One of the leading causes of infection-related cancer is human papillomavirus (HPV). Since 2007, the bivalent (2vHPV) and quadrivalent (4vHPV) HPV vaccines have been included in the Spanish immunization calendar. The new nonavalent HPV vaccination (9vHPV), which was licensed in Europe in 2015, comprises nine HPV strains (6/11/16/18/31/45/52/58) and has been accessible in Spain since May 2017. This study will evaluate the epidemiological effects and cost-effectiveness of a girls-only and a gender-neutral 9vHPV vaccination program to the present vaccination program in Spain. A dynamic transmission model modeling the natural history of HPV infections was calibrated for the Spanish context and used to assess the costs and QALYs associated with vaccination methods from the payer’s perspective over a 100-year time horizon. When compared to 4vHPV, a girls-only vaccination approach with 9vHPV at the age of 12 years was determined to be cost-effective. Gender-neutral vaccination with 9vHPV was associated with further reductions of up to 28.5 percent in the incidence of cervical intraepithelial neoplasia (CIN) 2/3 and 17.1 percent in the incidence of cervical cancer, as well as a 14.0 percent reduction in cervical cancer mortality when compared to girls-only vaccination with 4vHPV.

Furthermore, a gender-neutral 9vHPV vaccination program might possibly be cost-effective when certain criteria such as head and neck protection or discount rates are considered, resulting in a reduction in the burden of HPV-related illnesses in both sexes in the Spanish population.