REVIEW ARTICLE
CURRENT ISSUES FACING THE INTRODUCTION OF HUMAN PAPILLOMAVIRUS VACCINE IN MALAYSIA
The pathogenesis of HPV-associated cervical cancer has been reviewed (Figure 2).16 HPV infects basal cells of the cervical epithelium via micro-abrasions. Ongoing viral replication is associated with progressively dysplastic histological changes, through cervical intraepithelial neoplasia (CIN) grades 1-3. The integration of HPV into the host DNA leads to up-regulation of the viral oncogenes E6 and E7, which disrupt host p53 and RB control of the cell cycle, and result in invasive cancer.
Figure 1. Illustration of oncogenic and non-oncogenic HPV type
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HPV VACCINES
Vaccines against HPV have been recently introduced in developed countries. The vaccines consist of recombinant HPV major capsid protein L1, which generate virus-like particles (VLP) resembling HPV virions, but which are non-infectious, and immunogenic. The US Food and Drug Administration (FDA) recently approved a quadrivalent vaccine (Gardasil, from Merck) against types 6, 11, 16 and 18. The vaccine is recommended for routine use in girls aged 11 to 12 years, and permissive use for females aged 9-26 years.17 A bivalent vaccine (Cervarix, from GlaxoSmithKline), which protects against HPV types 16 and 18, should become available soon.
Both vaccines have shown excellent efficacy and safety. The quadrivalent vaccine was 90.7-100% effective in preventing infection of the four HPV types, and associated genital warts, CIN, vulval intraepithelial neoplasia, and vaginal intraepithelial neoplasia.17,18 The bivalent vaccine also showed similarly high efficacy in protecting against persistent HPV infection and CIN.19 Although antibody levels and clinical efficacy appear to be sustained for at least 4.5 years after vaccination,19,20 the full duration of protection and the possible need for boosters is unclear. Indeed, the limited follow-up duration of current studies may be insufficient to detect persistent high-grade cervical dysplasia, which may take many years to develop.
It should be emphasised that the vaccines do not protect against less common or unidentified strains of HPV that are associated with cervical cancer. Furthermore, HPV infection alone may not be sufficient to induce cervical cancer. Potentially important co-factors in the development of neoplasia include smoking, multiparity, prolonged oral contraceptive use, herpes simplex virus type 2, and other sexually transmitted infections (STIs).21,22 There is also the theoretical possibility that other oncogenic types may fill the biological niche left behind if types 16 and 18 are eradicated, leading to a rise in cervical cancers caused by non-16 and 18 types.23
Figure 2. Schematic representation of HPV infection
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