Département de médecine sociale et préventive, Université Laval, QC, Canada; Centre de recherche du CHU de Québec, Université Laval, QC, Canada.
Centre de recherche du CHU de Québec, Université Laval, QC, Canada.
Lancet Glob Health. 2023 Jan;11(1):e48-e58. doi: 10.1016/S2214-109X(22)00475-2.
The WHO Strategic Advisory Group of Experts recommended that an extended interval of 3-5 years between the two doses of the human papillomavirus (HPV) vaccine could be considered to alleviate vaccine supply shortages. However, three concerns have limited the introduction of extended schedules: girls could be infected between the two doses, the vaccination coverage for the second dose could be lower at ages 13-14 years than at ages 9-10 years, and identifying girls vaccinated with a first dose to give them the second dose could be difficult. Using mathematical modelling, we examined the potential effect of these concerns on the population-level impact and efficiency of extended dose HPV vaccination schedules.
We used HPV-ADVISE, an individual-based, transmission-dynamic model of multitype HPV infection and disease, calibrated to country-specific data for four low-income and middle-income countries (India, Viet Nam, Uganda, and Nigeria). For the extended dose scenarios, we varied the vaccination coverage of the second dose among girls previously vaccinated, the one-dose vaccine efficacy, and the one-dose vaccine duration of protection. We also examined a strategy in which girls aged 14 years were vaccinated irrespective of their previous vaccination status. We used a scenario of girls-only two-dose vaccination at age 9 years (vaccine=9 valent, vaccine-type efficacy=100%, duration of protection=lifetime, and coverage=80%) as our comparator. We estimated two outcomes: the relative reduction in the age-standardised cervical cancer incidence (population-level impact) and the number of cervical cancers averted per 100 000 doses (efficiency).
Our model projected substantial reductions in cervical cancer incidence over 100 years with the two-dose schedule (79-86% depending on the country), compared with no vaccination. Projections for the 5-year extended schedule, in which the second dose is given only to girls previously vaccinated at age 9 years, were similar to the current two-dose schedule, unless vaccination coverage of the second dose is very low (reductions in cervical cancer incidence of 71-78% assuming 30% coverage at age 14 years among girls vaccinated at age 9 years). However, when the dose at age 14 years is given to girls irrespective of vaccination status and assuming high vaccination coverage, the model projected a substantially greater reduction in cervical cancer incidence compared with the current two-dose schedule (reductions in cervical cancer incidence of 86-93% assuming 70% coverage at age 14 years, irrespective of vaccination status). Efficiency of the extended schedule was greater than the two-dose schedule, even with a drop in vaccination coverage.
The three concerns are unlikely to have a substantial effect on the population-level impact of extended dose schedules. Hence, extended dose schedules will likely provide similar cervical cancer reductions as two-dose schedules, while reducing the number of doses required in the short-term, providing a more efficient use of scarce resources, and offering a 5-year time window to reassess the necessity of the second dose.
WHO, Canadian Institute of Health Research Foundation, Fonds de recherche du Québec-Santé, Digital Research Alliance of Canada, and Bill & Melinda Gates Foundation.
世界卫生组织（WHO）战略咨询专家组建议，HPV 疫苗两剂之间的间隔时间可延长至 3-5 年，以缓解疫苗供应短缺的问题。然而，有三个问题限制了延长接种时间表的引入：女孩在两剂疫苗接种之间可能会被感染，在 13-14 岁时接种第二剂疫苗的覆盖率可能低于 9-10 岁时的覆盖率，并且确定接种了第一剂疫苗的女孩以接种第二剂疫苗可能具有一定难度。我们使用数学模型，研究了这些问题对 HPV 疫苗延长接种计划的人群影响和效率的潜在影响。
我们使用 HPV-ADVISE，一种基于个体的多型 HPV 感染和疾病传播动力学模型，针对四个低收入和中等收入国家（印度、越南、乌干达和尼日利亚）的具体数据进行了校准。对于延长剂量方案，我们改变了之前接种过疫苗的女孩第二剂疫苗的接种覆盖率、一剂疫苗的疗效和一剂疫苗的保护期。我们还研究了一种策略，即 14 岁的女孩无论之前的接种状况如何都可以接种疫苗。我们将女孩仅在 9 岁时进行两剂疫苗接种的方案（疫苗=九价，疫苗型效力=100%，保护期=终身，覆盖率=80%）作为对照。我们估计了两个结果：年龄标准化宫颈癌发病率的相对降低（人群影响）和每 100000 剂疫苗可预防的宫颈癌病例数（效率）。
与不接种疫苗相比，两剂疫苗接种方案在 100 年内可显著降低宫颈癌发病率（取决于国家，降低 79-86%）。在仅对 9 岁时接种过疫苗的女孩接种第二剂的 5 年延长方案中，预测结果与目前的两剂方案相似，除非第二剂疫苗的接种覆盖率非常低（在 9 岁时接种疫苗的女孩中，假设 14 岁时女孩的接种覆盖率为 30%，宫颈癌发病率降低 71-78%）。然而，如果在 14 岁时为女孩接种一剂疫苗，而不论其接种状况如何，并假设高接种覆盖率，与目前的两剂方案相比，模型预测宫颈癌发病率将显著降低（假设在 14 岁时的覆盖率为 70%，无论接种状况如何，宫颈癌发病率降低 86-93%）。即使接种覆盖率下降，延长方案的效率也高于两剂方案。
这三个问题不太可能对 HPV 疫苗延长接种计划的人群影响产生重大影响。因此，与两剂方案相比，延长接种计划可能会提供类似的宫颈癌减少效果，同时在短期内减少所需的剂量数，更有效地利用稀缺资源，并提供 5 年的时间窗口来重新评估第二剂疫苗的必要性。
世界卫生组织、加拿大卫生研究院基金会、魁北克省卫生研究基金会、加拿大数字研究联盟和比尔和梅琳达盖茨基金会。
