李娟,胡杨,杨雷,李晓梅,潘静彬,卢莉,吴疆

• 1:北京市疾病预防控制中心北京市预防医学研究中心
• 2:空军研究院
• 3:北京大学肿瘤医院暨北京市肿瘤防治研究所北京市肿瘤防治研究办公室

摘要(Abstract)：

目的构建北京市人乳头瘤病毒(HPV)疫苗不同免疫策略的Markov模型,进行北京市女性宫颈癌发病的远期预测。方法收集模型参数,构建Markov模型;在构建和验证宫颈癌自然史模型和筛查模型的基础上构建HPV疫苗接种模型,预测实施三种HPV疫苗(2价、4价和9价疫苗)接种和9价HPV疫苗四种免疫策略(接种年龄和接种率:10-15岁80%、16-44岁10%;10-19岁80%、20-44岁10%;10-15岁90%、16-44岁30%;10-19岁90%、20-44岁30%)后2017-2100年宫颈癌发病。结果本研究成功构建北京市HPV疫苗接种的Markov模型。模型预测结果显示,2017-2100年实施3种HPV疫苗免疫策略后北京市女性宫颈癌的预测发病数均逐年下降。在9价疫苗免疫策略中,策略1与策略2、策略3与策略4的宫颈癌预测发病曲线几乎相同;将策略1改为策略3或将策略2改为策略4,宫颈癌发病明显下降。与筛查模型的同年预测发病率相比,实施四种9价疫苗免疫策略后2030年宫颈癌发病率分别下降34%、36%、48%、48%,2060年分别下降84%、85%、90%、90%。结论 HPV疫苗不同免疫策略均可降低女性宫颈癌发病;青少年女性高水平接种率与成年女性低水平接种率相结合策略可达到较好的宫颈癌防控效果。

关键词(KeyWords)： 宫颈癌;人乳头瘤病毒疫苗;Markov模型;发病;预测

Abstract:

Keywords:

基金项目(Foundation): 北京市疾病预防控制中心、北京市预防医学研究中心科研培育专项(2018-BJYJ-04)

作者(Author): 李娟,胡杨,杨雷,李晓梅,潘静彬,卢莉,吴疆

参考文献(References)：

• [1] CHEN W, ZHENG R, BaAADE PD, et al. Cancer statistics in China, 2015[J]. Ca:a Cancer Journal f or Clinicians,2016, 66(2):115-132.
• [2] DOORBAR J, QUINT W, BANKS L, et al. The biology and lif e-cycle of human papillomaviruses[J]. Vaccine,2012, 30(Suppl 5):55-70.
• [3] INSINGA RP, DASBACH EJ, ELBASHA EH, et al.Progression and regression of incident cervical HPV 6,11, 16 and 18 infections in young women[J]. Infectious Agents and Cancer, 2007, 2(1):15-24.
• [4] PITISUTTITHUM P, VELICER C, LUXEMBOURG A.9-valent HPV vaccine for cancers, pre-cancers and genital warts related to HPV[J]. Expert Review of Vaccines, 2015,14(11):1405-1419.
• [5] World Heal th Organizat ion. Human papi l lomavi rus vaccines:WHO position paper[J]. Wkly Epidemiol Rec,2017, 92(19):241-268.
• [6] GARLAND SM, KJAER SK, MU袿Z N, et al. Impact and effectiveness of the quadrivalent human papillomavirus vaccine:a systematic review of 10 years of real-world experience[J]. Clinical Infectious Diseases, 2016, 63(4):519-527.
• [7] DEMARTEAU N, TANG CH, CHEN HC, et al. Costeffectiveness analysis of the bivalent compared with the quadrivalent human papillomavirus vaccines in Taiwan[J].Value in Health, 2012, 15(5):622-631.
• [8] KONNO R, SASAGAWA T, FUKUDA T, et al. Costef f ectiveness analysis of prophylactic cervical cancer vaccination in Japanese women[J]. International Journal of Gynecological Cancer, 2010, 20(3):385-392.
• [9]沈洁,高丽丽,张月,等.北京市宫颈癌筛查妇女中高危型HPV感染状况及在宫颈癌前病变中的分布[J].中华预防医学杂志, 2018, 52(5):493-497.SHEN J, GAO LL, ZHANG Y, et al. Prevalence of highrisk HPV and its distribution in cervical precancerous lesions among 35-64 years old women who received cervical cancer screening in Beijing[J]. Chinese Journal of Preventive Medicine, 2018, 52(5):493-497.
• [10]高丽丽,沈洁,张月,等.北京地区35~64岁农村妇女高危型HPV感染情况分析[J].中国妇产科临床杂志, 2015,16(6):494-497.GAO LL, SHEN J, ZHANG Y, et al. Analysis of highrisk type HPV infection in 35 to 64 years old rural women in Beijing[J]. Chinese Journal of Clinical Obstetrics and Gynecology, 2015, 16(6):494-497.
• [11]毕惠,赵更力.子宫颈癌综合防控技术培训教程[M].北京:人民卫生出版社, 2015:27-68.BI H, ZHAO GL. Training course on comprehensive prevention and control of cervical cancer[M]. Bei jing:People’s Medical Publishing House, 2015:27-68.
• [12] MOSCICKI AB. Risks for incident human papillomavirus infection and low-grade squamous intraepithelial lesion development in young females[J]. JAMA, 2001, 285(23):2995-3002.
• [13]中华预防医学会妇女保健分会.子宫颈癌综合防控指南[M].北京:人民卫生出版社, 2017:8-15.Women’s Health Branch of Chinese Preventive Medicine Association. Guidelines for comprehensive prevention and control of cervical cancer[M]. Beijing:People’s Medical Publishing House, 2017:8-15.
• [14]全国肿瘤防治研究办公室.中国试点市、县恶性肿瘤的发病与死亡(1998-2002)[M].北京:人民卫生出版社, 2003.Nat ional Of f ice of Cancer Prevent ion and Research.Incidence and death of malignant tumors in pilot cities and counties of China(1998-2002)[M]. Beijing:People’s Medical Publishing House, 2013.
• [15]全国肿瘤防治研究办公室.中国试点市、县恶性肿瘤的发病与死亡(2003-2007)[M].北京:人民卫生出版社, 2008.Nat ional Of f ice of Cancer Prevent ion and Research.Incidence and death of malignant tumors in pilot cities and counties of China(2003-2007)[M]. Beijing:People’s Medical Publishing House, 2008.
• [16]赵平,陈万青.中国肿瘤登记年报[M].北京:军事医学科学出版社, 2009.ZHAO P, CHEN WQ. Annual report of cancer registration in China[M]. Bei jing:Military Medical Science Press,2009.
• [17]赵平,陈万青.中国肿瘤登记年报[M].北京:军事医学科学出版社, 2010.ZHAO P, CHEN WQ. Annual report of cancer registration in China[M]. Bei jing:Military Medical Science Press,2010.
• [18]赫捷,赵平,陈万青.中国肿瘤登记年报[M].北京:军事医学科学出版社, 2011.HAO J, ZHAO P, CHEN WQ. Annual report of cancer regist ration in China[M]. Bei jing:Mili tary Medical Science Press, 2011.
• [19]赫捷,陈万青.中国肿瘤登记年报[M].北京:军事医学科学出版社, 2012.HAO J, CHEN WQ. Annual report of cancer registration in China[M]. Bei jing:Military Medical Science Press,2012.
• [20]赫捷,陈万青.中国肿瘤登记年报[M].北京:清华大学出版社, 2013.HAO J, CHEN WQ. Annual report of cancer registration in China[M]. Beijing:Tsinghua University Press, 2013.
• [21]赫捷,陈万青.中国肿瘤登记年报[M].北京:清华大学出版社, 2014.HAO J, CHEN WQ. Annual report of cancer registration in China[M]. Beijing:Tsinghua University Press, 2014.
• [22]赫捷,陈万青.中国肿瘤登记年报[M].北京:清华大学出版社, 2015.HAO J, CHEN WQ. Annual report of cancer registration in China[M]. Beijing:Tsinghua University Press, 2015.
• [23]赫捷,陈万青.中国肿瘤登记年报[M].北京:清华大学出版社, 2016.HAO J, CHEN WQ. Annual report of cancer registration in China[M]. Beijing:Tsinghua University Press, 2016.
• [24]韩历丽.子宫颈癌、乳腺癌筛查策略概述[J].北京医学,2014, 36(11):893-894.HAN LL. Summary of screening strategies for cervical cancer and breast cancer[J]. Bei jing Medical Journal,2014, 36(11):893-894.
• [25]高丽丽,沈洁,张月,等. 2008—2014年北京市子宫颈癌筛查数据分析[J].中国妇产科临床杂志, 2017, 18(2):124-127.GAO LL, SHEN J, ZHANG Y, et al. Data analysis of cervical cancer screening in Beijing f rom 2008 to 2014[J].Chinese Journal of Clinical Obstetrics and Gynecology,2017, 18(2):124-127.
• [26]韩历丽,赵同香,邓小虹.宫颈癌筛查工作评价指标的比较研究[J].中华妇幼临床医学杂志(电子版), 2014, 10(6):757-761.HAN LL, ZHAO TX, DENG XH. Comparative study of evaluating indicators for cervical cancer mass screening[J]. Chinese Journal of Obstet rics&Gynecology and Pediatrics(electronic edition), 2014, 10(6):757-761.
• [27] HPV Inf ormation Cent re. Human papillomavirus and related diseases report China[EB/OL].(2018-11-30)[(2019-01-30)]. http://www.hpvcentre.net/statistics/reports/CHN.pdf?t=1548831780029.
• [28] SUáREZ E, SMITH JS, BOSCH FX, et al. Cost-effectiveness of vaccination against cervical cancer:a multi-regional analysis assessing the impact of vaccine characteristics and alternative vaccination scenarios[J]. Vaccine, 2008,26(Suppl 5):29-45.
• [29] ZHAO FH, TIGGELAAR SM, HUA SY, et al. A multicenter survey of age of sexual debut and sexual behavior in Chinese women:suggest ions f or opt imal age of human papillomavirus vaccination in China[J]. Cancer Epidemiology, 2012, 36:384-390.
• [30]北京市人民政府.北京市2014年度卫生与人群健康状况报告[M].北京:人民卫生出版社, 2015.Bei jing Municipal People’s Government. Bei jing health and population health report 2014[M]. Beijing:People’s Medical Publishing House, 2015.
• [31]北京市人民政府.北京市2015年度卫生与人群健康状况报告[M].北京:人民卫生出版社, 2016.Bei jing Municipal People’s Government. Bei jing health and population health report 2015[M]. Beijing:People’s Medical Publishing House, 2016.
• [32]北京市人民政府.北京市2016年度卫生与人群健康状况报告[M].北京:人民卫生出版社, 2017.Bei jing Municipal People’s Government. Bei jing health and population health report 2016[M]. Beijing:People’s Medical Publishing House, 2017.
• [33]北京市人民政府.北京市2017年度卫生与人群健康状况报告[M].北京:人民卫生出版社, 2018.Bei jing Municipal People’s Government. Bei jing health and population health report 2017[M]. Beijing:People’s Medical Publishing House, 2018.
• [34]宋晓彬,茅范贞,周鼒,等.发展中国家人乳头瘤病毒疫苗卫生经济学评价研究的系统综述[J].中华预防医学杂志,2016, 50(1):85-90.SIONG XB, MAO FZ, ZHOU Z, et al. Health economic evaluat ion of human papillomavi rus vaccines in the developing count ries:systematic reviews[J]. Chinese Journal of Preventive Medicine, 2016, 50(1):85-90.
• [35]方亚,宋晓彬,周鼒,等.数学模型在HPV疫苗经济学评估中的研究进展[J].中国卫生统计, 2014, 31(2):348-351+356.FANG Y, SONG XB, ZHOU Z, et al. Progress of mathematical model in economic evaluation of HPV vaccine[J]. Chinese Journal of Health Statistics, 2014, 31(2):348-351+356.
• [36]王朝,武明辉,韩历丽,等.宫颈癌与乳腺癌筛查信息系统设计与实现[J].中国卫生信息管理杂志, 2014, 11(2):144-148.WANG Z, WU MH, HAN LL, et al. System design and implementation f or cervical cancer and breast cancer screening[J]. Chinese Journal of Health Informatics and Management, 2014, 11(2):144-148.
• [37] GARLAND SM, KJAER SK, MUNZN,等.四价人乳头瘤病毒疫苗的效力和效果:10年真实世界研究的系统综述[J].中国病毒病杂志, 2018, 8(4):329-335+346.GARLAND SM, KJAER SK, MU OZN, et al.Effectiveness and efficacy of tetravalent human papillomavirus vaccine:a systematic review of 10 years of real world research[J]. Chinese Journal of Viral Diseases,2018, 8(4):329-335+346.
• [38] GARLAND SM, KJAER SK, MUNZN, et al. Impact and effectiveness of the quadrivalent human papillomavirus vaccine:a systematic review of 10 years of real-world experience[J]. Clinical Infectious Diseases, 2016, 63(4):519-527.