Predictive value of high-risk HPV DNA load, genotyping, and E6 oncoprotein for the progression of cervical precancer
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摘要:
目的 探讨预测高危型人乳头瘤病毒（high risk human papillomavirus，hrHPV）阳性和宫颈上皮内瘤样病变1级（cervical intraepithelial neoplasia grade 1，CIN1）妇女进展的生物学标志物。 方法 2010年10月至2012年8月在山西省、河南省和江西省招募7 543名妇女，采用hrHPV DNA检测和E6蛋白检测（Onco E6）等方法进行宫颈癌筛查，任一结果阳性者转诊阴道镜并取活检，于1年后随访。纳入基线hrHPV阳性或病理诊断CIN1者。 结果 共纳入794例满足条件妇女，1年后88例妇女病理级别发生进展。基线hrHPV DNA中高载量者进展的风险是低载量者的2.9倍（95%CI为1.8~4.8），hrHPV16/18/45、E6蛋白阳性者进展的风险分别是阴性者的2.4倍（95%CI为1.5~3.9）、2.9倍（95%CI为1.5~5.9），其进展至宫颈上皮内瘤样病变2级及以上（cervical intraepithelial neoplasia grade 2 or worse，CIN2+）的绝对风险分别为4.9%（95%CI为3.2~7.4）、9.0%（95%CI为5.5~14.3）、18.8%（95%CI为10.2~31.9）。hrHPV16/18/45中高载量且E6蛋白（Onco E6）阳性妇女进展的绝对风险高达32.4%（11/34）。 结论 hrHPV DNA中高载量、hrHPV16/18/45分型以及E6蛋白（Onco E6）可作为妇女hrHPV阳性和CIN1进展的生物学标志物，特别是hrHPV中高载量且E6蛋白（Onco E6）阳性妇女，临床应给予密切随访。 Abstract:Objective To explore biomarkers of predicting the progression of cervical intraepithelial neoplasia grade 1 (CIN1) in women with positive human papillomavirus (hrHPV). Methods From October 2010 to August 2012 in Shanxi, Henan, Jiangxi province, 7, 543 women underwent hrHPV DNA and E6 protein (OncoE6) screening tests. Women with either positive results were referred to colposcopy for biopsy and followed up after one year. Women with hrHPV positivity or CIN1 were included in the analysis. Results A total of 794 eligible women were included in the final analysis; among them, 88 women progressed histologically in one year. The relative risk of progression for women with intermediate/high hrHPV viral load compared to low hrHPV viral load was 2.9 (95%CI: 1.8-4.8); correspondingly, the figures in women with positive HPV16/18/45 and OncoE6 were 2.4 (95%CI: 1.5-3.9) and 2.9 (95%CI: 1.5-5.9), respectively. The corresponding absolute risks for progression to CIN2+ were 4.9% (95%CI: 3.2-7.4), 9.0% (95%CI: 5.5-14.3), and 18.8% (95% CI: 10.2-31.9), respectively. The absolute risk of progression for women with intermediate/high hrHPV 16/18/45 viral load and positive OncoE6 was as high as 32.4%. Conclusions The hrHPV intermediate/high viral load, HPV16/18/45 genotyping, and E6 protein (OncoE6) showed promising predictive value for cervical precancer. In particular, women with intermediate/high hrHPV viral load and OncoE6 positivity should be followed up closely. -
表 1 794例纳入分析和164例未纳入分析的妇女基线人口学特征比较
表 2 不同转归组基线筛查结果分布
表 3 基线筛查结果对病理进展预测作用的单因素分析
表 4 hrHPV16/18/45载量联合E6蛋白对病理进展的预测作用
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