Phase II trial of imiquimod and HPV therapeutic vaccination in patients with vulval intraepithelial neoplasia.
Phase II trial of imiquimod and HPV therapeutic vaccination in patients with vulval intraepithelial neoplasia.
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DOI：
10.1038/sj.bjc.6605611
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发表时间：
2010-03-30
影响因子：
8.8
通讯作者：
中科院分区：
文献类型：
--
作者：
外阴上皮内瘤变（VIN）是一种恶性前病变，通常与HPV16型感染有关，多灶性疾病的手术治疗失败率很高。我们报道了一项局部免疫调节剂咪喹莫特的II期临床试验，为期8周，随后在19名VIN等级为2级和3级的女性中进行了3次（第10、14和18周）治疗性人乳头瘤病毒（HPV）疫苗接种（TA-CIN，融合蛋白HPV16 E6E7L2）。在第0、10、20和52周进行组织学和HPV活检检测。还评估了瘤内t细胞亚群浸润和淋巴细胞增殖对HPV全身免疫反应的影响。在第10周，32%（19人中的6人）的女性观察到病变反应（VIN在组织学上的完全消退），在第20周增加到58%（19人中的11人），在第52周增加到63%（19人中的12人）。此时，36%（5 / 14）的病变显示HPV16清除，79%（15 / 19）的女性无症状。第20周，在咪喹莫特治疗和疫苗接种后，病灶应答者CD8和CD4 T细胞的局部浸润显著增加；相比之下，无应答者（组织学上的持续性VIN）显示T调节细胞密度增加。接种疫苗后，只有病变应答者对HPV疫苗抗原的淋巴细胞增殖显著增加。治疗的效果取决于反应者和无反应者对局部和全身的不同免疫反应。
Vulval intraepithelial neoplasia (VIN) is a premalignant condition, which is frequently associated with type HPV16 infection, and multifocal disease has high rates of surgical treatment failure. We report a phase II clinical trial of the topical immunomodulator, imiquimod, for 8 weeks, followed by 3 doses (weeks 10, 14 and 18) of therapeutic human papillomavirus (HPV) vaccination (TA-CIN, fusion protein HPV16 E6E7L2) in 19 women with VIN grades 2 and 3. Histology and HPV testing of biopsies were performed at weeks 0, 10, 20 and 52. Intralesional infiltration of T-cell subsets and lymphocyte proliferation for HPV systemic immune responses were also assessed. Lesion response (complete regression of VIN on histology) was observed in 32% (6 out of 19) of women at week 10, increasing to 58% (11 out of 19) at week 20 and 63% (12 out of 19) at week 52. At this time, 36% (5 out of 14) of lesions showed HPV16 clearance and 79% (15 out of 19) of women were symptom free. At week 20, after treatment with imiquimod and vaccination, there was significantly increased local infiltration of CD8 and CD4 T cells in lesion responders; in contrast, non-responders (persistent VIN by histology) showed an increased density of T regulatory cells. After vaccination, only lesion responders had significantly increased lympho-proliferation to the HPV vaccine antigens. The therapeutic effect of treatment depends on the differential immune response of responders and non-responders with affect locally and systemically.
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DOI：
10.1016/j.ogc.2007.10.003
发表时间：
2007-12-01
影响因子：
3.2
作者：
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发表时间：
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