Human papillomavirus first and second generation vaccines-current status and future directions. 
It has been more than 10 years that the first prophylactic papillomavirus vaccine became available, although distribution has been mainly limited to the more affluent countries.  The first two vaccines have been a great success, hundreds of millions of women and a much smaller number of men have been vaccinated ever since.  In a few countries with high vaccination coverage, in particular Australia but also parts of Great Britain and others, clinical impact of vaccination programs is already visible and there are indications for herd immunity as well.  Vaccine efficacy is higher than originally estimated and the vaccines have an excellent safety profile.  Gardasil9 is a second generation HPV virus-like particle vaccine that was licensed in 2015 and there are more to come in the near future.  Currently, burning questions in respect to HPV vaccination are the duration of protection - especially in regard to cross-protection - reduction of the three-dose regimen and its impact on cross-protection; and duration of response, as well as protection against oropharyngeal HPV infections.  Furthermore, researchers are seeking to overcome limitations of the VLP vaccines, namely low thermal stability, cost, invasive administration, limited coverage of non-vaccine HPV types, and lack of therapeutic efficacy.  In this review we summarize the current status of licensed VLP vaccines and address questions related to second and third generation HPV vaccines.