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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 - 04/01/12

Doi : 10.1016/S1470-2045(11)70286-8 
Matti Lehtinen, ProfPhD a, ⁎ , Jorma Paavonen, ProfMD b, Cosette M Wheeler, ProfPhD c, Unnop Jaisamrarn, ProfMD d, Suzanne M Garland, ProfFRCPA e, Xavier Castellsagué, PhD f, S Rachel Skinner, PhD g, Dan Apter, MD h, Paulo Naud, ProfPhD i, Jorge Salmerón, ProfPhD j, Song-Nan Chow, ProfMD k, Henry Kitchener, ProfMD l, Júlio C Teixeira, MD m, James Hedrick, MD n, Genara Limson, ProfMD o, Anne Szarewski, PhD p, Barbara Romanowski, ProfMD q, Fred Y Aoki, ProfMD r, Tino F Schwarz, ProfMD s, Willy A J Poppe, ProfPhD t, Newton S De Carvalho, ProfPhD u, Maria Julieta V Germar, MD v, Klaus Peters, MD w, Adrian Mindel, ProfMD x, Philippe De Sutter, MD y, F Xavier Bosch, PhD f, Marie-Pierre David, MSc z, Dominique Descamps, MD z, Frank Struyf, MD z, Gary Dubin, MD aa

for the HPV PATRICIA Study Group‡

  For the HPV PATRICIA Study Group see Supplementary Material

a University of Tampere, School of Public Health, Tampere, Finland 
b Department of Obstetrics and Gynaecology, University of Helsinki, Helsinki, Finland 
c Departments of Pathology and Obstetrics and Gynecology, University of New Mexico Health Sciences Center, Albuquerque, NM, USA 
d Department of Obstetrics and Gynaecology, Faculty of Medicine, Chulalongkorn University, Bangkok, Thailand 
e Department of Microbiology and Infectious Diseases, Royal Women’s Hospital, Department of Microbiology, Royal Children’s Hospital, Murdoch Children’s Research Institute, and Department of Obstetrics and Gynaecology, University of Melbourne, Parkville, VIC, Australia 
f Unit of Infections and Cancer, Cancer Epidemiology Research Program, Institut Català d’Oncologia, L’Hospitalet de Llobregat, IDIBELL, CIBER-ESP, Catalonia, Spain 
g Vaccines Trials Group, Telethon Institute for Child Health Research, Perth, WA and Sydney University Discipline of Paediatrics and Child Health, Children’s Hospital Westmead, Sydney, NSW, Australia 
h Family Federation of Finland, Sexual Health Clinic, Helsinki, Finland 
i Department of Gynecology & Obstetrics, Federal University of Rio Grande do Sul, UFRGS/HCPA, Hospital de Clínicas de Porto Alegre, Brazil 
j Unidad de Investigación Epidemiológica y en Servicios de Salud, Instituto Mexicano del Seguro Social, Morelos, Mexico 
k Department of Obstetrics and Gynecology, College of Medicine and the Hospital, National Taiwan University, Taipei, Taiwan 
l Manchester Academic Health Science Centre, Central Manchester University Hospitals NHS Foundation Trust, St Mary’s Hospital, Manchester, UK 
m Departamento de Tocoginecologia da Unicamp, University of Campinas, Campinas, Sao Paulo, Brazil 
n Kentucky Pediatric and Adult Research, Bardstown, KY, USA 
o College of Medicine, University of the Philippines, Philippine General Hospital, Makati Medical Centre, Makati City, Philippines 
p Centre for Cancer Prevention, Wolfson Institute of Preventive Medicine, Queen Mary University of London, London, UK 
q Division of Infectious Diseases, Department of Medicine, Faculty of Medicine and Dentistry, University of Alberta, Edmonton, AB, Canada 
r Department of Medical Microbiology, University of Manitoba, Winnipeg, MB, Canada 
s Central Laboratory and Vaccination Centre, Stiftung Juliusspital, Academic Teaching Hospital of the University of Wuerzburg, Wuerzburg, Germany 
t Department of Gynaecology, University Hospital KU Leuven Gasthuisberg, Leuven, Belgium 
u Department of Gynecology and Obstetrics, Federal University of Paraná, Infectious Diseases in Gynecology and Obstetrics Sector, Curitiba, Parana, Brazil 
v University of the Philippines College of Medicine, Philippine General Hospital, Manila, Philippines 
w Facharzt für Frauenheilkunde und Geburtshilfe, Berner Heerweg 157, Hamburg Germany 
x Sexually Transmitted Infections Research Centre, University of Sydney, Westmead Hospital, NSW, Australia 
y Department of Gynaecology, University Hospital Brussels, Brussels, Belgium 
z GlaxoSmithKline Biologicals, Wavre, Belgium 
aa GlaxoSmithKline Biologicals, King of Prussia, PA, USA 

* Correspondence to: Prof Matti Lehtinen, University of Tampere, School of Public Health, Tampere, Finland

Summary

Background

Cervical intraepithelial neoplasia grade 2 or greater (CIN2+) is the surrogate endpoint used in licensure trials of human papillomavirus (HPV) vaccines. Vaccine efficacy against CIN3+, the immediate precursor to invasive cervical cancer, is more difficult to measure because of its lower incidence, but provides the most stringent evidence of potential cancer prevention. We report vaccine efficacy against CIN3+ and adenocarcinoma in situ (AIS) in the end-of-study analysis of PATRICIA (PApilloma TRIal against Cancer In young Adults).

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

GlaxoSmithKline Biologicals.

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Vol 13 - N° 1

P. 89-99 - janvier 2012 Retour au numéro
Article précédent Article précédent
  • Human papillomavirus testing for the detection of high-grade cervical intraepithelial neoplasia and cancer: final results of the POBASCAM randomised controlled trial
  • Dorien C Rijkaart, Johannes Berkhof, Lawrence Rozendaal, Folkert J van Kemenade, Nicole WJ Bulkmans, Daniëlle AM Heideman, Gemma G Kenter, Jack Cuzick, Peter JF Snijders, Chris JLM Meijer
| Article suivant Article suivant
  • Cross-protective efficacy of HPV-16/18 AS04-adjuvanted vaccine against cervical infection and precancer caused by non-vaccine oncogenic HPV types: 4-year end-of-study analysis of the randomised, double-blind PATRICIA trial
  • Cosette M Wheeler, Xavier Castellsagué, Suzanne M Garland, Anne Szarewski, Jorma Paavonen, Paulo Naud, Jorge Salmerón, Song-Nan Chow, Dan Apter, Henry Kitchener, Júlio C Teixeira, S Rachel Skinner, Unnop Jaisamrarn, Genara Limson, Barbara Romanowski, Fred Y Aoki, Tino F Schwarz, Willy A J Poppe, F Xavier Bosch, Diane M Harper, Warner Huh, Karin Hardt, Toufik Zahaf, Dominique Descamps, Frank Struyf, Gary Dubin, Matti Lehtinen, for the HPV PATRICIA Study Group ‡

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