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AS04-Adjuvanted Human Papillomavirus (HPV) Types 16 and 18 Vaccine (Cervarix®)

A Review of its Use in the Prevention of Premalignant Cervical Lesions and Cervical Cancer Causally Related to Certain Oncogenic HPV Types

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Abstract

The AS04-adjuvanted human papillomavirus (HPV) 16/18 vaccine (Cervarix®) is a noninfectious recombinant vaccine produced using purified virus-like particles (VLPs) that induce a strong immunogenic response eliciting high levels of anti-L1 VLP antibodies that persist at levels markedly greater than those observed with natural infection. The vaccine adjuvant (AS04) is composed of monophosphoryl-lipid A, which enhances cellular and humoral immune response, adsorbed to aluminium hydroxide. The vaccine is indicated for the prevention of premalignant cervical lesions and cervical cancer causally related to certain oncogenic HPV types in females aged ≥10 years.

The AS04-adjuvanted HPV 16/18 vaccine administered in a three-dose schedule over 6 months elicits a high immunogenic response and is highly protective against cervical intraepithelial neoplasia and infection causally related to high-risk oncogenic HPV types. In well designed clinical trials in young women aged 15–25 years who were HPV 16/18 seronegative and DNA negative to 14 HPV high-risk types, high levels of immunogenicity and protection were sustained for follow-up periods of up to 8.4 years. High and persistent immunogenicity against infection with HPV 16/18 has also been demonstrated in older and younger females (aged 10–55 years) who were seronegative for vaccine HPV types. The AS04-adjuvanted HPV 16/18 vaccine elicited a greater immunogenic response than the quadrivalent HPV vaccine in women aged 18–45 years who were seronegative and DNA negative for HPV 16/18. The AS04-adjuvanted HPV 16/18 vaccine confers cross protection against certain non-vaccine, high-risk HPV types. A rapid and strong anamnestic humoral immune response was elicited following a fourth dose of the vaccine. The AS04-adjuvanted HPV 16/18 vaccine is generally well tolerated, and pharmacoeconomic analyses have demonstrated the potential for public health benefits and cost effectiveness when vaccination programmes are run in conjunction with screening programmes. Thus, the AS04-adjuvanted HPV 16/18 vaccine prevents cervical disease associated with certain oncogenic HPV types, thereby reducing the burden of premalignant cervical lesions and, very likely, cervical cancer.

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  1. Adis, a Wolters Kluwer Business, 41 Centorian Drive, Private Bag 65901, Mairangi Bay, North Shore 0754, Auckland, New Zealand

    Kate McKeage

  2. Division of Infectious Diseases, University of Alberta, Edmonton, Alberta, Canada

    Barbara Romanowski

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Correspondence to Kate McKeage.

Additional information

Various sections of the manuscript reviewed by: N. De Carvalho, Federal University of Parana, Curitiba, Brazil; M. Diaz, Unit of Infections and Cancer, Catalan Institute of Oncology, Barcelona, Spain; J. Garcia-Sicilia, Department of Paediatrics, La Paz Hospital, Madrid, Spain.

Data Selection

Sources: Medical literature (including published and unpublished data) on ‘human papillomavirus vaccine’ was identified by searching databases since 1996 (including MEDLINE, EMBASE and in-house AdisBase), bibliographies from published literature, clinical trial registries/databases and websites (including those of regional regulatory agencies and the manufacturer). Additional information (including contributory unpublished data) was also requested from the company developing the drug.

Search strategy: MEDLINE, EMBASE and AdisBase search terms were ‘human papillomavirus vaccine’ or ‘human papillomavirus HPV types 16 and 18’ or ‘human papillomavirus 16’ and ‘human papillomavirus 18’ or ‘AS04-adjuvanted HPV vaccine’. Searches were last updated 7 February 2011.

Selection: Studies in females who received AS04-adjuvanted human papillomavirus (HPV) 16/18 vaccine (Cervarix®). Inclusion of studies was based mainly on the methods section of the trials. When available, large, well controlled trials with appropriate statistical methodology were preferred. Relevant pharmacodynamic and pharmacokinetic data are also included.

Index terms: Cervarix®, HPV types 16/18 vaccine, immunogenicity, prophylactic efficacy, tolerability, pharmacoeconomics.

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McKeage, K., Romanowski, B. AS04-Adjuvanted Human Papillomavirus (HPV) Types 16 and 18 Vaccine (Cervarix®). Drugs 71, 465–488 (2011). https://doi.org/10.2165/11206820-000000000-00000

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