Quadrivalent human papillomavirus (types 6, 11, 16, 18) recombinant vaccine (Gardasil®): a review of its use in the prevention of premalignant genital lesions, genital cancer and genital warts in women.

Quadrivalent human papilloma virus (HPV) [types 6, 11, 16, 18] recombinant vaccine (Gardasil®; Silgard®) is composed of virus-like particles (VLPs) formed by self-assembly of recombinant L1 capsid protein from each of HPV types 6, 11, 16 and 18. The VLPs are noninfectious, containing no DNA, and are highly immunogenic, inducing high levels of neutralizing antibodies against the particular HPV types when administered to animals or humans. Quadrivalent HPV vaccine is indicated for use from the age of 9 years for the prevention of premalignant genital lesions (cervical, vulvar and vaginal), cervical cancer and external genital warts (condyloma acuminata) causally related to certain oncogenic or specific HPV types. In placebo-controlled clinical trials, quadrivalent HPV vaccine administered as three doses over 6 months provided high-level protection against infection or disease caused by the vaccine HPV types over 2-4 years of follow-up in females aged 15-45 years who were naive to the vaccine HPV types. A degree of cross-protection against certain other non-vaccine high-risk HPV types was also observed. The vaccine is not effective against current infection with a vaccine HPV type. Girls or women with current infection with one or more of the vaccine HPV types gained protection from infection or disease caused by the remaining vaccine HPV types and they were also protected against reinfection with the same HPV type after clearance of an infection caused by a vaccine HPV type. High seroconversion rates and high levels of anti-HPV antibodies were observed in all vaccinated individuals of all age ranges from 9 to 45 years. No correlation was found between antibody levels and protective efficacy of the vaccine. Rechallenge with quadrivalent HPV vaccine produced a potent anamnestic humoral immune response. The vaccine is generally well tolerated and is projected to be cost effective in most pharmacoeconomic models. Therefore, quadrivalent HPV vaccine offers an effective means, in combination with screening programmes, to substantially reduce the burden of HPV-related precancerous lesions and cancer, particularly cervical cancer, as well as anogenital warts.