摘要目的 探讨叶酸与人乳头瘤病毒16型(HPV16) E6/E7 mRNA表达在宫颈癌变中的交互作用.方法 选取经病理学确诊的宫颈鳞状细胞癌(SCC)患者64例、低度宫颈上皮内瘤样变(CINl)患者55例、高度宫颈上皮内瘤样变(CIN2+)患者55例和正常宫颈(NC)者80例作为研究对象.采用微生物法测定血清叶酸和红细胞叶酸水平,应用real-time PCR法检测HPV16 E6/E7mRNA表达水平.利用SPSS 16.0软件进行相关资料的x2检验、方差分析、Welch检验、Kruskal-Wallis H检验、有序logistic回归和Spearman秩相关分析,应用相加模型进行交互作用分析.结果 随着宫颈癌变的进展,血清叶酸和红细胞叶酸水平均呈逐渐降低趋势(x2=32.71,P＜0.001;x2=16.32,P＜0.001),且血清叶酸和红细胞叶酸含量呈正相关(r=0.41,P＜0.001);HPV16 E6/E7 mRNA表达水平随着宫颈癌变的进展呈逐渐升高趋势(x2=30.11,P＜0.001;x2=38.99,P＜0.00l);红细胞叶酸含量与HPV16 E6/E7 mRNA表达量呈负相关(E6:r=-0.14,P=0.009;E7:r=-0.21,P=0.001),红细胞叶酸缺乏与HPV16 E6/E7mRNA高表达在CIN1、CIN2+和SCC组均存在正相加交互作用.结论 叶酸缺乏和HPV16 E6/E7 mRNA高表达均可增加宫颈癌及癌前病变发生的风险,两者在宫颈癌变进展中存在协同作用.

abstractsObjective To explore the interaction between folate and the expression of HPV16 E6/E7 mRNA in the progression of cervix carcinogenesis.Methods Subjects were selected from the participants who were diagnosed pathologically,including 64 patients with cervical squamous cell carcinoma (SCC),55 patients with low-grade cervical intraepithelial neoplasm (CIN1),55 patients with high-grade cervical intraepithelial neoplasm (CIN2 +) and 80 with normal cervix (NC).The levels of serum folate and RBC folate were detected by microbiological assay,and the expression levels of HPV16 E6/E7 mRNA were measured,using the real-time polymerase chain reaction (real-time PCR).Data was analyzed by methods as chi-square test,analysis of variance (ANOVA),Welch test,Kruskal-Wallis H test and ordinal logistic regression.Spearman correlation was tested using the SPSS statistical software (version 16.0) while the interaction effects were evaluated by additive model.Results There was a positive correlation seen between the serum folate and RBC folate (r=0.41,P＜0.001).The levels of serum folate and RBC folate decreased gradually along with the severity of cervical lesions (x2=32.71,P＜0.001;x2=16.32,P＜0.001).The expression levels of HPV 16 E6/E7 mRNA increased gradually with the severity of cervical lesions (x2 =30.11,P＜ 0.001;x2 =38.99,P＜0.001).There was a negative correlation between the levels of RBC folate,expression levels of HPV16 E6 (E6:r=-0.14,P=0.009) and HPV16 E7 mRNA (E7:r=-0.21,P=0.001),respectively.Both RBC folate deficiency and HPV16 E6/E7 mRNA high expression showed additive interaction in CIN 1,CIN2 + and SCC.Conclusion Folate deficiency and high expression of HPV16 E6/E7 mRNA might increase the risk of cervical cancer and cervix precancerous lesions,and having a synergistic action in the progression of cervix carcinogenesis.