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探索中国女性高危型人乳头瘤病毒（High-risk human papillomavirus,HR-HPV）感染的自然转归状况，以指导开展正确的健康教育以及HPV感染相关的治疗药物或疫苗的研发。从PubMed,Embase,CNKI，万方等数据库中检索和筛选自建库以来至2024年5月有关中国女性HR-HPV感染自然消退以及持续感染相关的文章。使用纽卡斯尔-渥太华量（NOS）评估所纳入文献的质量，采用随机效应模型计算HR-HPV感染的自然转阴率（95%CI）以及HR-HPV感染的持续阳性率（95%CI），并分析随访时间与HR-HPV自然转阴率、HR-HPV持续阳性率之间的关联。最后通过漏斗图、Egger′s检验评价发表偏倚，采用敏感性分析评估合并参数值的稳健程度。共纳入54篇文章，涉及HR-HPV持续感染的文章共52篇，HR-HPV感染自然转阴的文章共51篇，NOS量表评分均≥5分共53篇。随访时间为6个月、12个月、24个月、36个月时，中国女性HR-HPV感染自然转阴率分别为0.3033(0.2238,0.3892),0.5174(0.4559,0.5786),0.6538(0.5834,0.7210),0.7608(0.6642,0.8455)。HR-HPV持续阳性率分别为0.6780(0.5897,0.7603),0.4528(0.3930,0.5133),0.2963(0.2319,0.3649),0.2294(0.1378,0.3362)。随着随访时间的延长，在中国高危人乳头瘤病毒（HR-HPV）的自然清除率逐渐增加，持续感染率逐渐下降。到了36个月时，约有22.94%的女性仍呈HR-HPV持续阳性。这一数据对于正确进行健康教育以及指导后续HPV感染相关的治疗药物或疫苗研发具有重要意义。
Abstract：This study aims to investigate the natural history of high-risk human papillomavirus(HR-HPV) infection in Chinese women to inform effective health education and support the development of therapeutic drugs and vaccines related to HPV infection. Relevant studies on the spontaneous regression and persistent infection of HR-HPV in Chinese women were systematically searched and manually screened from Embase, PubMed, CNKI, and Wanfang databases, covering the period from database inception to May 2024. The quality of included studies was assessed using the Newcastle-Ottawa Scale(NOS). A random-effects model was applied to calculate the natural clearance rate(95% CI) and the persistent positivity rate(95% CI) of HRHPV infection. The association between follow-up duration and both the natural clearance rate and persistent positivity rates of HR-HPV was analyzed. Publication bias was evaluated using funnel plots and Egger's test, and sensitivity analysis was performed to assess the robustness of the combined parameter estimates. A total of 54 studies were included in the analysis, with 52 studies focused on persistent HR-HPV infection and 51 on natural clearance. Among these,53 studies had NOS score ≥5. The natural clearance rates of HR-HPV infection in Chinese women at 6, 12, 24, and 36 months were 0.3033(0.2238, 0.3892), 0.5174(0.4559, 0.5786), 0.6538(0.5834, 0.7210), and 0.7608(0.6642, 0.8455), respectively. The corresponding persistent positivity rates were 0.6780(0.5897, 0.7603), 0.4528(0.3930, 0.5133), 0.2963(0.2319, 0.3649), and 0.2294(0.1378, 0.3362). With the extended of follow-up duration, the natural clearance rate of HR-HPV increases while the rate of persistent infection declines. By 36 months, approximately 22.94% of women remain persistently positive for HR-HPV. These findings provide important insights for implementing targeted health education and guiding the development of therapeutic drugs and vaccines for HPV infection.
[1]Gu X,Sun G,Zheng R,et al.Incidence and mortality of cervical cancer in China in 2015[J].J Natl Cancer Cent,2022,2(2):70-77.DOI:10.1016/j.jncc.2022.01.002.
[2]胡尚英,郑荣寿,赵方辉,等.1989至2008年中国女性子宫颈癌发病和死亡趋势分析[J].中国医学科学院学报,2014,36(2):119-125.DOI:10.3881/j.issn.1000-503X.2014.02.001.
[3]Yuan Y,Cai X,Shen F,et al.HPV post-infection microenvironment and cervical cancer[J].Cancer Lett,2021,497:243-254.DOI:10.1016/j.canlet.2020.10.034.
[4]Schlecht NF,Kulaga S,Robitaille J,et al.Persistent human papillomavirus infection as a predictor of cervical intraepithelial neoplasia[J].JAMA,2001,286(24):3106-3114.DOI:10.1001/jama.286.24.3106.
[5]Gravitt PE.The known unknowns of HPV natural history[J].J Clin Invest,2011,121(12):4593-4599.DOI:10.1172/JCI57149.
[6]Yu MC,Austin RM,Lin J,et al.The role of high-risk human Papilloma virus testing in the surveillance of cervical cancer after treatment[J].Arch Pathol Lab Med,2015,139(11):1437-1440.DOI:10.5858/arpa.2014-0534-OA.
[7]Wong MCS,Vlantis AC,Liang M,et al.Persistence and clearance of oral human papillomavirus infections:a prospective population-based cohort study[J].J Med Virol,2020,92(12):3807-3814.DOI:10.1002/jmv.26130.
[8]Huh WK,Ault KA,Chelmow D,et al.Use of primaryhigh-risk human papillomavirus testing for cervical cancer screening:interim clinical guidance[J].Gynecol Oncol,2015,136(2):178-182.DOI:10.1016/j.ygyno.2014.12.022.
[9]中华预防医学会肿瘤预防与控制专业委员会,中国医师协会妇产科医师分会阴道镜与宫颈病变专业委员会,中国优生科学协会阴道镜和子宫颈病理学分会,等.人乳头状瘤病毒核酸检测用于宫颈癌筛查中国专家共识(2022)[J].中华医学杂志,2023,103(16):1184-1195.DOI:10.3760/cma.j.cn112137-20230117-00096.
[10]Schmeink CE,Massuger LF,Lenselink CH,et al.Prospective follow-up of 2,065 young unscreened women to study human papillomavirus incidence and clearance[J].Int J Cancer,2013,133(1):172-181.DOI:10.1002/ijc.27986.
[11]Bae J,Seo SS,Park YS,et al.Natural history of persistent high-risk human papillomavirus infections in Korean women[J].Gynecol Oncol,2009,115(1):75-80.DOI:10.1016/j.ygyno.2009.06.016.
[12]Giuliano AR,Harris R,Sedjo RL,et al.Incidence,prevalence,and clearance of type-specific human papillomavirus infections:the young women's health study[J].J Infect Dis,2002,186(4):462-469.DOI:10.1086/341782.
[13]耿建祥,黄华艺,刘建华,等.HPV感染疾病相关问题专家共识(2017)[J].医学研究生学报,2017,30(12):1238-1241.DOI:10.16571/j.cnki.1008-8199.2017.12.002.
[14]蔡虹,关婷,唐晖,等.相同人群连续3年HPV感染状况分析[J].中国妇幼保健,2008,23(11):1528-1530.
[15]郭艳利,耿力,游珂,等.高危型人乳头瘤病毒检测在宫颈上皮内瘤变Ⅰ随访中的价值[J].中国实用妇科与产科杂志,2008,24(12):925-927.
[16]江维,李隆玉.宫颈上皮内瘤变Ⅰ级的自然转归与随访观察[J].实用癌症杂志,2009,24(2):188-190.DOI:10.3969/j.issn.1001-5930.2009.02.024.
[17]刘莹,荣晅,周艳秋,等.轻度宫颈上皮内瘤变自然转归的前瞻性研究[J].中国肿瘤,2010,19(6):372-376.
[18]秦广益,陶敏芳.宫颈高危型人乳头状瘤病毒潜伏感染者病毒自然清除率的研究[J].中国临床医学,2011,18(3):307-309.DOI:10.3969/j.issn.1008-6358.2011.03.013.
[19]王凤文,林杨,崔满华.TCT检查正常妇女HPV的消退规律及其与CIN的关系[J].中国妇幼保健,2011,26(35):5493-5495.
[20]王欢华,陈丽,陈梅,等.高危型HPV监测在宫颈上皮内瘤变Ⅰ随访中的意义[J].中国妇幼保健,2012,27(6):820-822.
[21]张桂香,周自秀,崔彭华,等.高危HPV检测及随访对宫颈癌预防的临床意义[J].中国妇幼保健,2013,28(20):3264-3267.DOI:10.7620/zgfybj.j.issn.1001-4411.2013.28.15.
[22]耿宇宁,张为远,吴玉梅.高危HPV阳性的低度宫颈上皮内瘤变的转归与治疗[J].中国医药导报,2014,11(36):39-42,46.
[23]Guo YL,You K,Qiao J,et al.Bacterial vaginosis is conducive to the persistence of HPV infection[J].Int J STD AIDS,2012,23(8):581-584.DOI:10.1258/ijsa.2012.011342.
[24]崔丽阳,岳天孚.高危型HPV持续感染的影响因素探讨[J].天津医科大学学报,2014,20(3):209-212.
[25]杨瑾,陈洪波,李柱南,等.下生殖道感染与子宫颈高危型HPV感染及转归的相关性[J].中华妇产科杂志,2014,49(3):222-223.DOI:10.3760/cma.j.issn.0529-567x.2014.03.016.
[26]王雪卿,孙丽芳,梁向华,等.高危型人乳头状瘤病毒的感染状态及分型与宫颈病变发生的相关性研究[J].生殖医学杂志,2014,23(8):633-638.DOI:10.3969/j.issn.1004-3845.2014.08.006.
[27]朱珍珍,郑洁,肖苹妹,等.育龄期妇女宫颈HPV感染自然转归的随访分析[J].中国妇幼健康研究,2015,26(4):769-772.DOI:10.3969/j.issn.1673-5293.2015.04.038.
[28]梁海燕,陈晓红,张苏伟.高危HPV持续感染与宫颈病变发生的相关性[J].中国现代医生,2017,55(10):52-55,58.
[29]沙静,崔健,邢军利.调整阴道内环境对HR-HPV感染的CINI的临床观察[J].新疆医学,2017,47(3):253-255.
[30]何明,吴玉梅,阴桢宏,等.未见上皮内病变或恶性病变妇女高危型HPV的自然变化——前瞻性随访一年[J].中华妇产科杂志,2017,52(11):740-744.DOI:10.3760/ema.j.issn.0529-567x.2017.11.005.
[31]杨华,张柳红.局部药物治疗在宫颈高危HPV感染患者中的临床应用[J].牡丹江医学院学报,2017,38(4):80-81,98.DOI:10.13799/j.cnki.mdjyxyxb.2017.04.029.
[32]申丽娟,黄昕,黄玉香,等.女性肥胖与宫颈人乳头瘤病毒持续性感染的相关性研究[J].中国医药科学,2018,8(10):7-11.DOI:10.3969/j.issn.2095-0616.2018.10.004.
[33]王鸿艳,邹淑波.高危型人乳头瘤病毒阳性妇女的门诊随访分析[J].中国妇幼保健,2018,33(7):1475-1477.DOI:10.7620/zgfybj.j.issn.1001-4411.2018.07.11.
[34]黄尾全,黄银萍.光动力治疗宫颈高危人乳头瘤病毒潜伏感染的疗效分析[J].皮肤病与性病,2020,42(1):49-50.DOI:10.3969/j.issn.1002-1310.2020.01.026.
[35]袁建晖,范燕燕,谢彤.高危型人乳头瘤病毒在2年内自然清除及持续感染与宫颈病变关系的研究[J].江西医药,2020,55(11):1566-1569,1579.DOI:10.3969/j.issn.1006-2238.2020.11.007.
[36]王泓沄,仇楹茹,谢意,等.CareHPV检测用于江苏盐城基层妇女宫颈癌筛查的研究[J].中国妇幼健康研究,2020,31(5):565-572.DOI:10.3969/j.issn.1673-5293.2020.05.004.
[37]Tuerxun G,Abudurexiti G,Abulizi G.Prevalence,persistence,clearance and risk factors for HPV infection in rural Uyghur women in China[J].BMC Womens Health,2023,23(1):433.DOI:10.1186/s12905-023-02558-y.
[38]杨颖,韦玉姣,韦桂红.高危型人乳头瘤病毒持续感染与阴道微生态环境及宫颈病变的相关性[J].中国热带医学,2023,23(2):151-156.DOI:10.13604/j.cnki.46-1064/r.2023.02.09.
[39]郭玉琳,吴绪峰,彭秋子,等.湖北地区948例生殖道高危型人乳头瘤病毒感染女性复查及自然转归[J].现代妇产科进展,2023,32(5):376-378,382.DOI:10.13283/j.cnki.xdfckjz.2023.05.004.
[40]谢家平,韩全水,万芬.某单位连续8年HPV与宫颈液基细胞学(TCT)检测结果分析[J].中外妇儿健康,2011,19(3):90-91.
[41]陈会波.诸城市育龄妇女HPV感染现状、转归及其与宫颈上皮增生的关联[D].济南:山东大学,2006.
[42]冯燕,贺静,朱宝生,等.无宫颈病变的高危型HPV感染者2年随访研究[J].实用妇产科杂志,2016,32(9):701-704.
[43]Li N,Hang D,Yang L,et al.Persistence of typespecific human papillomavirus infection among Daqing City women in China with normal cytology:a pilot prospective study[J].Oncotarget,2017,8(46):81455-81461.DOI:10.18632/oncotarget.20188.
[44]周姝,仲建新.无宫颈病变的高危人乳头瘤病毒感染妇女的2年随访研究[J].海南医学,2017,28(17):2802-2804.DOI:10.3969/j.issn.1003-6350.2017.17.016.
[45]何紫常,范保维,石少连,等.HR-HPV感染临床自然转归、影响因素探究[J].数理医药学杂志,2018,31(6):859-860.DOI:10.3969/j.issn.1004-4337.2018.06.033.
[46]龙馨,杨君,周德平,等.2784例同步HPV分型及标准化定量检测预测高危型H P V感染转归的临床研究[J].第三军医大学学报,2020,42(15):1555-1561.DOI:10.16016/j.1000-5404.202003322.
[47]郭艳阳,林青.北京市永乐店镇2016—2018年农村妇女宫颈高危型人乳头状瘤病毒感染现状及转归分析[J].中国乡村医药,2021,28(23):72-74.DOI:10.19542/j.cnki.1006-5180.005797.
[48]郭珍,赵冬梅,贾漫漫,等.基线细胞学正常女性高危型人乳头瘤病毒感染与宫颈病变发病风险的3年随访研究[J].中国肿瘤,2022,31(5):394-400.DOI:10.11735/j.issn.1004-0242.2022.05.A012.
[49]Wang W,Yao Y,Liu Y,et al.Focused ultrasound for high-risk human papillomavirus infection-related lowgrade cervical lesions:a prospective cohort study[J].Int J Hyperthermia,2022,39(1):1327-1334.DOI:10.1080/02656736.2022.2130443.
[50]邓婷.聚焦超声治疗子宫颈上皮内瘤样变的临床初期研究[D].重庆:重庆医科大学,2010.
[51]王玉欢,王芳,李妍芹.苦参软膏治疗宫颈HPV感染的临床研究[J].西南国防医药,2013,23(2):189-191.DOI:10.3969/j.issn.1004-0188.2013.02.031.
[52]张倩,曹頔,马茜,等.760名女性生殖道高危型人乳头瘤病毒感染自然转归规律及影响因素[J].中国医学科学院学报,2015,37(5):534-540.DOI:10.3881/j.issn.1000-503X.2015.05.008.
[53]陈雪,张敏,张翠,等.高危型人乳头瘤病毒感染的病毒清除和持续感染的随访与观察[J].山西医科大学学报,2016,47(7):628-632.DOI:10.13753/j.issn.1007-6611.2016.07.011.
[54]王澜.遵义市妇科门诊宫颈HR-HPV持续感染危险因素调查[D].遵义医学院,2018.
[55]Wang W,Zhang H,Lin L,et al.Efficient combination of human papillomavirus genotyping for the triage of women with atypical squamous cells of undetermined significance in Chinese rural population:a populationbased study[J].J Cancer,2021,12(10):2815-2824.DOI:10.7150/jca.55771.
[56]孟丹,宋丽,祁卓,等.高危型人乳头瘤病毒感染的转归特点及阴道微环境因子对其转归影响的研究[J].中华流行病学杂志,2021,42(6):1103-1107.DOI:10.3760/cma.j.cn112338-20200829-01107.
[57]刘虹岚,兰建,张晓娟,等.高危型人乳头状瘤病毒持续感染病毒清除分析[J].中华医院感染学杂志,2017,27(20):4751-4753,4757.
[58]隋霜,玛依努尔·尼牙孜,王琳,等.维吾尔族妇女型别特异性持续HPV感染状况及病毒学因素[J].现代肿瘤医学,2019,27(4):643-646.DOI:10.3969/j.issn.1672-4992.2019.04.027.
[59]裴蕊欣,武彩红,闫佳欣,等.多环芳烃暴露对高危型人乳头瘤病毒感染转归影响的前瞻性队列研究[J].中华流行病学杂志,2021,42(11):2060-2065.DOI:10.3760/cma.j.cn112338-20210406-00278.
[60]张乐.宫颈正常和低级别宫颈上皮内瘤变妇女HRHPV感染转归特征的比较及风险预测[D].山西医科大学,2023.DOI:10.27288/d.cnki.gsxyu.2023.000454.
[61]严珞媛,王乐丹.阴道微环境因子对高危型HPV感染者24个月后转归的影响[J].中国计划生育学杂志,2023,31(11):2587-2592.DOI:10.3969/j.issn.1004-8189.2023.11.013.
[62]陶萍萍,寿清和,王运根,等.派特灵对宫颈高危型人乳头瘤病毒感染转归的影响[J].国际流行病学传染病学杂志,2014,41(1):28-32.DOI:10.3760/cma.j.issn.1673-4149.2014.01.007.
[63]陈琦.新型筛查技术在宫颈癌筛查中的应用效果初步评价[D].大连:大连医科大学,2019.DOI:10.26994/d.cnki.gdlyu.2019.000088.
[64]王豆,昆阿依木·叶尔江,董璇,等.新疆哈萨克族妇女中、高危型人乳头瘤病毒感染自然转归及影响因素分析[J].中国公共卫生,2023,39(6):740-746.DOI:10.11847/zgggws1139406.
[65]黄凌霄,郭敏,董晓霞,等.派特灵宫颈用药对HPV E6/E7mRNA表达的影响[J].中国现代医生,2018,56(25):74-78.
[66]姚星妹.中国18-45岁健康女性高危型人乳头瘤病毒感染特征的前瞻性队列研究[D].厦门:厦门大学,2022.DOI:10.27424/d.cnki.gxmdu.2022.000250.
[67]赵冉冉.影响高危型HPV感染患者转阴的相关因素分析[D].新疆医科大学,2023.DOI:10.27433/d.cnki.gxyku.2023.000776.
[68]Bosch FX,Burchell AN,Schiffman M,et al.Epidemiology and natural history of human papillomavirus infections and type-specific implications in cervical neoplasia[J].Vaccine,2008,26(Suppl 10):K1-K16.DOI:10.1016/j.vaccine.2008.05.064.
[69]Stensen S,Kjaer SK,Jensen SM,et al.Factors associated with type-specific persistence of high-risk human papillomavirus infection:a population-based study[J].Int J Cancer,2016,138(2):361-368.DOI:10.1002/ijc.29719.
[70]Sammarco ML,Del Riccio I,Tamburro M,et al.Type-specific persistence and associated risk factors of human papillomavirus infections in women living in central Italy[J].Eur J Obstet Gynecol Reprod Biol,2013,168(2):222-226.DOI:10.1016/j.ejogrb.2013.01.012.
[71]Ralston Howe E,Li Z,McGlennen RC,et al.Type-specific prevalence and persistence of human papillomavirus in women in the United States who are referred for typing as a component of cervical cancer screening[J].Am J Obstet Gynecol,2009,200(3):245.e1-245.e7.DOI:10.1016/j.ajog.2008.10.050.
[72]Schmeink CE,Melchers WJ,Siebers AG,et al.Human papillomavirus persistence in young unscreened women,a prospective cohort study[J].PLoS One,2011,6(11):e27937.DOI:10.1371/journal.pone.0027937.
[73]胥莎莎,何鑫,刘英俏,等.高危型人乳头瘤病毒感染患者病毒清除及持续感染的随访性研究[J].首都医科大学学报,2015,36(2):212-218.DOI:10.3969/j.issn.1006-7795.2015.02.010.
[74]陈飞,狄文,胡元晶,等.外用红色诺卡菌细胞壁骨架治疗子宫颈高危型HPV持续感染的有效性及安全性研究[J].中华妇产科杂志,2023,58(7):536-545.DOI:10.3760/cma.j.cn112141-20230331-00154.
[75]张娟,苏展影.中国女性宫颈高危型人乳头瘤病毒感染危险因素的Meta分析[J].中国临床医生杂志,2018,46(12):1482-1486.DOI:10.3969/j.issn.2095-8552.2018.12.031.
[76]Hu YM,Bi ZF,Zheng Y,et al.Immunogenicity and safety of an Escherichia coli-produced human papillomavirus(types 6/11/16/18/31/33/45/52/58)L1 virus-like-particle vaccine:a phase 2 double-blind,randomized,controlled trial[J].Sci Bull,2023,68(20):2448-2455.DOI:10.1016/j.scib.2023.09.020.
基本信息:
DOI：10.13242/j.cnki.bingduxuebao.004672
中图分类号:R737.33
引用信息:
[1]匡雪凤,贾鑫华,王哲,等.中国女性高危型HPV感染自然史的系统综述及Meta分析[J].病毒学报,2025,41(05):1619-1632.DOI:10.13242/j.cnki.bingduxuebao.004672.
基金信息:
中国医学科学院医学与健康科技创新工程项目(项目号：2021-I2M-1-004),题目：适合我国国情的消除宫颈癌综合防控技术与策略研究~~
2024-08-28
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