Vaccination against HPV-16 Oncoproteins for Vulvar Intraepithelial Neoplasia.
Vaccination against HPV-16 Oncoproteins for Vulvar Intraepithelial Neoplasia.
复制标题
DOI：
10.1056/nejmoa0810097
复制
发表时间：
2009-11-05
影响因子：
158.5
通讯作者：
Melief, Cornelis J. M.
中科院分区：
文献类型：
--
作者：
Kenter, Gemma G.;Welters, Marij J. P.;Melief, Cornelis J. M.
背景资料：外阴上皮内瘤变是一种由高危型人乳头瘤病毒（HPV）引起的慢性疾病，最常见的是HPV 16型（HPV-16）。自发消退发生在不到1.5%的患者，治疗后复发率高。方法：我们调查了合成的长肽疫苗的免疫原性和有效性的妇女与HPV-16阳性，高级别外阴上皮内瘤变。20名HPV-16阳性、3级外阴上皮内瘤变的妇女用来自HPV-16病毒癌蛋白E6和E7的长肽在不完全弗氏佐剂中的混合物接种疫苗3或4次。终点是临床和HPV-16特异性T细胞respons.Results：最常见的不良事件是局部肿胀，100%的患者和64%的患者发热，这些事件都没有超过美国国家癌症研究所不良事件通用术语标准2级。在最后一次疫苗接种后3个月，20例患者中有12例（60%; 95%置信区间[CI]，36 - 81）出现临床应答，并报告症状缓解。5名妇女的病变完全消退，其中4名不再检测到HPV-16。在12个月随访时，19例患者中有15例出现临床缓解（79%; 95% CI，54 - 94），19例患者中有9例完全缓解（47%; 95% CI，24 - 71）。在24个月的随访中，完全缓解率保持不变。所有患者都有疫苗诱导的T细胞应答，事后分析表明，与没有完全应答的患者相比，在3个月时有完全应答的患者具有显著更强的干扰素-（γ）相关增殖性CD4 + T细胞应答和CD8+干扰素-（γ）T细胞的广泛应答。HPV-16阳性、3级外阴上皮内瘤变的女性的临床反应可以通过接种针对HPV-16癌蛋白E6和E7的合成长肽疫苗来实现。完全应答似乎与HPV-16特异性免疫的诱导相关. N Engl J Med 2009; 361：1838 - 47.
Background: Vulvar intraepithelial neoplasia is a chronic disorder caused by high-risk types of human papillomavirus (HPV), most commonly HPV type 16 (HPV-16). Spontaneous regression occurs in less than 1.5% of patients, and the rate of recurrence after treatment is high.Methods: We investigated the immunogenicity and efficacy of a synthetic long-peptide vaccine in women with HPV-16-positive, high-grade vulvar intraepithelial neoplasia. Twenty women with HPV-16-positive, grade 3 vulvar intraepithelial neoplasia were vaccinated three or four times with a mix of long peptides from the HPV-16 viral oncoproteins E6 and E7 in incomplete Freund's adjuvant. The end points were clinical and HPV-16-specific T-cell responses.Results: The most common adverse events were local swelling in 100% of the patients and fever in 64% of the patients; none of these events exceeded grade 2 of the Common Terminology Criteria for Adverse Events of the National Cancer Institute. At 3 months after the last vaccination, 12 of 20 patients (60%; 95% confidence interval [CI], 36 to 81) had clinical responses and reported relief of symptoms. Five women had complete regression of the lesions, and HPV-16 was no longer detectable in four of them. At 12 months of follow-up, 15 of 19 patients had clinical responses (79%; 95% CI, 54 to 94), with a complete response in 9 of 19 patients (47%; 95% CI, 24 to 71). The complete-response rate was maintained at 24 months of follow-up. All patients had vaccine-induced T-cell responses, and post hoc analyses suggested that patients with a complete response at 3 months had a significantly stronger interferon-(gamma)-associated proliferative CD4+ T-cell response and a broad response of CD8+ interferon-(gamma) T cells than did patients without a complete response.Conclusions: Clinical responses in women with HPV-16-positive, grade 3 vulvar intraepithelial neoplasia can be achieved by vaccination with a synthetic long-peptide vaccine against the HPV-16 oncoproteins E6 and E7. Complete responses appear to be correlated with induction of HPV-16-specific immunity.N Engl J Med 2009;361:1838-47.