中国大陆女性体检人群中人乳头瘤病毒型别感染率及九价疫苗中HPV各型别分布的系统评价

摘要

目的:探讨人乳头瘤病毒(human papillomavirus,HPV)在我国大陆女性体检人群中感染及型别分布特征,为体检人群接种九价HPV疫苗提供科学依据.方法:采用系统评价法综合检索评价1995年1月1日~2016年12月31日在Pubmed、Medline、知网、维普和万方数据库收录的所有关于中国正常女性人群HPV感染及型别分布的研究.由2 位研究者独立筛选文献、提取数据资料和评价纳入研究的文献质量,采用Stata 12. 0 软件进行分析.结果:研究共纳入19 篇文献,总人数为83 561 人;随机效应模型结果显示,我国正常体检女性人群中HPV的感染率为16. 18% [95% CI(14. 16,18. 20)% ],高危型、低危型的感染率分别为12. 95%和3. 28% ,九价疫苗中高危型和低危型的感染率为10. 59%和1. 56% ,而九价疫苗中所有型的感染率是12. 15% [95% CI(10. 18,14. 13)% ],其中大陆体检女性人群中比较常见的型别是HPV16／52／58／33／18／68.七大区的HPV感染率及型别均不同,正常体检人群女性中总HPV、高危型以及低危型的感染率最高的是华东地区,分别为17. 54% [95% CI(16. 82,18. 27)% ]、14. 17% [95% CI(13. 50,14. 83)% ]和3. 75% [95% CI(2. 11,6. 11)% ],总HPV感染率最低的是西北地区[8. 79% ,95% CI(7. 47, 10. 26)% ],高危型感染率最低的是西南地区[3. 04% ,95% CI(2. 22,4. 04)% ],低危型感染率最低的是西南地区[0. 14% ,95% CI(0. 02,0. 49) % ];九价HPV疫苗中高危型的感染率最高的华中和华东地区分别为11. 36% [95% CI (9. 33,13. 40)% ]和11. 36% [95% CI(10. 75,11. 97)% ],最低的是东北地区,为7. 83% [95% CI(7. 18,8. 51)% ];九价HPV疫苗中低危型的感染率最高的华北地区为3. 50% [95% CI(1. 93,5. 80)% ],感染率最低的是华中地区,为0. 30% [95% CI(0. 06,0. 87)% ];九价 HPV 疫苗中所有型的感染率最高的华北地区为12. 75% [95% CI(9. 64, 16. 42)% ],最低是东北地区,为8. 34% [95% CI(7. 67,9. 03)% ].正常体检女性人群中HPV总的感染率、高危型和低危型感染率均是南方高于北方,差异有统计学意义;九价疫苗的低危型感染率则相反,南北方感染的HPV型别以及感染率均不同,而九价疫苗中高危型及全部型别的南北方感染率差异无统计学意义.经非条件Logistic 回归分析,使用GP5+／6+引物系统检测出的HPV调整感染率显著高于其它引物系统(P<0. 001);总HPV调整感染率随发表年限增加而增加(P<0. 001).结论:中国大陆地区健康体检的女性人群中HPV的感染率较高,常见的型别为HPV16／52／58／33／18／68,不同地区型别分布及感染率不同,其中华中地区最高,西北地区最低,且南北方存在差异.因此,预计在体检人群中接种九价HPV疫苗防治效果明显,但还是需要进行宫颈癌的筛查.受纳入研究的文献检测方法多样性和质量的限制,上述结论尚需要更多研究予以证实.%Objective: We aimed to assess the genotype-specific prevalence and distribution of cervical human papilloma-virus (HPV) in women undergoing health check-ups in mainland China by systematic reviews, in order to provide scientific evidence for promoting HPV 9-valent vaccine. Methods: Population-based studies on HPV prevalence published between Jan 1995 and Dec 2016 were retrieved from Pubmed, Medline and Chinese databases (CNKI, VIP and Wanfang). Detailed information like populations, cytological or pathological diagnosis, methods for HPV DNA detection and type was collected. In total, 19 studies were left for final evaluation using Stata 12. 0. Results: The overall prevalence of HPV infection among 83,561 women in mainland China was 16. 18% (95% CI: 14. 16, 18. 20). The prevalence of high-risk type and low-risk type HPV was 12. 95% and 3. 82% , respectively. The prevalence of high-risk type, low-risk type and all-type HPV covered by 9-valent vaccine was 10. 59% , 1. 56% , and 12. 15% [95% CI (10. 18, 14. 13)% ]. The most common HPV types were HPV-16, HPV-52, HPV-58, HPV-33, HPV-18 and HPV-68. The genotype-specific prevalence of HPV varied in sev-en regions. The prevalence of all-type, high-risk type and low-risk type HPV in East China were 17. 54% [95% CI (16. 82, 18. 27)% ], 14. 17% [95% CI (13. 50, 14. 83)% ] and 3. 75% [95% CI (2. 11, 6. 11)% ], respectively; the Northwest reported the lowest prevalence of HPV [8. 79% , 95% CI (7. 47, 10. 26)% ], while the Southwest saw the lowest prevalence of high-risk and low-risk type HPV [3. 04% , 95% CI (2. 22, 4. 04)% vs 0. 14% , 95% CI (0. 02, 0. 49) % ]. The high-est prevalence of high-risk type HPV covered by 9-valent vaccine was seen in central China and East China [11. 36% , 95% CI (9. 33, 13. 40)% vs 11. 36% , 95% CI (10. 75, 11. 97)% ], while the lowest prevalence of that was in the northeast [7. 83% , 95% CI (7. 18, 8. 51)% ]. The highest and the lowest prevalence of low-risk type HPV covered by 9-valent vac-cine were in North China and central China [3. 50% , 95% CI (1. 93, 5. 80)% vs 0. 30% , 95% CI (0. 06, 0. 87)% ], re-spectively. The highest and lowest prevalence of all-type HPV covered by 9-valent vaccine were in North China and Northeast China [12. 75% , 95% CI (9. 64, 16. 42)% vs 8. 34% , 95% CI (7. 67, 9. 03)% ], respectively. The data were higher in southern China than those in northern China in the prevalence of overall, high-risk and low-risk HPV, and the difference was statistically significant. The prevalence of the low-risk HPV covered by 9-valent vaccine was higher in the northern China than that in the southern China. The genotype of low-risk HPV was different in northern and southern China. There was no statistically significant difference between northern and southern China in the prevalence of high-risk type and all-type HPV covered by 9-valent vaccine. In non-conditional Logistic regression analysis, the adjusted prevalence of HPV detected by GP5+／6+ primer system was significantly higher than that by other primer systems (P<0. 001); the total HPV infection rate increased as the publication year of included articles increased (P<0. 001). Conclusion: The incidence of HPV was relatively high among female health examinees in mainland China, and the most common types of HPV were HPV16, 52, 58, 33, 18 and 68. The genotype of HPV differs when the region varies. The highest incidence rate was observed in central China, while the lowest was observed in Northwest China. Therefore, the nine-valent HPV vaccine may be effective for health female examinees. The screening of cervical cancer, however, is still needed. More studies are expected to confirm the above conclusions.