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

摘要 目前的估计数字表明，每年有5 250名妇女（粗发病率为20.5）被诊断患有宫颈癌。 肯尼亚和3 286人（粗死亡率为12.8）死于该病。宫颈癌是第二大常见癌症 是肯尼亚妇女中最常见的癌症，在15-44岁妇女中居第一位。关于 据估计，一般人群中9.1%的女性携带人乳头瘤病毒（HPV）16/18，63.1%的女性携带HPV 16/18。 的浸润性宫颈癌归因于HPV 16/18。在乌干达，宫颈癌是宫颈癌的头号病因。 女性癌症相关死亡。6，413名乌干达妇女（粗患病率28.8）被诊断患有宫颈癌 4,301人（粗死亡率19.3）死于该病。约3.6%的普通人群携带HPV 16/18和 57%的浸润性癌症可归因于HPV 16/18。感染艾滋病毒的妇女的患病率、发病率 和HPV感染的持续性，在具有严重免疫损害的妇女中更是如此。艾滋病病毒已经被证明 以增加宫颈上皮内瘤形成的发展、进展和复发的风险。几 研究一致表明，感染HIV的妇女存在更高的CIN持续或复发风险 在标准治疗后。肯尼亚和乌干达的艾滋病毒/艾滋病流行率都很高，分别为7%和12.9%， 分别在可以使用、可接近和可接受环形电外科切除术（LEEP）的情况下 WHO推荐适当的LEEP治疗。然而，目前缺乏研究评估 LEEP治疗HIV感染妇女的疗效以及LEEP后CIN 2/3病变的特征。核心 本申请的目的是了解HIV感染者中复发性CIN 2/3病变的自然史 LEEP术后的女性。为了帮助指导基于HIV/HPV科学的管理，我们提出了一个流行病学和 LEEP术后宫颈的免疫组织化学研究，以探讨宫颈破坏的价值 防止癌症的转化带。我们计划招募300名患有CIN 2/3的HIV感染女性患者， LEEP并随访2年，每6个月进行一次阴道镜检查，适当时进行活检。扎实做 复发性CIN 2/3病变重复LEEP治疗。 本拟定研究的具体目的是： 1.评估HIV感染女性LEEP术后“复发性”CIN 2/3的发生率和风险因素。 2.在接受LEEP治疗的CIN 2/3型HIV感染女性中确定基线HR-HPV类型（组织中） 与HR-HPV型在第二次LEEP后“复发”宫颈病变相比， 3.为了确定LEEP患者初次和重复LEEP标本之间的免疫组织化学差异， 患有“复发性”CIN 2/3的HIV感染女性

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