HPV16 DNA存在状态在宫颈病变筛查和预测中的应用价值

摘要

Objective To evaluate the correlation between physical status of human papillomavirus 16 (HPV16 )and degree of cervical lesion and the role of HPV-16 integration in prediction and diagnosis of high squmous intrepithelil lesion(HSIL).Methods A total of 165 cervical cells samples were collected from the patients with HPV positive.All patients' pathological results were definite, including 18 cases of cervicitis, 24 cases with cervical intraepithelial neoplasia(CIN)1,45 cases with CIN2,51 cases with CIN3 and 27 cases with cervical cancer.The total genomic DNA were extracted and multiplex PCR were performed for detection of the level of HPV E2 and E6 genes.Comparing the physical status of HPV16 in different degrees of cervical lesions according to the E2/E6 ratio.Results The single infection ratios of HPV16 in cervicitis,CIN1,CIN2,CIN3 and cervical cancer were 6.73%(7/104), 10.58%(11/104),29.81%(31/104),30.77%(32/104),22.11%(23/104),respectively.Single HPV infection rate was gradually increasing with the processing of cervical lesion level.Theintegration ratios of HPV16 in cervicitis,CIN1,CIN2,CIN3 and cervical cancer were 16.67%(3/18),20.83%(5/24),46.67%(21/45),62.74%(32/51),77.78%(21/27),respectively.The difference was statistically significant(P<0.05).The sensitivity and specificity of diagnosis of cervical lesions by HPV16 DNA integrate status were 60.16% and 79.07% and the positive predictive value and negative predictive value were 40.96% and 90.24%.Conclusion The E2/E6 ratio of HPV16 can be used as indicators to j udge the state of viral integration, and the integration status of HPV16 was accompanied with the processing of cervical lesion level.%目的 研究人乳头瘤病毒16(human papillomavirus 16,HPV16)阳性患者病毒存在状态与宫颈病变级别的关系,以及HPV16整合型对高级别宫颈病变的预测和诊断价值.方法 选择已明确病理学结果 且为HPV16阳性的165例患者为研究对象,其中宫颈炎18例,子宫颈上皮内瘤变(cervical intraepithelial neoplasia,CIN)1为24例,CIN2为45例,CIN3为51例,宫颈癌27例.应用多重PCR检测165例患者宫颈脱落细胞中HPV16 DNA的E2、E6基因,通过比较E2和E6的面积灰度值得到E2/E6比值,比较不同级别病变中HPV16 DNA存在状态.结果 在炎症中HPV16单一型别感染的检出率为6.73%(7/104),CIN1中其检出率为10.58%(11/104),CIN2中为29.81%(31/104),CIN3中为30.77%(32/104),宫颈癌组中为22.11%(23/104).随着宫颈病变级别的升高,HPV16单一型别感染的检出率逐渐增加(Z=3.119,P=0.002).在宫颈炎、CIN1、CIN2、CIN3、宫颈癌中混合型的检出率分别为16.67%(3/18)、20.83%(5/24)、46.67%(21/45)、62.74%(32/51)、77.78%(21/27),将不同级别宫颈病变整合型的检出率进行统计学分析,差异有统计学意义(χ2=28.009,P<0.05).HPV16 DNA整合状态诊断宫颈病变的灵敏度为60.16%,特异度为79.07%,阳性预测值为90.24%,阴性预测值为40.96%,其诊断宫颈病变有较高的特异度和阳性预测值.结论 运用多重PCR扩增HPV16的E2和E6基因,E2/E6比值可以作为判断病毒存在状态的指标,与宫颈病变的级别相关.此外,整合在HPV感染进程中是一个早期事件,随着宫颈病变级别的升高,整合的发生率增加.