisted of 240 women infected with HPV (72 with adenocarcinoma and 168 with cervical intraepithelial lesions), and 169 healthy control women. There was a significant increase in the frequency of the IL10 -1082G allele in both cervical dysplasia (OR = 1.39; P = 0.0372) and adenocarcinoma patients (OR = 2.19; P = 0.0002). For the TNF-α -308 polymorphism, there was higher susceptibility to cervical lesions, in relation to risk factors such as: age &gt; 35 years old (OR = 2.57; p = 0.0057), age of first sexual intercourse 1st &lt; 18 years old (OR = 6.6224, p &lt; 0.0001), smoking (OR = 3.80; P = 0.0003), African ancestry (OR=5.18, p &lt; 0.0001) and co-infection with Chlamydia trachomatis (OR=2.41, p=0.0315). Our findings suggest that polymorphisms in the IL-10 and TNF-α genes may play a role in the susceptibility or severity of cervical disease in the study population.&#x0D; Keywords: Tumor Necrosis Factor-alpha; Interleukin 10; Cervical lesions; Adenocarcinoma; HPV.

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.

Correlation between Lactobacillus and expression of E-cadherin, β-catenin, N-cadherin, and Vimentin in postmenopausal cervical lesions.

To detect the correlation between Lactobacillus vaginalis and the expression of epithelial-mesenchymal transition (EMT)-related factors, E-cadherin, β-catenin, N-cadherin, and Vimentin, in postmenopausal cervical squamous intraepithelial lesions (SILs) and cervical squamous cell carcinoma (SCC), and to explore the possible mechanism. From January 2016 to January 2020, 30 postmenopausal patients with low-grade SIL (LSIL), 18 patients with high-grade SIL (HSIL), and 30 patients with SCC who underwent colposcopy biopsy in the Outpatient Department of the First Affiliated Hospital of Inner Mongolia Medical University were selected as the experimental group, and 30 postmenopausal normal women were selected as the control group. The expression of 16SrRNA of Lactobacillus vaginalis in each group was determined by the 16S third-generation full-length amplification sequencing technique. The mRNA expression levels of E-cadherin, β-catenin, N-cadherin, and Vimentin were detected by quantitative real-time polymerase chain reaction (qPCR). The correlation between the 16SrRNA expression level of Lactobacillus vaginalis and the mRNA expression level of the EMT-related proteins was compared among all groups. (I) The progression of postmenopausal cervical SILs to cervical SCC was significantly positively correlated with age, number of pregnancies, smoking, pH value, positive rate of HPV16, and negatively correlated with total Lactobacillus 16SrRNA expression (P<0.0001). (II) The level of vaginal microbiota in postmenopausal women showed that Lactobacillus iners was dominant. With the progression of the disease, the expression levels of 16SrRNA in Lactobacillus iners and Lactobacillus total vagina decreased gradually, and the differences were statistically significant (P<0.05). (III) With the disease progresses. The expression of total Lactobacillus 16SrRNA was positively correlated with the mRNA expression of β-catenin and E-cadherin (r>0; P<0.05), and negatively correlated with the mRNA expression of Vimentin and N-cadherin (r<0; P<0.05). In postmenopausal women, Lactobacillus vaginalis interacts with HPV and is associated with the occurrence of EMT, promoting the development of cervical lesions.

Distinction between vaginal and cervical microbiota in high-risk human papilloma virus-infected women in China

BackgroundHigh-risk human papilloma virus (hrHPV) is the main causal factor of cervical precancer and cancer when persistent infection is left untreated. Previous studies have confirmed the vaginal microbiota is associated with HPV infection and the development of cervical lesions. The microbiota at different parts of the female genital tract is closely related but different from each other. To analyze the distinction between the vaginal and cervical microbiota of hrHPV(+) women in China, one hundred subjects were recruited, including 10 patients with HPV16/18(+) and cervical carcinoma, 38 patients with HPV16/18(+) but no cervical carcinoma, 32 patients with other hrHPV(+) and 20 healthy controls with HPV(−). Vaginal and cervical microbiota were separately tested through next-generation sequencing (NGS) targeting the variable region (V3-V4) of the bacterial ribosome 16S rRNA gene.ResultsHrHPV(+) subjects had higher percentages of vaginal douching history (P = 0.001), showed more frequent usage of sanitary pads (P = 0.007), had more sex partners (P = 0.047), were more sexually active (P = 0.025) and more diversed in ways of contraception (P = 0.001). The alpha diversity of the cervical microbiota was higher than that of the vagina. The cervical microbiota consisted of a lower percentage of Firmicutes and a higher percentage of Proteobacteria than the vagina at the phylum level. Sphingomonas, belonging to α-Proteobacteria, was almost below the detection limit in the vagina but accounted for five to 10 % of the bacteria in the hrHPV(−) cervix (P<0.001) and was inversely associated with hrHPV infection (P<0.05). Pseudomonas, belonging to γ-Proteobacteria, could hardly be seen in the normal vagina and shared a small percentage in the normal cervix but was significantly higher in the HPV16/18(+) (P<0.001) and cancerous cervix (P<0.05). No significant difference was shown in the percentage of BV associated anaerobes, like Gardnerella, Prevotella, Atopobium and Sneathia, between the cevix and vigina.ConclusionsThe proportion of Proteobacteria was significantly higher in the cervical microbiota than that of vagina. The hrHPV infection and cervical cancer was positively associated with Pseudomonas and negatively associated with Sphingomonas. It is of great improtance to deeply explore the cervical microbiota and its function in cervical cacinogenesis.

Prevalence of oncogenic human papillomavirus (HPV 16/18) infection, cervical lesions and its associated factors among women aged 21-49 years in Amhara region, Northern Ethiopia.

Human papillomavirus (HPV) infection is considered as the major risk factor for the development of cervical cancer, second most frequent cancer in Ethiopia. However, the magnitude of the problem and the associated factors remain unrevealed in the Amhara region. This study aimed to determine the prevalence of HPV infection and factors contributing to the progression of HPV infection to cervical cancer. Facility-based cross-sectional study design was employed among women aged 21 to 49 years of age who came for routine cervical cancer screening to 4 randomly selected hospitals (2 general and 2 referral) of Amhara region from May to October, 2019. The sample size was calculated by using the single population proportion formula, proportionated to hospitals, and women were recruited consecutively. Socio demographic and clinical data were collected using a pretested questionnaire and detection of HPV infection was done using HPV test (OncoE6TM Cervical Test) specific to HPV16/18 in cervical swabs. Visual inspection with acetic acid (VIA) was used to determine cervical lesions (precancerous and cancerous). Descriptive statistics and bivariate and multivariate logistic regression were used to describe HR-HPV and cervical lesions burden and association between HR-HPV, and cervical lesions and potential risk factors. Among 337 women 21 to 49 years (median age of 35 years ±SD = 7.1 years) of age enrolled in the study, The overall prevalence of oncogenic HPVs (HPV16/18) and the VIA-positivity rate, possible an indicative of cervical lesions, were 7.1% and 13.1%, respectively. Logistic regression analysis showed a significant association between early age of first sexual intercourse (COR = 2.26; 95% CI: 1.0-5.05) and level of education (COR = 0.31; 95% CI: 0.12-0.78) with cervical lesions. Higher odds of HPV positivity (COR = 1.56; 95% CI: 0.59-4.11, p = 0.36) and VIA positivity (COR = 1.39; 95% CI: 0.64-3.00, p = 0.39) were observed among participants who had a history of sexually transmitted illnesses (STIs). There was a relatively low prevalence of oncogenic HPV 16/18 and VIA-positivity in women attending four hospitals in the Amhara Region. Early age sexual contact, high parity, and being uneducated/low level of education were independently associated factors with HR-HPV infection and development of cervical lesions, highlighting the importance of prioritizing the limited HPV testing to those risk groups.

Silencing Anti-Silencing Function 1B Inhibited Proliferation and Migration of Cervical Cancer Cells and Promoted Apoptosis by Down-Regulating Chromatin Assembly Factor 1, Subunit B

The expression of anti-silencing function 1B (ASF1B) in cervical cancer patients were previously reported, indicating its implications as a new candidate gene related to the development of cervical lesions and cancer. In this study, we investigated the possible role of ASF1B in cervical carcinogenesis. ASF1B messenger RNA and protein expression was assessed in five cervical cancer cell line models, Hela, C-33A, SiHa, CaSKi, HCC-94 and normal cervical epithelium cell Ect. Gene silencing approach was employed to investigate the potential role of ASF1B in cellular growth, proliferation, colony-forming ability, migration and invasion in Hela cells. Our data indicated that ASF1B was expressed in all cervical cancer cells at the gene and protein level. Gene silencing of ASF1B caused significant inhibition in cellular proliferation, colony-forming ability, migration and invasion ability, and promote apoptosis of Hela cells. However, the biological effects of ASF1B silencing on Hela cells were reversing after down-regulating recombinant chromatin assembly factor 1, subunit B (CHAF1B). Collectively, our findings concluded that silencing ASF1B inhibits proliferation and migration of Hela cells and promotes apoptosis by down-regulating CHAF1B.

Human Papillomavirus Coinfection in the Cervical Intraepithelial Lesions and Cancer of Mexican Patients.

According to their oncogenic properties, Human Papillomaviruses (HPVs) are classified into two types: Low-Risk (LR-HPVs) and High-Risk Human Papillomaviruses (HR-HPVs). The immune system naturally controls the majority of HPV infections; however, when the HR-HPV infection is persistent, the risk of developing cervical cancer increases. Previous studies indicate that multiple-infection or coinfection with HR-HPV occurs frequently and can potentiate the development of cervical lesions. This study aimed to establish the HPV coinfection rate in squamous intraepithelial lesions from Mexican patients. For HPV detection, we performed PCR on 55 cervical lesions diagnosed by colposcopy. We detected the presence of HPV infection in 87.27% (48/55) of the lesions; interestingly, HPV coinfection was observed in 70.83% (34/48) of these samples. We also evaluated HPV infection in adjacent areas without morphological changes from 25 samples. The results showed that 80% (20/25) of these were HPV-positive and, curiously, all presented HPV-16 infection. In conclusion, our results revealed a high prevalence of HPV coinfection in cervical lesions in Mexican patients, and these results contribute to future research focused on the role that HPV coinfection plays in the development of cervical cancer.