Roman L D, Wilczynski S, Muderspach L I, Burnett A F, O'Meara A, Brinkman J A, Kast W M, Facio G, Felix J C, Aldana M, Weber J S
Department of Obstetrics and Gynecology, Keck School of Medicine of the University of Southern California, Los Angeles, CA 90089, USA.
Gynecol Oncol. 2007 Sep;106(3):558-66. doi: 10.1016/j.ygyno.2007.05.038. Epub 2007 Jul 12.
Approximately 2 million women worldwide are infected with high-risk human papillomaviruses (HPV), resulting in a substantial risk for the development of invasive lower genital malignancies. This study was undertaken to determine the effects of vaccination with a protein encoding a bacterial heat shock protein fused to sequences from the oncogenic E7 protein of HPV-16 in women with high-grade cervical intraepithelial neoplasia. Endpoints included lesion regression, immune response, and viral clearance.
Twenty-one women were prospectively entered into an IRB-approved Phase II study. All women had biopsy-proven high-grade cervical intraepithelial neoplasia and persistent post-biopsy lesions visible by colposcopy. Four injections of HPV-16 Hsp E7 fusion protein at a dose of 500 mug were given 3 weeks apart after which Loop Electrosurgical Excision of the Transformation Zone (LLETZ) was performed. Immune parameters were evaluated pre-vaccine and at the time of LLETZ, and HPV testing was performed at intervals before and after LLETZ. Study subjects were followed for 1 year after LLETZ.
Seven of 20 women (35%) evaluable for response had complete regression of their intraepithelial neoplasia at the time of LLETZ, 1 (5%) had regression to CIN I, 11 (55%) had stable disease and 1 (5%) had progression due to enlargement of her lesion. Immune responses were seen in 9 of the 17 women tested; 5 of the 7 complete responders had an immune response. Only 5 of 21 women had HPV-16 or -18. HPV clearance was not associated with lesion regression.
Hsp-7 (SGN-00101), at this dose and schedule induced lesion regression in women with high-grade intraepithelial neoplasia. The fact that regression was correlated with immune response suggests that enhancing the immunogenicity of this vaccine may lead to improvement in the rate of lesion eradication.
全球约200万女性感染高危型人乳头瘤病毒（HPV），这会大幅增加发生浸润性下生殖道恶性肿瘤的风险。本研究旨在确定接种一种融合了HPV-16致癌E7蛋白序列的细菌热休克蛋白编码蛋白疫苗对高级别宫颈上皮内瘤变女性的影响。观察指标包括病变消退、免疫反应和病毒清除。
21名女性前瞻性地进入一项经机构审查委员会批准的II期研究。所有女性均经活检证实为高级别宫颈上皮内瘤变，且在阴道镜检查下可见活检后持续存在的病变。每隔3周注射4次剂量为500微克的HPV-16 Hsp E7融合蛋白，之后进行转化区环形电切术（LLETZ）。在接种疫苗前和进行LLETZ时评估免疫参数，并在LLETZ前后定期进行HPV检测。LLETZ后对研究对象随访1年。
在可评估反应的20名女性中，7名（35%）在LLETZ时上皮内瘤变完全消退，1名（5%）消退至CIN I，11名（55%）病情稳定，1名（5%）因病变增大而病情进展。在接受检测的17名女性中，9名出现免疫反应；7名完全缓解者中有5名出现免疫反应。21名女性中只有5名感染HPV-16或-18。HPV清除与病变消退无关。
在此剂量和方案下，Hsp-7（SGN-00101）可使高级别上皮内瘤变女性的病变消退。消退与免疫反应相关这一事实表明，增强该疫苗的免疫原性可能会提高病变根除率。
