PMID- 19890126
OWN - NLM
STAT- MEDLINE
DCOM- 20091113
LR  - 20220408
IS  - 1533-4406 (Electronic)
IS  - 0028-4793 (Linking)
VI  - 361
IP  - 19
DP  - 2009 Nov 5
TI  - Vaccination against HPV-16 oncoproteins for vulvar intraepithelial neoplasia.
PG  - 1838-47
LID - 10.1056/NEJMoa0810097 [doi]
AB  - 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.
CI  - Copyright 2009 Massachusetts Medical Society.
FAU - Kenter, Gemma G
AU  - Kenter GG
AD  - Department of Gynecology, Leiden University Medical Center, Leiden, The 
      Netherlands. g.g.kenter@lumc.nl
FAU - Welters, Marij J P
AU  - Welters MJ
FAU - Valentijn, A Rob P M
AU  - Valentijn AR
FAU - Lowik, Margriet J G
AU  - Lowik MJ
FAU - Berends-van der Meer, Dorien M A
AU  - Berends-van der Meer DM
FAU - Vloon, Annelies P G
AU  - Vloon AP
FAU - Essahsah, Farah
AU  - Essahsah F
FAU - Fathers, Lorraine M
AU  - Fathers LM
FAU - Offringa, Rienk
AU  - Offringa R
FAU - Drijfhout, Jan Wouter
AU  - Drijfhout JW
FAU - Wafelman, Amon R
AU  - Wafelman AR
FAU - Oostendorp, Jaap
AU  - Oostendorp J
FAU - Fleuren, Gert Jan
AU  - Fleuren GJ
FAU - van der Burg, Sjoerd H
AU  - van der Burg SH
FAU - Melief, Cornelis J M
AU  - Melief CJ
LA  - eng
PT  - Clinical Trial, Phase II
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - United States
TA  - N Engl J Med
JT  - The New England journal of medicine
JID - 0255562
RN  - 0 (Cancer Vaccines)
RN  - 0 (E6 protein, Human papillomavirus type 16)
RN  - 0 (Oncogene Proteins, Viral)
RN  - 0 (Papillomavirus E7 Proteins)
RN  - 0 (Papillomavirus Vaccines)
RN  - 0 (Repressor Proteins)
RN  - 0 (Vaccines, Synthetic)
RN  - 0 (oncogene protein E7, Human papillomavirus type 16)
RN  - 9007-81-2 (Freund's Adjuvant)
SB  - IM
CIN - N Engl J Med. 2009 Nov 5;361(19):1899-901. PMID: 19890134
CIN - N Engl J Med. 2010 Feb 18;362(7):655-6; author reply 656. PMID: 20164490
MH  - Adult
MH  - Cancer Vaccines/adverse effects/immunology/*therapeutic use
MH  - Carcinoma in Situ/*therapy/virology
MH  - Female
MH  - Freund's Adjuvant
MH  - *Human papillomavirus 16/immunology/isolation & purification
MH  - Humans
MH  - Middle Aged
MH  - Oncogene Proteins, Viral/immunology
MH  - Papillomavirus E7 Proteins
MH  - Papillomavirus Infections/complications/immunology/*therapy
MH  - Papillomavirus Vaccines/adverse effects/immunology/*therapeutic use
MH  - Repressor Proteins/immunology
MH  - T-Lymphocytes/*immunology
MH  - Treatment Outcome
MH  - Vaccines, Synthetic
MH  - Vulvar Neoplasms/*therapy/virology
MH  - Young Adult
EDAT- 2009/11/06 06:00
MHDA- 2009/11/17 06:00
CRDT- 2009/11/06 06:00
PHST- 2009/11/06 06:00 [entrez]
PHST- 2009/11/06 06:00 [pubmed]
PHST- 2009/11/17 06:00 [medline]
AID - 361/19/1838 [pii]
AID - 10.1056/NEJMoa0810097 [doi]
PST - ppublish
SO  - N Engl J Med. 2009 Nov 5;361(19):1838-47. doi: 10.1056/NEJMoa0810097.