宫颈轻度上皮内瘤变的转归及其与p16基因甲基化的关系

Natural History of Low-grade Cervical Intraepithelial Neoplasia and Its Relationship with p16 Hypermethylation

[目的]研究轻度宫颈上皮内瘤变(CIN1)的转归,并探索p16基因甲基化能否成为预测其预后的生物学指标。[方法]以2002年山西省阳城县人群子宫颈癌筛查发现的CIN1患者和宫颈正常者为研究对象,抽取所有的CIN1共139例,同时随机抽取正常120例,运用甲基化特异性PCR(MS-PCR)-DH-PLC组合检测技术对基线病理蜡块进行p16基因甲基化检测。追踪随访CIN1患者6年,观察病变的转归,并评价p16基因甲基化对CIN1病变进展的危险性。[结果]随访6年后,CIN1病变逆转、持续和进展的比例分别为70.3%、13.2%和16.5%。对基线标本进行p16基因甲基化检测,CIN1组的甲基化率(24.2%)高于正常组(17.6%),但差别无统计学意义(χ2=1.60,P=0.21);基线HPVDNA阳性组的甲基化率(23.5%)高于阴性组(15.6%),差别无统计学意义(χ2=2.01,P=0.17)。CIN1中甲基化和非甲基化组病变持续或进展的比例分别为20.0%和34.9%,差异无统计学意义(χ2=2.30,P=0.13),病变预后与p16基因甲基化状态无明显关联(RR=0.57,0.26～1.24)。[结论]经过6年随访,约有三分之二的CIN1逆转,仅有三分之一的病变维持原状或发生进展。尚不能证明CIN1病变进展与p16基因甲基化有关,该指标不能用于预测CIN1的预后。

[Purposel To investigate the natural history of low-grade cervical intraepithelial neoplasia （CIN 1）, and to explore the validity of p16 hypermethylation for predicting the prognosis of CIN 1,[Methods] The women with CIN l or normal cervix biopsically proved during the cervical cancer screening program conducted at Yangcheng County, Shanxi Province in 2002 were enrolled in this study, p16 hypermethylation was detected in 139 cases with CIN1 and 120 cases with normal cervix by the methylation-specific PCR-DHPLC on tissue blocks. The CIN cases were followed up for 6 years, and pl6 hypermethylation as a marker to predict CIN risk was evaluated. [Results ] After the 6-year follow-up, the proportion of regression, persistence and progression of CIN 1 was 70.3%, 13.2% and 16.5%, respectively. For the baseline screening, the p16 hypermathylation of CIN 1 （24.2%） was higher than that of women with normal eervix（17.6%）, but the difference between them was not significant （χ2=1.60, P=0.21）; Although the hypermathylation in HPV positive women （23.5%） was higher than that in HPV negative women （15.6%）, there was no significant difference between them （χ2=2.01, P=0. 17）. The persistence or progression of CIN 1 among the population with or without hypermathylaion was 20.0% and 34.9%, respectively. No obvious correlation between CIN 1 prognosis and pl6 hypermethylatiou was observed （RR=0.57, 0.26-1.24）. [Conclusion] After 6 years follow up, about two thirds of CIN 1 regresses, only one third of them persists or progresses. The relationship between p16 hypennethylation and CIN 1 has not been confirmed, so p16 hypermethylation can not be used as a biomarker to predict the prognosis of CIN 1.