Intraepithelial Neoplasia Patients Research Articles

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.

CT findings and clinical effects of high grade pancreatic intraepithelial neoplasia in patients with intraductal papillary mucinous neoplasms.

To investigate the common CT findings of high-grade (HG) PanIN and clinical effects in the remnant pancreas in patients with intraductal papillary mucinous neoplasm (IPMN) of the pancreas. Two hundred fifty-one patients with surgically confirmed IPMNs (118 malignant [invasive carcinoma/high-grade dysplasia] and 133 benign [low-grade dysplasia]) were retrospectively enrolled. The grade of PanIN (233 absent/low-grade and 18 high-grade) was recorded, and all patients underwent serial CT follow-up before and after surgery. Two radiologists analyzed CT findings of high-risk stigmata or worrisome features according to 2017 international consensus guidelines. They also analyzed tumor recurrence on serial follow-up CT after surgery. Statistical analyses were performed to identify significant predictors and clinical impact on postoperative outcomes of HG PanIN. PanIN grade showed a significant association with IPMN grade (p = 0.012). Enhancing mural nodules ≥5 mm, abrupt main pancreatic duct (MPD) changes with distal pancreatic atrophy, increased mural nodule size and MPD diameter were common findings in HG PanIN (P<0.05). In multivariate analysis, abrupt MPD change with distal pancreatic atrophy (odds ratio (OR) 6.59, 95% CI: 2.32-18.72, <0.001) and mural nodule size (OR, 1.05; 95% CI, 1.02-1.08, 0.004) were important predictors for HG PanIN. During postoperative follow-up, HG PanIN (OR, 4.98; 95% CI, 1.22-20.33, 0.025) was significantly associated with cancer recurrence in the remnant pancreas. CT can be useful for predicting HG PanIN using common features, such as abrupt MPD changes and mural nodules. In HG PanIN, extra caution is needed to monitor postoperative recurrence during follow-up.

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.

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.

Abstract A132: Time to treatment by neighborhood among endometrial intraepithelial neoplasia and endometrial cancer patients

Abstract Objective: To examine interval wait time for surgery in EIN and Endometrial Cancer patients at a single institution and identify potential disparities in access to care Methods: At this single institution, five priority neighborhoods where medically underserved populations reside have been designated from a Community Health Needs Assessment. We performed a retrospective chart review of patients with EIN or endometrial cancer at a single institution between 2016-2019. Patients from one of five priority neighborhoods were compared with patients from other zip codes within the same state. Results: 100 patients from priority neighborhoods and 104 patients from other neighborhoods within the same state were identified. Mean age was similar (59.74 vs 58.15 yrs, p 0.372) and rates of private insurance status were similar (66% vs 52%, p 0.08). Priority neighborhood patients were more likely to identify as Black or Hispanic (30.0% vs 4.81%; 18.0% vs 0%, p &amp;lt;0.001), and were more likely to speak a non-English primary language (19.0% vs 2.88%, p 0.005). Priority neighborhood patients had a higher Charlson Deyo co-morbidity score (2.44 vs 2.49, p 0.809). Patients had a similar rates of advanced stage disease (Stage III or IV 16 vs 16, p 0.213) and histologic subtype (Endometrioid 47.5% vs 59.6%; Serous or Clear Cell 13.46% vs 14.75%, p 0.962). The mean interval to treatment by primary surgery from referral visit was 68.9 days for non-priority neighborhood patients compared to 80.12 days for priority neighborhood patients (p 0.478). In univariate analysis, race/ethnicity, primary language, and insurance status were not significant factors impacting time to treatment. Conclusion: Interval wait time to primary surgery among a single institution cohort was longer for priority neighborhood patients. This study highlights potential barriers to healthcare access that are unaddressed by current systems. Citation Format: Victoria Wang, Hadley Reid, Andrea Pelletier, Trinity Russell, Lucy Chen, Reagan Marsh, Colleen Feltmate, Alexi Wright, Kevin Elias. Time to treatment by neighborhood among endometrial intraepithelial neoplasia and endometrial cancer patients [abstract]. In: Proceedings of the 16th AACR Conference on the Science of Cancer Health Disparities in Racial/Ethnic Minorities and the Medically Underserved; 2023 Sep 29-Oct 2;Orlando, FL. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2023;32(12 Suppl):Abstract nr A132.

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.

Incidence and Predictors of Gastric Neoplastic Lesions in Corpus-Restricted Atrophic Gastritis: A Single-Center Cohort Study.

Corpus-restricted atrophic gastritis is a chronic inflammatory disorder leading to possible development of type 1 neuroendocrine tumors (T1gNET), intraepithelial neoplasia (IEN), and gastric cancer (GC). We aimed to assess occurrence and predictors of gastric neoplastic lesions in patients with corpus-restricted atrophic gastritis at long-term follow-up. A prospective single-center cohort of patients with corpus-restricted atrophic gastritis adhering to endoscopic-histological surveillance was considered. Follow-up gastroscopies were scheduled according to the management of epithelial precancerous conditions and lesions of the stomach guidelines. In case of new/worsening of known symptoms, gastroscopy was anticipated. Cox regression analyses and Kaplan-Meier survival curves were obtained. Two hundred seventy-five patients with corpus-restricted atrophic gastritis (72.0% female, median age 61 [23-84] years) were included. At a median follow-up of 5 (1-17) years, the annual incidence rate person-year was 0.5%, 0.6%, 2.8%, and 3.9% for GC/high-grade IEN, low-grade IEN, T1gNET, and all gastric neoplastic lesions, respectively. All patients showed at baseline operative link for gastritis assessment (OLGA)-2, except 2 low-grade (LG) IEN patients and 1 T1gNET patient with OLGA-1. Age older than 60 years (hazard ratio [HR] 4.7), intestinal metaplasia without pseudopyloric metaplasia (HR 4.3), and pernicious anemia (HR 4.3) were associated with higher risk for GC/HG-IEN or LG-IEN development and shorter mean survival time for progression (13.4, 13.2, and 11.1, respectively, vs 14.7 years, P = 0.01). Pernicious anemia was an independent risk factor for T1gNET (HR 2.2) and associated with a shorter mean survival time for progression (11.7 vs 13.6 years, P = 0.04) as well as severe corpus atrophy (12.8 vs 13.6 years, P = 0.03). Patients with corpus-restricted atrophic gastritis are at increased risk for GC and T1gNET despite low-risk OLGA scores, and those aged older than 60 years with corpus intestinal metaplasia or pernicious anemia seem to display a high-risk scenario.

Clinical characteristics of early esophageal cancer and squamous intraepithelial neoplasia in patients of different ages

Clinical characteristics of early esophageal cancer and squamous intraepithelial neoplasia in patients of different ages

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.

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.

Serum Tie-1 is a Valuable Marker for Predicting the Progression and Prognosis of Cervical Cancer.

Objective: To investigate whether serum Tie-1 (sTie-1) is a valuable marker for predicting progression and prognosis of cervical cancer. Methods: Enzyme-linked immunosorbent assay (ELISA) was used to detect serum sTie-1 concentrations in 75 cervical cancer patients, 40 cervical intraepithelial neoplasia (CIN) patients, and 55 healthy controls without cervical lesions, and sTie-1 levels were compared between the groups. Receiver operating characteristic curves was used to evaluate the diagnostic value of sTie-1. The relationship between sTie-1 concentrations in patients with cervical cancer and clinicopathological features and prognosis were analyzed, and the risk factors for postoperative recurrence were determined using univariate and multivariable Cox proportional hazards regression. Results: We found that sTie-1 concentrations gradually increased according to lesion severity (i.e., cancer vs. CIN; p < 0.05) and were significantly elevated in adenocarcinoma compared with healthy controls. sTie-1 levels strongly distinguished between cervical cancer patients and the healthy controls (area under the curve = 0.846; cut-off value = 1,882.64 pg/ml; sensitivity = 74.6%; specificity = 96.4%). Moreover, sTie-1 levels in cervical cancer patients were significantly associated with tumor size, advanced tumor stage, lymph node metastasis, and reduced 4-years progression-free survival. Cervical cancer patients with high sTie-1 concentrations had a 3.123-fold [95% confidence interval (CI): 1.087–8.971, p = 0.034] higher risk for tumor recurrence. Conclusions: Elevated sTie-1 levels in patients with cervical carcinoma were associated with tumor progression and poor prognosis, indicating that sTie-1 may be a valuable marker for predicting progression and prognosis of cervical cancer.

Circulating and tissue miR-100 acts as a potential diagnostic biomarker for cervical cancer.

MicroRNAs (miRNA) are promising biomarkers for cancer diagnosis and prognosis; miR-100 expression is decreased in cervical cancer tissues. To determine whether miR-100 is a useful biomarker for early cervical cancer diagnosis. Total RNA was extracted from the sera of 34 healthy controls (HC), 64 cervical intraepithelial neoplasia patients (CIN), and 46 cervical cancer patients (CC). miR-100 expression levels were measured with quantitative real-time PCR. Correlations between clinicopathological factors and miR-100 expression levels were also assessed. The cut-off value for miR-100 was calculated from the Receiver Operating Characteristic (ROC) curve. Relative expression levels of miR-100 in serum were 1.84 ± 1.72, 3.93 ± 2.52, and 5.32 ± 3.39 in CC, CIN, and HC, respectively; it was significantly lower in CC (p< 0.001). The area under the ROC curve was 0.879 and the cut-off value was 2.451. miR-100 expression levels were significantly higher in metastasis cases that were lymph node negative than positive (p< 0.05). CC patients with miR-100 expression levels below the cut-off value tended to have a poor prognosis. Serum miR-100 may be a useful diagnostic biomarker for CC, and for predicting lymph node metastasis and disease free survival in CC patients.

A retrospective study of cytology and HPV genotypes results of 3229 vaginal intraepithelial neoplasia patients.

To analyze the distribution of human papillomavirus (HPV) genotype, cytology, and the clinical characteristics of vaginal intraepithelial neoplasia (VaIN). All patients with histological-proven VaIN at West China Second University Hospital, between January 1, 2014, and October 1, 2020, were retrospectively identified. The demographics, medical history, HPV genotype, viral load, and cytology results were retrieved. Standard statistical analyses were conducted. Of 3229 patients included, 42.3% were diagnosed with VaIN 1, 30.3% with VaIN 2% and 27.4% with VaIN 3. Patients with VaIN 3 were the oldest (p < 0.001). The leading HPV genotypes were HPV 16, 52, 58, 53, 56 and 81. The positive rate of HPV 16 was positively correlated with the grade of VaIN and infected most VaIN 3 patients (76.0%). The sensitivities of cytology for VaIN only, concomitant VaIN, and VaIN after hysterectomy were 75.6%, 78.8%, and 82.9%, respectively (p = 0.013), and the sensitivities of HPV were 91.1%, 93.5%, and 91.7%, respectively (p = 0.205). Cotesting improved the sensitivities, up to 96.9%, 97.1%, and 98.1%, respectively. VaIN can occur alone or be concomitant with cervical or vulvar intraepithelial neoplasia. Most of those with VaIN 2/3 are infected with HPV 16. The sensitivity of cytology and HPV testing is non-inferior to that of cervical intraepithelial neoplasia 2+. Therefore, these testings might be helpful in the early detection of VaIN.

Epidemiological Characteristics of Human Papillomavirus (HPV) Infection in Different Groups of Women in Chongqing, China.

Persistent high-risk (HR) human papillomavirus (HPV) infection is an essential risk factor for cervical carcinoma and precancerous lesion. There are differences in HPV distribution among different countries, regions and ethnic groups. The aim of this research was to reveal the epidemiological characteristics of HPV in Chongqing, China. In this study, 13,788 women aged 18 to 78 were screened for 23 HPV genotypes by PCR-reverse dot blot hybridization. The total HPV-positive rate was 19.9% (2,745/13,788), while the positive rates for HR, and low-risk (LR) HPV were 17.3% (2,379/13,788), and 4.6% (638/13,788), respectively. In addition to cervical cancer (CC) and cervical intraepithelial neoplasia (CIN) patients, the HPV infection rates among infertile women and women with gynecological diseases were markedly higher than that among healthy women. The HPV and HR-HPV infection rates in the different age groups showed statistically significant differences, and the prevalence peaks were observed in women under 20 years and over 50 years of age. Overall, HPV-52, HPV-16 and HPV-58 ranked as the top 3 most common subtypes among women in Chongqing. The results of this research provide epidemiological information regarding HPV infection in Chongqing. These data constitute valuable evidence for the prevention and management of cervical carcinoma and development of HPV vaccines.

Treatment Outcomes of Patients With Cervical Intraepithelial Neoplasia or Invasive Carcinoma Who Underwent Loop Electrosurgical Excision Procedure.

BackgroundThis study aimed to evaluate the treatment outcomes of cervical intraepithelial neoplasia (CIN) or cancer patients who underwent loop electrosurgical excision procedure (LEEP) in terms of primary outcome and factors associated with persistence/recurrence.MethodsPatients with CIN or cancer who underwent LEEP from January 2007 to December 2015 were reviewed. Data collected were age, parity, menopausal status, human immunodeficiency virus (HIV) infection, smoking, cervical cytology, histopathology from cervical biopsy and LEEP including margin status, final histopathology, and follow-up data.ResultsThe mean age of 385 patients was 41.9 ± 10.8 years (range 18 - 79 years). Majority were multiparous (81.6%) and premenopausal (78.2%). There were 15.3% of patients with HIV infection. The most common cervical cytology was high-grade squamous cell intraepithelial lesion (HSIL, 44.1%), followed by atypical squamous cells of undetermined significance (ACS-US, 21%). Minor complications of bleeding or infection from LEEP were encountered in 7.3%. Among 153 patients (39.7%) who had positive margin(s), 43 underwent second LEEP, whereas 76 had hysterectomy. From all patients, 47 had failure after treatment (12.2%), being either persistence (30 patients; 7.8%) or recurrence (17 patients; 4.4%). Factors associated with persistence or recurrence by multivariate analysis were age ≥ 55 years old, HIV infection, final diagnosis of invasive cancer, and positive endocervical margin or both ecto- and endo- cervical margins.ConclusionsLEEP had low rate of persistence/recurrence. Age ≥ 55 years old, HIV infection, final diagnosis of cancer, and positive endocervical or both endo- and ecto- surgical margin(s) were significantly associated with persistent or recurrent diseases.

Validating METCAM/MUC18 as a Novel Biomarker to Predict the Malignant Potential of Prostate Cancer at an Early Stage by Using a Modified Gold Nanoparticles-Based Lateral Flow Immunoassay.

(1) Background: To further validate METCAM/MUC18 as a diagnostic biomarker for prostate cancer, a modified Lateral Flow Immune Assay (LFIA) with increased sensitivity and specificity was designed by taking advantage of the extremely high affinity between biotin and streptavidin and used. (2) Methods: The combination of a commercial biotinylated rabbit antibody (EPP11278), or the home-made biotinylated chicken antibody, and the nano-gold conjugated home-made chicken antibody or a commercial rabbit antibody (EPP11278), had the higher sensitivity and specificity in this modified LFIA to establish calibration curves from the two recombinant METCAM/MUC18 proteins and were used for determining METCAM/MUC18 concentrations in serum specimens from normal individuals, benign prostatic hyperplasia (BPH) patients, prostatic intraepithelial neoplasia (PIN) patients, prostate cancer patients with various Gleason scores, and treated patients. (3) Results: Data obtained by this modified LFIA were statistically better than traditional LFIA and prostate-specific antigen (PSA) test. Interestingly, serum METCAM/MUC18 concentrations were higher in pre-malignant PIN patients than prostate cancer patients and both were higher than normal individuals, BPH patients, and treated patients. Serum METCAM/MUC18 concentrations were directly proportional to most serum PSA. (4) Conclusions: Elevated serum METCAM/MUC18 concentrations may be used for predicting the malignant potential of prostate cancer at an early premalignant (PIN) stage, which is not achievable by the current PSA test.

Diagnostic Value of Serum N1-Methylnicotinamide in Cervical Cancer Patients

The current study evaluated the level of serum N1-methylnicotinamide (me-NAM) in cervical cancer patients and further explored whether serum me-NAM was related to the prognosis of cervical cancer. Fifty-eight cases of cervical intraepithelial neoplasia patients, 78 cases of cervical cancer patients, and 52 healthy women were included in the present study. Serum me-NAM concentrations were determined by liquid chromatography with tandem mass spectrometry. Receiver operating characteristic (ROC) curve was used to assess me-NAM as a biomarker and Kaplan-Meier analysis was carried out to evaluate the survival rate. Our data showed that the level of serum me-NAM in cervical cancer patients was significantly higher than that in the cervical intraepithelial neoplasia group and the healthy control group. Furthermore, the level of me-NAM in cervical cancer tissues of stage I, II, III, and IV was higher than that of those without lymph node metastasis. The area under the receiver operating characteristic curve (ROC) for me-NAM was higher than that of squamous cell carcinoma antigen (SCC Ag) and carbohydrate antigen 125 (CA125) when comparing cervical cancer from CIN or healthy control. The combination of me-NAM and SCC Ag or CA125 could improve the diagnostic efficiency better than SCC Ag or CA125 alone. Compared with me-NAM low expression group, the survival rate and time of me-NAM high expression group were lower and shorter. Altogether, elevated serum me-NAM levels contribute to the progression of cervical cancer and may be used as a marker for the prognosis of patients with cervical cancer.

Revealing the Disturbed Vaginal Micobiota Caused by Cervical Cancer Using High-Throughput Sequencing Technology.

Cervical cancer is the fourth most prevalent cancer type among all malignancies, so it is of great significance to find its actual pathogenesis mechanisms. In the present study, 90 women were enrolled, and high-throughput sequencing technology was firstly used to analyze the vaginal microbiota of healthy women (C group), cervical intraepithelial neoplasia patients (CIN group) and cervical cancer patients (CER group). Our results indicates that compared with C group, a higher HPV infection rate as well as increased Neutrophil ratio and tumor marker squamous cell carcinoma antigen (SCCA) were obtained, and a decrease in Lymphocyte ratio and Hemoglobin were also present. In addition, the cervical cancer showed a strong association with reduced probiotics Lactobacillus, increased pathogens Prevotella spp., Sneathia spp. and Pseudomonas spp. These results prove that the immunological changes generated by the cervical cancer and the vaginal microbiota can interact with each other. However, further study investigating the key bacteria for cervical cancer is still needed, which can be a clue for the diagnosis or treatment of cervical cancer.