A persistent infection with human papillomavirus (HPV) is a prerequisite for the development of cervical cancer. Clinical trials with HPV-vaccines have been very successful in preventing persistent HPV16/18 infections, the two most oncogenic HPV-genotypes. We assessed the introduction of universal HPV-vaccination for preadolescent girls in the Dutch National Immunization Programme. Long-term vaccine efficacy, the need and extent of a catch-up programme for young women, and the impact of vaccination on the cervical cancer screening programme are major unresolved issues. Preliminary conservative estimates (80% vaccine efficacy and no effects on the screening programme, transmission rate, non-cervical cancer incidence, and cross protection) predict an acceptable cost-effectiveness ratio for universal vaccination of preadolescent girls.