A novel cervical cancer screen-and-treat demonstration project with HPV self-testing and thermocoagulation for HIV-infected women in Malawi

摘要 浸润性宫颈癌(ICC)每年导致27万名妇女死亡，每年新增诊断病例44.5万例。国际商会 可通过接种人乳头瘤病毒(HPV)疫苗、宫颈筛查和治疗宫颈 发育不良。然而，84%的新国际刑事法院病例发生在低收入和中等收入国家，如马拉维、 由于很难获得所有三项预防战略。这一挑战在撒哈拉以南非洲地区更加严重。 (SSA)，艾滋病毒流行的震中，因为感染艾滋病毒的妇女患艾滋病毒的风险增加 宫颈发育不良，患ICC的风险是未感染HIV的女性的20倍。在SSA，女性 占感染艾滋病毒的成年人的59%，ICC是女性中最常见的癌症。《世界卫生》 世界卫生组织(WHO)建议采用高危(Hr)筛查--HPV检测/冰醋酸目视检查 (VIA)和冷冻治疗是预防LMICs ICC的首选方法。马拉维曾试图 自2004年开始实施VIA和冷冻治疗，但筛查和治疗率仍然很低。 此外，马拉维还没有HPV疫苗，即使在2019年推出，也会有大量的 此后，大多数马拉维妇女将继续未接种疫苗或年龄不合格，这与其他资源有限的妇女类似 在SSA国家，只有青春期女孩才有资格获得它。即使对青春期女孩广泛接种疫苗 尽管如此，国际刑事法院发病率的下降预计在几十年内都不会出现，数以百万计的非洲妇女 会被怀念的。因此，迫切需要一种改进的、可扩展的ICC预防方法。我们计划 在马拉维艾滋病毒感染妇女中评估一种新的ICC筛查和治疗算法 策略：自行采集阴道拭子进行HR-HPV检测，然后在当天通过和宫颈拭子进行检测 热凝适用于VIA阳性和符合消融条件的患者。这一战略还没有得到有力的支持。 评估，利用专门为低资源环境开发的新技术(Xpert HPV快速检测， 热凝)，可在一天内完成。这些属性可能会处理Coverage 以及限制了当前方法的自然减员问题。具体地说，目标1将评估当天 在马拉维625名感染艾滋病毒的妇女中完成了这项新的ICC筛查和治疗策略，登记人数超过 在首都利隆圭的抗逆转录病毒治疗诊所工作了12个月。目标2将对性能进行评估 在感染艾滋病毒的妇女中实施拟议的筛查和治疗战略，方法是估计 HR-HPV阳性/VIA阳性的妇女和艾滋病毒感染妇女中未得到充分治疗的比率 HR-HPV阳性/VIA阴性。AIM 3将确定热凝治疗HIV感染者的24周疗效 感染的高度宫颈发育不良妇女(CIN2/3)。这项研究将提供必要的数据以供 马拉维和其他艾滋病毒和国际刑事法院感染率高的国家的国家政策，它还将 促进未来宫颈癌和全球肿瘤学合作临床试验小组的申请。

ABSTRACT Invasive cervical cancer (ICC) kills 270,000 women/year, and 445,000 new cases are diagnosed annually. ICC is preventable with human papillomavirus (HPV) vaccination, cervical screening, and treatment of cervical dysplasia. However, 84% of new ICC cases occur in low-and-middle income countries (LMICs) such as Malawi, due to poor access to all three prevention strategies. This challenge is compounded in Sub-Saharan Africa (SSA), the epicenter of the HIV epidemic, because HIV-infected women are at increased risk for developing cervical dysplasia and have a >20-fold increased risk for ICC than HIV-uninfected women. In SSA, women comprise 59% of adults infected with HIV, and ICC is the most common cancer among women. The World Health Organization (WHO) recommends screening with high-risk (hr)-HPV testing/visual inspection with acetic acid (VIA) and treatment with cryotherapy as the preferred approach to prevent ICC in LMICs. Malawi has attempted to implement VIA and cryotherapy since 2004, but both screening and treatment rates remain abysmal. Furthermore, the HPV vaccine is not yet available in Malawi, and even when it does roll out in 2019, the vast majority of Malawian women will remain unvaccinated or age ineligible since, similar to other resource-limited SSA countries, only adolescent girls will be eligible for it. Even if widespread vaccination of adolescent girls is achieved, the consequent decline in ICC incidence is not anticipated for decades, and millions of African women will be missed. Therefore, an improved and scalable ICC prevention approach is urgently needed. We plan to evaluate a novel ICC screen-and-treat algorithm among HIV-infected women in Malawi with the following strategy: self-collected vaginal swabs for hr-HPV testing, followed by same-day VIA and cervical thermocoagulation for those who are VIA positive and eligible for ablation. This strategy has not yet been robustly evaluated, utilizes new technologies developed specifically for low-resource settings (rapid Xpert HPV testing, thermocoagulation), and can be completed in a single day. These attributes are likely to address the coverage and attrition problems that have limited current approaches. Specifically, Aim 1 will assess same-day completion of this novel ICC screen-and-treat strategy among 625 HIV-infected women in Malawi, enrolled over 12 months from antiretroviral therapy clinics in the capital city of Lilongwe. Aim 2 will evaluate the performance of the proposed screen-and-treat strategy among HIV-infected women, by estimating the overtreatment rate for women who are hr-HPV positive/VIA positive and the undertreatment rate among HIV-infected women who are hr-HPV positive/VIA negative. Aim 3 will determine the 24-week efficacy of thermocoagulation among HIV- infected women with high-grade cervical dysplasia (CIN2/3). This study will provide essential data to inform national policy in Malawi and other countries where both HIV and ICC prevalence are high, and it will also facilitate applications for future cooperative clinical trials groups in cervical cancer and global oncology.