不同人乳头瘤病毒高危亚型与宫颈病变发生的关系

Relationship between HPV high-risk genotypes and cervical lesions

目的探讨人乳头瘤病毒(HPV)各亚型感染在不同级别宫颈病变中的分布差异,为HPV检测尤其是高危HPV亚型检测引入宫颈癌筛查方案提供理论依据。方法收集2007年7月―2012年8月间于上海交通大学医学院附属仁济医院妇科门诊行机会性宫颈癌筛查人群的宫颈脱落细胞标本,完成HPV分型检测和液基薄层细胞检测。对HPV高危亚型阳性、TCT结果为无明确意义的非典型鳞状上皮细胞改变(ASCUS)及以上级别者,进一步行阴道镜检查并取宫颈组织行活组织检查。经病理确诊为宫颈癌和子宫颈上皮肉瘤变(CIN)患者共348例,以病理诊断CINⅡ作为临界终点,分析常见HPV高危亚型与宫颈高级别及其以上级别病变的关系。结果完成HPV分型检测10838例,高危亚型阳性1712例,占筛查总数的15.8%。最常见的6种HPV高危亚型分别为HPV16、58、52、33、18和31。不同程度宫颈病变患者间,除HPV18外,其他常见HPV亚型间检出率的差异均有统计学意义,且宫颈浸润癌患者的HPV16检出率最高(χ2=26.784,P=0.000);慢性宫颈炎患者的HPV58(χ2=23.909,P=0.000)、HPV52(χ2=31.870,P=0.000)、HPV33(χ2=14.281,P=0.002)、HPV31(χ2=12.839,P=0.004)的检出率均最高。HPV感染总体人群中,HPV16和18感染的患者中确诊为宫颈高级别病变患者的比例均显著高于HPV33、58、31和52感染的患者(χ2=47.2,P=0.000)。单一亚型感染人群中,HPV16单一感染者中发生宫颈高级别病变的比例最高(χ2=59.8,P=0.000)。多重感染人群中,HPV18多重感染者中发生宫颈高级别病变的比例最高(χ2=28.3,P=0.000),显著高于HPV18单一感染者(OR=11.9,P=0.000)。结论 HPV16、18是引起宫颈癌变的最重要的亚型,引入HPV亚型检测行宫颈癌筛查和术后随访监测具有较大的临床优势和应用价值。

Objective To analyze the distribution difference of human papilloma virus （HPV） high-risk genotypes in different cervical lesions and to study the value of HPV genotype test in cervical screening. Methods Cervical exfoliative cells were collected from the people for cervical cancer screening in our hospital from July 2007 to August 2012. Then HPV genotyping test and liquid based cytology test were taken. Colposcopy and cervical biopsy were performed in patients whose HPV high-risk genotype was positive and liquid based cytology results were greater than or equal to atypicai squamous cells of unknown significance（ASC-US）. Eventually cervical lesions were found in 348 patients, including cervical cancer and cervical intraepithelial neoplasia confirmed by pathology. Taking to the pathological diagnosis of cervical intraepithelial neoplasia （CIN） Ⅱ^＋ as critical endpoint, we analyzed the relationship between HPV genotypes and cervical lesions. Results Among of 10 838 cases, positive high-risk genotypes appeared in 1 712 cases, accounting for 15.8%. The six most common high-risk genotypes were HPV 16, 58, 52, 33, 18 and 31. There were significant differences in the detection rates of HPV 16, 58, 52, 33 and 31 between different cervical lesions, especially HPV 16 （X2 =26.784, P=0.000）. In the patients with chronic cervicitis, the most common high risk genotypes were HPV58 （χ^2 = 23.909, P = 0.000）, HPV52 （χ^2 =31.870, P=0.000）, HPV33 （χ^2=14.281, P=0.002） andHPV31 （χ^2=12.839, P= 0. 004）. The incidence of canceration in the patients with HPV16 and HPV18 infection was significantly higher than those with other genotype infections （ P = 0. 000）. In single infection, HPV16 had a higher pathogenic risk than other genotypes （χ^2= 59.8, P = 0. 000）. In multiple infection, HPV18 had a higher pathogenics risk than other genotypes （χ^2 = 28.3, P = 0. 000）. And the patients with multiple infection including HPV18 were much more than the patients with single infection of HPV 18 （OR = 11.9, P= 0. 000）. Conclusion HPV16 and HPV18 are the most genotypes for the development of cervical cancer. HPV genotyping test is recommended for cervical screening and follow up after surgery.