HPV vaccines in Brazil and the world

Human papillomavirus (HPV), the most common newly acquired, sexually transmitted infection worldwide, infects about 75% of sexually active individuals in their lifetimes. The high-risk HPV types, the most common of which are HPV 16 and 18, cause cervical and other anogenital cancers, as well as some head and neck cancers [1]. Different HPV types are related to different lesion grades. HPV16 is found in about half of cervical cancers, the majority of anal cancers and about 30% of oropharyngeal cancers, besides a significant proportion of vulvar, vaginal and penile carcinomas. The low-risk types, the most common of which are HPV 6 and 11, cause genital warts, low-grade cervical dysplasias and recurrent respiratory papillomatosis. Most of our understanding of HPV and carcinogenesis is derived from studies of women and cervical cancer. However, it is clear that HPV causes a significant proportion of tumors in both women and men [2]. Therefore, new prophylactic HPV vaccines have the power to prevent many HPV infections, thus reducing the burden of HPV-associated diseases. Two vaccines have been developed, a quadrivalent vaccine that protects against HPV 16, 18, 6 and 11 (Merck & Co., USA) and a bivalent vaccine that protects against HPV 16 and 18 (Glaxo Smith-Kline, Belgium). Both vaccines are composed of HPV L1 proteins that have spontaneously self-assembled into virus-like particles (VLPs). However, they have different manufacturers, valencies, adjuvants and are produced in different types of cells. Both are administered by intramuscular injection, in three doses (0, 1 or 2 and 6 months). In a number of clinical trials conducted in thousands of subjects in many countries since 1998, the safety, immunogenicity and efficacy of these HPV VLP vaccines have been demonstrated [3]. Prophylactic efficacy was measured considering HPV infection and disease endpoints, particularly high-grade cervical intraepithelial neoplasia or worse for the bivalent and quadrivalent vaccines, as well as vulvar intraepithelial neoplasia (VIN) or vaginal intraepithelial neoplasia and genital warts, for the quadrivalent vaccine only. For both the bivalent and quadrivalent vaccines, results of different trials allow for the examination of broad trends in efficacy in preventing HPV 6/11/16/18related disease in several groups of patients categorized according to their HPV status at baseline. Very high efficacy rates were observed in naive women for the vaccineHPV types which led to the recommendation of the vaccine to young individuals, prior to exposure to HPV which occurs concomitant to sexual activity onset. Crossprotection against non-vaccine types was also noted, but the significance and durability of protection is yet to be defined. To increase the coverage to more than 70% of cervical cancers attributable to HPV 16 and 18, it is possible that the best and most efficient responses will be obtained with multivalent vaccines against a larger number of genital, anal and oropharyngeal HPV infections which are presently under development [4]. VLPs are noninfectious protein subunit vaccines and show safety profiles similar to other protein subunit vaccines such as tetanus or hepatitis B vaccines. Both vaccines were generally well tolerated in clinical trials and maintain a good safety profile after licensure. Since the VLP vaccines were designed primarily to protect by inducing virion neutralizing antibodies, type specific antibody responses to the VLPs have been the primary focus of immunogenicity studies. Both vaccines were shown to be highly immunogenic in the clinical trials, resulting in essentially 100% seroconversion in the different populations studied which included both females and males. Both vaccines induce the expected B cell memory response which is a property of vaccines with durable immune responses. Although the long term persistence of stable antibody levels is an encouraging finding, the antibody levels needed to prevent infection or disease are currently unknown. However, long-term follow-up studies have shown that efficacy is maintained for at least ten years and modeling studies suggest protection may School of Medicine, University of São Paulo, São Paulo, Brazil Villa BMC Proceedings 2014, 8(Suppl 4):O7 http://www.biomedcentral.com/1753-6561/8/S4/O7