Human papillomavirus (HPV)-16/18 AS04-adjuvanted vaccine for the prevention of cervical cancer and HPV-related diseases

ABSTRACT

Vaccines are available against human papillomavirus (HPV), the causal agent of cervical and other cancers. Efficacy data from the HPV-16/18 AS04-adjuvanted vaccine clinical trial program were reviewed. Six randomized, controlled phase II/III trials evaluating cervical endpoints enrolled women from diverse populations and geographical locations. The program analyzed extensively the cohorts most relevant from a public health perspective: the total vaccinated cohort (TVC), approximating a general population including those with existing or previous HPV infection, and TVC-naïve, approximating a population of young women before sexual debut. Results show that the vaccine reduces HPV-16/18 infection and associated cervical endpoints in women regardless of age, location, or sexual experience. It provides cross-protection against some non-vaccine oncogenic HPV types and types causing genital warts, and may be effective against vulvar, oral, and anal HPV infection. Early epidemiology data following its introduction suggest a decline in the prevalence of vaccine and some non-vaccine HPV types.

KEYWORDS:

• Cervical cancer
• efficacy
• HPV
• vaccination
• human papillomavirus
• literature review
• randomized controlled trial

Acknowledgments

The authors would like to thank the patients for their participation in the respective studies. They also thank Walid Kandeil (GSK Vaccines, Wavre) for his input during the initial stages of the paper’s development, Mary Greenacre (An Sgriobhadair, Isle of Barra, UK) and Annick Moon (Moon Medical Communications Ltd, Oxford, UK) for publication writing assistance provided on behalf of GSK Vaccines, and Matthieu Depuydt (Business & Decision Life Sciences, Belgium) and Jean-Michel Heine (Keyrus Biopharma, Belgium) for publication coordination and management provided on behalf of GSK Vaccines.

Financial & competing interests’ disclosure

GlaxoSmithKline Biologicals SA took in charge all costs associated with the development and publication of this manuscript. N Burlet, A Mihalyi, and F Struyf report being employees by the GSK group of companies and own share/stock options in the GSK group of companies. R Skinner received funds through her institution to cover expenses involved in the collection of data and travel expenses to conferences to present data from the PATRICIA and VIVIANE clinical trials, advisory board membership honorarium, and grant support. R Skinner was also coinvestigator on an investigator-driven educational research grant funded by bioCSL. D Apter reports grants from the GSK group of companies for the conduct of HPV vaccination studies. R Konno reports lecture fees from MSD and the GSK group of companies. J Paavonen has received research grants from Merck & Co and the GSK group of companies through the University of Helsinki to conduct clinical trials of HPV vaccines, and has received consulting fees or lecture fees from both companies. B Romanowski received through her institution grant support from the GSK group of companies and personal fees to cover travel expenses for speaking engagement. C Roteli-Martins reports personal fees and grants from the GSK group of companies. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.

Key issues

• Vaccines are available against HPV, the causal agent of cervical and certain other cancers.

• Data from an extensive clinical trial program show that the HPV-16/18 AS04-adjuvanted vaccine reduces infection with HPV-16/18 and associated cervical endpoints in women regardless of age or sexual experience, and provides cross-protection against some non-vaccine HPV types.

• Six randomized, controlled phase II/III trials enrolling women from different populations and locations, including Europe, North America, Latin America, Australia, South-East Asia, China, and Japan were identified in this review. The program included two cohorts of high relevance from a public health perspective: the TVC, approximating a general population including those with existing or previous HPV infection, and the TVC-naïve, approximating from an immunological standpoint a population of young women before sexual debut. CIN3+, irrespective of whether HPV is detected in the lesion, is the closest endpoint to cervical cancer.

• In PATRICIA, efficacy against CIN3+ irrespective of HPV was 45.6% in the TVC and 93.2% in the TVC-naïve. High efficacy against CIN2+ irrespective of HPV was consistently reported in various trials.

• In women with no evidence of infection with the HPV type under analysis, efficacy against persistent HPV-16/18 infection was 93.4–100% in women aged ≤25 years and 82.9% in women aged >25 years (ATP cohorts).

• Analysis of the CVT suggested similar efficacy against persistent HPV-16/18 infection with one, two, or three vaccine doses.

• Cross-protection against HPV-31 and HPV-45 was seen consistently throughout all the studies, and an extensive analysis in PATRICIA also showed efficacy against HPV-33 and HPV-51.

• Efficacy against vulvar, oral, and anal HPV infection was observed in the CVT.

• Early epidemiology data following introduction of the vaccine suggest that the prevalence of vaccine and certain non-vaccine HPV types is declining.