Overall efficacy of HPV-16/18 AS04-adjuvanted vaccine against grade 3 or greater cervical intraepithelial neoplasia: 4-year end-of-study analysis of the randomised, double-blind PATRICIA trial.
Abstract | BACKGROUND: METHODS: Healthy women aged 15-25 years with no more than six lifetime sexual partners were included in PATRICIA, irrespective of their baseline HPV DNA status, HPV-16 or HPV-18 serostatus, or cytology. Women were randomly assigned (1:1) to receive an HPV-16/18 AS04-adjuvanted vaccine or a control hepatitis A vaccine via an internet-based central randomisation system using a minimisation algorithm to account for age ranges and study sites. The patients and study investigators were masked to allocated vaccine. The primary endpoint of PATRICIA has been reported previously. In the present end-of-study analysis, we focus on CIN3+ and AIS in the populations of most clinical interest, the total vaccinated cohort (TVC) and the TVC-naive. The TVC comprised all women who received at least one vaccine dose, approximating catch-up populations and including sexually active women ( vaccine n=9319; control=9325). The TVC-naive comprised women with no evidence of oncogenic HPV infection at baseline, approximating early adolescent HPV exposure ( vaccine n=5824; control=5820). This study is registered with ClinicalTrials.gov, number NCT00122681. FINDINGS:
Vaccine efficacy against CIN3+ associated with HPV-16/18 was 100% (95% CI 85·5-100) in the TVC-naive and 45·7% (22·9-62·2) in the TVC. Vaccine efficacy against all CIN3+ (irrespective of HPV type in the lesion and including lesions with no HPV DNA detected) was 93·2% (78·9-98·7) in the TVC-naive and 45·6% (28·8-58·7) in the TVC. In the TVC-naive, vaccine efficacy against all CIN3+ was higher than 90% in all age groups. In the TVC, vaccine efficacy against all CIN3+ and CIN3+ associated with HPV-16/18 was highest in the 15-17 year age group and progressively decreased in the 18-20 year and 21-25 year age groups. Vaccine efficacy against all AIS was 100% (31·0-100) and 76·9% (16·0-95·8) in the TVC-naive and TVC, respectively. Serious adverse events occurred in 835 (9·0%) and 829 (8·9%) women in the vaccine and control groups, respectively; only ten events (0·1%) and five events (0·1%), respectively, were considered to be related to vaccination. INTERPRETATION: PATRICIA end-of-study results show excellent vaccine efficacy against CIN3+ and AIS irrespective of HPV DNA in the lesion. Population-based vaccination that incorporates the HPV-16/18 vaccine and high coverage of early adolescents might have the potential to substantially reduce the incidence of cervical cancer. FUNDING:
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Authors | Matti Lehtinen, Jorma Paavonen, Cosette M Wheeler, Unnop Jaisamrarn, Suzanne M Garland, Xavier Castellsagué, S Rachel Skinner, Dan Apter, Paulo Naud, Jorge Salmerón, Song-Nan Chow, Henry Kitchener, Júlio C Teixeira, James Hedrick, Genara Limson, Anne Szarewski, Barbara Romanowski, Fred Y Aoki, Tino F Schwarz, Willy A J Poppe, Newton S De Carvalho, Maria Julieta V Germar, Klaus Peters, Adrian Mindel, Philippe De Sutter, F Xavier Bosch, Marie-Pierre David, Dominique Descamps, Frank Struyf, Gary Dubin, HPV PATRICIA Study Group |
Journal | The Lancet. Oncology
(Lancet Oncol)
Vol. 13
Issue 1
Pg. 89-99
(Jan 2012)
ISSN: 1474-5488 [Electronic] England |
PMID | 22075171
(Publication Type: Journal Article, Multicenter Study, Randomized Controlled Trial, Research Support, Non-U.S. Gov't)
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Copyright | Copyright © 2012 Elsevier Ltd. All rights reserved. |
Chemical References |
- ASO4 mixture
- Adjuvants, Immunologic
- DNA, Viral
- Lipid A
- Papillomavirus Vaccines
- human papillomavirus vaccine, L1 type 16, 18
- Aluminum Hydroxide
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Topics |
- Adenocarcinoma
(diagnosis, pathology, prevention & control, virology)
- Adjuvants, Immunologic
(administration & dosage)
- Adolescent
- Adult
- Age Factors
- Aluminum Hydroxide
(administration & dosage)
- Asia
- Australia
- DNA, Viral
(analysis)
- Double-Blind Method
- Europe
- Female
- Human papillomavirus 16
(genetics, immunology)
- Human papillomavirus 18
(genetics, immunology)
- Humans
- Lipid A
(administration & dosage, analogs & derivatives)
- Neoplasm Grading
- North America
- Papillomavirus Infections
(diagnosis, prevention & control, virology)
- Papillomavirus Vaccines
(administration & dosage)
- South America
- Time Factors
- Treatment Outcome
- Uterine Cervical Neoplasms
(diagnosis, pathology, prevention & control, virology)
- Young Adult
- Uterine Cervical Dysplasia
(diagnosis, pathology, prevention & control, virology)
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