The relationship between long non-coding gene CASC21 polymorphisms and cervical cancer.

BACKGROUND: CASC21 was reported to be a hotspot gene in cervical cancer. The relationship between CASC21 genetic polymorphisms and cervical cancer has not been reported. Genetic factors influence the occurrence of cervical cancer. Thus, we explored the correlation between CASC21 polymorphisms and cervical cancer. METHODS: A total of 973 participants within 494 cervical cancer cases and 479 healthy controls were recruited. Five single nucleotide polymorphisms (SNPs) in the CASC21 gene were genotyped using the Agena MassARRAY platform. Chi-squared test, logistic regression analysis, odds ratio (OR), multifactor dimensionality reduction (MDR), and 95% confidence interval (95%CI) were used for data analysis. RESULTS: In the overall analysis, rs16902094 (p = .014, OR = 1.86, 95% CI = 1.12-3.08) and rs16902104 (p = .014, OR = 1.86, 95% CI = 1.12-3.09) had the risk-increasing correlation with the occurrence of cervical cancer. Stratification analysis showed that rs16902094 and rs16902104 were still associated with cervical cancer risk in the subgroups with age > 51, BMI < 24 kg/m2, smokers, and patients with cervical squamous cell carcinoma. MDR analysis displayed that rs16902094 (.49%) and rs16902104 (.52%) were the main influential attribution factor for cervical cancer risk. CONCLUSION: Our finding firstly determined that two CASC21 SNPs (rs16902094, rs16902104) were associated with an increased risk of cervical cancer, which adds to our knowledge regarding the effect of CASC21 on cervical carcinogenesis.

Analysis of somatic mutations and key driving factors of cervical cancer progression.

We investigated the somatic mutations and key driving factors of cervical cancer by whole exome sequencing . We found 22,183 somatic single nucleotide variations (SNVs) in 52 paired samples. Somatic SNVs in cervical cancer were significantly higher than those in high-grade intraepithelial lesion and low-grade squamous intraepithelial lesion groups (P < 0.05). C → T/G accounted for 44.12% of base substitution. Copy number variation (false discovery rate < 0.05) was found in 57 chromosome regions. The three regions with significant differences between cervical cancer and non-cervical cancer groups were 1q21.1, 3q26.33, and 13q33.1, covering genes related to tumor proliferation, differentiation, and apoptosis. The frequency of human papillomavirus (HPV) insertion/integration and the number of "tCw" mutations in the cervical cancer group were significantly higher than those in the non-cervical cancer group (P < 0.05). The total number of mutations was positively correlated with the number of "tCw" mutations (R 2 = 0.7967). HPV insertion/integration (OR = 2.302, CI = 1.523-3.589, P = 0.0005), APOBEC enrichment (OR = 17.875, CI = 2.117-150.937, P = 0.001), and HLA-B*39 in HLA-I (OR = 6.435, CI = 0.823-48.919, P = 0.0042) were risk factors for cervical cancer, while HLA-DQB1*05 in HLA-II was a protective factor (OR = 0.426, CI = 0.197-0.910, P = 0.032). Conclusively, HPV insertion/integration, APOBEC mutagenesis, and HLA polymorphisms are high-risk factors for cervical cancer and may be causes of genome instability and somatic mutations. This study provides experimental data for revealing the molecular mechanism of cervical cancer.

Implementation of visual inspection with acetic acid and Lugol's iodine for cervical cancer screening in rural China.

OBJECTIVE: To address the value of visual inspection where HPV-based screening is not yet available, we evaluated the real-world effectiveness of visual inspection with acetic acid (VIA) and with Lugol's iodine (VILI) as a primary screening method for cervical cancer in rural China. METHODS: A total of 206 133 women aged 30-59 years received two rounds of VIA/VILI screening for cervical cancer in 2006-2010. Women with positive screening results underwent colposcopy and direct biopsy, and were treated if cervical intraepithelial neoplasia grade 2 or worse (CIN2+) was diagnosed. Clinical effectiveness of VIA/VILI was evaluated by process and outcome measures. RESULTS: The VIA/VILI positivity rate, biopsy rate and detection rate of CIN2+ in the second round were significantly lower than in the first round. The 2-year cumulative detection rate of CIN2+ varied from 0.53% to 0.90% among the four cohorts initiated in 2006, 2007, 2008, and 2009. The first round of screening detected 60%-83% of CIN2, 70%-86% of CIN3, and 88%-100% of cervical cancer. Over 92% of CIN2+ were found at the early stage. CONCLUSION: Multiple rounds of visual inspection with continuous training and quality assurance could act as a temporary substitutional screening method for cervical cancer in resource-restricted settings.

Evaluation of triage strategies for high-risk human papillomavirus-positive women in cervical cancer screening: A multicenter randomized controlled trial in different resource settings in China.

Objective: We aimed to evaluate the effectiveness of different triage strategies for high-risk human papillomavirus (hrHPV)-positive women in primary healthcare settings in China. Methods: This study was undertaken in 11 rural and 9 urban sites. Women aged 35-64 years old were enrolled. HrHPV-positive women were randomly allocated to liquid-based cytology (LBC), visual inspection with acetic acid and Lugol's iodine (VIA/VILI) (rural only) triage, or directly referred to colposcopy (direct COLP). At 24 months, hrHPV testing, LBC and VIA/VILI were conducted for combined screening. Results: In rural sites, 1,949 hrHPV-positive women were analyzed. A total of 852, 218 and 480 women were randomly assigned to direct COLP, LBC and VIA/VILI. At baseline, colposcopy referral rates of LBC or VIA/VILI triage could be reduced by 70%-80%. LBC (n=3 and n=7) or VIA/VILI (n=8 and n=26) could significantly decrease the number of colposcopies needed to detect one cervical intraepithelial neoplasia (CIN) 2 or worse and CIN3+ compared with direct COLP (n=14 and n=23). For the 24-month cumulative detection rate of CIN2+, VIA/VILI triage was 0.50-fold compared with LBC triage and 0.46-fold with the direct COLP. When stratified by age, baseline LBC triage+ performed best (P<0.001), peaking among women aged 35-44 years (Ptrend=0.002). In urban sites, 1,728 women were hrHPV genotyping test positive. A total of 408, 571 and 568 women were randomly assigned to direct COLP for HPV16/18+, direct COLP for other hrHPV subtypes+, and LBC triage for other hrHPV subtypes+. LBC (n=12 and n=31) significantly decreased the number of colposcopies needed to detect one CIN2+ and CIN3+ compared with direct COLP (n=14 and n=44). HPV16/18+ increased the 24-month cumulative detection rate of CIN2+ (17.89%, P<0.001). Conclusions: LBC triage for hrHPV-positive women in rural settings and direct COLP for HPV16/18+ women and LBC triage for other hrHPV subtype+ women in urban settings might be feasible strategies.

Period Analysis of Intraracial Differences in Incidence and Survival Rates in Epithelial Ovarian Cancer.

BACKGROUND: To explain the difference in the incidence and relative survival in a population-based cohort of women with epithelial ovarian cancer (EOC) postdiagnosis in the last forty years. EOC is the most common type of all ovarian cancers, but there is inadequate information about the variations related to long-term EOC survival. METHODS: We acquired the incidence and relative survival rate data from the Surveillance, Epidemiology, and End Results (SEER) registries to analyze the epidemiological variations from 1974 to 2013 in EOC-affected individuals. The survival disparities in EOC-specific individuals due to age, race, and socioeconomic status (SES) were performed by Kaplan-Meier analysis. The Results. The overall incidence of EOC progressively declined to 9.0 per 100,000 from 11.4 in the last forty years. The median survival rate improved to 48 months in the first decade from a previous of 27 months in the fourth decade. The 5-year relative survival rate (RSR) increased to 44.3% that was previously 32.3% at the same time. However, between whites and blacks, an increase from 11 to 18 months was observed in the median survival differences. Between the low and high poverty groups, it was increased from 7 months to 12 months, respectively. CONCLUSIONS: The incidence rate of RSR and EOC-specific individuals in the last forty years was improved. However, the survival rates among different races and SES differed over time.

ThinPrep cytology combined with HPV detection in the diagnosis of cervical lesions in 1622 patients.

The timely detection of precancerous lesions and early intervention can greatly reduce cervical cancer occurrence. The current study aimed to assess the diagnostic value and accuracy of different methods of cervical lesion screening. A total of 1622 females who visited the Outpatient Department of Xinjiang Uyghur Autonomous Region People's Hospital between January and December 2018 were consecutively enrolled. All participants underwent separate high-risk human papilloma virus (HR-HPV) DNA detection, ThinPrep cytology testing (TCT) and colposcopic biopsy. Their medical records were retrospectively analyzed. While considering biopsy outcomes as the gold standard, the diagnostic values of TCT, HR-HPV testing, and TCT+HR-HPV testing for cervical cancer screening were compared. The sensitivity, specificity and Youden index of each method were calculated. Among the different methods, TCT+HR-HPV testing had the highest sensitivity (89.8%), followed by TCT (79.9%) and HR-HPV testing (49.2%). The combined method also had the highest Youden value, and its screening outcomes exhibited the highest consistency with those of biopsy. In addition, the combined method had the largest area under the receiver operating characteristic (ROC) curve, which was 0.673 (0.647, 0.699), compared with any other screening method. Compared with TCT or HR-HPV testing alone, TCT+HR-HPV testing serves as a better screening method for cervical cancer and precancerous lesions.

Clinical analysis of uterine arterial interventional chemoembolization combined with radiotherapy in mid-advanced cervical cancer.

PURPOSE: To compare the efficacy and safety of uterine arterial interventional chemoembolization (UAIC) combined with radiotherapy and intravenous chemotherapy combined with radiotherapy in the treatment of mid-advanced cervical cancer. METHODS: The clinical data of 128 patients with mid-advanced cervical cancer were retrospectively analyzed. According to different treatment methods, the patients were divided into two groups. Docetaxel+nedaplatin UAIC combined with intensity-modulated radiotherapy was performed in UAIC group (n=64), while docetaxel+nedaplatin intravenous chemotherapy combined with intensity-modulated radiotherapy (IMRT) was performed in the control group (n=64). The short-term clinical efficacy and incidence of adverse reactions were compared between the two groups. The tumor recurrence and survival status were recorded during follow-up, and the progression-free survival (PFS) and overall survival (OS) were compared between the two groups. RESULTS: The short-term clinical response rate was 70.3% (45/64) and 48.4% (31/64), respectively, in the UAIC and the control group. In the functional scales of European Organization for Research and Treatment of Cancer-Quality of Life Questionnaire-Core 30 (EORTC-QLQ-C30), the scores of physical function, role function, cognitive function, emotional function and social function were higher in the UAIC group than in the control group, but only the emotional function score had a statistically significant difference. In the symptom scales, the scores of sleep disturbance, nausea and vomiting, pain and fatigue were obviously lower in the UAIC group than those in the control group. The general health score was 79.46±11.28 points and 78.17±13.49 points, respectively, in the UAIC and the control group. Follow-up results revealed that the 3-year OS was 70.3% (45/64) and 73.4% (47/64), and the 3-year PFS was 64.1% (41/64) and 65.6% (42/64), respectively, in the UAIC and the control group. Log-rank test showed that OS and PFS had no statistically significant differences between the two groups. CONCLUSIONS: UAIC combined with radiotherapy has better short-term clinical efficacy than intravenous chemotherapy combined with radiotherapy in the treatment of mid-advanced cervical cancer, with fewer adverse reactions and higher quality of life, but it had no significant effect on the long-term survival and tumor progression.

Effectiveness of High-risk Human Papillomavirus Testing for Cervical Cancer Screening in China: A Multicenter, Open-label, Randomized Clinical Trial.

IMPORTANCE: Evidence is needed regarding the introduction of high-risk human papillomavirus (hrHPV) testing into China's national cervical cancer screening program. OBJECTIVE: To evaluate hrHPV testing as a new screening modality for the national program. DESIGN, SETTING, AND PARTICIPANTS: This population-based, multicenter, open-label, randomized clinical trial took place across 20 primary health care centers in urban and rural areas across China. At least 3000 women aged 35 to 64 years per site were invited to participate, for a total of 60 732 women evaluated. INTERVENTIONS: At baseline, women were randomly assigned to cytology, hrHPV testing, or visual inspection with acetic acid and Lugol iodine (VIA/VILI) (rural only). Women who tested positive for hrHPV were randomized into cytology-triage, VIA/VILI-triage (rural only), or direct colposcopy arms. Regarding primary or triaging tests, women with cytological abnormalities or who tested positive with VIA/VILI were referred to colposcopy. After 24 months, combined screening of cytology, hrHPV testing, and VIA/VILI was performed, and all women with positive results were referred to colposcopy. MAIN OUTCOMES AND MEASURES: The primary outcomes were cervical intraepithelial neoplasia grade 2 or worse (CIN2+) and CIN3+ yields. The secondary outcome was colposcopy referral rate. RESULTS: A total of 60 732 women were included in this study, with median (interquartile range) age of 47 (41-52) years. Among urban women, 8955 were randomized to cytology and 18 176 to hrHPV genotyping; among rural women, 11 136 were randomized to VIA/VILI, 7080 to cytology, and 15 385 to hrHPV testing. Participants who tested positive for hrHPV with direct colposcopy had higher risk ratios for disease yields at baseline (urban hrHPV vs cytology, CIN2+ 2.2 [95% CI, 1.6-3.2] and CIN3+ 2.0 [95% CI, 1.2-3.3]; rural hrHPV vs cytology, 2.6 [95% CI, 1.9-4.0] and 2.7 [95% CI, 2.0-3.6]; rural hrHPV vs VIA/VILI, 2.0 [95% CI, 1.6-2.3] and 2.3 [95% CI, 1.8-3.1]). At 24 months, baseline-negative women in the hrHPV arm had significantly lower risk ratios than those with cytology, or VIA/VILI for CIN2+ (0.3 [95% CI, 0.2-0.5], 0.3 [95% CI, 0.2-0.6]) and CIN3+ (0.3 [95% CI, 0.1-0.6], 0.4 [95% CI, 0.2-0.8]) in rural sites. The colposcopy referral rate for hrHPV-positive rural women was reduced to 2.8% by cytology triage, with significantly higher CIN2+ yields than cytology (2.1 [95% CI, 1.3-2.6]) or VIA/VILI arm (1.6 [95% CI, 1.03-2.1]). Genotyping for hrHPV with cytology triage significantly reduced the colposcopy referral rate compared with cytology (0.8 [95% CI, 0.7-0.9]) for urban women. CONCLUSIONS AND RELEVANCE: In this randomized clinical trial, testing for hrHPV was an effective primary screening method in primary health care centers. Incorporating hrHPV testing (polymerase chain reaction-based for urban areas, hybrid capture-based for rural areas) into China's national screening program is reasonable. TRIAL REGISTRATION: Chinese Clinical Trial Registry Identifier: ChiCTR1900022530.

Genetic polymorphisms of PGF and TNFAIP2 genes related to cervical cancer risk among Uygur females from China.

BACKGROUND: PGF and TNFAIP2 are important angiogenic factors, which were abnormal expression in cervical cancer (CC). However, there is currently no report investigating the relationship of PGF and TNFAIP2 gene polymorphisms to CC risk. METHODS: We conducted a case-control study of 342 CC patients and 498 cancer-free controls in a Chinese Uygur female population. Three SNPs (PGF rs8019391, PGF rs2268615, and TNFAIP2 rs710100) were selected and genotyped to assess the possible association of PGF and TNFAIP2 polymorphisms with CC susceptibility. Logistic regression analysis adjusted by age was used. RESULTS: PGF rs2268615 (OR = 1.39, 95% CI = 1.04-1.86, p = 0.024) and TNFAIP2 rs710100 (OR = 1.44, 95% CI =1.07-1.95, p = 0.018) polymorphisms were associated with the increased risk of CC. Moreover, T allele of PGF rs8019391 was highly represented in patients with stage III-IV compared with stage I-II (OR = 2.17, p = 4.58 × 10- 4). MDR analysis revealed a positive interaction between the SNPs. CONCLUSION: Our data indicated that PGF rs2268615, and TNFAIP2 rs710100 polymorphisms might be risk factors for CC susceptibility, which contributed to the increased risk of CC. TRIAL REGISTRATION: Not applicable.

Association between APOBEC3s and HPV16 E2 gene hypermutation in Uygur females with cervical cancer.

The present study aimed to investigate whether apolipoprotein B mRNA-editing enzyme catalytic polypeptides (A3) are involved in the regulation of cervical cancer development and human papilloma virus (HPV)16 sustained infection in Uighur females. Cervical tissues of Uygur patients with HPV16 with cervical lesions were collected. Expression levels of A3C, A3F and A3G were detected using reverse transcription-quantitative PCR and western blotting. A model of SiHa cells with high expression levels of A3C, A3F and A3G was constructed. Hypermutation was detected using the differential DNA denaturation PCR and positive samples were amplified and sequenced. There were significant differences in A3 expression levels in cervical lesions of different grades. A3C and A3F mRNA and protein expression in cervical cancer tissues were significantly lower, whereas the A3G mRNA and protein expression levels were significantly higher compared with the cervicitis and cervical intraepithelial neoplasia (CIN) I-III groups. Hypermutation rates were increased with cervical lesion development. C>T and G>A base substitutions were detected in all hypermutation samples and numbers of C>T and G>A base substitutions in single samples in the cervical cancer group were significantly higher compared with those in the CIN I-III and cervicitis groups. Following transfection of A3F and A3G, HPV E2 mRNA and protein expression levels were significantly decreased in SiHa cells. Numerous C>T and G>A base substitutions were detected in the HPV E2 gene in A3G and A3C overexpressing SiHa cells. A3 family proteins inhibit viral replication during HPV16 infection and regulate the HPV16 integration by inducing C>T and G>A hypermutations in the HPV16 E2 gene, thus affecting the cervical cancer pathogenesis and development.

Meta-analysis of the diagnostic accuracy of HE4 for endometrial carcinoma.

OBJECTIVE: To analyze and evaluate the value of serum human epididymis protein 4 (HE4) for the diagnosis of endometrial cancer (EC). METHODS: Studies involving HE4 and the diagnosis of EC were retrieved from the following medical literature databases: Medline, PubMed, Web of Science, China National Knowledge Infrastructure, China Biology Medicine Disc, Vip Journal Integration Platform, and Wanfang Data Knowledge Service Platform. Quality assessment was performed independently by two reviewers using Review Manager 5.3 (Cochrane Collaboration Group). A quality table of included studies was made using Review Manager 5.3, and the pooled sensitivity (SEN), specificity (SPE), positive likelihood ratio (PLR), negative likelihood ratio (NLR), diagnostic accuracy, and receiver operating characteristic curve (SROC) were analyzed using Review Manager 5.3 and Meta-Disc 1.4 software. RESULTS: Of 887 studies, 17 passed quality assessment and were included in the final study. The pooled SEN was 0.65 (95 % confidence interval [CI]: 0.63-0.67), SPE was 0.913 (95 % CI: 0.92-0.95), PLR was 10.06 (95 % CI: 4.75-21.35), NLR was 0.41 (95 % CI: 0.33-0.50), diagnostic odds ratio (DOR) was 26.7 (95 % CI: 11.7-60.93), and the area under curve (AUC) of the receiver operating characteristic curve (SROC) curve was 0.75 (95 % CI: 0.81-0.87). CONCLUSIONS: HE4 is a potential biomarker for the diagnosis of EC with a high specificity and relatively low sensitivity. Considering high heterogeneity and selection bias, the value of HE4 for diagnosing EC should be further evaluated in strictly-designed diagnostic studies as well as in different pathological types and stages of EC.

RIPK1 polymorphisms alter the susceptibility to cervical Cancer among the Uyghur population in China.

BACKGROUND: RIPK1 (receptor-interacting protein kinase-1) plays a role in cancer development, whereas no clear studies focused on the cervical cancer. The objective of this study was to evaluate the relationship between RIPK1 polymorphisms and cervical cancer risk among the Uyghur population. METHODS: We performed a case-control study including 342 cervical cancer patients and 498 age-matched healthy controls. Four RIPK1 genetic variants (rs6907943, rs2077681, rs9503400 and rs17548629) were genotyped with Agena MassARRAY platform. The associations between RIPK1 polymorphisms and cervical cancer risk were assessed under Binary logistic regression models. False discovery rate (FDR) was used to improve the results reliability. RESULTS: The results showed rs2077681 was significantly associated with cervical cancer risk under various genetic models (codominant: OR = 3.14, 95% CI = 1.40-7.07, p = 0.006, FDR-p = 0.018; recessive: OR = 3.20, 95% CI = 1.43-7.16, p = 0.005, FDR-0.018). The stratified analysis indicated that the relationships of rs6907946, rs9503400 and rs17548629 with cervical cancer risk were statistically significant in the subgroup of clinical stage (p < 0.05). CONCLUSION: Our findings demonstrated that RIPK1 polymorphisms were associated with cervical cancer susceptibility among the Uyghur population in China, and RIPK1 polymorphisms might be involved in the development of cervical cancer.

Association study between the polymorphisms of angiogenesis-related genes and cervical cancer susceptibility in Chinese Uygur population.

BACKGROUND: Cervical cancer is the second most common malignant tumor in women, and its invasion and metastasis are regulated by tumor angiogenic growth factors and their cognate receptors. In this study, we explored the relationship between genetic polymorphisms of angiogenesis-related genes (VEGF-C, VEGFR-2, and VEGFR-3) and the risk of cervical cancer in Chinese Uygur population. METHODS: We investigated four single-nucleotide polymorphisms (SNPs) in 342 cervical cancer cases and 498 controls to evaluate their association with the risk of cervical cancer. Their correlations were evaluated by chi-squared test, Fisher's exact test, t test, and genetic model analyses. Odds ratios (ORs) and 95% confidence intervals (95% CIs) were calculated using unconditional logistic regression. RESULTS: We observed that rs12646659 in VEGF-C was associated with a lower cervical cancer risk in allele, dominant, and log-additive models (allele: p = .017; dominant: p = .018; log-additive: p = .018). For the individuals older than 43, rs4604006 (VEGF-C) was related to an increased cervical cancer risk under codominant model (p = .035), and rs12646659 was significantly associated with a reduced cervical cancer risk in allele, dominant, log-additive models (allele: p = .028; codominant: p = .037; log-additive: p = .037) However, there were no significant correlation of rs1000611 (VEGFR-2) and rs1195571 (VEGFR-3) with cervical cancer risk in Chinese Uygur population. CONCLUSION: Our study firstly provided evidence that rs4604006 and rs12646659 of VEGF-C gene were related to the susceptibility of cervical cancer in Chinese Uygur population.

TNFAIP8L1 and FLT1 polymorphisms alter the susceptibility to cervical cancer amongst uyghur females in China.

TNFAIP8L1 and FLT1 play critical roles in the occurrence and development of tumors, but no in-depth studies have been carried out in cervical cancer. The present study aims to research the correlation between polymorphisms of these two genes and the risk of cervical cancer in the Uygur women. The study involved 342 cervical cancer patients and 498 healthy women. Five single nucleotide polymorphisms (SNPs) from the TNFAIP8L1 gene and the FLT1 gene were selected and genotyped. Odds ratio and 95% CIs were calculated by logistic regression analysis to evaluate the correlation between SNPs and cervical cancer risk. The alleles rs9917028-A (P=0.032), rs10426502-A (P=0.007), and rs1060555-G (P=0.026) of TNFAIP8L1 were associated with a decreased risk of cervical cancer. In the multiple genetic models, these three SNPs were also associated with the risk of cervical cancer. The stratified analysis showed that TNFAIP8L1-rs10426502, -rs1060555, and FLT1-rs9513111 were associated with a decreased risk of cervical cancer amongst people older than 43 years. Moreover, the haplotypes AG (P=0.007) and GC (P=0.026) of linkage disequilibrium block rs10426502|rs1060555 in TNFAIP8L1 were significantly associated with an increased risk of cervical cancer. Our results suggested that the relationships between TNFAIP8L1 and FLT1 polymorphisms and the risk of cervical cancer amongst Uyghur females.

Factors associated with high-risk HPV infection and cervical cancer screening methods among rural Uyghur women aged > 30 years in Xinjiang.

BACKGROUND: Cervical cancer is the most common genital malignant tumor in women worldwide. However, the reliability of different detection methods may vary according to populations and epidemics. This study analyzed factors relevant to high-risk human papillomavirus (hrHPV) infection among rural Uyghur women aged > 30 years and evaluated the value of different screening methods for cervical precancerous lesions. METHODS: From July 2015 to May 2016, 225 rural Uyghur women aged > 30 years were recruited from local health clinics throughout Pishan, Xinjiang, China. HrHPV DNA testing, colposcopy, biopsy of cervical precancerous lesions, and surveys were conducted. The results of different screening methods were compared, and factors associated with hrHPV infection were analyzed. RESULTS: The rates of hrHPV infection and cervical epithelial lesions were 9.3 and 1.8%, respectively. The area under the ROC curve was 0.538 (95% CI: 0.292, 0.784; P = 0.753) for the HPV test and 0.995 (95% CI: 0.988, 1.003; P < 0.001) for colposcopy. Factors associated with HPV infection included widowhood (OR = 13.601 (2.170, 85.263), P = 0.005) and ≥ 3 sexual partners in the past 5 years (OR = 16.808 (4.148, 68.101), P < 0.001). . CONCLUSIONS: Among rural Uyghur women aged > 30 years, the main factors for HPV infection include marriage and frequent sexual intercourse. Colposcopy has a higher screening value for cervical epithelial lesions than hrHPV testing.

Clinical Value of Human Papillomavirus E6/E7 mRNA Detection in Screening for Cervical Cancer in Women Positive for Human Papillomavirus DNA or.

BACKGROUND: The detection of human papillomavirus (HPV) E6/E7 mRNA indicates a risk of further deterioration in cervical lesions. We explored the clinical value of HPV E6/E7 mRNA detection in cervical cancer screening in women positive for HPV or with abnormal thin-prep cytology test (TCT) results in the Xinjiang region of China. METHODS: A total of 6,800 women were screened in our hospital for cervical cancer by both TCT and HPV DNA testing from August 2013 to June 2015. Of these, 197 had abnormal cytological or HPV test results and subsequently underwent HPV E6/E7 mRNA detection and histopathological examination, while 101 underwent an HPV DNA typing test. Using pathological results as the gold standard, we compared the accuracies of HPV E6/E7 mRNA detection or HPV DNA type testing alone, in parallel, and in series for diagnosing high-grade cervical lesions. RESULTS: Pathological examination revealed 80 cases of chronic cervicitis, 16 cases of cervical intraepithelial neoplasia (CIN)-I, 50 cases of CIN-II-III, and 51 cases of cervical cancer. The area under the receiver operating characteristic (ROC) curve (AUC) for diagnosing high-grade cervical lesions by HPV E6/E7 mRNA detection was 74.95% (sensitivity, 85.15%; specificity, 66.67%; Youden index, 0.139; positive predictive value, 72.9%; negative predictive value, 81.0%; positive likelihood ratio, 2.555; negative likelihood ratio, 0.222; and post-test probability, 72.9%). CONCLUSIONS: HPV E6/E7 mRNA detection is superior to HPV DNA type testing for diagnosing high-grade cervical lesions.

MicroRNA-505 predicts prognosis and acts as tumor inhibitor in cervical carcinoma with inverse association with FZD4.

PURPOSE: We investigated the expression and mechanisms of microRNA-505 (miR-505) and its downstream target gene Frizzled-4 (FZD4) in cervical cancer. METHODS: miR-505 expression was evaluated by qRT-PCR in cervical cancer cell lines and human carcinomas. Cancer patients' clinicopathological factors and survival were analyzed based on their tumorous miR-505 levels. Ca-Ski and HeLa cells were transduced with lentivirus to upregulate or downregulate miR-505. Their impacts on cervical cancer were evaluated by in vitro proliferation, invasion and in vivo tumorigenicity assays, respectively. Target gene of miR-505, FZD4, was evaluated by dual-luciferase reporter assay. Its expression in cervical cancer cell was evaluated by qRT-PCR. FZD4 was either upregulated or downregulated in cervical cancer cells to further assess its impact on modulating cervical cancer development in vitro. RESULTS: MiR-505 is lowly expressed in cervical cancer cell lines and human carcinomas. Low tumorous miR-505 expression was associated with patients' advanced tumor stage and short survival. In Ca-Ski and HeLa cells, lentivirus-mediated miR-505 upregulation suppressed cancer proliferation and invasion in vitro, and tumorigenicity in vivo, whereas miR-505 downregulation had no functional effects. FZD4 was confirmed to be a downstream target of miR-505, and found to be upregulated in cervical cancer. Genetic modification of FZD4 in cervical cancer cells yielded a significant change in cancer growth, as FZD4 upregulation suppressed whereas FZD4 downregulation promoted cervical cancer proliferation and invasion In vitro. CONCLUSION: MiR-505 may act as a cancer inhibitor and prognostic factor in cervical cancer. FDZ4 is reversely expressed as miR-505, and has dramatic regulatory function in cervical cancer.

Prevalence of and risk factors for high-risk human papillomavirus infection: a population-based study from Hetian, Xinjiang, China.

Human papillomavirus (HPV) infection contributes to most cases of cervical cancer, and HPV genotypes exhibit different distributions according to geographic region. This study evaluates the prevalence of HPV infection in Hetian Prefecture, Xinjiang, and establishes risk factors associated with high-risk HPV (HR-HPV) genotypes in this region. In this cross-sectional, population-based study, 883 healthy women 15-54 years of age were enrolled. All participants completed a questionnaire regarding sociocultural and sexual activity characteristics. Visual inspections with acetic acid, colposcopies and biopsies were performed using the Preventive Oncology International microbiopsy protocol for pathological diagnosis. Cervical epithelial tissue specimens were collected and tested for HPV using linear array assays. According to the results of HR-HPV infection status, individuals infected with HR-HPV were classified into one group, and the remaining individuals were classified into the control group. The risk factors for HR-HPF infection were analyzed. The participants included 66 women (7.47%) with HR-HPV, 10 women (1.13%) with low-risk HPV, and 14 women (1.59%) with HPV of unknown risk. The five most prevalent types of HR-HPV were HPV-16 (0.31%), HPV-51 (0.08%), HPV-31 (0.07%), HPV-58 (0.07%), and HPV-39 (0.06%). Vulvovaginal ulcers and vulvovaginal inflammation were found in 190 participants (21.52%) and 256 participants (28.99%), respectively. The HR-HPV and control groups significantly differed with respect to age at first marriage, number of marriages, and the presence of vulvovaginal ulcers and vulvovaginal inflammation (p<0.05). Based on this study, an immunization strategy targeting HPV-16 should be prioritized in Hetian Prefecture. These findings contribute to the understanding of HPV infection.

A Serological Epidemiological Survey of Antibodies against 4 HPV Subtypes in Uygur Women in Xinjiang.

This study evaluated the distribution of antibodies against 4 human papillomavirus (HPV) subtypes and their related factors among Uygur women in Xinjiang. A cross-sectional study was conducted from March 2006 to May 2007 involving 883 Uygur women aged 17-54 years living in Yutian County. Demographic indicators, disease history, sexual behavior history, and other parameters were recorded at the interview using a questionnaire. A fluorescence detection method was used to quantify anti-HPV6, -11, -16, and -18 antibodies in venous blood serum. The rate of positive detection of any anti-HPV antibody (anti-HPV6, -11, -16, and -18) in the study population was 13.4%, and the individual positivity rates were 9.5%, 2.6%, 4.3%, and 0.7%, respectively. Peak rates of positivity for the anti-HPV16 antibody were found in women who were 36-40 and 46-50 years old. Seroprevalence of HPV16, which is high-risk for cervical cancer, was associated with the numbers of sexual partners. The rate of infection with high-risk HPV was low among Uygur women from rural areas, although there is a high incidence of cervical cancer in this group. Loyalty to one sexual partner decreased the risk of high-risk HPV infection. This study may provide useful reference data for the prevention and treatment of HPV and cervical cancer and for the application of HPV vaccines.

Comparative study of HPV16 integration in cervical lesions between ethnicities with high and low rates of infection with high-risk HPV and the correlation between integration rate and cervical neoplasia.

The etiology of a high incidence of cervical cancer in populations with a low human papillomavirus (HPV) infection rate is unclear. The current study aimed to investigate the role of HPV16 DNA integration in cervical lesions in women of Han and Uygur ethnicity and to explore the association between viral integration and a high cervical cancer morbidity with a low HPV infection rate. DNA was extracted from the biopsy specimens of cervical lesions of 379 patients of Uygur ethnicity and 464 patients of Han ethnicity, and multiple quantitative polymerase chain reaction (qPCR) assays were performed to determine the copy numbers of the HPV16 E2 and E6 genes. The copy number of the HPV16 DNA was evaluated according to the E2/E6 ratio. Among these cases, 122 Uygur and 121 Han specimens were found to be HPV16 positive. In the two populations, the percentage of cases with HPV16 integration (the sum of integrated-type infection only or a mixture of free-and integrated-type infection) increased with the grade of the cervical lesions (P<0.001). Within groups with the same cervical lesion grade, no significant differences in HPV16 integration were found between women of Uygur and Han ethnicity (rank sum test, P>0.05). No significant differences in the distribution of the HPV16 integration rate according to lesion grade were found in either population (P>0.05). When the two subpopulations were considered as one sample population, the integration rate significantly increased with lesion grade (P=0.02). These results indicate that the integration rate of HPV16 E2 may serve as a molecular biological marker for the development of cervical lesions.