Research paper
Human Vaccines 7:7, 768-775; July 2011; © 2011 Landes Bioscience
Safety and reactogenicity of a quadrivalent human papillomavirus (types 6, 11, 16, 18) L1 viral-like-particle vaccine in older adolescents and young adults Edson D. Moreira Jr.,1,* Joel M. Palefsky,2 Anna R. Giuliano,3 Stephen Goldstone,4 Carlos Aranda,5 Heiko Jessen,6 Richard J. Hillman,7 Daron Ferris,8 Francois Coutlee,9 Eftyhia Vardas,10,11 J. Brooke Marshall,12 Scott Vuocolo,12 Richard M. Haupt,12 Dalya Guris12 and Elizabeth I.O. Garner12 Associação Obras Sociais Irmã Dulce and Oswaldo Cruz Foundation; Centro de Pesquisa Gonçalo Moniz; Fundação Oswaldo Cruz; Brazilian Ministry of Health; Bahia, Brazil; Department of Medicine; University of California San Francisco; San Francisco, CA USA; 3Risk Assessment, Detection and Intervention Program; H. Lee Moffitt Cancer Center and Research Institute; Tampa, FL USA; 4Mount Sinai School of Medicine; New York, NY USA; 5University Medical Center; National Public Health Institute; Morelos, Mexico; 6 J2: Private Clinic for Infectious Diseases; Berlin, Germany; 7STI Research Centre; University of Sydney; Sydney, NSW Australia; 8Medical College of Georgia; Augusta, GA USA; 9 Centre de recherche du CHUM; Université de Montréal; Montréal, QU Canada; 10Division of Medical Virology; University of Stellenbosch; Stellenbosch, South Africa; 11 Lancet Laboratories; Johannesburg, South Africa; 12Merck & Co., Inc.; North Wales, PA USA 1
2
Key words:human papillomavirus (HPV), vaccine, safety, male, adult, adolescent
Background: Prophylactic vaccination with a quadrivalent HPV (types 6, 11, 16, 18) vaccine (qHPV) has been shown to prevent infection with HPV 6/11/16/18 and associated disease in women and more recently, in men. Here we report on the safety and reactogenicity of the qHPV vaccine in males. A total of 4,065 healthy males aged 16–26 years were enrolled into a randomized, placebo-controlled, double-blind trial. Subjects were randomized 1:1 to receive qHPV vaccine or placebo at day 1, month 2 and month 6. Safety and tolerability were assessed via the collection of reported adverse experiences (AEs). All serious AEs (vaccine- or procedure-related or not) and all deaths occurring during the study were recorded. Safety analyses were conducted in all subjects who received at least one dose of vaccine or placebo. The proportion of subjects who reported at least one injection-site AE was higher in the qHPV vaccine group versus the placebo group (60.1% vs. 53.7%, respectively), however most of these AEs were mild/moderate in intensity. The incidence of at least one systemic AE was comparable between the vaccine and placebo groups (31.7% vs. 31.4%, respectively). There were no vaccine-related serious AEs or deaths. The occurrence of AEs did not increase with each successive injection, and among trial participants who were seropositive for at least one vaccine HPV type at enrollment, the profile of adverse events was similar to that of the entire study cohort. The qHPV vaccine was generally well tolerated in males aged 16–26 years and had a favorable safety profile.
Introduction Infection with human papillomaviruses (HPVs) is common; the lifetime risk of becoming infected with HPV exceeds 50%.1 Approximately 35–40 HPV types are capable of infecting the genital epithelium, although not all of these types are oncogenic. While HPV infections can be transient in nature and largely clinically inapparent, HPV infection can also result in genital warts2 and a variety of premalignant and malignant anogenital lesions in both males2,3 and females.4-7 The epidemiology of genital HPV infection in men is likely similar to that of women. In a 12-month period, the probability of acquiring a new genital HPV infection in men is estimated to be between 0.29–0.39;13-15 comparable to estimates reported for women. The duration of genital HPV infection in men appears similar to that of females,
with approximately 70% of both sexes clearing infections in a 12-month period.16 Two large pivotal clinical trials have demonstrated that a prophylactic quadrivalent HPV (qHPV) (types 6, 11, 16, 18) L1 virus-like particle (VLP) vaccine was highly effective in preventing HPV 6, 11, 16 or 18-related cervical, vulvar or vaginal intraepithelial neoplasia, as well as adenocarcinoma in situ in females aged 16 to 26.17,18 These trials have also shown that the qHPV vaccine is generally well tolerated in young women,17,18 although a slightly higher occurrence of overall adverse experiences (AEs) and vaccine-related AEs were reported by those receiving the qHPV vaccine when compared with placebo. This is largely due to the higher incidence of overall and vaccinerelated injection-site AEs reported by vaccinees. Combined data from both key clinical trials in women 16–26 years old show that
*Correspondence to: Edson D. Moreira; Email:
[email protected] Submitted: 02/07/11; Revised: 03/16/11; Accepted: 03/23/11 DOI: 10.4161/hv.7.7.15579 768
Human Vaccines
Volume 7 Issue 7
research paper
Research paper
Table 1A. Summary of adverse experiences among all subjects during days 1–15 following vaccination qHPV
Placebo
(N = 2020)
(N = 2029)
n
(%)
n
Subjects in analysis population
2020
2029
Subjects with follow-up
1945
1950
Risk difference qHPV-placebo
95% confidence interval
p value§
5.357
(2.39, 8.32)
