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Objective@#To investigate the role of human papillomavirus (HPV) 16 early genes E2 and E6 and heterogeneous nuclear ribonucleoprotein (hnRNP) E2 and their interaction effects in the progression of the cervical cancer.@*Methods@#Women with normal cervix (NC), low cervical intraepithelial neoplasia (CIN Ⅰ) and high cervical intraepithelial neoplasia (CIN Ⅱ/Ⅲ) from the cervical lesions cohort in Jiexiu County of Shanxi Province from June 2014 to September 2014, and patients with cervical squamous cell carcinoma (SCC) treated at the Second Hospital of Shanxi Medical University in the same period were enrolled in this study. There were 257 participants, about 67 NC cases (26.07%), 69 CIN Ⅰ cases (26.85%), 68 CIN Ⅱ/Ⅲ cases (26.46%), and 53 SCC cases (20.62%), respectively. The information of demographic characteristics, life health habits and cervical lesions were collected by using the structured questionnaire. Cervical exfoliated cells and cervical biopsy tissues were collected to detect the infection of HPV16 and the protein expression levels of hnRNP E2, HPV16 E2 and E6. According to the median-value of the protein expression levels of hnRNP E2, HPV16 E2 and E6 and E2/E6 ratio in the NC group, the study participants were divided into the high and low expression groups/ratio groups. The multivariate logistic regression model was used to analyze the correlation between HPV16 early gene E2 and E6, hnRNP E2 and cervical cancer. The interaction effect was analyzed by using the generalized multifactor dimensionality reduction (GMDR) model.@*Results@#The ages of NC, CIN Ⅰ, CIN Ⅱ/Ⅲ and SCC groups were (47.00±9.07), (47.64±7.35), (46.37±8.67) and (51.26±8.03) years old, respectively. The multivariate logistic regression model analysis showed that the HPV16 E2 low expression, E6 high expression and E2/E6 low ratio could increase the risk of CIN Ⅱ/Ⅲ, about OR (95%CI) values 11.11 (1.63-75.56), 8.00 (1.28-50.04), and 9.75 (1.22-77.72), respectively and SCC, about OR (95%CI) values 14.22 (2.11-95.88), 10.33 (1.67-64.00), and 12.38 (1.56-97.91), respectively. The hnRNP E2 low expression could increase the risk of CIN Ⅱ/Ⅲ and SCC, about OR (95%CI) values 3.35 (1.39-8.10) and 5.53 (1.54-19.88). The result of GMDR showed that there were interaction effects of the hnRNP E2 low expression, HPV16 E2 low expression and HPV16 E6 high expression in both CIN Ⅱ/Ⅲ and SCC groups.@*Conclusion@#The HPV16 E2 low expression, HPV16 E6 high expression and hnRNP E2 low expression could increase the risk of high-grade cervical intraepithelial neoplasia and cervical cancer, and they might have an important interaction effect in the progression of the cervical cancer.
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Objective@#To explore the effects of hnRNP E1 and both early genes E2 and E6 of HPV16 as well as their interactions in the progression of cervical carcinogenesis.@*Methods@#Subjects of this study included 56 women with normal cervix (NC), 58 patients with low-grade cervical intraepithelial neoplasm (CINⅠ) and 50 patients with high-grade cervical intraepithelial neoplasm (CINⅡ/Ⅲ) who were all recruited from the 'Cervical Lesions Study Cohort Project’ in Jiexiu of Shanxi province from June to September, 2014. Another 40 patients with cervical squamous cell carcinoma (SCC) were from the Shanxi Tumor Hospital during the same period. Information related to cervical lesions were collected, using a structured questionnaire, with cervical tissues and cervical exfoliated cells gathered from all the participants. HPV infection was detected by flow-through hybridization, while the levels of expression on hnRNP E1, HPV16 E2 and E6 protein were measured by Western Blot. Kruskal-Wallis H test, χ2 test, trend χ2 test were analyzed by SPSS 22.0 software, while interaction was evaluated by generalized multifactor dimensionality reduction (GMDR).@*Results@#The overall infection rates of HPV16 related to CINⅠ (15.52%, 9/58), CINⅡ/Ⅲ (40.00%, 20/50) and SCC (67.50%, 27/40) groups were all higher than that of the NC group (8.93%, 5/56) and with an increasing trend on the severity of cervical lesions (trend χ2=43.613, P<0.001). The levels of expression on hnRNP E1 protein were significantly different in the groups with different cervical lesions (H=9.98, P=0.019), showing a decreasing trend with the severity of cervical lesions (trend χ2=9.495, P=0.002). The levels of expression on HPV16 E2 (H=16.20, P=0.001) and HPV16 E6 (H=15.44, P=0.001) were significantly different in groups with different cervical lesions. Results of GMDR showed that the best interaction model in both groups of CINⅡ/Ⅲ and SCC appeared as hnRNP E1 low expression, HPV16 E2 low expression and HPV16 E6 high expression. However, no similar interaction was seen in CINⅠ (P>0.05).@*Conclusions@#Both low expressions of hnRNP E1 and abnormal expression of HPV16 E2 and E6 could increase the risk of high-grade CIN and cervical cancer. It seemed that they might have an important synergistic effect on the progression of cervical cancer.
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Objective To explore the effect of vaginal micro-environment alterations and HPV1 6 infection and their interaction in the progression of cervical intraepithelial neoplasia.Methods The participants of this study came from the cervical lesions study cohort in Shanxi province,including 623 women with normal cervical (NC),303 patients with pathogenically diagnosed low-grade cervical intraepithelial neoplasia (CIN Ⅰ) and 93 patients with pathogenieally diagnosed high-grade cervical intraepithelial neoplasia (CIN Ⅱ/Ⅲ).The data of the demographic characteristics of the study subjects and factors related to cervical intraepithelial neoplasia were collected,and HPV16 infection were detected by using flow-through hybridization technology and H2O2,β-glucuronidase,clotting enzyme,neuraminidase and leucocyte esterase in vaginal secretions were detected by using the combined detection kit of aerobic vaginitis and bacterial vaginosis.pH value and vaginal cleanliness were also detected at the same time.The database was established and analyzed by SPSS statistical software (version 22.0).Results The HPV16 infection rate (trend x2=55.45,P＜0.001) and the abnormal rates of H2O2 (trend x2 =26.19,P＜0.001),pH (trend x2=5.06,P=0.024),vaginal cleanliness (trend x2=19.55,P＜0.001),β-glucuronidase (trend x2 =17.52,P＜0.001) and neuraminidase (trend x2 =14.90,P＜ 0.001) increased gradually along with the severity of cervical intraepithelial neoplasia,but the abnormal rates of clotting enzyme and leucocyte esterase showed no same trend.The results of GMDR model analysis showed that there was interaction between HPV16 infection and abnormalities of H2O2,β-glucuronidase,clotting enzyme and neuraminidase in CIN Ⅰ group,and the interaction between HPV16 infection and the abnormalities of vaginal cleanliness,H2O2,β-glucuronidase and neumminidase in CIN Ⅱ/Ⅲ group.Conclusion Our findings indicated that the vaginal micro-environment alterations and HPV1 6 infection could increase the risk of cervical intraepithelial neoplasia,and they might have an important synergistic effect in the progression of cervical intraepithelial neoplasia.
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Objective To evaluate the effects of polycyclic aromatic hydrocarbons (PAHs) and high risk human papillomavirus (HR-HPV) infection and their interaction on the progression of cervical intraepithelial neoplasia.Methods A total of 486 patients,including 208 women with normal cervix (NC),154 patients with low-grade cervical intraepithelial neoplasm (CIN Ⅰ),124 patients with high-grade cervical intraepithelial neoplasm (CIN Ⅱ/Ⅲ),were selected from the cervical lesions cohort from June to December,2014.HR-HPV was detected by using flow-through hybridization technology and the urine concentration of 1-hydroxypyrene (1-OHP) was detected with high performance liquid chromatography.By using software SPSS 22.0,the x2 test,trend x2 test,Kruskal-Wallis H test,Nemenyi rank test and Spearman rank correlation analysis were performed.And the interaction effects were evaluated by additive model.Results The HR-HPV infection rates in NC,CIN Ⅰ and CIN Ⅱ/Ⅲ groups were 27.9％,37.0％ and 58.9％,respectively.The urine concentrations of 1-OHP (pmol/molCr) were 0.07 ± 0.09,0.11 ± 0.10 and 0.17 ± 0.15,respectively.With increasing severity of the cervical lesions,the HR-HPV infection rate gradually increased (trend x2=29.89,P＜0.001) and the high exposure rate of PAHs gradually increased (trendx2 =27.94,P＜0.001).HR-HPV infection was positively correlated with 1-OHP exposure (r=0.680,P＜0.001).There was a positive additive interaction between HPV infection and PAHs exposure in CIN Ⅱ/Ⅲ group,but it was not found in CIN Ⅰ group.Conclusion Both HR-HPV infection and high exposure of PAHs might increase the risk of cervical intraepithelial neoplasm,and might have a synergistic effect on the progression of high-grade cervical intraepithelial neoplasia.
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Objective To explore the effect of vaginal micro-environment alterations and HPV1 6 infection and their interaction in the progression of cervical intraepithelial neoplasia.Methods The participants of this study came from the cervical lesions study cohort in Shanxi province,including 623 women with normal cervical (NC),303 patients with pathogenically diagnosed low-grade cervical intraepithelial neoplasia (CIN Ⅰ) and 93 patients with pathogenieally diagnosed high-grade cervical intraepithelial neoplasia (CIN Ⅱ/Ⅲ).The data of the demographic characteristics of the study subjects and factors related to cervical intraepithelial neoplasia were collected,and HPV16 infection were detected by using flow-through hybridization technology and H2O2,β-glucuronidase,clotting enzyme,neuraminidase and leucocyte esterase in vaginal secretions were detected by using the combined detection kit of aerobic vaginitis and bacterial vaginosis.pH value and vaginal cleanliness were also detected at the same time.The database was established and analyzed by SPSS statistical software (version 22.0).Results The HPV16 infection rate (trend x2=55.45,P＜0.001) and the abnormal rates of H2O2 (trend x2 =26.19,P＜0.001),pH (trend x2=5.06,P=0.024),vaginal cleanliness (trend x2=19.55,P＜0.001),β-glucuronidase (trend x2 =17.52,P＜0.001) and neuraminidase (trend x2 =14.90,P＜ 0.001) increased gradually along with the severity of cervical intraepithelial neoplasia,but the abnormal rates of clotting enzyme and leucocyte esterase showed no same trend.The results of GMDR model analysis showed that there was interaction between HPV16 infection and abnormalities of H2O2,β-glucuronidase,clotting enzyme and neuraminidase in CIN Ⅰ group,and the interaction between HPV16 infection and the abnormalities of vaginal cleanliness,H2O2,β-glucuronidase and neumminidase in CIN Ⅱ/Ⅲ group.Conclusion Our findings indicated that the vaginal micro-environment alterations and HPV1 6 infection could increase the risk of cervical intraepithelial neoplasia,and they might have an important synergistic effect in the progression of cervical intraepithelial neoplasia.
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Objective To evaluate the effects of polycyclic aromatic hydrocarbons (PAHs) and high risk human papillomavirus (HR-HPV) infection and their interaction on the progression of cervical intraepithelial neoplasia.Methods A total of 486 patients,including 208 women with normal cervix (NC),154 patients with low-grade cervical intraepithelial neoplasm (CIN Ⅰ),124 patients with high-grade cervical intraepithelial neoplasm (CIN Ⅱ/Ⅲ),were selected from the cervical lesions cohort from June to December,2014.HR-HPV was detected by using flow-through hybridization technology and the urine concentration of 1-hydroxypyrene (1-OHP) was detected with high performance liquid chromatography.By using software SPSS 22.0,the x2 test,trend x2 test,Kruskal-Wallis H test,Nemenyi rank test and Spearman rank correlation analysis were performed.And the interaction effects were evaluated by additive model.Results The HR-HPV infection rates in NC,CIN Ⅰ and CIN Ⅱ/Ⅲ groups were 27.9％,37.0％ and 58.9％,respectively.The urine concentrations of 1-OHP (pmol/molCr) were 0.07 ± 0.09,0.11 ± 0.10 and 0.17 ± 0.15,respectively.With increasing severity of the cervical lesions,the HR-HPV infection rate gradually increased (trend x2=29.89,P＜0.001) and the high exposure rate of PAHs gradually increased (trendx2 =27.94,P＜0.001).HR-HPV infection was positively correlated with 1-OHP exposure (r=0.680,P＜0.001).There was a positive additive interaction between HPV infection and PAHs exposure in CIN Ⅱ/Ⅲ group,but it was not found in CIN Ⅰ group.Conclusion Both HR-HPV infection and high exposure of PAHs might increase the risk of cervical intraepithelial neoplasm,and might have a synergistic effect on the progression of high-grade cervical intraepithelial neoplasia.