Papiloma

aREVIEW

A novel vaccine for cervical cancer: quadrivalent human papillomavirus (types 6, 11, 16 and 18) recombinant vaccine (Gardasil®)
Vandana A Govan
Division of Medical Virology, Department of Clinical Laboratory Sciences and Institute of Infectious Diseases and Molecular Medicine, Faculty of Health Sciences, University of Cape Town, Observatory, Cape Town, South Africa

Abstract: Humanpapillomaviruses (HPVs) are one of the most common sexually transmitted infections and remains a public health problem worldwide. There is strong evidence that HPV causes cervical, vulva and vaginal cancers, genital warts and recurrent respiratory papillomatosis. The current treatments for HPV-induced infections are ineffective and recurrence is commonplace. Therefore, to reduce the burden ofHPV-induced infections, several studies have investigated the efficacy of different prophylactic vaccines in clinical human trials directed against HPV types 6, 11, 16, or 18. Notably, these HPV types contribute to a significant proportion of disease worldwide. This review will focus on the published results of Merck & Co’s prophylactic quadrivalent recombinant vaccine targeting HPV types 6, 11, 16,and 18 (referred to as Gardasil®). Data from the Phase III trial demonstrated that Gardasil was 100% efficacious in preventing precancerous lesions of the cervix, vulva, and vagina and effective against genital warts. Due to the success of these human clinical trials, the FDA approved the registration of Gardasil on the 8 June 2006. In addition, since Gardasil has been efficacious for 5 years postvaccination, the longest evaluation of an HPV vaccine, it is expected to reduce the incidence of these type specific HPV-induced diseases in the future. Keywords: Gardasil, HPV, prophylactic vaccine, cervical disease

Introduction
Papillomaviruses (PVs) are DNA tumor viruses and infect squamous or mucosal epithelia (Stanely 2003). To date, there are over 100 different human PV (HPV) genotypes thathave been fully sequenced and can be divided into low-risk, nononcogenic, or high-risk oncogenic types (de Villiers et al 2004; Bernard 2005) by their viral ability to cause malignant disease (Munoz et al 2003) (Table 1). The predominant low-risk types are HPV 6 and 11 and cause 90% of genital warts (condyloma acuminata) while HPV 16 and 18 are the most prevalent high-risk types, causing 70% ofcervical cancer and cervical intra-epithelial neoplasia (CIN) (de Villiers et al 2004) and are considered to be the most destructive oncogenic viruses worldwide. Globally, the incidence and mortality rates of new cases, caused by HPV-related cervical cancer were estimated to be approximately 500,000 in 2002 (Ferlay et al 2004). In addition, it is estimated that sexually active men and women have a50% lifetime risk of HPV infection (WHO 2004). Interestingly, although the prevalence of HPV DNA among most sexually active women in the general population is high, these infections are generally transient and infected individuals are able to eliminate the virus without intervention and do not develop cancer (Koutsky 1997). Thus an effective host immune response and the genetic make-up of theindividual may be an important determinant for the persistence and progression of HPV induced cervical cancer (Magnusson and Gyllensten 2000).

Correspondence: Vandana A Govan Room S3.26.1 Wernher and Beit South Wing,Institute of Infectious Diseases and Molecular Medicine, Faculty of Health Sciences University of Cape Town, Medical School, Observatory, Cape Town South Africa Tel +27 21 4066366 Fax+27 21 4066681 Email vandana.govan@uct.ac.za

Therapeutics and Clinical Risk Management 2008:4(1) 65–70 © 2008 Dove Medical Press Limited. All rights reserved

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Table 1 The major high- and low-risk HPV types
Classification High-risk types Low-risk types Potentially high-risk HPV types 16, 18, 31, 33, 35, 39, 45, 51, 52, 56, 58, 59, 68, 73, 82 6, 11, 40, 42, 43, 44, 54, 61, 70,...