宫颈上皮内瘤变和宫颈癌患者人乳头瘤病毒基因型流行率和归因分析

背景　在全球范围内，宫颈癌的发病率和死亡率均排在女性肿瘤第2位，仅次于乳腺癌。人乳头瘤病毒（HPV）持续感染是导致宫颈恶性病变的直接原因。了解特定地区女性群体中HPV基因型分布情况，对于宫颈癌的筛查和疫苗预防策略的制订均具有重要的意义。目的　探讨宫颈上皮内瘤变（CIN）和宫颈癌患者HPV基因型流行率和归因率。方法　收集2012—2015年在青岛市中心医院和青岛市肿瘤医院就诊确诊为CIN和宫颈癌的患者共1 664例，其中CIN1级376例，CIN2级408例，CIN3级336例，宫颈鳞癌440例，宫颈腺癌104例，收集所有患者的宫颈脱落细胞标本，采用聚合酶链式反应（PCR）-反向点杂交法进行23种HPV基因型检测后，分析HPV基因型在不同分级CIN和宫颈癌患者中的流行率、归因率。结果　不同宫颈病变患者HPV阳性率、单一基因型感染、2种基因型感染、3种基因型感染、4种及以上基因型感染阳性率比较，差异均有统计学意义（P<0.05）。在CIN1级患者中，HPV52（19.1%）是流行率最高的基因型，随后依次是HPV16（17.4%）、HPV58（8.7%）；在CIN2级和CIN3级患者中，流行率排在前5位的HPV基因型依次为HPV16、HPV52、HPV31、HPV33、HPV58；在宫颈鳞癌患者中，最常见的HPV基因型是HPV16（43.1%），随后依次是HPV52（16.3%）、HPV31（8.9%）、HPV58（7.3%）；在宫颈腺癌患者中，最常见的HPV基因型是HPV18（57.1%），随后依次是HPV16（28.6%）、HPV52（14.3%）。30.7%的CIN2级和43.3%的CIN3级归因于HPV16；49.1%的宫颈鳞癌和65.1%的宫颈腺癌归因于HPV16和HPV18。在CIN和宫颈癌患者中，除HPV16外，HPV52的归因率最高。结论　青岛地区的HPV疫苗接种计划和宫颈癌预防策略，在关注HPV16和HPV18的同时，也应当关注HPV52、31、58、33。探究HPV基因型流行率和归因率有助于临床针对性治疗。

Human Papillomavirus Genotype Prevalence and Attribution in Patients with Cervical Intraepithelial Neoplasia and Cancer

Background　Globally，cervical cancer ranks second in terms of both incidence and mortality among women，only to breast cancer.Persistent infection with high risk human papillomavirus （HPV） is a necessary cause of malignant cervical lesion.Accurate evaluation of the regional distribution of HPV genotypes is essential for the development of screening and vaccine preventative strategies for cervical cancer.Objective　The aim of this study was to investigate HPV genotype prevalence and attribution in patients with cervical intraepithelial neoplasia （CIN） and cancer.Methods　A total of 1 664 patients 〔including 376 with CIN1，408 with CIN2，336 with CIN3，440 with cervical squamous cell carcinoma （SCC），104 with adenocarcinoma of the uterine cervix （AUC）〕 from Qingdao Central Hospital and Qingdao Cancer Hospital were enrolled from 2012 to 2015.Samples of cervical exfoliated cells were collected and HPV genotypes in them were detected using polymerase chain reaction and reverse dot blot hybridization.23 HPV genotypes were characterized and genotype prevalence and attribution rates in the participants were calculated.Results　HPV positive ratio，rate of single genotype infection，and rates of 2，3 and 4 or more genotypes infection differed significantly in patients with different cervical lesions （P<0.05）．In CIN1 patients，the top 3 prevalent HPV genotypes were as follows：HPV52 （19.1%），HPV16 （17.4%），and HPV58 （8.7%）．In CIN2/3 patients，the top 5 prevalent HPV genotypes were as follows：HPV16，HPV52，HPV31，HPV33 and HPV58.In cervical SCC patients，the top 4 prevalent HPV genotypes were as follows：HPV16（43.1%），HPV52 （16.3%），HPV31（8.9%），and HPV58（7.3%）．In AUC patients，the top 3 prevalent HPV genotypes were as follows：HPV18 （57.1%），HPV16 （28.6%），and HPV52（14.3%）．30.7% of CIN2 and 43.3% of CIN3 were attributed to HPV16；49.1% of cervical SCC and 65.1% of AUC were attributed to HPV16 and HPV18.CIN and cervical cancer were attributable to HPV16 the most，followed by HPV52.Conclusion　The HPV vaccination program and cervical cancer prevention strategies in Qingdao should also focus on HPV52，HPV31，HPV58 and HPV33 while focusing on HPV16 and HPV18.Exploring HPV genotype prevalence and attribution analysis are helpful for clinical targeted treatment.