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

针对马拉维感染艾滋病毒的妇女开展的新型宫颈癌筛查和治疗示范项目，包括 HPV 自检和热凝

• 批准号: 10020969
• 负责人: Lameck Chinula
• 金额: $ 13.7万
• 依托单位: UNIV OF NORTH CAROLINA CHAPEL HILL
• 依托单位国家: 美国
• 财政年份: 2019
• 资助国家: 美国
• 起止时间: 2019-09-19 至 2022-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10020969
• 关键词: Ablation; Acetic Acids; Address; Adopted; Adult; Africa South of the Sahara; African; Aftercare; Age; Algorithms; Biological Assay; Biopsy; Capital; Cervical; Cervical Cancer Screening; Cervical dysplasia; Cervix Uteri; Cities; Clinic; Clinical Trials Cooperative Group; Cold Therapy; Colposcopy; Country; Data; Detection; Diagnosis; Disease; Electrocoagulation; Enrollment; Epidemic; Female; Female Adolescents; Future; Gases; HIV; HIV Seropositivity; HPV-High Risk; Health Personnel; High Prevalence; Hour; Human Papilloma Virus Vaccination; Human Papilloma Virus Vaccine; Human Papillomavirus; Incidence; Lesion; Malawi; Malignant Neoplasms; Malignant neoplasm of cervix uteri; Oncogenic; Oncology; Pelvic Examination; Performance; Policies; Prevalence; Prevention approach; Prevention strategy; Provider; Resources; Risk; Sampling; Sensitivity and Specificity; Swab; Test Result; Testing; Triage; Vaccination; Vagina; Visual; Woman; World Health Organization; antiretroviral therapy; base; cancer risk; cervical biopsy; cervical cancer prevention; cost; effectiveness evaluation; follow-up; high risk; improved; innovation; intraepithelial; low and middle-income countries; mortality; new technology; novel; overtreatment; premalignant; prevent; screening; screening guidelines

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.

摘要 侵袭性宫颈癌（ICC）每年导致270，000名妇女死亡，每年诊断出445，000例新病例。ICC 可通过接种人乳头瘤病毒（HPV）疫苗、宫颈筛查和宫颈癌治疗来预防。 发育不良然而，84%的新ICC案件发生在马拉维等中低收入国家， 这是因为很难获得所有三种预防战略。这一挑战在撒哈拉以南非洲地区更为严峻 (SSA)艾滋病毒流行病的中心，因为感染艾滋病毒的妇女患上艾滋病的风险增加， 子宫颈发育不良的妇女患ICC的风险比未感染HIV的妇女高20倍以上。在撒南非洲，妇女 包括59%的成年艾滋病毒感染者，ICC是妇女中最常见的癌症。世界卫生 世卫组织（WHO）建议使用高危（hr）-HPV检测/醋酸目视检查进行筛查 (VIA)冷冻治疗是预防LMIC ICC的首选方法。马拉维试图 自2004年以来，美国一直在实施VIA和冷冻疗法，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， 大多数马拉维妇女将仍然没有接种疫苗或年龄不合格，因为，类似于其他资源有限的国家， 在撒哈拉以南非洲国家，只有青春期少女才有资格接种。 实现，因此ICC发病率的下降预计在几十年内不会出现，数百万非洲妇女 都会被怀念因此，迫切需要改进和可扩展的ICC预防方法。我们计划 在马拉维的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，然后在同一天进行VIA和宫颈 对于VIA阳性且符合消融条件的患者进行热凝。这一战略尚未得到有力实施。 评估，利用专门为低资源环境开发的新技术（快速Xpert HPV检测， 热凝固），并且可以在一天内完成。这些属性可能会解决覆盖范围 以及限制当前方法的损耗问题。具体来说，Aim 1将评估当天 在马拉维的625名艾滋病毒感染妇女中完成了这项新的ICC筛查和治疗战略， 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将评估性能 艾滋病毒感染妇女中拟议的筛查和治疗战略， hr-HPV阳性/VIA阳性的妇女以及 hr-HPV阳性/VIA阴性。目的3将确定热凝在HIV-1感染者中的24周疗效。 高度宫颈不典型增生（CIN 2/3）的感染妇女。这项研究将提供必要的数据， 马拉维和其他艾滋病毒和ICC流行率高的国家的国家政策， 促进宫颈癌和全球肿瘤学未来合作临床试验小组的申请。