Project 2-Understanding CIN2+ among HIV infected women after LEEP: An epidemiological and immunohistochemical study

项目 2 - 了解 LEEP 后 HIV 感染女性中的 CIN2：流行病学和免疫组织化学研究

• 批准号: 10477369
• 负责人: SUSAN CU-UVIN
• 金额: $ 12.56万
• 依托单位: INDIANA UNIV-PURDUE UNIV AT INDIANAPOLIS
• 依托单位国家: 美国
• 财政年份: 2020
• 资助国家: 美国
• 起止时间: 2020-09-07 至 2025-08-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10477369
• 关键词: AIDS/HIV problem; Acetic Acids; Address; Adopted; Africa; Age-Years; Appearance; Back; Biopsy; Cancer Etiology; Cervical; Cervical Intraepithelial Neoplasia; Cervix Uteri; Cessation of life; Characteristics; Cold Therapy; Colposcopy; Country; Development; Diagnosis; Disease; Enrollment; Epidemiology; Excision; General Population; HIV; HIV Seropositivity; HPV-High Risk; High Prevalence; Histocompatibility Testing; Human Papillomavirus; Human papilloma virus infection; Human papillomavirus 16; Immune; Incidence; Intercellular Junctions; International Agency for Research on Cancer; Kenya; Lesion; Malignant Neoplasms; Malignant neoplasm of cervix uteri; Natural History; Recommendation; Recurrence; Resources; Risk; Risk Factors; Science; Specimen; Tissues; Uganda; Visit; Visual; Woman; base; cancer invasiveness; healing; high risk; loop electrosurgical excision procedure; novel strategies; prevent; screening; standard of care

Abstract Current estimates indicate that every year 5,250 women (crude rate 20.5) are diagnosed with cervical cancer in Kenya and 3,286 (crude rate 12.8) die from the disease. Cervical cancer ranks as the 2nd most frequent cancer among women in Kenya and the 1st most frequent cancer among women between 15-44 years of age. About 9.1% of women in the general population are estimated to harbor human papillomavirus (HPV) 16/18 and 63.1% of invasive cervical cancers are attributed to HPV 16/18. In Uganda, cervical cancer is the number one cause of cancer related death in women. 6,413 Ugandan women (crude rate 28.8) are diagnosed with cervical cancer and 4,301(crude rate 19.3) die from the disease. About 3.6% of the general population harbor HPV 16/18 and 57% of invasive cancer is attributable to HPV 16/18. HIV-infected women have higher prevalence, incidence, and persistence of HPV infections, more so in women with severe immune compromise. HIV has been shown to increase the risk of the development, progression and recurrence of cervical intraepithelial neoplasia. Several studies have consistently shown that HIV-infected women present higher risk of CIN persistence or recurrence after standard therapy . Both Kenya and Uganda have high prevalence for HIV/AIDS at 7% and 12.9%, respectively. In settings where loop electrosurgical excision procedure (LEEP) is available, accessible and appropriate, treatment with LEEP is recommended by the WHO. However, there is a paucity of studies assessing the efficacy of LEEP among HIV-infected women and the characteristics of CIN2/3 lesions after LEEP. The core objective of this application is to understand the natural history of recurrent CIN2/3 lesions among HIV-infected women after LEEP. To help guide management based on HIV/HPV science, we propose an epidemiologic and immunohistochemical study of the cervix following LEEP to address the value of destruction of the cervical transformation zone to prevent cancer. We propose to enroll 300 HIV-infected women with CIN2/3 undergoing LEEP and follow them every 6 months for 2 years with colposcopy and biopsy when appropriate. We will do a repeat LEEP for recurrent CIN2/3 lesions. The Specific Aims for this proposed study are: 1. To assess the incidence and risk factors for “recurrent” CIN2/3 after LEEP among HIV- infected women. 2. To determine baseline HR-HPV types (in tissue) among HIV-infected women with CIN2/3 undergoing LEEP compared to the HR-HPV types with “recurrent” cervical lesions after a second LEEP. 3. To determine the immunohistochemical differences between the initial and repeat LEEP specimens among HIV-infected women with “recurrent” CIN2/3

摘要 目前的估计表明，在#年，每年有5250名妇女(粗率20.5)被诊断为宫颈癌。 肯尼亚和3286人(粗率12.8)死于该病。宫颈癌在最常见的癌症中排名第二 在肯尼亚女性中，癌症发病率位居15-44岁女性癌症发病率的首位。关于 总人口中9.1%的女性估计携带人类乳头瘤病毒(HPV)16/18和63.1% 在乌干达，宫颈癌是人类乳头瘤病毒感染的头号原因。 女性与癌症相关的死亡。6413名乌干达妇女(粗发病率28.8%)被诊断为宫颈癌 死亡4301人(粗率19.3%)。约3.6%的一般人口感染HPV16/18型及 57%的浸润性癌是由HPV16/18引起的。感染艾滋病毒的妇女有更高的患病率，发病率， 以及HPV感染的持久性，在免疫严重受损的女性中更是如此。艾滋病毒已被证实 增加宫颈上皮内瘤变发生、进展和复发的风险。几个 研究一直表明，感染艾滋病毒的妇女具有更高的CIN持久性或复发风险。 在标准治疗之后。肯尼亚和乌干达的艾滋病毒/艾滋病感染率都很高，分别为7%和12.9%， 分别进行了分析。在环状电外科切除程序(LEEP)可用的设置中，可访问和 适当时，世界卫生组织推荐使用LEEP治疗。然而，很少有研究评估 女性HIV感染者的LEEP疗效及LEEP后CIN2/3病变特点其核心是 此应用的目的是了解HIV感染者中CIN2/3复发皮损的自然病史。 LEEP之后的女人。为了帮助指导基于HIV/HPV科学的管理，我们提出了一种流行病学和 LEEP术后宫颈的免疫组织化学研究对宫颈破坏的价值 转型地带，预防癌症。我们建议招募300名患有CIN2/3的HIV感染女性 LEEP，每6个月随访一次，连续2年，适当时行阴道镜和活检。我们将做一个 对于复发的CIN2/3病变，重复LEEP。 这项拟议研究的具体目标是： 1.评估HIV感染妇女LEEP术后CIN2/3复发的发生率及危险因素。 2.确定患有CIN2/3的HIV感染妇女接受LEEP治疗的组织中HR-HPV的基线类型 与第二次LEEP后宫颈病变“复发”的HR-HPV类型相比。 3.确定首次和重复的LEEP标本之间的免疫组织化学差异 感染艾滋病毒的女性CIN2/3反复发作