血清叶酸与宫颈上皮内瘤变Ⅰ级转归的关系及其与高危型人乳头瘤病毒感染的交互作用

Relationship between serum folate and CIN1 prognosis and its interaction with HR-HPV infection

目的探讨血清叶酸与宫颈上皮内瘤变Ⅰ级(CIN1)转归的关系及其与高危型人乳头瘤病毒(HR-HPV)感染的交互作用。方法基于2014年6—12月在山西省介休市和阳曲县建立的已婚妇女社区队列,选取经病理学诊断为CIN1的564例患者为研究对象,12个月后再次行病理学检查,根据CIN1转归情况,将患者分为CIN1消退组、持续和进展组。采用巢式病例对照研究方法分析血清叶酸与CIN1转归的关系,采用相加模型分析血清叶酸与HR-HPV感染的交互作用。结果564例患者中,479例再次行病理学检查,CIN1消退组331例,持续和进展组148例。CIN1消退组与持续和进展组患者的血清叶酸分别为(18.890±8.360)和(15.640±5.550)nmol/L,差异有统计学意义(Z=-6.937,P<0.001)。154例患者检出HPV感染,其中148例为HR-HPV感染,6例为低危型人乳头瘤病毒感染。单因素分析显示,消退组与持续和进展组在年龄、被动吸烟、清洗阴部频率、性生活后清洗、换洗内裤频率、血清叶酸及HR-HPV感染方面差异有统计学意义(均P<0.05)。多因素Logistic回归分析显示,清洗阴部频率(OR=0.422,95%CI为0.238~0.750)、换洗内裤频率(OR=0.574,95%CI为0.355~0.928)、血清叶酸(13.06~16.78 nmol/L:OR=4.806,95%CI为2.355~9.810;≤13.05 nmol/L:OR=8.378,95%CI为4.024~17.445)、HR-HPV感染(OR=1.852,95%CI为1.170~2.933)是CIN1转归的独立影响因素。交互作用分析显示,血清叶酸低水平和HR-HPV感染对CIN1持续和进展的相对超额危险度=4.992(95%CI为0.189~9.796),归因危险度=0.552(95%CI为0.279~0.824),交互作用指数=2.632(95%CI为1.239~5.588),血清叶酸≤16.78 nmol/L且HR-HPV感染阳性的aOR=9.055(95%CI为4.878~16.807)。结论低血清叶酸水平可增加CIN1持续和进展的风险,且与HR-HPV感染存在协同作用。

Objective To evaluate the relationship between serum folate and the prognosis of cervical intraepithelial neoplasia grade I(CIN1)and the interaction between folate and high risk human papillomavirus(HR-HPV)infection.Methods From a community-based married women cohort established in Jiexiu and Yangqu County of Shanxi Province from June to December 2014,a total of 564 eligible women with CIN1 by pathologically diagnosed were recruited.The pathological examination was performed again 12 months later.According to the prognosis of CIN1,participants were divided into CIN1 regression group,persistence and progression group,respectively.Nested case-control study was used to explore the relationship between serum folate and CIN1 prognosis,and additive model was used to analyze the interaction between serum folate and HR-HPV infection.Results Among 564 CIN1 patients,479 cases underwent pathological examination again,331 were divided in CIN1 regression group and other 148 in persistence and progression group.The levels of serum folate in CIN1 regression group and persistence and progression group were(18.890±8.360)and(15.640±5.550)nmol/L,respectively,and the difference was statistically significant(Z=-6.937,P<0.001).HPV infection was detected in 154 patients,including 148 cases of HR-HPV infection and 6 cases of low risk human papillomavirus(LR-HPV)infection.Univariate analysis showed that there were significant differences in the age,passive smoking,frequency of pudendal cleaning,frequency of cleaning after sex,frequency of changing underwear,serum folate and HR-HPV infection between regression group and persistence and progression group(P<0.05).Multivariate logistic regression analysis showed that the frequency of pudendal cleaning(OR=0.422,95%CI:0.238-0.750),frequency of changing underwear(OR=0.574,95%CI:0.355-0.928),serum folate(13.06-16.78nmol/L:OR=4.806,95%CI:2.355-9.810;≤13.05nmol/L:OR=8.378,95%CI:4.024-17.445),HR-HPV infection(OR=1.852,95%CI:1.170-2.933)were the independent influencing factors of CIN1 prognosis.Interaction analysis showed that the relative excess risk of low serum folate level and HR-HPV infection for the CIN1 persistence and progression was 4.992(95%CI:0.189-9.796),attributable proportion due to interaction was 0.552(95%CI:0.279-0.824),synergy index was 2.632(95%CI:1.239-5.588),aOR of serum folate≤16.78 nmol/L and HR-HPV infection positive was 9.055(95%CI:4.878-16.807).Conclusion Low serum folate level could increase the risk of CIN1 persistence and progression,and might enhance the risk when combined with HR-HPV infection.