PHASE II CLINICAL STUDIES OF CHEMOPREVENTION AGENTS - WORKSTATEMENT 80: AN EX

这个子项目是许多研究子项目中利用 资源由NIH/NCRR资助的中心拨款提供。子项目和 调查员(PI)可能从NIH的另一个来源获得了主要资金， 并因此可以在其他清晰的条目中表示。列出的机构是 该中心不一定是调查人员的机构。 这项工作的总体目标是确定免疫疗法是否可以解决表现为轻度(宫颈)异型性的女性持续的生殖器致癌HPV感染。为此，该项目的短期目标是在使用巴氏试验证明存在低度细胞异型性的妇女中测试针对生产性HPV-16型(HPV-16)感染的治疗性疫苗的比较效果。在这项研究中，感兴趣的暴露是HPV-16E7/HSP65的三剂疗程 疫苗(Stressgen BioTechnologies生产的HspE7)，将具有免疫和病理意义的抗原(E7)与热休克蛋白(一种刺激巨噬细胞和促进细胞免疫反应的佐剂)结合在一起。令人感兴趣的结果是病毒从宫颈阴道区清除。 这是一项随机的安慰剂对照试验，在研究期间，受试者和研究人员对治疗分配都是盲目的。简而言之，140名18至50岁的女性，假设保留率为91%(即5%的随访失败率，4%的失访率)，在巴氏试验中发现低度鳞状上皮内病变(LSIL)或不典型鳞状细胞(ASCUS)，HPV-16检测呈阳性，前一年未发现高度SIL，并符合其他资格标准，将随机接受三剂疫苗或安慰剂接种，每隔一个月接种一次。妇女将在第一次接种疫苗后20周和32周接受HPV-16检测。

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. The overall goal of this work is to determine whether an immunotherapy can resolve persistent genital oncogenic HPV infection in women who evidence mild (cervical) atypias. To this end, the short term goal of this project is to test the comparative efficacy of a therapeutic vaccine for productive HPV Type-16 (HPV-16) infection among women who evidence low-grade cellular atypias using Pap test. For this study, the exposure of interest is a three-dose course of HPV-16 E7/HSP65 vaccine (HspE7 made by Stressgen Biotechnologies), that couples together antigens that are immunologically and pathologically meaningful (E7) with heat shock protein, an adjuvant that stimulates macrophages and promotes cellular immune responses. The outcome of interest is viral clearance from the cervicovaginal area. This is a randomized, placebo-controlled trial where both subjects and the investigators will be blinded to treatment assignment for the duration of the study. Briefly, 140 women, assuming a 91% retention rate (i.e. 5% loss-to-follow-up, 4% loss-to-protocol-violation) who are 18 to 50 years old, who evidence low grade squamous intraepithelial lesions (LSIL) or atypical squamous cells of unknown significance (ASCUS) on Pap test, who test positive for HPV-16, who have not evidenced high grade SIL in the prior year and who meet other eligibility criteria will be randomized to receive vaccine or placebo in three doses, spaced one month apart. Women will be tested for the presence of HPV-16 at 20 and 32 weeks following their first vaccine dose.