Vaccination against HPV-16 oncoproteins for vulvar intraepithelial neoplasia.

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-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.

• Authors: Gemma G Kenter, Marij J P Welters, A Rob P M Valentijn, Margriet J G Lowik, Dorien M A Berends-van der Meer, Annelies P G Vloon, Farah Essahsah, Lorraine M Fathers, Rienk Offringa, Jan Wouter Drijfhout, Amon R Wafelman, Jaap Oostendorp, Gert Jan Fleuren, Sjoerd H van der Burg, Cornelis J M Melief
• Journal: The New England journal of medicine (N Engl J Med) Vol. 361 Issue 19 Pg. 1838-47 (Nov 05 2009) ISSN: 1533-4406 [Electronic] United States
• PMID: 19890126 (Publication Type: Clinical Trial, Phase II, Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright 2009 Massachusetts Medical Society.

Chemical References

• Cancer Vaccines
• E6 protein, Human papillomavirus type 16
• Oncogene Proteins, Viral
• Papillomavirus E7 Proteins
• Papillomavirus Vaccines
• Repressor Proteins
• Vaccines, Synthetic
• oncogene protein E7, Human papillomavirus type 16
• Freund's Adjuvant

Topics

• Adult
• Cancer Vaccines (adverse effects, immunology, therapeutic use)
• Carcinoma in Situ (therapy, virology)
• Female
• Freund's Adjuvant
• Human papillomavirus 16 (immunology, isolation & purification)
• Humans
• Middle Aged
• Oncogene Proteins, Viral (immunology)
• Papillomavirus E7 Proteins
• Papillomavirus Infections (complications, immunology, therapy)
• Papillomavirus Vaccines (adverse effects, immunology, therapeutic use)
• Repressor Proteins (immunology)
• T-Lymphocytes (immunology)
• Treatment Outcome
• Vaccines, Synthetic
• Vulvar Neoplasms (therapy, virology)
• Young Adult