Vaccination against HPV-16 Oncoproteins for Vulvar Intraepithelial Neoplasia  

Oleh:

Kenter, Gemma G. ; Welters, Marij J.P. ; Valentijn, A. Rob P.M. ; Lowik, Margriet J.G. ; Meer, Dorien M.A. Berends-van der

Jenis: Article from Journal - ilmiah internasional
Dalam koleksi: The New England Journal of Medicine (keterangan: ada di Proquest) vol. 361 no. 19 (Nov. 2009), page 1838-1847.
Topik: Vaccination; HPV-16; Oncoproteins; Vulvar Intraepithelial Neoplasia

Ketersediaan

Perpustakaan FK Nomor Panggil: N08.K.2009.06 Non-tandon: 1 (dapat dipinjam: 0) Tandon: tidak ada

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Isi artikel

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-?–associated proliferative CD4+ T-cell response and a broad response of CD8+ interferon-? 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.

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