Cervical Intraepithelial Neoplasia Patients Research Articles

Correlation analysis of human papillomavirus E6/E7 mRNA detection with diagnosis, prognosis and recurrence risk in patients with cervical epithelioma.

Cervical intraepithelial neoplasia (CIN) is an important precursor of cervical cancer. Early detection and treatment can reduce the incidence of cervical cancer. To investigate the detection rate of human papillomavirus (HPV) E6/E7 mRNA in cervical tissue of patients with different types of epithelial cell neoplasia (CIN) and its relationship with CIN progression and diagnosis. One hundred women with HPV infection detected by cervical exfoliation cytology between January 2022 and January 2023 were retrospectively selected. These patients were graded CIN based on colposcopy and cervical pathology. The positive expression rates of HPV E6/E7 mRNA and HPV [polymerase chain reaction (PCR)-reverse dot crossing] were compared among all groups. Patients with HPV E6/E7 mRNA expression in the grade 1 CIN group were followed up for 1 yr. The relationship between atypical squamous epithelium and high malignant epithelial neoplasia was investigated by univariate and multivariate analysis. The diagnostic sensitivity, specificity, and sensitivity of PCR-reverse point hybridization technology for secondary CIN were 70.41%, 70.66%, and 0.714, respectively. Sensitivity and specificity for secondary CIN were 752% and 7853%, respectively, the area under the curve value was 0.789. Logistic Multifactorial model analysis revealed that the HPV positive rates and the HPV E6/E7 mRNA positive rates were independent risk factors of CIN grade I (P < 0.05). In CIN grade I patients with positive for HPV E6/E7 mRNA, in its orientation to grade CIN patients, in its orientation to grade CIN patients, at 69.2%, compared with patients negative for HPV E6/E7 mRNA (30.8%), significant difference (P < 0.05). HPV E6/E7 mRNA and HPV (PCR-reverse dot hybrid) positive expression have a close relationship with CIN-grade disease progression and is an independent risk factor for high-grade CIN lesions.

Colposcopic Detection of CIN in Patients with Clinically Abnormal Cervix at a Tertiary Care Center in Bangladesh

Background: Cervical cancer poses a significant public health challenge globally, especially in regions like Bangladesh where access to effective screening programs is limited. Early detection and management of cervical intraepithelial neoplasia (CIN) play crucial roles in preventing the progression to cervical cancer. This study investigates the diagnostic accuracy of colposcopy, compared with histopathological findings, in detecting various grades of CIN and cervical cancer. Methods: This retrospective observational study reviewed hospital records of 200 VIA-positive cases from January 2021 to December 2023 at the Obstetrics and Gynecology Department of Holy Family Red Crescent Medical College Hospital Dhaka, Bangladesh. Colposcopic examinations were conducted, followed by histopathological evaluations of biopsied tissues to confirm the presence and grade of CIN. Data on demographic characteristics, clinical findings, and outcomes were analyzed using descriptive statistics. Result: Of the participants, 44% had normal colposcopic findings, while the prevalence of CIN I, CIN II, CIN III, and cervical cancer was 22.5%, 17%, 11%, and 4%, respectively. Histopathological correlation confirmed 46% as normal, with discrepancies noted in higher-grade lesion diagnosis. The study highlighted the high sensitivity but variable specificity of colposcopy in detecting and grading cervical lesions. Conclusion: Colposcopy serves as a valuable diagnostic tool in the early detection of cervical abnormalities. However, discrepancies in lesion grading underscore the need for integrating colposcopy with histopathological evaluations to enhance diagnostic accuracy and optimize patient management.

TPP1 is associated with risk of advanced precursors and cervical cancer survival.

It is unclear how telomere-binding protein TPP1 interacts with human telomerase reverse transcriptase (hTERT) and influences cervical cancer development and progression. This study included all eligible 156 cervical cancers diagnosed during 2003-2008 and followed up through 2014, 102 cervical intraepithelial neoplasia (CIN) patients, and 16 participants with normal cervix identified at the same period. Correlation of expression of TPP1 and hTERT in these lesions was assessed using Kappa statistics. TPP1 was knocked down by siRNA in three cervical cancer cell lines. We assessed mRNA expression using quantitative real-time polymerase chain reaction and protein expression using tissue microarray-based immunohistochemical staining. We further analyzed the impact of TPP1 expression on the overall survival of cervical cancer patients by calculating the hazard ratio (HR) with 95% confidence intervals (CIs) using the multivariable-adjusted Cox regression model. Compared to the normal cervix, high TPP1expression was significantly associated with CIN 3 and cervical cancers (P<0.001 for both). Expressions of TPP1 and hTERT were highly correlated in CIN 3 (Kappa statistics = 0.50, P = 0.005), squamous cell carcinoma (Kappa statistics = 0.22, P = 0.011), and adenocarcinoma/adenosquamous carcinoma (Kappa statistics = 0.77, P = 0.001). Mechanistically, knockdown of TPP1 inhibited the expression of hTERT in both mRNA and protein levels. High expression of TPP1 (HR = 2.61, 95% CI 1.23-5.51) and co-high expression of TPP1 and hTERT (HR = 2.38, 95% CI 1.28-4.43) were independently associated with worse survival in cervical cancer patients. TPP1 and hTERT expression was correlated and high expression of TPP1 was associated with high risk of CIN 3 and cervical cancer and could predict a worse survival in cervical cancer.

Imiquimod Is Effective in Reducing Cervical Intraepithelial Neoplasia: A Systematic Review and Meta-Analysis.

Topical Imiquimod is an immune response modifier approved for the off-label use of vulvar intraepithelial neoplasia. We conducted this systematic review and meta-analysis to investigate the efficacy and safety of Imiquimod in treating cervical intraepithelial neoplasia (CIN) and human papillomavirus (HPV)-positive patients. The study was prospectively registered (CRD420222870) and involved a comprehensive systematic search of five medical databases on 10 October 2022. We included articles that assessed the use of Imiquimod in cervical dysplasia and HPV-positive patients. Pooled proportions, risk ratios (RRs), and corresponding 95% confidence intervals (CIs) were calculated using a random effects model to generate summary estimates. Statistical heterogeneity was assessed using I2 tested by the Cochran Q tests. Eight articles reported on 398 patients who received Imiquimod out of 672 patients. Among CIN-2-3 patients, we observed a pooled regression rate of 61% (CI: 0.46-0.75; I2: 77%). When compared, Imiquimod was inferior to conization (RR: 0.62; CI: 0.42-0.92; I2: 64%). The HPV clearance rate in women who completed Imiquimod treatment was 60% (CI: 0.31-0.81; I2: 57%). The majority of side effects reported were mild to moderate in severity. Our findings indicate that topical Imiquimod is safe and effective in reducing cervical intraepithelial neoplasia and promoting HPV clearance. However, it was found to be inferior compared to conization. Imiquimod could be considered a potential medication for high-grade CIN patients and should be incorporated into guidelines for treating cervical dysplasia.

Randomized Phase II Trial of Imiquimod with or without 9-Valent HPV Vaccine versus Observation in Patients with High-grade Pre-neoplastic Cervical Lesions (NCT02864147).

We report the results of a randomized phase II trial of imiquimod, a topical immune-response modulator versus imiquimod plus a 9-valent human papillomavirus (HPV) vaccine (9vHPV) versus clinical surveillance in cervical intraepithelial neoplasia (CIN2/3) patients. We randomly allocated 133 patients with untreated CIN2/3 in equal proportions to a 4-month treatment with self-applied vaginal suppositories containing imiquimod (Arm B) or imiquimod plus a 9vHPV (Arm C) versus clinical surveillance (Arm A). The main outcome was efficacy, defined as histologic regression to CIN1 or less. Secondary outcomes were HPV clearance and tolerability. Exploratory objectives included the comparison of cervical CD4/CD8 T-cell infiltration at baseline, mid-study, and posttreatment by flow cytometry among study arms. Of the 114 evaluable patients 77% and 23% harbored CIN2 and CIN3, respectively. Regression to CIN1 or less was observed in 95% of patients in the imiquimod group (Arm B) compared with 79% in the control/surveillance (Arm A); P = 0.043 and 84% in the imiquimod+9vHPV group (Arm C; P = 0.384 vs. Arm A). Neither of the treatment-arm differences from Arm A reached the prespecified α = 0.025 significance level. No significant differences were noted in the secondary outcome of rate of HPV clearance. The number of tissue-resident memory CD4/CD8 T cells in cytobrush samples demonstrated a >5-fold increase in Arm B/imiquimod when compared with Arm A/surveillance (P < 0.01). In contrast, there was no significant difference in T-cell responses among participants in Arm C when compared with Arm A. Imiquimod treatment was well tolerated. Although imiquimod induced a higher regression to CIN1 or less and significant increases in CD4/CD8 T cells infiltrating the cervix, it did not meet its prespecified statistical outcome for efficacy. A higher regression rate than expected was observed in the surveillance arm of this prospective trial. Future clinical trials with imiquimod targeting CIN3 patients are warranted.

YAP/TAZ-TEAD activity promotes the malignant transformation of cervical intraepithelial neoplasia through enhancing the characteristics and Warburg effect of cancer stem cells

A number of studies have confirmed that Yes-associated protein (YAP)/transcriptional co-activator with PDZ-binding motif (TAZ)-transcriptional enhanced associate domain (TEAD) activity is the driver of cancer development. However, the role and mechanism of the YAP/TAZ-TEAD pathway in cervical intraepithelial neoplasia (CIN) remain to be clarified. Therefore, this study was designed to observe the effect of YAP/TAZ-TEAD activity on the development of CIN and provide new ideas for the diagnosis and treatment of CIN. Firstly, cervical tissues were collected from CIN patients in different stages [CIN grade 1 (CIN1) tissue, CIN grade 2/3 (CIN 2/3) and squamous cell carcinoma (SCC)] and healthy volunteers. Next, the expression levels of YAP, TAZ and TEAD in cervical tissues and cells were observed by immunohistochemistry, qRT-PCR and western blot. Besides, Z172 and Z183 cells were transfected with siRNA-YAP/TAZ (si-YAP/TAZ) and YAP/TAZ overexpression vector (YAP-5SA). Also, Z172 cells were co-transfected with YAP-5SA and si-TEAD2/4. Subsequently, the stemness characteristics, glycolysis level and malignant transformation of cells in each group were observed by sphere-formation assay, commercial kit, MTT, Transwell, scratch experiment, xenotransplantation and western blot.The expression of YAP, TAZ and TEAD increased significantly in cervical cancer tissue and cell line at the stage of CIN2/3 and SCC. When YAP/TAZ was knocked down, the stemness characteristics, glycolysis level and malignant transformation of cancer cells were notably inhibited; while activating YAP/TAZ exhibited a completely opposite result. In addition, activating YAP/TAZ and knocking down the TEAD expression at the same time significant weakened the effect of activated YAP/TAZ signal on precancerous cells and reduced inhibitory effect of knocking down TEAD alone. YAP/TAZ-TEAD signal activates the characteristics and Warburg effect of cancer stem cells, thereby promoting the malignant transformation of CIN.

Correlations between C-myc expression, BMI-1 expression, and vaginal microecology with HPV-DNA load in patients with different cervical lesions.

To investigate the correlations between the expressions of proto-oncogenes C-myc and B-cell-specific Moloney leukemia virus integration site-1 (BMI-1), vaginal microecology, and human papillomavirus-DNA (HPV-DNA) load in patients with different cervical lesions. A total of 51 patients with cervix squamous cell carcinoma (CSCC), 72 patients with cervical intraepithelial neoplasia (CIN) and 50 patients with normal cervix (NC) who were diagnosed or admitted between Jan. 1st 2020 and Dec. 31st 2022 at the Suzhou Hospital of Integrated Traditional Chinese and Western Medicine were selected and divided into three groups, i.e., the CSCC group, the CIN group and the NC group, for a retrospective analysis. Hybrid capture 2 (hc2) was used to detect the HPV-DNA load in each group. Immunohistochemistry was performed to detect C-myc and BMI-1 expressions in each group. The indicators of vaginal microecology in patients were compared among groups to analyze the correlations between C-myc, BMI-1 expressions, vaginal microecology and HPV-DNA load. The HPV-DNA load and expression levels of positive C-myc and BMI-1 in the CSCC group were all higher than those of the CIN and NC groups (P<0.05). The detection rate of lactobacillus in the CSCC group was lower than that of the CIN and NC groups. The percentages of leukocyte esterase (LE) positivity and pH ≥4.6 were higher in the CSCC group than those in the CIN and NC groups (P<0.05). The difference in the detection rate of spores among the three groups was not significant (P>0.05). Both C-myc and BMI-1 scores were positively correlated with HPV-DNA load in the 173 samples. The proto-oncogenes C-myc and BMI-1 were highly expressed in the cervical tissues of CIN and CSCC patients, whose vaginal microecology was also altered. Both may play an important role in the progression of cervical lesions.

The effects of the LaSota strain of oncolytic Newcastle disease virus vaccine on cervical intraepithelial neoplasia Patients-Clinical cohort study

BackgroundCervical cancer is one of the most common malignancies in women, and its treatment has many side effects. Therefore, in this research, the effects of the LaSota strain of oncolytic Newcastle disease virus vaccine on cervical intraepithelial neoplasia (CIN) patients were investigated. Methods15 patients who met the inclusion criteria and diagnosed as CIN II and CIN III were included in the study. The vaccine was injected inside the cervix (neoplasia site) at increasing doses during 21 days, and they were evaluated for adverse events. NDV antibody titer was measured in 90 days and the levels of ki-67 and p16 proteins were studied by immunohistochemistry. Also, the levels of some important inflammatory cytokines in the serum of CIN patients were measured and finally the patients were evaluated according to the final outcomes and the reduction of tumor lesions. ResultsOnly in the first dose of vaccine some patients showed flu-like symptoms. The accumulation of NDV antibodies started on the 7th day of the study and increased until the 90th day. Administration of LaSota vaccine had no significant effect on the expressions of Ki-67 and p16 proteins. Nevertheless, a decrease in the serum levels of Il-1β was observed in patients after the administration of the vaccine, but the serum levels of both Il-2 and INF-γ upregulated significantly. Also, vaccine administration had no significant effect in reducing CIN grades and lesions. ConclusionsIn general, we concluded that LaSota strain of NDV vaccine has no therapeutic effectiveness in CIN patients.

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.

A pilot study of repeated 5-aminolevulinic acid photodynamic therapy for cervical intraepithelial neoplasia by a newly developed intravaginal irradiation system

The pilot study was performed to assess the usefulness of a newly developed patientand physician-friendly intravaginal irradiation system for photodynamic therapy with 5-aminolevulinic acid (5-ALA PDT) for cervical intraepithelial neoplasia (CIN). We used an intravaginal balloon applicator to make the cervix upright and to adjust the position and direction of the laser source in the vagina, resulting in minimal patient discomfort and minimal effort required by the physician during irradiation. Ten outpatients of CIN2 or 3 with high-risk human papillomavirus (HPV) infection without a history of HPV vaccination were treated by 5-ALA PDT. Each patient underwent PDT four times every two weeks. Nine patients showed pathological improvement, and the HPV clearance rate was 80%, and no recurrence was observed at two-years follow-up. Serum anti-HPV16 antibodies were detected in seven patients, and the antibody levels of three patients were high, equivalent to those acquired after HPV vaccination. Our newly developed irradiation system enabled easy repeat 5-ALA PDT in the outpatient clinic resulting in the improvement of CIN lesions and HPV clearance. Our results also suggested that repeated 5-ALA PDT might enhance HPV antibody production in CIN patients.

Persistent HPV infection after conization of cervical intraepithelial neoplasia—— a systematic review and meta-analysis

ObjectiveTo systematically evaluate several factors of persistent human papillomavirus (HPV) infection following conization in patients with cervical intraepithelial neoplasia (CIN).MethodsPubMed, EMBASE and the Cochrane Library were searched from January 1, 1998 to September 10, 2021. Random-effects models for meta-analyses were used and pooled relative risks with 95% confidence intervals were reported. Literature screening, data extraction, and assessment of the risk of bias in the included studies were conducted independently by two researchers. Data analysis was performed with Stata software, version 12.0.ResultsA total of 28 studies were included in this study. Meta-analysis revealed that surgical margin and residual disease were positively correlated with persistent HPV infection after conization. Compared with patients infected with other types of HPV, CIN patients with HPV 16 had a higher persistent infection rate (OR = 1.967, 95% CI (1.232–3.140), P < 0.05).ConclusionsCIN patients who are postmenopausal, have positive surgical margins and residual lesions, and are positive for HPV 16 are prone to persistent HPV infection after conization.

Effect of Zhikang Capsule Assisted LEEP on Postoperative Recovery Speed and the Incidence of Complications of Patients with Cervical Intraepithelial Neoplasia

Objective: To investigate the role of Zhikang capsule assisted loop electrosurgical excision procedure (LEEP) operation for intervening cervical intraepithelial neoplasia (CIN) on improving the recovery speed and reducing the incidence of complications. Methods: Altogether 91 CIN patients in our hospital were selected as the research participants. Patients treated with Zhikang capsule assisted LEEP operation were the research group (RG) (48 cases), and patients treated with LEEP operation were the control group (CG) (43 cases). The related indexes and incidence of postoperative complications between the CG and the RG were compared. Inflammatory reaction, immune function, psychological status score, total bleeding, hospital stay and quality of life were evaluated. Results: The drainage time, bleeding time and wound healing time in the RG were shorter than those in the CG (P&lt;0.05). The incidence of complications in the RG was evidently lower than that in the CG (P=0.034). IL-4 in the RG was evidently lower than that in the CG (P&lt;0.05), while IFN-γ and IL-2 were evidently higher than those in the CG (P&lt;0.05). CD3+ and CD4+ in the RG were evidently higher than those in the CG (P&lt;0.05), while CD8+ in the RG were evidently lower than those in the CG (P&lt;0.05). After intervention, SDS and SAS scores in the RG were evidently lower than those in the CG (P&lt;0.05). The total bleeding and hospital stay in the RG were less than those in the CG (P&lt;0.05). The quality of life in the RG was better than that in the CG (P&lt;0.05). Conclusion: Zhikang capsule assisted LEEP operation can effectively improve the recovery rate of patients and reduce the incidence of complications, which is worthy of clinical application.

Complications of Loop Electrosurgical Excision Procedure Following Treatment of Cervical Intra-Epithelial Neoplasia 2 &amp; 3

Background: The loop electrosurgical excision procedure (LEEP) is currently one of the most commonly used approaches to treat high grade cervical squamus intraepithelial lesion confirmed on colposcopic guided biopsy examination. Complications of electrosurgical excision procedure (LEEP) are rare. But in Bangladesh, we have very limited research-based information regarding this issue. Aim of the Study: The aim of the study was to assess the complications of loop electrosurgical excision procedure following treatment of cervical intra-epithelial neoplasia (CIN) 2 and 3. Methods: This descriptive cross-sectional study was conducted in OPD, Gynaecology and Obstetrics Department, Rangpur Medical College Hospital, Rangpur, Bangladesh during the period of July 2011 to June 2012. In total, 75 patients with CIN 2 and/or 3 were enrolled in this study as study subjects. The study was approved by the ethical committee of the mentioned hospital. Proper informed written consents were taken from all the participants before data collection. The criteria for inclusion were colposcopic guided biopsy revealing CIN 2 or 3 whose lesion remains confined to ectocervix. The least amount of power that will effectively perform the electrosurgery should be used, so as to minimize the risk to the patient’s normal tissues and ensure that the excised specimen is inacceptable condition for pathological assessment. Data analysis was done by using statistical package for social science (SPSS) 16 versions. Results: In analyzing the post procedure complications of the participants, we observed that, 64% participants were from vaginal discharge. Besides this 21%, 9%, 4% and 1% cases were found with pain, bleeding, fever and cervical stenosis consequently. Distributing persistence of vaginal discharge, 44% participants taken 5-10 days which was noticeable. Only 5.33% participants had vaginal discharge in between 21-25 days. In distributing persistence of pain, we observed that, 8% participants had taken 30 days to be cured which was the highest number of patients. Within one week, all the patients become free from fever. Cervical Stenosis occurred as a delayed complication during follow up at 9-12 months after LEEP in only 1(1.3%) case and occurred at 270th day. Conclusion: As per the findings of this study we can mention vaginal discharge as the most common complication for the cervical intra-epithelial neoplasia patients by treating loop electrosurgical excision procedure. Besides these, physicians should be aware about the sufferings of patients from pain and bleeding. Finally, we can conclude that, LEEP as an easy safe and acceptable treatment for high grade CIN with high cure rate.

Construction of a diagnostic classifier for cervical intraepithelial neoplasia and cervical cancer based on XGBoost feature selection and random forest model.

The pathological phenotype of early-stage cervical cancer (CC) is similar to that of cervical intraepithelial neoplasia (CIN), which provides a challenge for the diagnosis of cervical precancerous lesions. Meanwhile, the existing diagnostic methods have certain subjectivity and limitations, resulting in the possibility of misdiagnosis or missed diagnosis. Hence, some methods are needed to assist diagnosis of CC and CIN. Based on the data of CIN and CC in gene expression omnibus (GEO) dataset, the eXtreme Gradient Boosting (XGBoost) algorithm was used to screen the feature genes between CIN and CC for constructing the classifier. Incremental feature selection (IFS) curve was also used for screening. The classifier was validated for reliability using principal component analysis (PCA) dimensionality reduction analysis and heat map analysis of gene expression. Then, differentially expressed genes of CIN and CC were intersected with the classifier genes. Genes in the intersection were used as seeds for protein-protein interaction network construction and restart random walk analysis. And the genes with the top 50 affinity coefficients were selected for gene ontology (GO) and kyoto encyclopedia of genes and genome (KEGG) enrichment analyses to observe the biological functions with differences between CIN and CC. The peripheral blood genes of CIN and CC were analyzed, and seven genes were screened. Using this gene for classifier construction, IFS curve screening revealed that the three-feature gene classifier constructed according to the random forest model had the best effect. The results of PCA dimensionality reduction analysis and gene expression heat map analysis showed that the three-gene classifier could effectively distinguish CIN from CC. A three-gene diagnostic classifier can effectively distinguish CIN patients from CC patients and provide a reference for the clinical diagnosis of early CC.

Relationship between positive margin and residual/recurrence after excision of cervical intraepithelial neoplasia: a systematic review and meta-analysis.

BackgroundThe relationship between endocervical and ectocervical margin status and residual or recurrence after cervical intraepithelial neoplasia (CIN) resection has been controversial. We investigated the relationship between the excision margins and residual/recurrence to assess indicators for the scope of resection and the risk of treatment failure by using meta-analysis.MethodsLiterature searches were performed in PubMed, Medline, Embase, Central, Wangfang and CNKI databases. Patients after CIN resection were grouped according to whether there was residual or recurrence, and the differences in exposure factors between the two groups were compared. Or they were grouped by exposure factor, and compare the differences in residual and recurrence rates under different grouping conditions. The observed outcome was postoperative residual or recurrence. The risk of bias in the literature was assessed using the Newcastle-Ottawa Scale (NOS). The chi-square test were used for heterogeneity. Subgroup explored the sources of heterogeneity. Publication bias was assessed using funnel plots and Egger's test.ResultsA total of 11 studies were included in this study, 8 studies were at low risk of bias and 3 studies were at high risk of bias. The 11 studies included 3065 patients, 774 patients with positive margins and 2,291 patients with negative margins. The rate of residual/recurrence after excision of CIN in patients with positive margins was significantly higher than in patients with negative margins [odds ratio (OR) =3.99, P<0.00001]. There was no heterogeneity among the studies (P=0.16), with publication bias (P<0.05). The residual/recurrence rate was significantly higher in patients with positive endocervical margins than in patients with negative endocervical margins (OR =2.59, P<0.00001). There was no heterogeneity among studies (P=0.78) and no publication bias (P<0.05). There was no significant difference in residual/recurrence rate between positive and negative ectocervical margins (OR =1.14, P=0.36). There was no heterogeneity among studies (P=0.32) and no publication bias (P<0.05).ConclusionsPositive endocervical margins, but not external cervical margins, are risk factors for residual/recurrence of CIN after resection. Close attention to the status of the endocervical margins is recommended. More aggressive treatment and frequent follow-up are needed for patients with positive endocervical margins.

Observation of the cervical microbiome in the progression of cervical intraepithelial neoplasia

ObjectiveCervical microbial community in the cervical intraepithelial neoplasia and cervical cancer patients was analysed to study its composition, diversity and signalling pathways by high-throughput 16S rDNA sequencing,and the candidate genes associated with occurrence and progression of cervical intraepithelial neoplasia were screened out and the model was established to predict the evolution of cervical intraepithelial neoplasia malignant transformation from the cervical microbial genes aspect.MethodsCervical tissues of normal, cervical intraepithelial neoplasia and cervical cancer patients without receiving any treatment were collected. The correlation between candidate genes and cervical intraepithelial neoplasia progression was initially determined by analyzing the microbial flora. Real-time fluorescence quantitative PCR was used to detect the expression of candidate genes in different cervical tissues, ROC curve and logistic regression was used to analyse and predict the risk factors related to the occurrence and progression of cervical intraepithelial neoplasia. Finally, the early warning model of cervical intraepithelial neoplasia occurrence and progression is established.ResultsCervical tissues from normal, cervical intraepithelial neoplasia and cervical cancer patients were collected for microbial community high-throughput 16S rDNA sequencing. The analysis revealed five different pathways related to cervical intraepithelial neoplasia. 10 candidate genes were selected by further bioinformatics analysis and preliminary screening. Real time PCR, ROC curve and Logistic regression analysis showed that human papillomavirus infection, TCT severity, ABCG2, TDG, PCNA were independent risk factors for cervical intraepithelial neoplasia. We used these indicators to establish a random forest model. Seven models were built through different combinations. The model 4 (ABCG2 + PCNA + TDG) was the best early warning model for the occurrence and progression of CIN.ConclusionsA total of 5 differential pathways and 10 candidate genes related to occurrence and progression of cervical intraepithelial neoplasia were found in cervical microbial community. This study firstly identified the genes from cervical microbial community that play an important role in the occurrence and progression of cervical intraepithelial neoplasia. At the same time, the early warning model including ABCG2 + PCNA+TDG genes provided a new idea and target for clinical prediction and blocking the evolution of cervical intraepithelial neoplasia malignant transformation from the aspect of cervical microbiological related genes.

Fas and Fas ligand are highly expressed in lymphocytes from cervical intraepithelial neoplasia and cervical cancer patients: A possible role for immune escaping.

Objective(s):Infection with high-risk human papillomavirus is required to develop cervical cancer. Some viruses modulate the Fas/FasL signaling to evade the immune response; the role of these molecules in cervical cancer is not clear. In this study, we measured the expression levels of Fas and FasL mRNA, soluble proteins, and cell surface proteins in peripheral blood mononuclear cells from patients with low- and high-grade squamous intraepithelial lesions and cervical cancer in relation to healthy women, to gain new insights into the role of Fas/FasL in cervical cancer development. Materials and Methods:Fas/FasL mRNA expression was measured in cervical tissues and peripheral blood mononuclear cells from patients and healthy subjects; serum soluble proteins Fas/FasL were measured by ELISA, and cell-surface protein expression was detected by flow cytometry. Results:Varying expression levels were found for both molecules. Cervical Fas and FasL mRNA expression was decreased in low- and high-grade lesions, but it was increased in cervical cancer cases. While, systemic Fas mRNA expression increased as malignity progressed; systemic FasL mRNA expression was increased in low- and high-grade lesions, but it was decreased in cancer patients. Soluble FasL levels decreased as lesions progressed, while soluble Fas levels increased. Finally, overexpression of Fas/FasL on the surface of peripheral blood mononuclear cells was found in patients with low-grade lesion with respect to healthy donors. Conclusion:Fas and FasL act as negative modulators of the immune response, probably by removing specific cytotoxic T lymphocytes against papillomavirus -infected cells and tumor cells.

31 The prevalence and risk factors of anal human papillomavirus infection in high-grade cervical intraepithelial neoplasia patients

Introduction and aims of the study: Cervical and anal cancers are the most common HPV-associated malignancies in women. Some studies suggest that high-risk cervical dysplasia (HRCD) patients have an increased risk for anal HPV-infection and anal high-grade dysplasia, however, this association is not well established. The aim of the study was to determine the incidence and to identify the possible risk factors (RF) of anal HPV infection in HRCD-patients. Methods: This was a cross-sectional study conducted in the Gynaecological department of Riga East Clinical University Hospital, involving 25 HRCD (CIN2+) patients with planned cervical excision.

Dysbiosis of Cervical and Vaginal Microbiota Associated With Cervical Intraepithelial Neoplasia.

Cervical intraepithelial neoplasia (CIN) is a precancerous condition inducing local lesions on the surface of the squamocolumnar junction of the cervix. Despite the role of vaginal microbiota having been under-discussed, the role of the cervical microbiome and the microbial migration across the reproductive tract involved in CIN was limitedly studied. We aimed to synchronously characterize the dysbiosis associated with CIN in both the cervix and vagina in a Chinese population. Profiling of cervical and vaginal microbiota from 60 CIN women and 60 healthy women was conducted. 16S rRNA sequencing was adopted. By comparing the microbial profiles between different parts of the reproductive tract, our results demonstrated an increased shift of microbial diversity in the cervix compared with that in the vagina for the CIN patients, specifically in CIN 1. Less dysbiosis was found between the CIN patients and controls, in either the vagina or cervix. The microbial community may be modulated by the onset of sexual activity, a known clinical risk factor for cervical neoplasia. Distinct patterns of perturbated bacteria were found in the vaginal and cervical microbiota, in which reduced Actinobacteria-related operational taxonomic units (OTUs) and increased Proteobacteria-related OTUs were found in the vagina and cervix, respectively. A good agreement between the direction of the top-significant perturbated OTUs was observed between the vaginal and cervical microbiome, suggesting a potential microbial migration in the reproductive tract. Enriched genera such as Sphingomonas and Stenotrophomonas were found in cervical microbiota-associated CIN. Multivariate analysis revealed Comamonas, Rhizobium, and Pseudomonas as independent genera contributing to CIN in the cervix. In summary, this study revealed the perturbation of microbiota in the presence of CIN and demonstrated a distinct pattern of characteristic bacteria community between the vagina and cervix involved in the development of CIN.

Analysis of related factors of cervical intraepithelial neoplasia complicated with vaginal intraepithelial neoplasia.

To explore the underlying risk factors and to prevent misdiagnosis of cervical intraepithelial neoplasia (CIN) coexisted with vaginal intraepithelial neoplasia (VaIN). Clinical data of patients pathologically diagnosed with CIN were collected from January 2017 to December 2018. A total of 446 cases were analyzed, including 406 cases of single lesions ('CIN single' group) and 40 cases complicated with VAIN ('VAIN concurrent' group). The median age of the VAIN concurrent group was 53years (46.25-59years), and the median age of the CIN single group was 44years (36-50years). Regarding menopausal status, there were 28 cases (70.0%) in the VAIN concurrent group and 89 cases (21.9%) in the CIN single group (P < 0.005). The median load of high-risk human papillomavirus (Hr-HPV) in the VAIN concurrent and CIN single group was 923.4 relative light units/cutoff (RLU/CO) (145-2172.2 RLU/CO) and 229.155 RLU/CO (18.615-638.1275 RLU/CO), respectively (P = 0.037). The results revealed that the menopausal status was an independent risk factor for VAIN occurrence in CIN patients. The risk of VAIN in menopausal patients was higher than that in non-menopausal CIN patients (OR = 8.311, 95% CI 4.062-17.005). Age and HPV load were also related to the concurrence of VAIN and CIN. Examinations regarding vaginal screening are of great importance in the diagnosis of perimenopausal and postmenopausal CIN patients, especially patients with Hr-HPV load. Colposcopy and tissue biopsy should also be performed, when necessary, to avoid misdiagnosis and the appearance of vaginal lesions.