高危型人乳头状瘤病毒风险分层在深圳地区人乳头状瘤病毒初筛阳性人群分流中的应用

Risk stratification of type-specific human papillomavirus for cervical precancers： evidence from across-sectional study in Shenzhen

目的探讨深圳地区女性人乳头状瘤病毒（HPV）感染基因亚型分布及其导致宫颈癌前病变的风险差异。方法2015年3月1日至6月15日，在深圳市选取18家社区健康服务中心，采用整群抽样的方法招募30～59岁2 717例女性参与宫颈癌筛查，分析HPV基因分型、液基细胞学检查、阴道镜和组织病理学检查结果，以宫颈上皮内瘤样病变2级及以上（CIN2＋）为终点，计算不同HPV基因亚型组合筛查方法的灵敏度、特异度、阳性预测值和阴性预测值。结果2 717例研究对象中，HPV感染率为15.9%（432/2 717）。高危型HPV感染率前5位分别为HPV52（22.9%，99/432）、HPV16（12.7%，55/432）、HPV53（10.0%，43/432）、HPV51（8.6%，37/432）和HPV58（8.1%，35/432）。HPV33/16阳性预测CIN2＋的灵敏度（57.1%）高于HPV16/18阳性（42.9%），差异有统计学意义（P〈0.05）；HPV33/16和HPV16/18阳性预测CIN2＋的特异度分别为87.3%和86.9%，差异无统计学意义（P〉0.05）。液基细胞学检查低度鳞状上皮内病变以上（LSIL＋）联合HPV33/16阳性和液基细胞学检查非典型鳞状上皮细胞及以上（ASC－US＋）预测CIN2＋的灵敏度分别为75.0%和64.3%，差异有统计学意义（P〈0.05），液基细胞学检查LSIL＋联合HPV33/16阳性和液基细胞学检查ASC－US＋预测CIN2＋的特异度分别为83.5%和89.2%，差异无统计学意义（P〉0.05）。结论深圳地区感染HPV的女性罹患子宫颈高级别CIN的风险因HPV基因亚型的不同而存在差异，风险排名前5位的基因亚型分别为HPV33、HPV16、HPV58、HPV56和HPV68。在HPV基因亚型检测技术普遍应用的前提下，液基细胞学检查LSIL＋联合HPV33/16分型可考虑作为发达地区城市人群HPV阳性者的分流策略。

ObjectiveTo analyze the epidemiological genotype features of human papillomavirus （HPV） in cervical infection and their risks for cervical precancers among women in Shenzhen area.MethodsA total of 2 717 individuals ranging in age from 30~59 years were recruited in 18 community health centers of Shenzhen city from March 1 to June 15, 2015 by a cluster sampling method. The results of genotype of HPV, liquid-based cytology （LBC）, colposcopy and pathology were analyzed. The clinical sensitivity and specificity as well as positive （PPV） and negative （NPV） predictive values of the combination of different HPV genotype in screening the cervical intraepithelial neoplasia （CIN） 2 and above were estimated.ResultsThe HPV infection rate in Shenzhen area was 15.9% （432/2 717）. The most common HPV genotype was HPV52 （22.9%）, followed by HPV16 （12.7%）, HPV53 （10.0%）, HPV51 （8.6%） and HPV58 （8.1%）. Compared with HPV16/18 genotyping, HPV33/16 genotyping had a higher sensitivity （57.1% vs. 42.9%, P〈0.05） and an analogous specificity （87.3% vs. 86.9%, P〉0.05） in predicting CIN2＋ . The sensitivity of combination of HPV33/16 genotyping and low grade squamous intraepithelial lesion （LSIL） positive tested by LBC in predicting CIN2＋ was 75.0%, significantly higher than 64.3% of atypical squamous cells of undetermined significance （ASC-US） positive tested by LBC alone （P〈0.05）. The specificities of these two methods mentioned above in predicting CIN2＋ were 83.5% and 89.2%, respectively, without statistical difference （P〉0.05）.ConclusionsWomen infected by HPV have distinct risks for CIN2＋ according to different high-risk HPV genotypes. The top five risks were HPV 33, 16, 58, 56, and 68. HPV-positive women triaged by LBC LSIL＋ combined with HPV33/16 genotyping may be a potential strategy for cervical cancer screening in developed urban area.