Article(id=1241035817368473948, tenantId=1146029695717560320, journalId=1227665162245664772, issueId=1241035810628235909, articleNumber=null, orderNo=null, doi=10.20043/j.cnki.MPM.202405294, pmid=null, cstr=null, oa=null, hot=null, price=null, onlineType=0, articleFormat=0, articleType=null, articleTypeStr=null, receivedDate=1716134400000, receivedDateStr=2024-05-20, revisedDate=null, revisedDateStr=null, acceptedDate=null, acceptedDateStr=null, onlineDate=1773815596191, onlineDateStr=2026-03-18, pubDate=1733760000000, pubDateStr=2024-12-10, doiRegisterDate=null, doiRegisterDateStr=null, onlineIssueDate=1773815596191, onlineIssueDateStr=2026-03-18, onlineJustAcceptDate=null, onlineJustAcceptDateStr=null, onlineFirstDate=null, onlineFirstDateStr=null, sourceXml=null, magXml=null, createTime=1773815596191, creator=13701087609, updateTime=1773815596191, updator=13701087609, issue=Issue{id=1241035810628235909, tenantId=1146029695717560320, journalId=1227665162245664772, year='2024', volume='51', issue='23', pageStart='4225', pageEnd='4416', issueExtLink='null', onlineDate='null', pubDate='null', beforeIssueId=null, nextIssueId=null, price=null, status=1, issueComplete=1, articleOrder=1, issueType=-1, specialIssue=null, createTime=1773815594584, creator=13701087609, updateTime=1773815743629, updator=13701087609, preIssue=null, nextIssue=null, ext={EN=IssueExt(id=1241036435843764756, tenantId=1146029695717560320, journalId=1227665162245664772, issueId=1241035810628235909, language=EN, specialIssueTitle=, coverIllustrator=null, specialIssueEditor=, specialIssueAbout=), CN=IssueExt(id=1241036435843764757, tenantId=1146029695717560320, journalId=1227665162245664772, issueId=1241035810628235909, language=CN, specialIssueTitle=, coverIllustrator=null, specialIssueEditor=, specialIssueAbout=)}, issueFiles=null}, startPage=4379, endPage=4385, ext={EN=ArticleExt(id=1241035819574677882, articleId=1241035817368473948, tenantId=1146029695717560320, journalId=1227665162245664772, language=EN, title=Prediction and analysis of HPV infection in Toli county, Xinjiang based on a transmission dynamics model, columnId=1228016573156360233, journalTitle=Modern Preventive Medicine, columnName=Disease Control and Prevention, runingTitle=null, highlight=null, articleAbstract=
Objective

To investigate the epidemiological trends of high-risk human papillomavirus (HR-HPV) in Toli county, Xinjiang, using a transmission dynamics model, and to quantitatively assess the impact of bivalent vaccine interventions, to provide a reference for the prevention of HR-HPV infections and vaccination strategies.

Methods

A transmission dynamics model was established based on the natural history of HPV infection. Data on cervical cancer screening in Toli county were collected, and simulations were conducted under scenarios of no intervention and bivalent vaccine coverage rates of 50%, 60%, and 70%to predict the infection rates, peak infection values, and the number of cancer patients. The future trends of infections and cervical cancer patients over the next 20 years were also forecasted.

Results

A total of 12 549 women underwent cervical cancer screening, with 1 744 cases of HR-HPV infection, resulting in a cumulative infection rate of 13.9%. In the absence of intervention, the predicted infection rate at the end of the study was 16.33%, with an estimated 1 914 infections and 294 cancer patients in a total population of 11 666. With bivalent vaccine coverage rates of 50%, 60%, and 70%, the predicted final infection rates were 15.31%, 15.07%, and 14.82%, respectively, with corresponding numbers of cervical cancer patients being 185, 164, and 142, and total populations of 11 949, 12 005, and 12 061, respectively. Sensitivity analysis of key parameters indicated that a higher clearance rate was more effective in reducing the number of infections, and a lower rate of recovered individuals becoming susceptible again led to fewer infections.

Conclusion

Implementing vaccination and increasing coverage rates can reduce the number of HR-HPV infections and cervical cancer patients in Toli county, which may help mitigate the decline in the total population. Emphasis should be placed on measures to improve clearance rates when preventing HR-HPV infections, as the effectiveness of further increasing clearance rates on infection control will gradually diminish.

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目的

应用传播动力学模型研究高危型人乳头瘤病毒(HR-HPV)在新疆维吾尔自治区(简称新疆)托里县的流行趋势并定量评价二价疫苗干预的效果。为预防HR-HPV感染、疫苗接种、治疗提供参考。

方法

根据HPV感染自然史建立传播动力学模型。收集新疆托里县宫颈癌筛查数据,采用考虑无干预以及二价疫苗覆盖率50%、60%和70%干预的传播动力学模型进行模拟预测,定量评估不同干预措施下感染率高峰值、癌症患者人数,预测未来20年该地区感染趋势及宫颈癌患者人数。

结果

该地接受宫颈癌筛查的妇女共12 549人,HR-HPV感染人数1 744例,累积感染率为13.9%。在无干预自然状态下,预测研究结束时感染率为16.33%,感染人数为1 914例,癌症患者为294例,总人口数为11 666人。采取二价疫苗覆盖率分别为50%、60%、70%干预措施后预测最终感染率分别为15.31%、15.07%、14.82%,宫颈癌患者分别为185、164和142例,总人口数分别为11 949、12 005和12 061人。重要参数的敏感性分析表明清除率越大对减少感染人数的效果越好,康复者再度成为易感者的率越低感染人数将越少。

结论

实施疫苗接种,增大接种覆盖率可减少托里县HR-HPV感染人数,减少宫颈癌患者的人数,有助于减缓总人口数的减少。预防HR-HPV感染时要重视采取措施提高清除率,进一步增加清除率对于感染人数的控制效果将逐渐减弱。

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贾慧民,E-mail:
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宋晓娟(1997—),女,硕士在读,研究方向:公共卫生

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tenantId=1146029695717560320, journalId=1227665162245664772, articleId=1241035817368473948, language=CN, label=图2, caption=2010—2019年HPV感染验证结果, figureFileSmall=Kx7Ie+QHDwIdWNX5MTEimA==, figureFileBig=R3H3GnmDViQY59g09LJw8g==, tableContent=null), ArticleFig(id=1241069125565469038, tenantId=1146029695717560320, journalId=1227665162245664772, articleId=1241035817368473948, language=EN, label=Figure 3, caption=Prediction of the annual population of women in each chamber in the HPV transmission model from 2025 to 2045, figureFileSmall=0Up/E9rvYQlK5FvD75n97g==, figureFileBig=9bwrZTO66O72AFPO/iqnFw==, tableContent=null), ArticleFig(id=1241069125632577906, tenantId=1146029695717560320, journalId=1227665162245664772, articleId=1241035817368473948, language=CN, label=图3, caption=2025—2045年HPV传播模型中每年的各仓室妇女人口数预测, figureFileSmall=0Up/E9rvYQlK5FvD75n97g==, figureFileBig=9bwrZTO66O72AFPO/iqnFw==, tableContent=null), ArticleFig(id=1241069125808738679, tenantId=1146029695717560320, 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articleId=1241035817368473948, language=CN, label=图5, caption=2025—2045年HPV传播模型中每年总人口数量预测, figureFileSmall=2bZ3+O0T6SzTvToVDD8/OQ==, figureFileBig=e7LLvZIX2rHA3rdQJOfUrA==, tableContent=null), ArticleFig(id=1241069126219780487, tenantId=1146029695717560320, journalId=1227665162245664772, articleId=1241035817368473948, language=EN, label=Figure 6, caption=Prediction of the population in the infected warehouse of HPV infection transmission model from 2025 to 2045, figureFileSmall=Bb6oH2gelmbG92JlvUTuqw==, figureFileBig=vuwVIqQywgRbLzBvAQuk9g==, tableContent=null), ArticleFig(id=1241069126316249485, tenantId=1146029695717560320, journalId=1227665162245664772, articleId=1241035817368473948, language=CN, label=图6, caption=2025—2045年HPV感染传播模型感染者仓室的人口数量预测

注:A为未施加干预措施;B为50%疫苗覆盖率;C为60%疫苗覆盖率;D为70%疫苗覆盖率。

, figureFileSmall=Bb6oH2gelmbG92JlvUTuqw==, figureFileBig=vuwVIqQywgRbLzBvAQuk9g==, tableContent=null), ArticleFig(id=1241069126404329871, tenantId=1146029695717560320, journalId=1227665162245664772, articleId=1241035817368473948, language=EN, label=Figure 7, caption=Prediction of the number of cancer patients and total population for different interventions from 2025 to 2045, figureFileSmall=WftJddCqMHOlgOmJBit6cA==, figureFileBig=L9lNnd32wuy9CyMg8zBJiQ==, tableContent=null), ArticleFig(id=1241069126530158994, tenantId=1146029695717560320, journalId=1227665162245664772, articleId=1241035817368473948, language=CN, label=图7, caption=2025—2045年不同干预措施每年宫颈癌仓室数量和总人口数量

注:A为不同干预措施下癌症仓室人口数;B为不同干预措施下总人口数量。

, figureFileSmall=WftJddCqMHOlgOmJBit6cA==, figureFileBig=L9lNnd32wuy9CyMg8zBJiQ==, tableContent=null), ArticleFig(id=1241069126664376728, tenantId=1146029695717560320, journalId=1227665162245664772, articleId=1241035817368473948, language=EN, label=Figure 8, caption=Sensitivity analysis of μI and μr, figureFileSmall=g17CgY5Up5h8sqZMZsjm3Q==, figureFileBig=w3EHXyAxTWzJjMosPO0ryw==, tableContent=null), ArticleFig(id=1241069126773428636, tenantId=1146029695717560320, journalId=1227665162245664772, articleId=1241035817368473948, language=CN, label=图8, caption=μIμr敏感性分析

注:A为不同μI值下感染者的人数;B为不同μr值下感染者人数。

, figureFileSmall=g17CgY5Up5h8sqZMZsjm3Q==, figureFileBig=w3EHXyAxTWzJjMosPO0ryw==, tableContent=null), ArticleFig(id=1241069126878286241, tenantId=1146029695717560320, journalId=1227665162245664772, articleId=1241035817368473948, language=EN, label=Table 1, caption=

Parameter values used in the model simulation

, figureFileSmall=null, figureFileBig=null, tableContent=
参数意义单位取值来源
DS易感者自然死亡率0.000 48第七次人口普查
DI感染者自然死亡率0.000 48第七次人口普查
DR恢复者自然死亡率0.000 48第七次人口普查
DC宫颈癌患者死亡率0.161 00文献[13]
μr康复者成为易感者的率0.500 00文献[14]
β易感者成为感染者的率0.139 00宫颈癌筛查
μI感染者的HPV清除率0.523 00项目数据[8]
γ感染者进展为癌症的率0.025 00文献[12]
), ArticleFig(id=1241069128405012901, tenantId=1146029695717560320, journalId=1227665162245664772, articleId=1241035817368473948, language=CN, label=表1, caption=

模型参数值

, figureFileSmall=null, figureFileBig=null, tableContent=
参数意义单位取值来源
DS易感者自然死亡率0.000 48第七次人口普查
DI感染者自然死亡率0.000 48第七次人口普查
DR恢复者自然死亡率0.000 48第七次人口普查
DC宫颈癌患者死亡率0.161 00文献[13]
μr康复者成为易感者的率0.500 00文献[14]
β易感者成为感染者的率0.139 00宫颈癌筛查
μI感染者的HPV清除率0.523 00项目数据[8]
γ感染者进展为癌症的率0.025 00文献[12]
), ArticleFig(id=1241069128497287593, tenantId=1146029695717560320, journalId=1227665162245664772, articleId=1241035817368473948, language=EN, label=Table 2, caption=

Cervical cancer screening for HPV infection

, figureFileSmall=null, figureFileBig=null, tableContent=
年份(年)筛查人数HPV阳性人数阳性率(%)HPV16/18感染例数感染率(%)
20224 18362114.84761.82
20234 18362614.961603.82
20244 18349711.88862.06
总计12 5491 74413.903222.57
), ArticleFig(id=1241069128606339500, tenantId=1146029695717560320, journalId=1227665162245664772, articleId=1241035817368473948, language=CN, label=表2, caption=

宫颈癌筛查HPV感染情况

, figureFileSmall=null, figureFileBig=null, tableContent=
年份(年)筛查人数HPV阳性人数阳性率(%)HPV16/18感染例数感染率(%)
20224 18362114.84761.82
20234 18362614.961603.82
20244 18349711.88862.06
总计12 5491 74413.903222.57
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Predicted results without intervention and under different vaccine coverage rates

, figureFileSmall=null, figureFileBig=null, tableContent=
干预措施结束时总人口数量结束时癌症患者感染高峰人数感染率峰值(%)结束时感染人数结束时感染率(%)
无干预措施11 6662942 19317.441 91416.33
二价疫苗接种覆盖率(%)
5011 9491852 05816.381 80115.31
6012 0051642 02716.141 77415.07
7012 0611421 99515.891 74614.82
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无干预和不同疫苗覆盖率下预测结果

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干预措施结束时总人口数量结束时癌症患者感染高峰人数感染率峰值(%)结束时感染人数结束时感染率(%)
无干预措施11 6662942 19317.441 91416.33
二价疫苗接种覆盖率(%)
5011 9491852 05816.381 80115.31
6012 0051642 02716.141 77415.07
7012 0611421 99515.891 74614.82
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基于传播动力学模型的新疆托里县HPV感染预测分析
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宋晓娟 1 , 王岩 2 , 贾慧民 2
现代预防医学 | 疾病预防控制 2024,51(23): 4379-4385
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现代预防医学 | 疾病预防控制 2024, 51(23): 4379-4385
基于传播动力学模型的新疆托里县HPV感染预测分析
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宋晓娟1, 王岩2, 贾慧民2
作者信息
  • 1.新疆医科大学公共卫生学院,新疆 乌鲁木齐 830011
  • 2.新疆医科大学附属肿瘤医院医务部,新疆 乌鲁木齐 830054
  • 宋晓娟(1997—),女,硕士在读,研究方向:公共卫生

通讯作者:

贾慧民,E-mail:
Prediction and analysis of HPV infection in Toli county, Xinjiang based on a transmission dynamics model
Xiao-juan SONG1, Yan WANG2, Hui-min JIA2
Affiliations
  • School of Public Health, Xinjiang Medical University, Urumqi, Xinjiang 830011, China
出版时间: 2024-12-10 doi: 10.20043/j.cnki.MPM.202405294
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目的

应用传播动力学模型研究高危型人乳头瘤病毒(HR-HPV)在新疆维吾尔自治区(简称新疆)托里县的流行趋势并定量评价二价疫苗干预的效果。为预防HR-HPV感染、疫苗接种、治疗提供参考。

方法

根据HPV感染自然史建立传播动力学模型。收集新疆托里县宫颈癌筛查数据,采用考虑无干预以及二价疫苗覆盖率50%、60%和70%干预的传播动力学模型进行模拟预测,定量评估不同干预措施下感染率高峰值、癌症患者人数,预测未来20年该地区感染趋势及宫颈癌患者人数。

结果

该地接受宫颈癌筛查的妇女共12 549人,HR-HPV感染人数1 744例,累积感染率为13.9%。在无干预自然状态下,预测研究结束时感染率为16.33%,感染人数为1 914例,癌症患者为294例,总人口数为11 666人。采取二价疫苗覆盖率分别为50%、60%、70%干预措施后预测最终感染率分别为15.31%、15.07%、14.82%,宫颈癌患者分别为185、164和142例,总人口数分别为11 949、12 005和12 061人。重要参数的敏感性分析表明清除率越大对减少感染人数的效果越好,康复者再度成为易感者的率越低感染人数将越少。

结论

实施疫苗接种,增大接种覆盖率可减少托里县HR-HPV感染人数,减少宫颈癌患者的人数,有助于减缓总人口数的减少。预防HR-HPV感染时要重视采取措施提高清除率,进一步增加清除率对于感染人数的控制效果将逐渐减弱。

人乳头瘤病毒  /  传播动力学模型  /  感染率
Objective

To investigate the epidemiological trends of high-risk human papillomavirus (HR-HPV) in Toli county, Xinjiang, using a transmission dynamics model, and to quantitatively assess the impact of bivalent vaccine interventions, to provide a reference for the prevention of HR-HPV infections and vaccination strategies.

Methods

A transmission dynamics model was established based on the natural history of HPV infection. Data on cervical cancer screening in Toli county were collected, and simulations were conducted under scenarios of no intervention and bivalent vaccine coverage rates of 50%, 60%, and 70%to predict the infection rates, peak infection values, and the number of cancer patients. The future trends of infections and cervical cancer patients over the next 20 years were also forecasted.

Results

A total of 12 549 women underwent cervical cancer screening, with 1 744 cases of HR-HPV infection, resulting in a cumulative infection rate of 13.9%. In the absence of intervention, the predicted infection rate at the end of the study was 16.33%, with an estimated 1 914 infections and 294 cancer patients in a total population of 11 666. With bivalent vaccine coverage rates of 50%, 60%, and 70%, the predicted final infection rates were 15.31%, 15.07%, and 14.82%, respectively, with corresponding numbers of cervical cancer patients being 185, 164, and 142, and total populations of 11 949, 12 005, and 12 061, respectively. Sensitivity analysis of key parameters indicated that a higher clearance rate was more effective in reducing the number of infections, and a lower rate of recovered individuals becoming susceptible again led to fewer infections.

Conclusion

Implementing vaccination and increasing coverage rates can reduce the number of HR-HPV infections and cervical cancer patients in Toli county, which may help mitigate the decline in the total population. Emphasis should be placed on measures to improve clearance rates when preventing HR-HPV infections, as the effectiveness of further increasing clearance rates on infection control will gradually diminish.

Human papillomavirus  /  Transmission dynamics model  /  Infection rate
宋晓娟, 王岩, 贾慧民. 基于传播动力学模型的新疆托里县HPV感染预测分析. 现代预防医学, 2024 , 51 (23) : 4379 -4385 . DOI: 10.20043/j.cnki.MPM.202405294
Xiao-juan SONG, Yan WANG, Hui-min JIA. Prediction and analysis of HPV infection in Toli county, Xinjiang based on a transmission dynamics model[J]. Modern Preventive Medicine, 2024 , 51 (23) : 4379 -4385 . DOI: 10.20043/j.cnki.MPM.202405294
人乳头瘤病毒(human papilloma virus, HPV)是一种无包膜的DNA病毒,可引起人类皮肤和黏膜的增生性病变,目前为止已鉴定出200多种HPV基因型别[1]。大多数新获得的人乳头瘤病毒感染在1~2年内会逐渐清除[2],虽然大多数HPV会被清除,但有些感染持续数年,如果不及时诊断和适当治疗,可能导致细胞异常和癌症[3]。HPV大量流行病学研究表明,HPV感染是宫颈癌的病因之一,特别是在高危HPV(high risk human papilloma virus, HR-HPV)持续感染的情况下[4-5],其中HPV16/18与70%的宫颈癌直接相关。
数学模型可以模拟病毒在人群中动态传播的过程[6],更能表示人群健康状态随时间的变化。目前,国内有关HPV传播动力学模型的研究较少,而关于新疆维吾尔自治区(简称新疆)妇女HPV感染的传播以及控制措施对传播感染峰值影响的研究几乎为空白。针对HPV的感染和传播机制,本研究根据既往的易感者-感染者-宫颈癌患者-恢复者(SICR)模型[7]进行改进,运用真实的数据构建动力学模型。该模型增加了新疆托里县妇女HPV感染的清除率,用于反映新疆托里县妇女2025—2045年HPV感染的流行趋势,比较纳入疫苗接种前后的不同状态人群人口变化,旨在掌握托里县HPV感染规律以期为更高质量的HPV防控措施及疫苗评价提供参考。
本研究的数据来源于新疆托里县2018—2023年2 000人HPV检测数据(具体HPV分型检测见前期工作文献[8])与《中国低卫生资源地区消除子宫颈癌示范项目》2022—2024年该地宫颈癌筛查14种HR-HPV数据(16、18、31、33、35、39、45、51、52、56、58、59、66和68)。所有研究对象年龄35~64岁之间,均有性生活史且知情同意。
本文主要收集新疆托里县妇女HPV筛查数据,考虑到模型所需参数较多,一些难以获得的参数则通过搜索新疆相关文献获得。如搜索“新疆农牧区妇女”“新疆HPV”等相关关键词,以确保数据的关键性和代表性。本研究在该地区的模拟时间为2025—2045年。
从HPV感染到宫颈癌的发生是复杂且循序渐进的过程。本文根据HPV感染宫颈癌的自然史建立动力学模型,在基础的SICR模型上增加了总人口概念,包含易感者仓室(S)、HR-HPV感染者仓室(I)、宫颈癌患者仓室(C)、康复者仓室(R),总人口(N)可表示为N=S+I+C+R,各仓室人群以不同的速率进出模型从而影响总人口数量。模型框架见图1
该模型描述了一个地区女性从易感者S感染HPV后经病毒清除恢复或持续感染HPV进展为宫颈癌C的过程。根据本课题前期流行病学数据及既往研究,大部分HPV感染为一过性感染[8],少数持续感染才会进展为宫颈癌。该模型假设HPV感染后有两种结局:一是HPV清除,二是HPV持续感染进展为宫颈癌。为准确描述建立宫颈癌自然史模型本研究做出以下假设:(1)感染者I在病毒清除后会再次感染。(2)所有基因型别中疾病进展是一致的。(3)妇女HPV感染率与总人数N有关。(4)假设该人群处于稳定且封闭的状态。
文献中大多数模型都是确定性的,它们很大程度上相对容易建立。确定性模型可以使用差分方程式或常微分方程式建立[9]。本研究使用常微分方程组建立HPV传播动力学模型,模型系统方程由4个一阶非线性常微分方程组成:
宫颈癌发生癌变过程中HPV感染是最为关键的一环,接种二价疫苗可预防引起约70%宫颈癌的两种亚型HPV(16和18)。接种疫苗后易感者(S)成为感染者(I)的率将有所降低,此外,感染者(I)进展为宫颈癌(C)的率也将降低70%,其余关系不变,该模型微分方程如下:
表1显示了模型使用的参数及参数值。根据相关文献数据及本课题实际研究数据来设置参数。
(1)根据第七次全国人口普查数据显示新疆托里县35~64岁女性人数为17 736名,模型初始规模人口设为接受筛查的12 549名适龄女性。模型初始易感者S0为10 805,感染者I0为1 744。数据来自《中国低卫生资源地区消除子宫颈癌示范项目》新疆塔城托里县示范地区12 549名接受子宫颈癌筛查妇女。
(2)基于新疆托里县2022—2024年宫颈癌筛查数据,计算HPV感染率,感染率β为0.139,见表2
(3)相关研究表明女性HPV的清除中位时间约为16个月[10]。本研究根据2018年新疆托里县建立的2 000名妇女的宫颈癌筛查队列研究计算HPV清除率,即感染者的清除率μI为每年0.523 3[8]
(4)根据世界卫生组织数据,具有正常免疫系统的女性通常需要15~20年才能患宫颈癌,本文的模型考虑一般女性群体并参考文献[11],因此,设感染者进展为癌症的概率γ为0.025[12]
(5)HPV发展为宫颈癌的概率很低,宫颈癌患者的自然死亡率较低可以忽略不计。宫颈癌患者如果不进行治疗5年生存率不足10%。根据相关文献新疆妇女宫颈癌的死亡率DC可设为0.161[13]
使用了Matlab R2021a软件进行整体建模,数据分析以及图像处理,微分方程求解使用基于四阶-五阶-龙格库塔法(ode45)。数据分类,过渡参数和初始人口数估计使用WPS进行录入。
利用新疆克拉玛依2010—2019年收集的参数[15]作为初始变量对模型进行验证,将预测的累积感染率与当地实际累积感染数据进行比较。模型预测与实际数据拟合效果较好,有类似趋势。见图2
图3显示每个隔间中的人群数量的变化输出,它模拟了2025—2045年的每个隔间的人口趋势。在研究结束时预测该地适龄女性总人口数为11 666人,其中易感者人口数、感染者人口数和康复者人口数分别为7 455、1 907和2 010人,癌症患者累积病例为294人。在模型运行时间内各仓室人口趋势达到稳定状态。
图4为2025—2045年HPV感染趋势图,预测感染率和感染人数在研究5年内达到最大值,随后出现持续下降趋势,初始的感染率为13.9%,随后上升至17.34%,预测2030—2045年感染率处于稳定状态,研究结束时感染率为16.33%,总人口数量随时间减少,从开始的12 549人减少至11 666人。见图5
二价疫苗可以预防HPV16/18型病毒感染,可预防超70%的宫颈癌。本研究假设该地妇女二价HPV疫苗接种覆盖率为50%,保护率为97.7%[16]。由2022—2024年托里县宫颈癌筛查数据可知HPV阳性患者共1 744例,感染率为0.139,其中HPV16/18感染患者322例,占阳性患者比例为18.5%,文献可知感染者进展为癌症的率为0.025。考虑干预因素的参数值如下:
干预后的感染力的值=易感者成为感染者的概率×(1-HPV16/18阳性患者占比×疫苗覆盖率×疫苗保护率)=0.139×(1-(0.185×0.5×0.977))=0.139×(1-0.078)=0.139×0.922=0.126
接种疫苗后感染者进展为癌症的率=感染者进展为癌症的率×[1-(1-70%)×疫苗覆盖率]=0.025×(1-30%×50%)=0.021 25
βintervention=0.126,γintervention=0.021 25。同理可计算60%,70%疫苗覆盖率下的βγ的值。
干预的效果如图6所示,显示了干预前及不同疫苗覆盖率下感染仓室内感染人数、感染率的变化。预测未来0~5年之间感染率峰值在干预前以及二价疫苗50%、60%、70%覆盖率干预后分别为17.44%、16.38%、16.14%、15.89%。感染人数为2 193、2 058、2 027和1 995人。研究结束时感染率分别为16.33%、15.31%、15.07%、14.82%,感染人数分别为1 914、1 801、1 774和1 746人,见表3。在采取疫苗干预后感染人数降低,达到感染率峰值时间提前,疫苗覆盖率越大感染率越小。
图7所示,与不采取干预措施相比,干预效果明显,宫颈癌患者人口数将逐渐减少,总人口数减少缓慢。50%疫苗覆盖率状态下2045年后宫颈癌患者将从294人减少至185人,60%、70%覆盖率下宫颈癌患者将分别为164和142人;总人口数分别为11 666、11 949、12 005和12 061人,也就是说在三个不同疫苗覆盖率下未来20年宫颈癌患者将分别减少109、130和142人,总人口分别挽救283、339和395名女性生命,疫苗接种覆盖率越大,效果越好。见表3
分析模型中感染者清除率μI与康复者成为易感者的率μr与对感染者的影响,对不同的μrμI值进行预测。
图8所示,增加清除率对减少感染人数的效果较好,进一步增加清除率对减少感染人数的效果逐渐减弱。清除率μI值增加20%,感染人数减少12.95%; 当μI值增加50%,感染人数减少27%。然而,μI值减少20%,感染人数增加17.53%;当μI值减少50%,感染人数将增加59.73%。
随着μr值的增加,康复者更容易再次成为易感者,从而导致感染人数的增长,康复者成为易感者的率越低,感染人数减少的效果越好。具体为当μr值增加50%,感染人数增加5.73%;μr值降低50%,感染人数将减少13.86%。
本研究所构建的模型与以往开发的模型略有不同,它包括了研究项目所得真实流行病学参数及干预方法对病毒发病率的影响[17]。参考此前马越等人[18]研究加入二价疫苗的干预措施,模型模拟2025—2045年间新疆塔城地区托里县妇女各健康状态下人群随时间的变化,观察干预如何随时间减少感染率,将干预结果与不干预结果进行图形化比较。模型模拟验证拟合效果较好,在整个预测期间,没有干预措施的情况下各仓室曲线出现短暂上升随后趋于平稳。预计2025—2045年该地感染率在13.9%~17.34%波动,其与报道中国普通女性人群HPV感染率13.1%~18.8%水平接近[19]。预测结果显示,该地5年内将达到HPV感染的高峰值17.34%,这或许与我国女性HPV感染“双峰”模式[20]有关,研究人群为35~64岁女性,30岁左右的女性免疫力功能较好,身体自我清除病毒能力强,随着时间的进展女性40岁以后免疫力降低,HPV感染后清除病毒的能力减弱,出现女性第二个感染高峰期。HPV感染高峰值提示在预防HPV感染时要关注免疫力功能降低的中年女性。
二价疫苗可预防HPV16/18病毒感染,50%二价疫苗覆盖率下结束时整体HPV感染率为15.31%,然而增加覆盖率对降低整体HPV感染的效果并不理想。事实上,该地宫颈癌筛查14种HPV型别数据,HPV16/18感染者在整体HPV感染中占比并不多,16/18型可引起大多数宫颈癌,其他HPV型别会引起生殖器疣等疾病,因此二价疫苗接种旨在减少宫颈癌的发病。未实施干预措施时,研究开始到结束该地总人口数量将从12 549人减少为11 666人,这表明如果不采取任何措施,该地将减少883名女性,二价疫苗接种覆盖率为70%时2045年后该地宫颈癌仓室数量将从无措施时294人减少至142人,总人口数量也将从11 666人增加为12 061人,与未实施措施相比宫颈癌仓室将减少88名妇女,总人口数也将增加395人,由此可见疫苗接种提供了明显的保护作用。对感染者清除率及康复者成为易感者的率进行敏感性分析预测,结果显示康复率提升50%将减少27%的感染人数,然而降低康复率50%则会增加59.73%的感染人数。此外,康复者的易感率降低50%,感染人数减少13.86%。这提示在预防HPV传播过程中注重清除率在传播过程的重要作用要比注重康复者成为易感者的率更具价值。规划干预措施时要关注清除率这一参数。对感染者进行治疗或增加运动锻炼,提高免疫力,增加清除率将有效减少感染的人数。
综上所述,通过HPV传播动力学模型预测分析可以估算托里县HPV未来20年的感染率感染高峰,癌症数量及总人口数,对不同二价疫苗覆盖率干预结果进行预测,预测结果可为该地宫颈癌预防措施和策略调整提供科学依据。因数据可获得性差,模型验证部分使用的是已经发表的文献中的数据,未使用当地实际数据,如果有当地连续多年的筛查数据模型验证效果将会更好。研究真实参数来自35~64岁的筛查妇女,我国《加速消除宫颈癌全球战略》提出2030年90%的女孩在15岁之前完成HPV疫苗接种,而本研究假设疫苗干预部分未考虑疫苗接种年龄的影响。此外,模型模拟的状况相对理想化,研究人群为固定的人群未考虑人口变化。
  • 多癌联筛早诊新体系的建立和全国推广应用新策略的评价(2022YFC2505100)
  • 自治区科技支疆项目计划(2022E02054)
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2024年第51卷第23期
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doi: 10.20043/j.cnki.MPM.202405294
  • 接收时间:2024-05-20
  • 首发时间:2026-03-18
  • 出版时间:2024-12-10
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  • 收稿日期:2024-05-20
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多癌联筛早诊新体系的建立和全国推广应用新策略的评价(2022YFC2505100)
自治区科技支疆项目计划(2022E02054)
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    1.新疆医科大学公共卫生学院,新疆 乌鲁木齐 830011
    2.新疆医科大学附属肿瘤医院医务部,新疆 乌鲁木齐 830054

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2种不同金属材料的力学参数

Family
属数
Number of
genus
种数
Number of
species
占总种数比例
Percentage of
total species (%)

Genus
种数
Number of
species
占总种数比例
Percentage of total
species (%)
鹅膏菌科Amanitaceae 2 11 5.26 鹅膏菌属 Amanita 10 4.78
小菇科 Mycenaceae 2 12 5.74 丝盖伞属 Inocybe 5 2.39
多孔菌科 Polyporaceae 8 14 6.70 蜡蘑属 Laccaria 5 2.39
红菇科 Russulaceae 3 23 11.00 小皮伞属 Marasmius 6 2.87
小菇属 Mycena 11 5.26
光柄菇属 Pluteus 5 2.39
红菇属 Russula 17 8.13
栓菌属 Trametes 5 2.39
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