Goldstone SE, Jessen H, Palefsky JM, Giuliano AR, Moreira ED Jr, Vardas E, Aranda C, Hillman RJ, Ferris DG, Coutlee F, Marshall JB, Vuocolo S, Haupt RM, Guris D, Garner E. Quadrivalent HPV vaccine efficacy against disease related to vaccine and non-vaccine HPV types in males. Vaccine. 2013 Aug 20;31(37):3849-55.
Purpose of study
Human papillomavirus (HPV) genital infection in males can result in asymptomatic infection, genital warts, and a variety of premalignant and malignant lesions in the anogenital epithelium. HPV infection is common in men, with a lifetime risk of greater than 50%.
HPV types 6 and 11 are implicated in the majority of genital warts cases. A small number of HPV types are related to neoplastic lesions in humans, with HPV 16 and 18 being most often implicated. Other recognized high-risk HPV types include HPV 31, 33, 35, 39, 45, 51, 52, 56, 58, and 59; eight of which share varying degrees of protein homology with HPV 16 and 18. This similarity has led to the question of whether vaccines against HPV 16 and 18 can induce protection against these other related high-risk HPV types.
This study reports data on the efficacy of the quadrivalent HPV vaccine (qHPV) GardasilTM (for HPV types 6, 11, 16, and 18) against anogenital disease in males due to the 10 additional non-vaccine HPV types, as well as efficacy regardless of HPV detection.
The study included 3,463 heterosexual males aged 16 to 24, and 602 men who have sex with men (MSM) aged 16 to 27. Participants had less than six lifetime sexual partners, no history of or current HPV genital lesions or other STIs, and were from 18 countries across 5 continents. See Figure 1 for the study design.
Figure 1: Accounting of men in the HPV-naive and intention-to-treat populations.
The intention to treat (ITT) population received >1 dose of the vaccine and returned for >1 follow up. The “HPV naïve” population included those found to be PCR negative to all 14 HPV types and seronegative to HPV 6, 11, 16, and 18 at baseline, and for the MSM cohort to also have a normal anal cytology test at baseline.
The measured endpoints were:
- external genital lesions (EGL) found on examination at day 1 and months 7, 12, 18, 24, 30, and 36;
- anal intraepithelial neoplasia (AIN) or worse (on cytology or biopsy of lesions) in the MSM cohort;
- swabs from penis, scrotum, and perineal/perianal regions at day 1, and months 7, 12, 18, 24, 30, and 36 for PCR of the 14 HPV types.
The authors presented data showing that vaccinating males against HPV 6, 11, 16, and 18 does not provide significant efficacy against disease (both EGL and AIN) due to non-vaccine HPV types. The data does show significant protection against HPV 6, 11, 16, and 18-related anogenital disease, reinforcing what has been previously demonstrated.
The major drawbacks of this study include the small sample size due to large numbers of participants that were lost to follow up at month 36, relatively short follow-up times as AIN requires longer time to develop, and the financial interests of Merck & Co. Inc. (maker of GardasilTM) in funding 11 of 16 authors, as well as its participation in the data collation, trial design, and provision of lab used.
Link to PubMed abstract: http://www.ncbi.nlm.nih.gov/pubmed/23831322
Link to full article (free with UBC Library membership, otherwise need to purchase): http://www.sciencedirect.com/science/article/pii/S0264410X13008499