【作者】 鲍彦平；

【导师】 乔友林；

【作者基本信息】 中国协和医科大学 ， 流行病与卫生统计学， 2007， 博士

【摘要】 目的:了解中国子宫颈癌高发区妇女人群HPV型别分布,并了解中国及亚洲地区ICC、HSIL、LSIL和正常子宫颈妇女中的HPV型别分布,估计HPV16/18疫苗的应用前景,为研发新一代HPV疫苗提供依据。材料和方法:2004年5月到6月,对山西阳城941名15-59岁智力正常的妇女进行以人群为基础的子宫颈癌筛查,用GP5+/6+为引物的PCR方法检测662份标本中HPV型别分布。之后对87个2006年10月之前发表的PCR检测子宫颈中HPV型别分布的研究进行Meta分析,分别包括6100、2047、1339和18008份ICC、HSIL、LSIL和正常子宫颈标本。调整非条件Logistic回归模型中有意义的变量后,得到总HPV调整感染率,并计算HPV6,16,18,31,33,35,39,45,51,52,56,58,59,66,68,70,73和82等18种HPV型别感染率。结果:山西省阳城县15-59岁妇女中HPV总感染率为14.8%,高危型HPV年龄别感染率曲线呈‘V’型,在20-24和50-54岁为感染高峰,30-34岁最低。HPV16,58,52,33和18为该人群中最常见的5种HPV型别。Meta分析显示,在不同子宫颈状态中,HPV16感染率均占首位,HPV16/18在ICC、HSIL和LSIL中的感染率依次为66.9%、40.4%和26.7%。ICC中,最常见的8种HPV型别(HPV16,18,58,33,52,45,31和35)的累积感染率为86.4%。结论:在该子宫颈癌高发区人群中,HPV16为最常见HPV型别。HPV16/18预防性疫苗对中国和亚洲分别有高达69.7%和67%的预防作用。HPV58和52是中国和亚洲相对其它地区的优势HPV型别。HPV16,18,58,33,52,45,31和35能够够预防亚洲86.4%的ICC。更多还原

【Abstract】 Background:Invasive cervical cancer(ICC) is the second most common cancer among women worldwide.According to the report from GLOBOCAN 2002,54 percent new cases of cervical cancer occurred in Asia each year where cervical cancer is significant problem threatening women health.These years,there was a breakthrough progress in the research of etiology of cervical cancer.HPV is acceptable as a necessary cause of cervical cancer and its precursors,including cervical intraepithelial neoplasia grade 3(CIN 3).The recent IARC monograph concluded that there was sufficient evidence in humans for the carcinogenicity of 13 HPV types in cervix.The primary and secondary cervical cancer prevention by the detection and vaccines of carcinogenic HPV types provide the possibility for conquering the cervical cancer eventually.Objective:To determine HPV type-distribution in women with ICC,high-grade squamous intraepithelial lesions(HSIL),low-grade squamous intraepithelial lesions(LSIL) and normal cytology/histology from China and Asia,and to estimate the potential future impact of an HPV 16/18 prophylactic vaccine in this region and the regional variance and to provide evidence for next generation prophylactic HPV vaccines.Methods:During May to June of 2004,A population-based cervical cancer screening was conducted in Yangcheng County of Shanxi Province,941 women aged 15-59 took part in the screening.HPV DNA type distribution in 662 cervical cell samples was detected.Then a Meta-analysis was conducted including 87 eligible papers that were published before October of 2006 and searched in Pubmed and CNKI.Among these 87 papers using polymerase chain reaction to detect HPV types,79 were published in the intemational journals as English version and 8 were in Chinese journals.A total of 6100,2047,1339 and 18008 women with ICC,HSIL, LSIL and normal cytology/histology were included,respectively.The variables of area, pathology type,specimen resource,PCR primers,publish years of literature were introduced into non-conditional Logistic regression.The adjusted overall HPV prevalence was estimated based on the significant variables in the final models.The overall and type-specific HPV prevalences were calculated stratified by cervical lesion degrees.Type specific prevalence of HPV types 6,16,18,31,33,35,39,45,51,52,56,58,59,66,68,70,73 and 82 were estimated,stratified by cervical lesion grade.Results:The overall HPV prevalence by PCR(GP5+/6+) was 14.8%,the age curve of high-risk HPV prevalence was shaped ’V’,with 2 peaks in ’20-24’ and ’50-54’ and ’30-34’ was lowest.The most common 5 HPV types were HPV16,58,52,33 and18 in Shanxi Province.In Meta analysis,the overall crude HPV prevalences were 85.9%,81.0%,72.9%and 14.4% respectively in Asian women with ICC,HSIL,LSIL and normal cytology/histology.In ICC, the predominant type was HPV 16 which type specific prevalence was 52.4%and was followed by HPV 18 and 58.In ICC,the most 8 common HPV types were as the descending order were HPV16,18,58,33,52,45,31 and 35 that the cumulative prevalence was 86.4%, and the most 5 common could account for 80%invasive cervical cancer in Asia.The estimated HPV 16/18-positive fraction was 66.9%,40.4%,26.7%and 3.3%in women with ICC,HSIL, LSIL and normal cytology or histology.In China,the overall crude HPV prevalence was 83.9%,77.4%,76.2%and 12.6% respectively in women with ICC,HSIL,LSIL and normal cytology/histology.Similarly,HPV 16 was the predominant type,type specific prevalences were 58.7%,35.4%,21.1%and 3.3% in women with ICC,HSIL,LSIL and normal cytology/histology.In ICC,HPV16,18,58,33, 52,45,31 and 35 accounts for 87.7%ICC in China,and the most 5 HPV types account for 84%.The estimated HPV 16/18-positive fraction was 69.7%,45.5%,32.2%and 4.6%in China women with ICC,HSIL,LSIL and normal cytology/histology.Conclusion:In the population of this high-risk area of cervical cancer,the HPV 16 was the most common HPV type,followed by HPV 58,52,33 and 18.HPV 16/18 prophylactic vaccines are estimated to provide about 69.7%and 67%protection against ICC in China and Asia.HPV 58 and 52 were special and priories HPV types in ICC in China Asia known from other areas.Aider HPV16 and 18,the next most 6 common HPV types were HPV 58,33,52, 45,31 and 35 which accounted for additional 20%of cervical cancer cases in Asia,totally the 8 HPV types could account for 87.7%and 86.4%invasive cervical cancer in China and Asia.For optimal population coverage,these HPV carcinogenic types should be considered for second generational HPV prophylactic vaccines.更多还原