Considerable gains at the individual and societal level would be obtained if cervical cancer could be prevented The cancer burden causally associated with human papillomavirus (HPV) infections is high. Cervical cancer is the second most common cancer among females in the world, with 500 000 new cases and 300 000 premature deaths a year.1 Because of the long preclinical period cervical cancer can be prevented by screening, diagnosis, and treatment of premalignant cervical lesions, but for developing countries preventive vaccination may be the only possibility to significantly reduce cervical cancer incidence. Also in the developed countries considerable gains at the individual and societal level would be obtained, if a significant proportion of cervical cancer and its precursor lesions could be prevented by HPV vaccination (for a systematic review see Lehtinen et al 2). In addition, other anogenital cancers, oropharyngeal and base of tongue cancers, and probably a small proportion of oesophageal cancers are all strongly associated with past HPV infection.3–5 For these and other possible HPV associated cancers, vaccination may be the only possibility for prevention. Overall prevention of HPV infections may result in a 5–10% reduction of cancer mortality worldwide. This editorial seeks to answer the following two questions: what kind of vaccines will be tested and how should their efficacy be defined? Preventive HPV vaccines entering clinical efficacy (phase III) trials are plain virus-like particles (VLPs), DNA free capsids comprising the major viral capsid (L1) protein (manufactured by Merck, GlaxoSmithKline, and by NIH), or chimeric VLPs (CVLP), containing various combinations of early viral proteins attached in different ways to the major L1 or the minor (L2) capsid proteins of the virus. In phase I and II trials HPV VLPs have proved to be safe and highly immunogenic.6 HPV VLP immunisation induces approximately 100-fold higher …