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Research Paper

Evaluation of quadrivalent HPV 6/11/16/18 vaccine efficacy against cervical and anogenital disease in subjects with serological evidence of prior vaccine type HPV infection

Sven-Eric Olsson, Susanne K. Kjaer, Kristján Sigurdsson, Ole-Erik Iversen, Mauricio Hernandez-Avila, Cosette M. Wheeler, Gonzalo Perez, Darron R. Brown, Laura A. Koutsky, Eng Hseon Tay, Patricia García, Kevin A. Ault, Suzanne M. Garland, Sepp Leodolter, Grace W.K. Tang, Daron G. Ferris, Jorma Paavonen, Matti Lehtinen, Marc Steben, F. Xavier Bosch, Joakim Dillner, Elmar A. Joura, Slawomir Majewski, Nubia Muñoz, Evan R. Myers and Luisa L. Villa

Objective
In the quadrivalent (types 6/11/16/18) HPV vaccine (GARDASIL®/SILGARD®) clinical program, 73% of women aged 16-26 were naïve to all vaccine HPV types. In these women, prophylactic administration of the vaccine was highly effective in preventing HPV 6/11/16/18-related cervical disease. Of the remaining women, 15% of had evidence of past infection with one or more vaccine HPV types (seropositive and DNA negative) at the time of enrollment. Here we present an analysis in this group of women to determine the efficacy of the HPV 6/11/16/18 vaccine against new cervical and external anogenital disease related to the same vaccine HPV type which had previously been cleared. Vaccine tolerability in this previously infected population was also assessed.
Methods
18,174 women were enrolled into 3 clinical studies. The data presented comprise a subset of these subjects (n = 2,617) who were HPV seropositive and DNA negative at enrollment (for ≥1 vaccine type). In each study, subjects were randomized in a 1:1 ratio to receive HPV 6/11/16/18 vaccine or placebo at day 1, month 2 and month 6 (without knowledge of baseline HPV status). Procedures performed for efficacy data evaluation included detailed genital examination, Pap testing, and collection of cervicovaginal and external genital specimens. Analyses of efficacy were carried out in a population stratified by HPV serology and HPV DNA status at enrollment.
Results
Subjects were followed for an average of 40 months. Seven subjects in the placebo group developed cervical disease, and eight subjects developed external genital disease related to a vaccine HPV type they had previously encountered. No subject receiving HPV 6/11/16/18 vaccine developed disease to a vaccine HPV type to which they were seropositive and DNA negative at enrolment.
Conclusions
These results suggest that natural HPV infection-elicited antibodies may not provide complete protection over time, however the immune response to the HPV 6/11/16/18 vaccine appears to prevent reinfection or reactivation of disease with vaccine HPV types. Vaccine-related adverse experiences were higher among subjects receiving vaccine, mostly due to increased injection site adverse experiences.

Authors

Sven-Eric Olsson

Karolinska Institute at Danderyd Hospital, Stockholm, Sweden

Susanne K. Kjaer

Department of Virus, Hormones and Cancer, Institute of Cancer Epidemiology, Danish Cancer Society/Rigshospitalet, University of Copenhagen, Denmark

Kristján Sigurdsson

National Cancer Detection Clinic, Reykjavik, Iceland

Ole-Erik Iversen

Department of Clinical Medicine, University of Bergen and Department of Obstetrics and Gynecology, Haukeland University Hospital, Bergen, Norway

Mauricio Hernandez-Avila

Institute of Public Health, Cuernavaca, Morelos, Mexico

Cosette M. Wheeler

Departments of Molecular Genetics and Microbiology and Obstetrics and Gynecology, University of New Mexico, Albuquerque NM, USA

Gonzalo Perez

Universidad del Rosario, Bogotá, Colombia

Darron R. Brown

Indiana University, Dept. of Medicine, Infectious Disease Division; Indianapolis, IN USA

Laura A. Koutsky

Department of Epidemiology, University of Washington, Seattle WA, USA

Eng Hseon Tay

KK Women's & Children's Hospital, Singapore

Patricia García

Epidemiology HIV and STD Unit, Universidad Peruana Cayetano Heredia, Lima Peru

Kevin A. Ault

Department of Gynecology and Obstetrics, Emory University School of Medicine Atlanta, GA US

Suzanne M. Garland

Microbiology and Infectious Diseases Department, Royal Women's Hospital and Department of Obstetrics and Gynecology, University of Melbourne, Melbourne, Victoria, Australia

Sepp Leodolter

Department of Gynecology and Obstetrics, Medical University of Vienna, Vienna, Austria

Grace W.K. Tang

Department of Obstetrics and Gynecology, University of Hong Kong, HKSAR

Daron G. Ferris

Department of Family Medicine and Obstetrics and Gynecology, Medical College of Georgia, Augusta, GA, USA

Jorma Paavonen

Department of Obstetric and Gynecology, University Central Hospital, Helsinki, Finland

Matti Lehtinen

School of Public Health, University of Tampere, Tampere, Finland

Marc Steben

Direction Risques Biologiques, Environnementaux et Occupationnels, Institut National de Santé Publique du Québec, Montréal, Qc, Canada

F. Xavier Bosch

Institut Catala d’Oncologia, IDIBELL, Barcelona, Spain

Joakim Dillner

Dept. of Medical Microbiology, Lund University, Sweden

Elmar A. Joura

Microbiology and Infectious Diseases Department, Royal Women's Hospital and Department of Obstetrics and Gynecology, University of Melbourne, Melbourne, Victoria, Australiaslawomir

Slawomir Majewski

Department of Dermatology and Venereology, Center of Diagnostics and Treatment of Sexually Transmitted Diseases, Warsaw Medical University, Warsaw, Poland

Nubia Muñoz

National Institute of Cancer, Bogotá, Colombia

Evan R. Myers

Department of Obstetrics and Gynecology, Duke University Medical Center, Durham, NC, USA

Luisa L. Villa

Department of Virology, Ludwig Institute for Cancer Research, Sao Paulo, Brazil