Centre de recherche du CHU de Québec, Université Laval, Quebec City, QC, Canada.
Centre for Mathematical Modelling of Infectious Disease, London School of Hygiene & Tropical Medicine, London, UK; Modelling and Economics Unit, Public Health England, London, UK; School of Public Health, University of Hong Kong, Hong Kong Special Administrative Region, China.
Lancet Infect Dis. 2021 Nov;21(11):1598-1610. doi: 10.1016/S1473-3099(20)30860-4. Epub 2021 Jul 7.
BACKGROUND: Introduction of human papillomavirus (HPV) vaccination has been slow in low-income and middle-income countries (LMICs) because of resource constraints and worldwide shortage of vaccine supplies. To help inform WHO recommendations, we modelled various HPV vaccination strategies to examine the optimal use of limited vaccine supplies and best allocation of scarce resources in LMICs in the context of the WHO global call to eliminate cervical cancer as a public health problem. METHODS: In this mathematical modelling analysis, we developed HPV-ADVISE LMIC, a transmission-dynamic model of HPV infection and diseases calibrated to four LMICs: India, Vietnam, Uganda, and Nigeria. For different vaccination strategies that encompassed use of a nine-valent vaccine (or a two-valent or four-valent vaccine assuming high cross-protection), we estimated three outcomes: reduction in the age-standardised rate of cervical cancer, number of doses needed to prevent one case of cervical cancer (NNV; as a measure of efficiency), and the incremental cost-effectiveness ratio (ICER; in 2017 international $ per disability-adjusted life-year [DALY] averted). We examined different vaccination strategies by varying the ages of routine HPV vaccination and number of age cohorts vaccinated, the population targeted, and the number of doses used. In our base case, we assumed 100% lifetime protection against HPV-16, HPV-18, HPV-31, HPV-33, HPV-45, HPV-52, and HPV-58; vaccination coverage of 80%; and a time horizon of 100 years. For the cost-effectiveness analysis, we used a 3% discount rate. Elimination of cervical cancer was defined as an age-standardised incidence of less than four cases per 100 000 woman-years. FINDINGS: We predicted that HPV vaccination could lead to cervical cancer elimination in Vietnam, India, and Nigeria, but not in Uganda. Compared with no vaccination, strategies that involved vaccinating girls aged 9-14 years with two doses were predicted to be the most efficient and cost-effective in all four LMICs. NNV ranged from 78 to 381 and ICER ranged from $28 per DALY averted to $1406 per DALY averted depending on the country. The most efficient and cost-effective strategies were routine vaccination of girls aged 14 years, with or without a later switch to routine vaccination of girls aged 9 years, and routine vaccination of girls aged 9 years with a 5-year extended interval between doses and a catch-up programme at age 14 years. Vaccinating boys (aged 9-14 years) or women aged 18 years or older resulted in substantially higher NNVs and ICERs. INTERPRETATION: We identified two strategies that could maximise efforts to prevent cervical cancer in LMICs given constraints on vaccine supplies and costs and that would allow a maximum of LMICs to introduce HPV vaccination. FUNDING: World Health Organization, Canadian Institute of Health Research, Fonds de recherche du Québec-Santé, Compute Canada, PATH, and The Bill & Melinda Gates Foundation. TRANSLATIONS: For the French and Spanish translations of the abstract see Supplementary Materials section.
背景:由于资源限制和全球疫苗供应短缺,在低收入和中等收入国家(LMICs)中,人乳头瘤病毒(HPV)疫苗的引入进展缓慢。为了帮助为世卫组织的建议提供信息,我们针对各种 HPV 疫苗接种策略进行了建模,以检查在全球消除宫颈癌作为公共卫生问题的世卫组织呼吁下,在 LMICs 中,如何最佳利用有限的疫苗供应和最佳分配稀缺资源。
方法:在这项数学建模分析中,我们开发了 HPV-ADVISE LMIC,这是一种 HPV 感染和疾病的传播动力学模型,针对四个 LMIC 进行了校准:印度、越南、乌干达和尼日利亚。对于涵盖使用九价疫苗(或假设高交叉保护的二价或四价疫苗)的不同疫苗接种策略,我们估计了三个结果:宫颈癌年龄标准化发病率的降低、预防一例宫颈癌所需的剂量数(NNV;作为效率的衡量标准),以及增量成本效益比(ICER;以 2017 年国际残疾调整生命年 [DALY] 每避免的成本衡量)。我们通过改变常规 HPV 疫苗接种的年龄和接种的年龄组数量、目标人群和使用的剂量数来检查不同的疫苗接种策略。在我们的基本情况下,我们假设 HPV-16、HPV-18、HPV-31、HPV-33、HPV-45、HPV-52 和 HPV-58 的终生保护率为 100%;疫苗接种覆盖率为 80%;时间范围为 100 年。对于成本效益分析,我们使用了 3%的贴现率。宫颈癌的消除定义为年龄标准化发病率低于每 100000 名女性 4 例。
结果:我们预测 HPV 疫苗接种可导致越南、印度和尼日利亚消除宫颈癌,但在乌干达则不能。与不接种疫苗相比,在所有四个 LMIC 中,为 9-14 岁女孩接种两剂疫苗的策略被预测为最有效和最具成本效益的策略。根据国家的不同,NNV 范围从 78 到 381,ICER 范围从每避免一个 DALY 成本 28 美元到每避免一个 DALY 成本 1406 美元不等。最有效和最具成本效益的策略是常规为 14 岁女孩接种疫苗,或在此基础上转为常规为 9 岁女孩接种疫苗,或常规为 9 岁女孩接种疫苗,并延长 5 年的接种间隔,以及在 14 岁时进行补种计划。为 9-14 岁男孩或 18 岁及以上妇女接种疫苗会导致 NNV 和 ICER 大幅上升。
解释:我们确定了两种策略,这些策略可以在疫苗供应和成本受到限制的情况下,最大限度地努力预防 LMICs 中的宫颈癌,并使尽可能多的 LMICs 能够引入 HPV 疫苗接种。
资助:世界卫生组织、加拿大卫生研究院、魁北克健康研究基金会、计算加拿大、PATH 和比尔和梅琳达盖茨基金会。
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