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.

Human papillomavirus Posttreatment Clearance Time in Cervical Intraepithelial Neoplasia and Invasive Cervical Cancer.

OBJECTIVE: The aim of the study was to determine an appropriate follow-up schedule for human papillomavirus (HPV) detection by evaluating the clearance time of HPV after treatment. MATERIALS AND METHODS: A retrospective study was conducted on 97 high-grade squamous intraepithelial lesion (HSIL) (cervical intraepithelial neoplasia 2-3) patients and 437 early invasive cervical cancer (CC) (stages Ia-IIa) patients who received radical surgery at the Affiliated Tumor Hospital of Xinjiang Medical University. Patient medical information, including personal information, pathological diagnosis, HPV infection status, and therapeutic methods, was obtained through the hospital's historical medical records management system. The clearance time of HPV was determined using Kaplan-Meier method analysis, and clearance time of HPV among different age groups, different grades, and different clinical stages were compared using the log-rank test. RESULTS: The median clearance time of all patients was 10.4 months. The median clearance time was longer in HSIL patients than in early invasive CC patients (p < .05). No statistical significance was found among different HSIL grades, CC stages, or patient age groups (P > 0.05). CONCLUSIONS: Delaying first posttreatment follow-up to 9 months in patients at high risk of noncompliance could potentially reduce burden of cost and repeated clinical visits. This follow-up approach could be consistently applied to all women regardless of age, severity, and extent of disease.

Serum Se, Ni, and As are associated with HPV infection and CIN2+ among Uyghur women in rural China.

BACKGROUND: Cervical cancer incidence and mortality is high in Uyghur ethnics. Their life style and dietary habit were different from other ethnics living together. Study on the role of trace elements in HPV infection and cervical lesion of Uyghur minority is needed for future intervention and prevention work. METHODS: In total, 833 Uyghur women were randomly selected from the screening site and hospital. The concentrations of the trace elements As, Fe, Cd, Ni, Cu, Zn, Mn, and Se were determined by atomic absorption spectrophotometry and inductively coupled plasma atomic emission spectroscopy. Univariate analysis was performed with chi-squared test between the HPV-positive and HPV-negative groups and between the case group and the control group. Multivariate analysis was performed with logistic regression. RESULTS: An As concentration ≥ 0.02 mg/kg was a risk factor for HPV infection (OR > 1, P < 0.05), and Ni concentration ≥ 0.1232 mg/kg and Se concentration ≥ 0.02 mg/kg were protective factors (OR < 1, P < 0.05). Concentrations of Fe ≥ 6.9153 mmol/L and As ≥0.02 mg/kg were risk factors for CIN2+ (OR > 1, P < 0.05), and concentrations of Ni ≥0.0965 mg/kg and Se ≥0.02 mg/kg were protective factors (OR < 1, P < 0.05). CONCLUSIONS: Low serum concentrations of Se and Ni and a high serum concentration of As might be related to HPV infection and CIN2+ in Uyghur women in rural China.

Knowledge of cervical cancer and Pap smear among Uyghur women from Xinjiang, China.

BACKGROUND: Cervical cancer is a significant public health issue in Xinjiang China. In order to provide scientific basis for cervical cancer intervention in Xinjiang, women's knowledge of cervical cancer was investigated in this study. Besides, relations between Uyghur women's awareness and their age, educational background, yearly household were evaluated. METHODS: Questionnaire survey was conducted to 7100 Uyghur women from Karkax Hotan and Payzivat Kashgar during 2008 and 2009. Women aged 21 to 70 years, had sexual activity, no history of cervical lesion or cervical cancer were considered to be eligible to the study. Information include participants' socio-demographic background, personal data, awareness about Pap smear, about cervical cancer and HPV, sources of information acquisition was investigated. RESULTS: 65.1% of the 7100 respondents with primary education level, and 95.0% participants were farmers. Only 7.4% had undertaken Pap smears before, not aware of the importance of the test (97.4% of 7100) was the main reason for not performing Pap smears. 29.3% of total participants had heard about cervical cancer, and only 0.14% (10 out of 7100) had heard about HPV. Top three route of knowledge acquire were television advertises (39.1%), neighbors (21.0%) and health care providers (15.0%). Women younger than 40 years, with higher educational levels and higher income had better awareness of cervical cancer and more willing to accept regular Pap smears. CONCLUSIONS: Uyghur women in Xinjiang had poor knowledge of cervical cancer and HPV infection. Low awareness of women was associated with less household income and lower educational levels. TV shows and education from health care providers may increase women's participation in cervical cancer control and prevention.

Evaluation of careHPV, Cervista Human Papillomavirus, and Hybrid Capture 2 Methods in Diagnosing Cervical Intraepithelial Neoplasia Grade 2+ in Xinjiang Uyghur Women.

OBJECTIVE: The study aimed to evaluate the value of the Cervista human papillomavirus (HPV), Hybrid Capture 2 (HC-2), and careHPV tests in diagnosing cervical intraepithelial neoplasia grade 2 (CIN2) or worse in Xinjiang Uyghur women. METHODS: Three high-risk human papillomavirus (HR-HPV) detection methods were studied on two different populations by different combination modes; a cytology specimen was obtained at the same time. An abnormal result of any test resulted in referral to colposcopy. Cervical biopsy was also performed. RESULTS: In population 1, HR-HPV-positive rates were 57.6% and 54.3% as detected by HC-2 and Cervista, respectively; κ = 0.892 for consistency check of HC-2 and Cervista (p < .001). Area under the receiver operating characteristic curve (AUC) of HC-2 and Cervista was 0.744 (95% confidence interval [CI]: 0.664∼0.824, p < .001) and 0.786 (95% CI: 0.715∼0.858, p < .001), respectively, for diagnosing CIN2+. The A9 probe can detect six subtypes of HPV, including HPV16, HPV31, HPV33, HPV35, HPV52, and HPV58. If one or more of these subtypes are postitive, then A9 will be positive. A diagnosis of class A9 by the Cerevista test correlated with pathological interpretations (chi-square = 43.063, p < .001). In population 2, HR-HPV-positive rates were 40.1% and 34.4%, respectively, by HC-2 and careHPV; κ value was 0.779 for the two tests (p < .001). AUC of HC-2 was 0.895 (95% CI: 0.849∼0.940, p < .001), and careHPV was 0.841 (95% CI: 0.770∼0.899, p < .001) for diagnosing CIN2+. CONCLUSION: Good consistency was shown between HC-2 and Cervista tests and also between the HC-2 and careHPV tests. In the detection of CIN2+, Cervista showed better specificity than HC-2, and interpretation of the A9 subgroup showed high predicted value. The HC-2 test demonstrated better sensitivity than careHPV in detection of CIN2+. HC-2, Cervista, and careHPV may be applied as a triage test for visual inspection with acetic acid/Lugol's iodine-positive or ThinPrep cytologic test-positive women. The careHPV test was comparatively economical and efficient and may be more suitable for resource-limited regions, such as Xinjiang. IMPLICATIONS FOR PRACTICE: This study was designed to evaluate the value of the Cervista human papillomavirus (HPV), Hybrid Capture 2 (HC-2), and careHPV tests in diagnosing cervical intraepithelial neoplasia grade 2 (CIN2) or worse (CIN2+) lesions in Xinjiang Uyghur women. Results showed that there was good consistency between the HC-2 and Cervista tests, as well as between the HC-2 and careHPV tests. In detecting CIN2+, Cervista had higher specificity than HC-2, whereas analysis of the A9 subgroup had high predictive value. (The A9 probe can detect six subtypes of HPV, including HPV16, HPV31, HPV33, HPV35, HPV52, and HPV58. If one or more of these subtypes are postitive, then A9 will be positive.) The HC-2 test demonstrated better sensitivity than careHPV in detecting CIN2+. HC-2, Cervista, and careHPV could be applied as a triage test for visual inspection with acetic acid/Lugol's iodine-positive or ThinPrep cytologic test-positive women. The careHPV test was comparatively economical and efficient and may be more suitable for resource-limited regions, such as Xinjiang.

Niraparib maintenance therapy using an individualised starting dose in patients with platinum-sensitive recurrent ovarian cancer (NORA): final overall survival analysis of a phase 3 randomised, placebo-controlled trial.

Background: Niraparib significantly prolonged progression-free survival versus placebo in patients with platinum-sensitive, recurrent ovarian cancer (PSROC), regardless of germline BRCA mutation (gBRCAm) status, in NORA. This analysis reports final data on overall survival (OS). Methods: This randomised, double-blind, placebo-controlled, phase 3 trial enrolled patients across 30 centres in China between 26 September 2017 and 2 February 2019 (clinicaltrials.gov, NCT03705156). Eligible patients had histologically confirmed, recurrent, (predominantly) high-grade serous epithelial ovarian cancer, fallopian tube carcinoma, or primary peritoneal carcinoma (no histological restrictions for those with gBRCAm) and had received ≥2 prior lines of platinum-based chemotherapy. Patients were randomised (2:1) to receive niraparib or placebo, with stratification by gBRCAm status, time to recurrence following penultimate platinum-based chemotherapy, and response to last platinum-based chemotherapy. Following a protocol amendment, the starting dose was individualised: 200 mg/day for patients with bodyweight <77 kg and/or platelet count <150 × 103/µL at baseline and 300 mg/day otherwise. OS was a secondary endpoint. Findings: Totally, 265 patients were randomised to receive niraparib (n = 177) or placebo (n = 88), and 249 (94.0%) received an individualised starting dose. As of 14 August 2023, median follow-up for OS was 57.9 months (IQR, 54.8-61.6). Median OS (95% CI) with niraparib versus placebo was 51.5 (41.4-58.9) versus 47.6 (33.3-not evaluable [NE]) months, with hazard ratio [HR] of 0.86 (95% CI, 0.60-1.23), in the overall population; 56.0 (36.1-NE) versus 47.6 (31.6-NE) months, with HR of 0.86 (95% CI, 0.46-1.58), in patients with gBRCAm; and 46.5 (41.0-NE) versus 46.9 (31.8-NE) months, with HR of 0.87 (95% CI, 0.56-1.35), in those without. No new safety signals were identified, and myelodysplastic syndromes/acute myeloid leukaemia occurred in three (1.7%) niraparib-treated patients. Interpretation: Niraparib maintenance therapy with an individualised starting dose demonstrated a favourable OS trend versus placebo in PSROC patients, regardless of gBRCAm status. Funding: Zai Lab (Shanghai) Co., Ltd; National Major Scientific and Technological Special Project for "Significant New Drugs Development" in 2018, China [grant number 2018ZX09736019].

Artificial intelligence in colposcopic examination: A promising tool to assist junior colposcopists.

Introduction: Well-trained colposcopists are in huge shortage worldwide, especially in low-resource areas. Here, we aimed to evaluate the Colposcopic Artificial Intelligence Auxiliary Diagnostic System (CAIADS) to detect abnormalities based on digital colposcopy images, especially focusing on its role in assisting junior colposcopist to correctly identify the lesion areas where biopsy should be performed. Materials and methods: This is a hospital-based retrospective study, which recruited the women who visited colposcopy clinics between September 2021 to January 2022. A total of 366 of 1,146 women with complete medical information recorded by a senior colposcopist and valid histology results were included. Anonymized colposcopy images were reviewed by CAIADS and a junior colposcopist separately, and the junior colposcopist reviewed the colposcopy images with CAIADS results (named CAIADS-Junior). The diagnostic accuracy and biopsy efficiency of CAIADS and CAIADS-Junior were assessed in detecting cervical intraepithelial neoplasia grade 2 or worse (CIN2+), CIN3+, and cancer in comparison with the senior and junior colposcipists. The factors influencing the accuracy of CAIADS were explored. Results: For CIN2 + and CIN3 + detection, CAIADS showed a sensitivity at ~80%, which was not significantly lower than the sensitivity achieved by the senior colposcopist (for CIN2 +: 80.6 vs. 91.3%, p = 0.061 and for CIN3 +: 80.0 vs. 90.0%, p = 0.189). The sensitivity of the junior colposcopist was increased significantly with the assistance of CAIADS (for CIN2 +: 95.1 vs. 79.6%, p = 0.002 and for CIN3 +: 97.1 vs. 85.7%, p = 0.039) and was comparable to those of the senior colposcopists (for CIN2 +: 95.1 vs. 91.3%, p = 0.388 and for CIN3 +: 97.1 vs. 90.0%, p = 0.125). In detecting cervical cancer, CAIADS achieved the highest sensitivity at 100%. For all endpoints, CAIADS showed the highest specificity (55-64%) and positive predictive values compared to both senior and junior colposcopists. When CIN grades became higher, the average biopsy numbers decreased for the subspecialists and CAIADS required a minimum number of biopsies to detect per case (2.2-2.6 cut-points). Meanwhile, the biopsy sensitivity of the junior colposcopist was the lowest, but the CAIADS-assisted junior colposcopist achieved a higher biopsy sensitivity. Conclusion: Colposcopic Artificial Intelligence Auxiliary Diagnostic System could assist junior colposcopists to improve diagnostic accuracy and biopsy efficiency, which might be a promising solution to improve the quality of cervical cancer screening in low-resource settings.

At what age should the Uyghur minority initiate cervical cancer screening if screened using careHPV.

BACKGROUND: The careHPV test as a primary screening method for cervical cancer has been proven to be the best option for Uyghur women in Xinjiang in a previous study. In this research, we aim to discuss the appropriate age for Uyghur women in Xinjiang to be screened for cervical cancer using careHPV. METHODS: Eleven thousand women aged 20-69 years old (mean age 38.93 ± 9.74) from South Xinjiang were screened using careHPV and liquid-based cytology, and the positive results were referred for colposcopy and cervical biopsy. A questionnaire regarding basic social characteristics, sexual practices, and reproductive history was administered to each woman. The age-specific prevalence of HPV positivity, cytology abnormality, and cervical intraepithelial neoplasia (CIN) 2+ in ≥25, ≥30, and ≥35 age groups were analyzed, and the diagnostic value of careHPV in the three age groups was evaluated. The chi-squared test was used to compare the differences between age groups. The sensitivity, specificity, positive predictive value, negative predictive value, and area under the receiver operating characteristic curve were calculated. RESULTS: The women were mostly married (76.3%) and delivered at 15-19 years of age (61.4%). The HPV infection rate was 9.15% and detection rates of CIN2+ and invasive cervical cancer were 1.53% (1530/100,000) and 0.25% (250/100,000), respectively. The first peak of HPV(+) appeared at the age of 30-34, while CIN2+ appeared at 35-39. CareHPV performed similarly well in the three age groups. CONCLUSION: Based on the results of our study, Uyghur women in Xinjiang should be recommended to initiate cervical cancer screening at the age of 30 years when screened using careHPV.

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.

Evaluation of multiple screening methods for cervical cancers in rural areas of Xinjiang, China.

This study is to evaluate the screening methods of cervical cancers for rural females in Kash bachu, Xinjiang, China.A total number of 3000 married females were surveyed, and subjected to the gynecological examination. In these subjects, 1993 females received the careHPV (human papillomavirus) test, while 1007 females underwent the visual inspection with acetic acid (VIA) and visual inspection with Lugol's iodine (VILI). The subjects positive for careHPV detection were subjected to Cervista, Cobas 4800, and Aptima HPV detection, and Thinprep Cytologic Test (TCT). The subjects positive for 1 detection only received colposcopy cervical biopsy.A total of 569 subjects received the cervical biopsy, and the positive rate was 2.3% (69/3000), while the detection rate for CIN (cervical intraepithelial neoplasia) II and above levels was 1.13% (34/3000). Receiver operator characteristic (ROC) curve analysis showed that, the area under the curve (AUC) value for the careHPV test was 0.671, which was higher than the VIA/VILI (0.619), suggesting higher diagnostic value for the careHPV test. For the Cervista, Cobas 4800, Aptima HPV detection, and TCT methods, the highest AUC value was observed for the TCT method, indicating that the TCT method is the most valuable for the cervical cancer screening.The diagnostic value of careHPV test is superior to the VIA/VILA detection method. The TCT method has the greatest value for the cervical cancer screening. The Cervista HPV detection method should be considered where the conditions are limited.

Tumor-suppressor gene SOX1 is a methylation-specific expression gene in cervical adenocarcinoma.

The present study is to analyze the difference of gene methylation in early cervical adenocarcinoma and to find molecular markers for predicting the occurrence and development of cervical adenocarcinoma.A total of 15 cases of primary cervical adenocarcinoma and 10 cases of primary cervical squamous cell carcinoma at stages IB1 or IIA1 were included in the study. Infinium MethylationEPIC BeadChip (850K) was used to screen specifically expressed genes in cervical adenocarcinoma tissues. Bisulfite sequencing polymerase chain reaction (BSP) and quantitative real-time polymerase chain reaction (qRT-PCR) were used to verify the methylation levels in cervical adenocarcinoma, cervical squamous cell carcinoma, and normal cervical tissues.Sex determining region Y-box 1 (SOX1) and cyclin D1 (CCND1) genes participated in multiple signaling pathways, being the central nodes of gene regulatory networks. SOX1 gene, but not CCND1 gene, was a specifically methylated gene in cervical adenocarcinoma according to BSP. According to qRT-PCR, methylation level of SOX1 in cervical adenocarcinoma tissues is significantly different from that in cervical squamous cell carcinoma tissues or normal cervical tissues, and the methylation level of CCND1 in cervical adenocarcinoma tissues or cervical squamous cell carcinoma tissues is significantly different from that in normal cervical tissues.The present study demonstrates that tumor-suppressor gene SOX1 is a methylation-specific expression gene of cervical adenocarcinoma and is expected to become a specific molecular marker for the diagnosis of cervical adenocarcinoma. However, CCND1 gene was not proven to be a specific methylation expression gene in cervical adenocarcinoma in the present study.

CDK6 3'UTR polymorphisms alter the susceptibility to cervical cancer among Uyghur females.

AIMS: Cyclin dependent kinase 6 (CDK6) plays a crucial role in malignant tumor whereas less is reported in cervical cancer development. The aim of this study was to evaluate the effects of CDK6 3' untranslated region (3'UTR) polymorphisms on cervical cancer susceptibility among Uyghur females. METHODS: The genotypes of the six CDK6 variants (rs8179, rs42032, rs42033, rs42034, rs42035, and rs42038) were identified among 306 cervical cancer cases and 310 healthy controls with the Agena MassARRAY platform. The associations of the candidate single nucleotide polymorphisms (SNPs) with the cervical cancer risk were evaluated under genetic models using conditional logistic regression analysis. Bioinformatics analysis was performed for SNP function prediction with the online databases. The expression differences between tumor tissues and normal cervix samples were also examined by Real-time PCR. RESULTS: CDK6 rs8179 and rs42033 were correlated to the decreased risk of cervical cancer in Uyghurs under the allele model (rs8179 and rs42033: OR = 0.60, 95% CI: 0.37-0.99, p = 0.043) and log-additive model (rs8179 and rs42033: OR = 0.62, 95% CI: 0.38-1.00, p = 0.047). Rs8179, rs42032, and rs42033 were associated with susceptibility to high-grade cervical cancer in different genetic models as well (p < 0.05). Dataset-based analysis also uncovered the potential effects of these significant SNPs. In addition, aberrant expression of CDK6 were detected in cervical tumors. CONCLUSIONS: Our results suggested the relationships between CDK6 3'UTR polymorphisms and cervical cancer pathogenesis, and the involvement of CDK6 in cervical cancer development among Uyghur females.

Bioinformatics analysis of methylation in cervical adenocarcinoma in Xinjiang, China.

This study is to investigate the genomic methylation in cervical adenocarcinoma in Xinjiang, China, using the DNA methylation analysis chips.Methylation of 5 cases of cervical adenocarcinoma tissues and 5 cases of normal cervical tissues were analyzed by the Illumina 850K methylation chip. The genes with abnormal methylation modification were screened out and analyzed by the gene ontology (GO) functional annotation analysis. Enrichment analysis of kyoto encyclopedia of genes and genomes (KEGG) signal transduction pathways was also performed.Totally 4056 sites showed differential expression patterns in cervical adenocarcinoma tissues compared to normal cervical tissues, of which 3738 were hypermethylated, and 318 were hypomethylated. The distribution of these sites covered from the 1st to 22nd chromosomes. GO functional annotation analysis showed that the differentially expressed genes in cervical adenocarcinoma tissues were mainly involved in the processes of tumor growth, development, metabolism, ion transport, transcriptional regulation, cell division, cell cycle regulation, and signal transduction. KEGG signaling pathway analysis showed that the most significantly different signaling pathway was the neuroactive ligand-receptor interaction. Gene-net-work analysis suggested that CCND1, CTNNB1, MAPK10, and PRKCA were involved.Methylated genes are specifically expressed in cervical adenocarcinoma tissues in Xinjiang, China. Four of these genes (CCND1, CTNNB1, MAPK10, and PRKCA) with differential expression patterns may play important regulatory roles in cervical adenocarcinoma development through affecting the neuroactive ligand-receptor interaction.

Risk factors for human papillomavirus infection prevalent among Uyghur women from Xinjiang, China.

We investigated the incidence of HPV and risk factors for infection among rural Uyghur women in the Xinjiang province of northwestern China, where there is a high incidence of cervical cancer. We used the careHPV kit to test 6000 sexually active Uyghur women aged 21 to 60 years for HPV, and conducted a comprehensive questionnaire survey to identify relevant HPV infection factors. Our data show the HPV infection rate to be 8.42%, which is lower than 11.7% reported worldwide, despite the higher cervical cancer incidence. Multivariate logistic regression revealed that Uyghur women that had (a) poor personal hygiene and care; (b) no previous gynecological examination; (c) a higher education level; (d) unprotected sex and inadequate personal hygiene; (e) used their fingers for vaginal cleaning (f) smoking husbands and (j) used sanitary napkins or toilet paper during menstruation or used clod as the bathroom wipe material were at greater risk for HPV infection. This suggests that proper interventions that improve personal hygiene, including not using ones fingers for vaginal cleaning, use of condoms, regular gynecological exams and a reduction in smoking by spouses could lower the cervical cancer risk by lowering HPV infection rates. In addition, increasing awareness among more educated women regarding HPV and implementation of effective interventions could reduce the risk of HPV infection in Uyghur women.

Expression of MAPK1 in cervical cancer and effect of MAPK1 gene silencing on epithelial-mesenchymal transition, invasion and metastasis.

OBJECTIVE: To discuss the expression of mitogen-activated protein kinase 1 (MAPK1) in the cervical cancer and effect of MAPK1 gene silencing on epithelial-mesenchymal transition and invasion and metastasis. METHODS: Immunohistochemistry, western blot and RT-PCR method were employed to detect the expression of MAPK1 protein and mRNA in cervical cancer tissue and adjacent normal tissue. The constructed siRNA-MAPK1 was transferred into human cervical cancer HeLa cells using Lipofectamine™2000. MTT method was used to detect the cell vitality, transwell method to detect the cell invasion, and western blot to detect the expression of matrix metalloproteinases (MMP)-2, MMP-9, tissue inhibitor of metalloproteinase (TIMP)-1, TIMP-2, zinc finger transcription factor (Snail), epithelial-mesenchymal transition related protein (EMT) E-cadherin and vimentin in cells. RESULTS: The expression of MAPK1 protein and mRNA in the cervical cancer tissue was significantly higher than the one in the adjacent normal tissue (P < 0.01); after transfecting the siRNA-MAPK1 into the human cervical cancer HeLa cells through liposome, compared with the control group, its cell vitality was significantly decreased (P < 0.01), cell invasion was significantly decreased (P < 0.01); expressed of MMP-2, MMP-9, Snail and vimentin was significantly decreased (P < 0.01), and expression of TIMP-1, TIMP-2 and E-cadherin was significantly increased (P < 0.01). CONCLUSIONS: Because of the high expression of MAPK1 in the cervical cancer tissue, the interference in the expression of MAPK1 can significantly inhibit the invasion and metastasis of cervical cancer HeLa cells, which is related to the interference in the expression of MMPs/TIMP and Snail-mediated generation of EMT.