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Previous Volume 361:1838-1847 November 5, 2009 Number 19 Next

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ABSTRACT

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.

Source Information

From the Departments of Gynecology (G.G.K., M.J.G.L., D.M.A.B.M.), Immunohematology and Blood Transfusion (M.J.P.W., A.P.G.V., F.E., R.O., J.W.D., C.J.M.M.), Clinical Pharmacy and Toxicology (A.R.P.M.V., L.M.F., A.R.W., J.O.), Pathology (G.J.F.), and Clinical Oncology (S.H.B.), Leiden University Medical Center, Leiden; and ISA Pharmaceuticals, Bilthoven (C.J.M.M., F.E.) — both in the Netherlands.

Drs. Kenter and Welters contributed equally to this article.

Address reprint requests to Dr. Kenter at the Department of Gynecology, Leiden University Medical Center, Mailbox 9600, 2300 RC Leiden, the Netherlands, or at g.g.kenter{at}lumc.nl.

Full Text of this Article

This article has been cited by other articles:

• Finn, O. J., Edwards, R. P. (2009). Human Papillomavirus Vaccine for Cancer Prevention. NEJM 361: 1899-1901 [Full Text]  
• (2009). Therapeutic HPV Vaccination for Preventing Progression of Vulvar Intraepithelial Neoplasia. JWatch Women's Health 2009: 1-1 [Full Text]