一项关于洛匹莫韦（洛匹那韦/利托那韦）治疗人乳头瘤病毒相关宫颈上皮内瘤变的单臂概念验证试验。
A Single-Arm, Proof-Of-Concept Trial of Lopimune (Lopinavir/Ritonavir) as a Treatment for HPV-Related Pre-Invasive Cervical Disease.
作者信息
Hampson Lynne, Maranga Innocent O, Masinde Millicent S, Oliver Anthony W, Batman Gavin, He Xiaotong, Desai Minaxi, Okemwa Parmenas M, Stringfellow Helen, Martin-Hirsch Pierre, Mwaniki Alex M, Gichangi Peter, Hampson Ian N
机构信息
University of Manchester Viral Oncology Laboratories, Institute of Cancer Sciences, Research Floor 5, St Mary's Hospital, Oxford Road, Manchester M13 9WL, United Kingdom.
Kenyatta National Hospital, Department of Reproductive Health, PO Box 20723-00202, Nairobi, Kenya.
出版信息
PLoS One. 2016 Jan 29;11(1):e0147917. doi: 10.1371/journal.pone.0147917. eCollection 2016.
BACKGROUND
Cervical cancer is the most common female malignancy in the developing nations and the third most common cancer in women globally. An effective, inexpensive and self-applied topical treatment would be an ideal solution for treatment of screen-detected, pre-invasive cervical disease in low resource settings.
METHODS
Between 01/03/2013 and 01/08/2013, women attending Kenyatta National Hospital's Family Planning and Gynaecology Outpatients clinics were tested for HIV, HPV (Cervista®) and liquid based cervical cytology (LBC-ThinPrep®). HIV negative women diagnosed as high-risk HPV positive with high grade squamous intraepithelial lesions (HSIL) were examined by colposcopy and given a 2 week course of 1 capsule of Lopimune (CIPLA) twice daily, to be self-applied as a vaginal pessary. Colposcopy, HPV testing and LBC were repeated at 4 and 12 weeks post-start of treatment with a final punch biopsy at 3 months for histology. Primary outcome measures were acceptability of treatment with efficacy as a secondary consideration.
RESULTS
A total of 23 women with HSIL were treated with Lopimune during which time no adverse reactions were reported. A maximum concentration of 10 ng/ml of lopinavir was detected in patient plasma 1 week after starting treatment. HPV was no longer detected in 12/23 (52.2%, 95%CI: 30.6-73.2%). Post-treatment cytology at 12 weeks on women with HSIL, showed 14/22 (63.6%, 95%CI: 40.6-82.8%) had no dysplasia and 4/22 (18.2%, 95%CI: 9.9-65.1%) were now low grade demonstrating a combined positive response in 81.8% of women of which 77.8% was confirmed by histology. These data are supported by colposcopic images, which show regression of cervical lesions.
CONCLUSIONS
These results demonstrate the potential of Lopimune as a self-applied therapy for HPV infection and related cervical lesions. Since there were no serious adverse events or detectable post-treatment morbidity, this study indicates that further trials are clearly justified to define optimal regimes and the overall benefit of this therapy.
TRIAL REGISTRATION
ISRCTN Registry 48776874.
背景
宫颈癌是发展中国家最常见的女性恶性肿瘤，在全球女性癌症中位列第三。一种有效、廉价且可自行应用的局部治疗方法，对于在资源匮乏地区治疗经筛查发现的宫颈浸润前疾病而言，将是一个理想的解决方案。
方法
在2013年3月1日至2013年8月1日期间，对前往肯雅塔国家医院计划生育和妇科门诊就诊的女性进行了艾滋病毒、人乳头瘤病毒（Cervista®）检测以及液基宫颈细胞学检查（LBC-ThinPrep®）。被诊断为高危人乳头瘤病毒阳性且伴有高级别鳞状上皮内病变（HSIL）的艾滋病毒阴性女性，接受了阴道镜检查，并给予为期2周的疗程，每天两次，每次1粒洛匹那韦（西普拉公司生产）胶囊，自行作为阴道栓剂使用。在治疗开始后的4周和12周重复进行阴道镜检查、人乳头瘤病毒检测和液基细胞学检查，并在3个月时进行最终的穿刺活检以进行组织学检查。主要结局指标是治疗的可接受性，疗效作为次要考虑因素。
结果
共有23名患有高级别鳞状上皮内病变的女性接受了洛匹那韦治疗，在此期间未报告不良反应。开始治疗1周后，在患者血浆中检测到洛匹那韦的最大浓度为10纳克/毫升。23例中有12例（52.2%，95%置信区间：30.6 - 73.2%）未再检测到人乳头瘤病毒。对患有高级别鳞状上皮内病变的女性在12周时进行的治疗后细胞学检查显示，22例中有14例（63.6%，95%置信区间：40.6 - 82.8%）无发育异常，22例中有4例（18.2%，95%置信区间：9.9 - 65.1%）现为低级别，表明81.8%的女性有联合阳性反应，其中77.8%经组织学证实。阴道镜图像支持了这些数据，显示宫颈病变消退。
结论
这些结果证明了洛匹那韦作为一种自行应用的疗法治疗人乳头瘤病毒感染及相关宫颈病变的潜力。由于没有严重不良事件或可检测到的治疗后发病率，本研究表明进一步试验显然是合理的，以确定最佳治疗方案和该疗法的总体益处。
试验注册
国际标准随机对照试验编号注册库48776874 。
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