宫颈上皮内瘤变及微浸润癌患者人乳头瘤病毒基因亚型分析

Human papillomavirus genotypes distribution in patients with cervical intraepithelial neoplasia and microinvasive cancer

目的明确陕西省宫颈上皮内瘤变（CIN）及微浸润癌（MICC）病例宫颈人乳头瘤病毒（HPV）感染的基因亚型分布特征。方法选取2009年10月至2015年10月在西安交通大学第一附属医院病理确诊的1 571例陕西地区宫颈病变患者,其中CIN 1、CIN 2、CIN 3、原位癌（CIS）、MICC分别为252、505、539、143、132例,采用凯普医用核酸分子快速导流杂交基因芯片技术检测宫颈样本中高危型HPV（HR-HPV）15种和低危型HPV（LR-HPV）6种（共21种）HPV基因亚型,分析HPV基因分型检测结果。结果总体HPV感染率为90.64%。HR-HPV感染率89.37%,占HPV阳性标本的98.60%;总体HPV感染率和HR-HPV感染率在CIN 1、CIN 2、CIN 3、CIS、MICC中分别为76.98%和73.02%、89.70%和88.51%、95.73%和94.99%、95.80%和95.80%、93.94%和93.94%,各组间差异除CIN3＋（即CIN3和CIS）与MICC组外均有统计学意义（χ^2=18.11～136.96,P〈0.001）。感染率最高者为HPV16（55.63%）,其他常见亚型为HPV58（16.74%）、52（11.01%）、33（7.00%）、31（6.62%）、18（5.86%）。LR-HPV感染率6.68%。LR-HPV感染率在前述各组中分别为10.32%、8.32%、4.64%、3.50%、5.30%。常见LR-HPV为HPV81（2.93%）、11（1.78%）、6（1.21%）。高危/低危HPV混合感染率5.41%。CIN1组HPV基因亚型分布特征明显不同于其他病变组。结论陕西地区宫颈病变中HPV感染水平符合疾病本质规律且随着病变加重显著增加,其基因型分布基本符合亚洲人群分布规律并具一定区域性差异。HPV基因亚型分布特征在不同病变中的差异反映了不同亚型在宫颈病变发生中作用的不同。本结果对理解宫颈病变的发生机制、宫颈癌防治和疫苗研制具有指导意义。

Objective To analyze the HPV genotype distribution among women with cervical intraepithelial neoplasia（CINs and CIS）and microinvasive cancer（MICC）in Shaanxi Province.Methods The study recruited1 571 patients with pathologically diagnosed cervical lesions,including 252 CIN1,505 CIN2,539 CIN3,143 CIS,and 132 MICC cases.All the patients were diagnosed in the First Affiliated Hospital of Xi＇an Jiaotong University between October 2009 and October 2015.21 HPV genotypes were examined by a PCR-based hybridization gene chip assay.Results The overall HPV prevalence was 90.64%.89.37% of the women had a high risk of HPVs（HRHPV）,which accounted for 98.60%in all HPV positive samples.The overall infection rate of HPV and infection rate of HR-HPV were 76.98% and 73.02%,89.70% and 88.51%,95.73% and 94.99%,95.80% and 95.80%,93.94% and 93.94%in CIN1,CIN2,CIN3,CIS,and MICC patients,respectively,which were significantly different among the groups（χ^2=18.11-136.96,P〈0.001）,except that between CIN3＋（CIN3 and CIS）and MICC.The infection was most prevalent in HPV16（55.63%）,followed by HPV58（16.74%）,HPV52（11.01%）,HPV33（7.00%）,HPV31（6.62%）and HPV18（5.86%）.6.68% of the women were positive for low-risk HPVs（LR-HPV）.The LR-HPV infection rate was 10.32%,8.32%,4.64%,3.50% and 5.30% in the above groups,respectively.It was most prevalent in HPV81（2.93%）,followed by HPV11（1.78%）and HPV6（1.21%）.The rate of mixed infection of both HR-HPV and LR-HPV was 5.41%.The spectra of HPV genotypes were different between CIN1 and the other groups.Conclusion The HR-HPV infection rates increase with increased lesion severity and the genotype distribution of HPV in Shaanxi area has a similar spectrum to those in the whole Asian regions with some difference.The different distribution of HPV genotypes in various cervical conditions indicates different pathogenetic role of different HPV genotypes in cervical lesions.This study provides some guidance for understanding the pathogenesis and prevention of cervical cancer as well as vaccination development.