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目的 评估人乳头瘤病毒(HPV)型别分布特征在宫颈癌筛查队列中随时间动态的变化.方法 采用线性反向探针杂交技术,对山西省宫颈癌筛查队列2005-2014年高危型HPV阳性女性宫颈脱落细胞标本进行HPV基因型别检测.利用线性混合模型分析不同型别HPV感染率在总人群中随时间的变化趋势,采用线性趋势x2检验比较宫颈上皮内瘤变2级及以上(CIN2+)人群中HPV型别随时间的变化,最后分析多重感染率随年龄增长的动态变化规律.结果 2005-2014年筛查总人群中最常见型别为HPV16和52,但HPV16感染率在筛查随访中,从2005年4.6％下降到2010年和2014年的2.2％(F=8.125,P＜0.001).HPV52感染率在筛查随访中相对稳定,HPV33、51和58感染率则先下降后升高.病理结果正常人群中HPV型别分布与总人群相似,CIN2+人群中HPV16感染率下降较为明显,由2005年65.22％,经2010年41.03％下降至2014年的31.58％(x2=4.420,P=0.036),HPV33感染率有升高趋势,其余HPV型别感染率在筛查过程中无明显变化.多重感染率随年龄增长而波动.结论 宫颈癌筛查队列在定期筛查和治疗随访中HPV型别分布特点有所变化,尤其是HPV16出现显著下降,提示宫颈癌人群筛查和随访时如采用HPV检测,应考虑型别随时间变化的规律.

Objective To evaluate the dynamic variation of genotypes distribution of human papillomavirus (HPV) over 10-year follow-up in a cervical cancer screening cohort.Methods Based on the Shanxi Province Cervical Cancer Screening Study Ⅰ cohort,we detected HPV genotypes on the well-preserved exfoliated cervical cells from women who were tested HPV positive from year 2005 to year 2014 using reverse linear probe hybridization assay.The changes of prevalence of type-specific HPV over time among the overall population were estimated using linear mixed models.The association between the type-specific HPV and cervical intraepithelial neoplasia grade 2 or worse (CIN2 +) was calculated by linear Chi-square test.Finally,the trends of multiple infections of HPV with the increase of the age were analyzed.Results During the cervical cancer screening of the overall population from 2005 to 2014,the most common genotypes among the population were HPV16 and 52.The prevalence of HPV16 decreased over time from 4.6％ in 2005 to 2.2％ in 2010 and 2014 (F=8.125,P＜0.001).The prevalence of HPV52 remained pretty stable and HPV33,51 and 58 slightly decreased then apparently increased.Further stratification analysis by pathological lesions showed the same trend of the HPV prevalence for the histology normal women with the overall population.Of note,for those women with the cervical intraepithelial neoplasia (CIN2 +),the detection rate of HPV16 decreased from 65.22％ in 2005 to 41.03％ in 2010 and finally to 31.58％ in 2014 (x2=4.420,P=0.036) and that of HPV33 substantially increased.No significant variation was found for other types of HPV.Multiple infection rate varied with the growing age of the women.Conclusions The genotypes prevalence of HPV tended to vary over time during cervical cancer screening in the context of regular screening combining with immediate treatment for those CIN2 + women.HPV16 prevalence significantly decreased over time,which indicated that the variation of type-specific HPV prevalence should be considered when regular cervical cancer screening was organized using HPV technique.