A Review of Clinical Trials of Human Papillomavirus Prophylactic Vaccines

Abstract

End of study analyses of the phase III trials of prophylactic human papillomavirus (HPV) virus-like particle (VLP) vaccines in young women are now largely completed. Two distinct vaccines were evaluated, Gardasil® (Merck & Co., Whitehouse Station, NJ USA) a quadrivalent vaccine containing VLPs of types 6, 11, 16 and 18 and Cervarix® (GlaxoSmithKline Biologicals, Rixensart, Belgium), a bivalent vaccine containing VLPs of types 16 and 18. Both vaccines exhibited excellent safety and immunogenicity profiles. The vaccines also demonstrated remarkably high and similar efficacy against the vaccine-targeted types for a range of cervical endpoints from persistent infection to cervical intraepithelial neoplasia grade 3 (CIN3) in women naïve to the corresponding type at the time of vaccination. However, protection from incident infection or disease from non-vaccine types was restricted, and the vaccines had no effect on prevalent infection or disease. Gardasil® also demonstrated strong protection against genital warts and vulvar/vaginal neoplasia associated with the vaccine types. In other trials, Gardasil® protected mid-adult women from incident infection and CIN caused by the vaccine types and protected men for incident infection, genital warts and anal intraepithelial neoplasia by the vaccine types. Cervarix® protected against vaccine-targeted anal infections in women in an end of study evaluation. For practical reasons, efficacy studies have not been conducted in the primary target populations of current vaccination programs, adolescent girls and boys. However, immunogenicity bridging studies demonstrating excellent safety and strong immune responses in adolescence, coupled with the documentation of durable antibody responses and protection in young adults, leads to an optimistic projection of the effectiveness of the vaccines in adolescent vaccination programs. Taken together, the excellent clinical trial results strongly support the potential of the vaccines as high value public health interventions and justify their widespread implementation to prevent anogenital HPV infections and their associated neoplasia. This article forms part of a special supplement entitled “Opportunities for comprehensive control of HPV infections and related diseases” Vaccine Volume 30, Supplement X, 2012.

Public health value of universal HPV vaccination

“…In males, the quadrivalent HPV (qHPV) vaccine efficacy against ano-genital lesions related to HPV 6,11, 16 and 18 has been reported by Giuliano et al (10[0]) up to 90% in perprotocol (PP) population and 65.5% in intention-to-treat (ITT) group. In the same study, vaccine efficacy against persistent incident infection and HPV-DNA detection was 47.8% and 27.1% in PP and ITT population, respectively.…”

“…Cross-protection against non-vaccine HPV types is an important consideration since nonvaccine HPV types are associated with 30% approximately of cervical cancer (16). Data on cross-protection against persistent infection and against disease endpoints are not easy to be evaluated so far for the differences in the experimental approaches and differences in the evaluation of efficacy results (16).…”

“…Data on cross-protection against persistent infection and against disease endpoints are not easy to be evaluated so far for the differences in the experimental approaches and differences in the evaluation of efficacy results (16). Furthermore, data from clinical studies show that the supposed cross-protection specially against non-vaccine HPV types 31, and 45, decreases during an increased follow-up, suggesting a waning of cross-protection (17).…”

HPV vaccine: Current status and future directions

“…15 Till then what we know for sure is that the vaccine does prevent fresh HPV infections, and HPV related CIN 2/3 disease and hence is likely to prevent development of HPV related Ca cervix. However presently available vaccines do not protect against all high risk oncogenic types of HPV and hence is not going to be 100% effective in preventing Ca cervix.…”

Comprehensive Control of Human Papillomavirus Infections and Related Diseases

“…Author manuscript; available in PMC 2014 November 22. Reproduced with permission from Schiller JT et al [13].…”