Centre de recherche du CHU de Québec - Universite Laval, Québec, QC, Canada; Department of Social and Preventive Medicine, Universite Laval, Québec, QC, Canada; MRC Centre for Global Infectious Disease Analysis, Department of Infectious Disease Epidemiology, Imperial College London, London, UK.
Center for Health Decision Science, Harvard T.H. Chan School of Public Health, Boston, MA, USA.
Lancet. 2020 Feb 22;395(10224):575-590. doi: 10.1016/S0140-6736(20)30068-4. Epub 2020 Jan 30.
BACKGROUND: The WHO Director-General has issued a call for action to eliminate cervical cancer as a public health problem. To help inform global efforts, we modelled potential human papillomavirus (HPV) vaccination and cervical screening scenarios in low-income and lower-middle-income countries (LMICs) to examine the feasibility and timing of elimination at different thresholds, and to estimate the number of cervical cancer cases averted on the path to elimination. METHODS: The WHO Cervical Cancer Elimination Modelling Consortium (CCEMC), which consists of three independent transmission-dynamic models identified by WHO according to predefined criteria, projected reductions in cervical cancer incidence over time in 78 LMICs for three standardised base-case scenarios: girls-only vaccination; girls-only vaccination and once-lifetime screening; and girls-only vaccination and twice-lifetime screening. Girls were vaccinated at age 9 years (with a catch-up to age 14 years), assuming 90% coverage and 100% lifetime protection against HPV types 16, 18, 31, 33, 45, 52, and 58. Cervical screening involved HPV testing once or twice per lifetime at ages 35 years and 45 years, with uptake increasing from 45% (2023) to 90% (2045 onwards). The elimination thresholds examined were an average age-standardised cervical cancer incidence of four or fewer cases per 100 000 women-years and ten or fewer cases per 100 000 women-years, and an 85% or greater reduction in incidence. Sensitivity analyses were done, varying vaccination and screening strategies and assumptions. We summarised results using the median (range) of model predictions. FINDINGS: Girls-only HPV vaccination was predicted to reduce the median age-standardised cervical cancer incidence in LMICs from 19·8 (range 19·4-19·8) to 2·1 (2·0-2·6) cases per 100 000 women-years over the next century (89·4% [86·2-90·1] reduction), and to avert 61·0 million (60·5-63·0) cases during this period. Adding twice-lifetime screening reduced the incidence to 0·7 (0·6-1·6) cases per 100 000 women-years (96·7% [91·3-96·7] reduction) and averted an extra 12·1 million (9·5-13·7) cases. Girls-only vaccination was predicted to result in elimination in 60% (58-65) of LMICs based on the threshold of four or fewer cases per 100 000 women-years, in 99% (89-100) of LMICs based on the threshold of ten or fewer cases per 100 000 women-years, and in 87% (37-99) of LMICs based on the 85% or greater reduction threshold. When adding twice-lifetime screening, 100% (71-100) of LMICs reached elimination for all three thresholds. In regions in which all countries can achieve cervical cancer elimination with girls-only vaccination, elimination could occur between 2059 and 2102, depending on the threshold and region. Introducing twice-lifetime screening accelerated elimination by 11-31 years. Long-term vaccine protection was required for elimination. INTERPRETATION: Predictions were consistent across our three models and suggest that high HPV vaccination coverage of girls can lead to cervical cancer elimination in most LMICs by the end of the century. Screening with high uptake will expedite reductions and will be necessary to eliminate cervical cancer in countries with the highest burden. FUNDING: WHO, UNDP, UN Population Fund, UNICEF-WHO-World Bank Special Program of Research, Development and Research Training in Human Reproduction, Canadian Institute of Health Research, Fonds de recherche du Québec-Santé, Compute Canada, National Health and Medical Research Council Australia Centre for Research Excellence in Cervical Cancer Control.
背景:世界卫生组织总干事呼吁采取行动,消除宫颈癌这一公共卫生问题。为了帮助指导全球努力,我们建立了数学模型,对低收入和中低收入国家(LMICs)的潜在人乳头瘤病毒(HPV)疫苗接种和宫颈筛查方案进行建模,以检验在不同阈值下消除的可行性和时间,并估计在消除宫颈癌的过程中可以预防多少宫颈癌病例。
方法:世界卫生组织宫颈癌消除建模联盟(CCEMC)由世卫组织根据预先确定的标准确定的三个独立的传播动力学模型组成,对 78 个 LMICs 中的宫颈癌发病率随时间的变化进行了预测,共进行了三种标准化的基本情况模拟:仅对女孩进行疫苗接种;仅对女孩进行疫苗接种和一次性终生筛查;以及仅对女孩进行疫苗接种和两次终生筛查。女孩在 9 岁时接种疫苗(包括 14 岁的补种),假设疫苗接种覆盖率为 90%,对 HPV 16、18、31、33、45、52 和 58 型的终生保护率为 100%。宫颈筛查包括在 35 岁和 45 岁时进行 HPV 检测一次或两次,检测率从 2023 年的 45%增加到 2045 年以后的 90%。我们考察的消除阈值为平均年龄标准化的宫颈癌发病率每 10 万妇女年 4 例或更少,以及每 10 万妇女年 10 例或更少,以及发病率降低 85%或以上。我们进行了敏感性分析,改变了疫苗接种和筛查策略以及假设。我们使用模型预测的中位数(范围)来总结结果。
结果:对女孩仅进行 HPV 疫苗接种预计将使 LMICs 的宫颈癌发病率从下个世纪的每 10 万妇女年 19.8(范围为 19.4-19.8)例降低到 2.1(2.0-2.6)例(89.4%[86.2-90.1]的降幅),并在此期间预防 6100 万(605-630)例宫颈癌。增加两次终生筛查将发病率降低至每 10 万妇女年 0.7(0.6-1.6)例(96.7%[91.3-96.7]的降幅),并额外预防 1210 万(9.5-13.7)例宫颈癌。根据每 10 万妇女年 4 例或更少的阈值,60%(58-65)的 LMICs 预计将通过仅对女孩进行疫苗接种实现消除;根据每 10 万妇女年 10 例或更少的阈值,99%(89-100)的 LMICs 将实现消除;根据发病率降低 85%或以上的阈值,87%(37-99)的 LMICs 将实现消除。当增加两次终生筛查时,所有三个阈值下的 100%(71-100)的 LMICs 都达到了消除。在所有国家都能通过对女孩进行疫苗接种实现宫颈癌消除的地区,消除可能在 2059 年至 2102 年之间发生,具体取决于阈值和地区。引入两次终生筛查可将消除时间提前 11-31 年。长期疫苗保护对于消除是必要的。
解释:我们的三个模型的预测结果一致,表明高 HPV 疫苗接种覆盖率可使大多数 LMICs 在本世纪末实现宫颈癌消除。高覆盖率的筛查将加速减少宫颈癌的发生,并将成为高负担国家消除宫颈癌的必要手段。
资金:世界卫生组织、联合国开发计划署、联合国人口基金、联合国儿童基金会-世界卫生组织-世界银行人类生殖研究、发展和研究培训特别方案、加拿大卫生研究院、魁北克省健康研究基金会、加拿大计算中心、澳大利亚国家卫生和医学研究理事会卓越研究中心宫颈癌控制。
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