Randomised trial of HPV vaccination for the control of HPV-related diseases in HIV-positive African populations: Preparatory phase (PH01/14-39)

在非洲 HIV 阳性人群中进行 HPV 疫苗接种以控制 HPV 相关疾病的随机试验：准备阶段 (PH01/14-39)

• 批准号: MR/M01231X/1
• 负责人: Philipp Mayaud
• 金额: $ 19.12万
• 依托单位: London School of Hygiene & Tropical Medicine
• 依托单位国家: 英国
• 项目类别: Research Grant
• 财政年份: 2014
• 资助国家: 英国
• 起止时间: 2014 至 无数据
• 项目状态: 已结题
• 来源: https://gtr.ukri.org/projects?ref=MR%2FM01231X%2F1
• 关键词: Randomised; trial; HPV; vaccination; control

The development & rollout of bivalent, quadrivalent and nonavalent vaccines against high-risk oncogenic human papillomavirus (HPV) affords a tremendous opportunity to control and possibly eradicate the cancer with the highest incidence among female populations in Africa. Currently, HPV vaccines are recommended for use among sexually unexperienced women, typically young girls aged 14 years or younger, leaving a huge female population unprotected and at risk of developing cervical cancer and other HPV related diseases (genital warts, other genital & oropharyngeal cancers), for which few affordable and implementable screening options are available in resource-poor settings. The HPV vaccines afford high protection against the types they target, with some element of cross-protection against other genotypes, but it is assumed that no protection is offered if subjects have been infected by a vaccine type.HIV+ women are at increased risk of acquisition and persistence of HPV leading on to the development of cervical cancer and other genital disease. We have conducted a study (called HARP) evaluating the performance of cervical cancer screening strategies among 1200 HIV+ women in South Africa (SA) and Burkina Faso (BF), which included HPV screening. We have found a huge burden of cervical precancer lesions (20% in SA, 5% on BF) and of high-risk HPV infection (>70% in SA, 55% in BF). We have recorded a good performance of HPV testing alone or in combination with cytology to detect these lesions. We would like to build upon this rich data source and the successful implementation of this study through the development of a clinical trial platform to develop the next phase of HARP, which will centre on the role of HPV control through screening and vaccination. We propose to develop a proposal for a randomised trial of HPV vaccination among HIV+ women to prevent cervical cancer lesions. There is currently no data on the efficacy of an HPV vaccine among HIV+ women, although a few trials have shown the safety and immunogenicity of the bivalent HPV vaccine in HIV+ populations, including one trial among SA women. The recent announcement by the SA government of the introduction of HPV vaccination countrywide offers the opportunity to explore the role of HPV vaccination in various sub groups.The proposed study, in preparation of the vaccine trial, will assess the potential effectiveness and cost-effectiveness of HPV vaccination embedded in an HPV screening programme in reducing the incidence of HPV-related infection and disease (CIN, ano-genital warts) in the target populations. It will investigate the response to vaccination depending on HIV related factors (plasma viral load/CD4 count/antiretroviral therapy status) and HPV related factors (current infection as determined by presence of HPV in the genital tract, or prior exposure as determined by HPV serology) on various trial outcomes (histological, cytological and virological). Finally, it will investigate the potential acceptability of such trial.Specifically, the PHINDS proposal will inform the development of an HPV vaccine study among HIV+ women in SA by:1) Estimating the potential impact and sample size required for a vaccination study among HIV+ women recruited within a cervical cancer screening programme based on HPV testing (HARP study). Statistical & modelling methodology will be employed, using HARP & another Johannesburg based study datasets.2) Evaluating the true exposure of the study population to HPV vaccine types by combining results of HPV genotyping (already done) & type-specific HPV serology (to be done).3) Evaluating the feasibility, acceptability & costs of HPV vaccination in the target population, service providers & other national stakeholders.4) Setting up a research network to implement the study through the recently awarded NIH Clinical Trials Unit at University of Witwatersrand, Johannesburg

针对高危致癌人乳头瘤病毒（HPV）的二价、四价和九价疫苗的开发和推出为控制并可能根除非洲女性人群中发病率最高的癌症提供了巨大的机会。目前，HPV疫苗被推荐用于没有性经验的女性，通常是14岁或以下的年轻女孩，使大量女性人口得不到保护，并有患宫颈癌和其他HPV相关疾病（生殖器疣，其他生殖器和口咽癌）的风险，在资源贫乏的环境中，几乎没有负担得起和可实施的筛查选择。HPV疫苗对它们所针对的类型提供高度保护，对其他基因型具有一定的交叉保护作用，但假设如果受试者已被疫苗类型感染，则不提供保护。HIV阳性妇女获得HPV的风险增加，并持续存在，导致宫颈癌和其他生殖器疾病的发展。我们进行了一项研究（称为HARP），评估了在南非（SA）和布基纳法索（BF）的1200名HIV阳性妇女中进行宫颈癌筛查策略的性能，其中包括HPV筛查。我们已经发现宫颈癌前病变（SA中20%，BF中5%）和高危HPV感染（SA中>70%，BF中55%）的巨大负担。我们已经记录了一个良好的性能HPV检测单独或结合细胞学检测这些病变。我们希望通过开发临床试验平台来建立这一丰富的数据源和本研究的成功实施，以开发HARP的下一阶段，该阶段将集中在通过筛查和疫苗接种控制HPV的作用上。我们建议在HIV阳性妇女中开展HPV疫苗接种预防宫颈癌病变的随机试验。目前还没有关于HPV疫苗在HIV+女性中的有效性的数据，尽管一些试验已经显示了二价HPV疫苗在HIV+人群中的安全性和免疫原性，其中包括一项在SA女性中进行的试验。南非政府最近宣布在全国推行人类乳头瘤病毒疫苗注射，这正好让我们有机会探讨人类乳头瘤病毒疫苗注射在不同组别的作用。这项拟议研究为疫苗试验作准备，将评估在人类乳头瘤病毒筛检计划中加入人类乳头瘤病毒疫苗注射，在减低人类乳头瘤病毒相关感染和疾病的发病率方面的潜在成效和成本效益（CIN，肛门生殖器疣）在目标人群中。它将根据HIV相关因素（血浆病毒载量/CD 4计数/抗逆转录病毒治疗状态）和HPV相关因素（通过生殖道中HPV的存在确定的当前感染，或通过HPV血清学确定的既往暴露）对各种试验结局（组织学、细胞学和病毒学）进行疫苗接种反应研究。最后，它将调查这种试验的潜在可接受性。具体来说，PHINDS提案将通过以下方式为在SA的HIV+妇女中开展HPV疫苗研究提供信息：1）估计在基于HPV检测的宫颈癌筛查计划中招募的HIV+妇女中进行疫苗接种研究的潜在影响和所需样本量（HARP研究）。将采用统计和建模方法，使用HARP和另一个约翰内斯堡的研究样本。2）通过结合HPV基因分型结果，评估研究人群对HPV疫苗类型的真实暴露（已完成）和类型特异性HPV血清学（待完成）。3）评估HPV疫苗接种在目标人群中的可行性、可接受性和成本，4）通过最近授予约翰内斯堡威特沃特斯兰德大学的NIH临床试验部门，建立一个研究网络，

项目成果

Report on In Depth Interviews with HIV+ Women Seeking Care for Pre-Cancerous Lesions of the Cervix

关于对寻求宫颈癌前病变护理的艾滋病毒妇女的深入访谈报告

• 发表时间: 2016
• 作者: Stadler J

Evidence of synergistic relationships between HIV and Human Papillomavirus (HPV): systematic reviews and meta-analyses of longitudinal studies of HPV acquisition and clearance by HIV status, and of HIV acquisition by HPV status.

• DOI: 10.1002/jia2.25110
• 发表时间: 2018-06
• 期刊: Journal of the International AIDS Society
• 影响因子: 6
• 作者: Looker KJ;Rönn MM;Brock PM;Brisson M;Drolet M;Mayaud P;Boily MC
• 通讯作者: Boily MC

Associations of Human Papillomavirus (HPV) genotypes with high-grade cervical neoplasia (CIN2+) in a cohort of women living with HIV in Burkina Faso and South Africa.

• DOI: 10.1371/journal.pone.0174117
• 发表时间: 2017
• 期刊: PloS one
• 影响因子: 3.7
• 作者: Kelly HA;Ngou J;Chikandiwa A;Sawadogo B;Gilham C;Omar T;Lompo O;Doutre S;Meda N;Weiss HA;Delany-Moretlwe S;Segondy M;Mayaud P;HARP Study Group
• 通讯作者: HARP Study Group

Concomitant Infection of HIV and HPV: What Are the Consequences?

HIV 和 HPV 同时感染：会产生什么后果？

• DOI: 10.1007/s13669-015-0132-0
• 发表时间: 2015
• 期刊: Current Obstetrics and Gynecology Reports
• 影响因子: 0.5
• 作者: Kelly H

Prevalence, incidence and correlates of low risk HPV infection and anogenital warts in a cohort of women living with HIV in Burkina Faso and South Africa.

• DOI: 10.1371/journal.pone.0196018
• 发表时间: 2018
• 期刊: PloS one
• 影响因子: 3.7
• 作者: Chikandiwa A;Kelly H;Sawadogo B;Ngou J;Pisa PT;Gibson L;Didelot MN;Meda N;Weiss HA;Segondy M;Mayaud P;Delany-Moretlwe S;HARP Study Group
• 通讯作者: HARP Study Group