Clinical update of the AS04-Adjuvanted human Papillomavirus-16/18 cervical cancer vaccine, cervarixA®

Persistent infection with human papillomavirus (HPV) is a necessary cause of cervical cancer, resulting annually in 274,000 deaths worldwide. Two prophylactic HPV vaccines are licensed in > 100 countries, and immunization programs in young, adolescent girls have been widely implemented. HPV-16/18 AS04-adjuvanted vaccine (CervarixA (R); GlaxoSmithKline Biologicals, Rixensart, Belgium) has demonstrated type-specific protection against the five most frequent cancer-causing types (16, 18, 31, 33, and 45) that are responsible for 82% of invasive cervical cancers globally. CervarixA (R) has demonstrated efficacy against HPV-45, which is the third most common HPV type in cervical cancer and adenocarcinoma. Final results of a large phase 3 trial recently showed CervarixA (R) substantially reduced the overall burden of cervical precancerous lesions (cervical intraepithelial neoplasia 2+) by 70.2% in an HPV-na < ve population approximating young girls prior to sexual debut, the target of most current vaccination programs. Protection offered by CervarixA (R) against nonvaccine types (mainly 31, 33, and 45) might potentially allow for 11%-16% additional protection against cervical cancers, compared to a vaccine only offering protection against HPV-16/18. Another recent study directly compared the antibody response of CervarixA (R) to that of quadrivalent HPV-6/11/16/18 vaccine (GardasilA (R); Merck, Whitehouse Station, NJ, USA). CervarixA (R) induced significantly superior neutralizing antibody levels as compared with GardasilA (R) for HPV-16 and HPV-18 in all age groups studied. This may translate into more women having detectable (neutralizing) antibodies in cervicovaginal secretions for HPV-16 and HPV-18 after vaccination with CervarixA (R) when compared with GardasilA (R). CervarixA (R) induced significantly higher frequencies of antigen-specific memory B-cells and T-cells in responders for HPV-16 and HPV-18 as compared with GardasilA (R). CervarixA (R) continues to show sustained high levels of total and neutralizing antibodies for HPV-16 and HPV-18, 7.3 years after vaccination. This is associated with high efficacy and no breakthrough cases in the HPV-na < ve population, and is the longest duration follow-up for safety, immunogenicity, and efficacy for any licensed HPV vaccine to date.