In contrast, in the United States, the coverage of the three-dose series of HPV vaccine was only 34.8% in 2011 and 33.4% in 2012 among 13 to 17 year old girls vaccinated by primary care physicians [78]. A higher coverage is being achieved through school-based vaccination programmes,

rather than through primary care-based programmes. However, school-based programmes need to make increased efforts to reach out-of-school children, especially in low-resource countries [70]. The high price of the current HPV vaccines has been a hurdle in the introduction of the vaccines, especially in developing countries [79]. Industrialised countries pay a price as high as 120 USD per dose [79]. Around 40 countries had introduced HPV vaccine into their national immunization programme by the beginning of 2012 [70]. Since May 2013, the GAVI Alliance, through Z-VAD-FMK manufacturer UNICEF, can purchase the quadrivalent vaccine at a reduced price of US$ 4.50 per dose, and the bivalent vaccine for US$ 4.60 per dose [80].

With this commitment, more countries will be able to introduce PLX3397 purchase this live-saving vaccine. The first countries benefitting from GAVI support through HPV demonstration projects include Kenya, Ghana, Lao PDR, Madagascar, Malawi, Niger, Sierra Leone and Tanzania [80]. However, middle-income countries have limited or no access to external funding for the introduction of new vaccines. As a consequence, these countries might lag behind in the introduction of new vaccines [81]. Members of the Pan American Health Organization (PAHO) can buy the HPV vaccine

at a reduced cost: the PAHO Revolving Fund offers the vaccines at around US$ 13 per dose [82]. Some other middle-income countries have received support for HPV vaccine introduction from external sources like donations from manufacturers and supported programme-assisted funding [81]. As of September 2012, 10 middle-income countries have introduced HPV vaccine and another 12 countries are conducting pilot studies [81]. The two available prophylactic HPV vaccines have the potential of considerably reducing HPV-related morbidity and mortality. Both vaccines are based on others VLPs of the L1 capsid protein, and are highly immunogenic and efficacious if given before exposure to HPV, i.e. to adolescent girls between 9 and 13 years old in a three-dose schedule. However, some challenges, such as the cost of the vaccines and the logistics and delivery of a vaccine to adolescent girls, prevent high global coverage of the HPV vaccine. With the recent price reduction offered to the GAVI Alliance, more low-income countries will be able to introduce the HPV vaccine, although challenges for co-payments and a sustainable delivery platform remain. Innovative financing mechanisms will be needed to address this, as well as the needs of middle-income countries.