A randomised, observer-blind, non-inferiority trial to evaluate alternative human papillomavirus vaccination schedules in young females in West Africa

一项随机、观察者盲法、非劣效性试验，旨在评估西非年轻女性的替代人乳头瘤病毒疫苗接种计划

• 批准号: MC_EX_MR/N006070/1
• 负责人: Ed Clarke
• 金额: $ 211.01万
• 依托单位: MRC Unit the Gambia
• 依托单位国家: 英国
• 项目类别: Research Grant
• 财政年份: 2015
• 资助国家: 英国
• 起止时间: 2015 至 无数据
• 项目状态: 已结题
• 来源: https://gtr.ukri.org/projects?ref=MC_EX_MR%2FN006070%2F1
• 关键词: randomised; observer; blind; non; inferiority

Cervical cancer is consistently associated with infection with the human papilloma virus (HPV). The cancer occurs more frequently in sub-Saharan Africa than anywhere else in the world and is the most common cause of cancer-related death in females in this setting. In addition, the burden of cervical cancer on the continent is expected to double over the next 15 years as the population gets older. For those diagnosed with cervical cancer, the chances of survival are also much lower in this setting than in many other parts of the world. In the absence of cervical screening programmes, the diagnosis is often made late and the treatment available may also be limited.Two different HPV types, type 16 and type 18, are associated with nearly three quarters of all cervical cancer worldwide, including in sub-Saharan Africa. Vaccines are already available against both HPV types and antibodies, which are thought to be responsible for protection, can be measured with a blood test after vaccination as an indicator of the immunity the vaccine generated.When given to adult women, 3 doses of an HPV vaccine have been shown to be extremely effective - generating high levels of antibody and providing sustained protection from HPV infection and hence cervical cancer for upwards of 10 years in studies so far. Further research has gone onto show that the level of antibody generated by the HPV vaccines in young adolescents is even higher than in adults. Indeed, in studies conducted in other parts of the world, young adolescents given just 2 doses of the vaccine have been shown to generate higher levels of antibody than those generated in adult women, even following 3 doses. Early data are now beginning to suggest that even a single dose of an HPV vaccine may provide sufficient levels of antibody to prevent infection, and hence cervical cancer, although this needs to be further studied.Given how effective at preventing HPV infection and cervical cancer the vaccines have been shown to be in other settings, the main hurdle to overcome if much of the burden of cervical cancer across sub-Saharan Africa is to be prevented is one of programme implementation - i.e. the capacity of countries to consistently deliver the required number of vaccine doses to a high proportion of the target female population. The WHO currently recommends that 2 doses of the vaccines are given to 9 to 13 year old girls and that a gap of at least 6 months is left between doses. However, there is no established system in place across much of sub-Saharan Africa to deliver such a programme and no easy way to reliably access adolescent females. While school-based programmes have shown some success, many females do not complete primary education or attend school only inconsistently at this age. Consequently ensuring the reliable delivery of 2 vaccine doses is a major challenge.This trial will ask 2 main questions, both of which aim to make it easier for countries across sub-Saharan Africa and elsewhere to reliably deliver HPV vaccine programmes:1. Are 2 or 3 HPV vaccine doses needed to provide protection or would 1 dose be enough?It would be much easier and cheaper to ensure all females get a single dose of an HPV vaccine than to ensure they all get 2 doses separated by at least 6 months.2. Could the HPV vaccines be given to girls younger than 9 years of age? School-based programmes could be designed more flexibly to target the age of peak school attendance. Also, the delivery of HPV vaccines through established child health programmes which continue to monitor growth and to provide vitamin and iron supplements to children until 5 or 6 years becomes possible thus impacting on cost as well as vaccine coverage.The costs of the various schedules and ways to deliver the vaccines will also be examined and vaccine acceptability in rural West Africa will also be explored to ensure the maximum future impact of the trial on public health policy

宫颈癌与人乳头瘤病毒（HPV）感染有关。这种癌症在撒哈拉以南非洲的发生率比世界上任何其他地方都要高，是该地区女性癌症相关死亡的最常见原因。此外，随着人口老龄化，预计在未来15年内，非洲大陆的宫颈癌负担将翻一番。对于那些被诊断患有宫颈癌的人来说，在这种情况下生存的机会也比世界上许多其他地区低得多。在缺乏宫颈筛查计划的情况下，诊断往往很晚，可用的治疗也可能有限。两种不同的HPV类型，即16型和18型，与全球近四分之三的宫颈癌有关，包括撒哈拉以南非洲。已经有针对两种HPV类型的疫苗和抗体，这些抗体被认为是负责保护的，可以在接种疫苗后通过血液测试来测量，作为疫苗产生的免疫力的指标。当给予成年女性时，3剂HPV疫苗已被证明是非常有效的-产生高水平的抗体，并提供持续的保护，免受HPV感染，因此，子宫颈癌超过10年的研究。进一步的研究表明，HPV疫苗在青少年中产生的抗体水平甚至高于成年人。事实上，在世界其他地区进行的研究表明，青少年仅接种两剂疫苗就产生的抗体水平高于成年妇女，即使接种三剂疫苗也是如此。早期的数据现在开始表明，即使是单剂量的HPV疫苗也可以提供足够的抗体水平来预防感染，从而预防宫颈癌，尽管这需要进一步研究。鉴于预防HPV感染和宫颈癌的有效性，疫苗已被证明在其他环境中，如果要在撒哈拉以南非洲预防宫颈癌的大部分负担，需要克服的主要障碍是方案的执行-即各国持续向高比例的目标女性人口提供所需疫苗剂量的能力。世卫组织目前建议9至13岁的女孩接种两剂疫苗，两剂疫苗之间至少间隔6个月。然而，在撒哈拉以南非洲的大部分地区，没有建立提供这种方案的系统，也没有可靠地接触少女的简便方法。虽然以学校为基础的方案取得了一些成功，但许多妇女在这个年龄没有完成小学教育或只是偶尔上学。因此，确保可靠地提供2剂疫苗是一项重大挑战。本试验将提出两个主要问题，这两个问题都旨在使撒哈拉以南非洲和其他地区的国家更容易可靠地提供HPV疫苗计划：1.是否需要2或3剂HPV疫苗才能提供保护，或者1剂就足够了？确保所有女性都接种一剂HPV疫苗比确保她们都接种两剂疫苗至少间隔6个月更容易和更便宜。2. HPV疫苗可以给9岁以下的女孩吗？可以更灵活地设计以学校为基础的方案，以针对入学高峰年龄。还有，通过已建立的儿童保健方案提供人乳头瘤病毒疫苗，这些方案继续监测儿童的生长情况，并为儿童提供维生素和铁补充剂，直到5岁或6岁成为可能，从而影响成本和疫苗覆盖率，还将审查提供疫苗的各种时间表和方式的成本，还将探讨西非农村地区疫苗的可接受性，以确保最大限度地提高未来的免疫力。试验对公共卫生政策的影响

项目成果

Prevalence of five treatable sexually transmitted infections among women in Lower River region of The Gambia.

• DOI: 10.1186/s12879-023-08399-2
• 发表时间: 2023-07-13
• 期刊: BMC INFECTIOUS DISEASES
• 影响因子: 3.7
• 作者: Butcher, Robert;Jarju, Sheikh;Obayemi, Dolapo;Bashorun, Adedapo Olufemi;Vasileva, Hristina;Bransbury-Hare, Hannah;Agboghoroma, Orighomisan;Drammeh, Lamin;Holland, Martin;Harding-Esch, Emma;Clarke, Ed
• 通讯作者: Clarke, Ed