A World Health Organization (WHO) expert group consensus report proposed histologically

confirmed high-grade CIN and adenocarcinoma in situ (AIS) or worse (i.e. including 17-AAG in vitro cervical cancer) associated with one of the target vaccine types as an acceptable surrogate end-point for Phase III vaccination trials [51]. Type-specific persistence of infection, defined as presence of the same HPV type at two or more consecutive visits separated by 6–12 months, is another interesting outcome measure that is a later and thus more informative end-point than protection against any infection [52]. Duration and consistency of the antibody response to VLPs.  Type-specific L1 VLP-antibodies reach maximum titres at month 7, i.e. 1 month after administration of the third dose. Titres decline until month 24

and remain rather stable thereafter [30,53]. At 3 years, antibody titres remain two- to 20-fold higher than in placebo controls [53]. Complete protection against HPV16 associated CIN lesions was observed over the whole follow-up duration of two Phase IIb trials: 6 years for the monovalent HPV16 vaccine, 5·5 years for the bivalent HPV16/18 vaccine [54,55] and 4 years for the quadrivalent vaccine (abstract presented at the 25th International Papillomavirus Conference, available at http://www.hpv2009.org). Follow-up is continuing, and continued protection

find more against HPV 16/18-associated disease end-points has been shown for the entire available observation time, even when specific antibody titres fall [55]. Optimal target age range for vaccination.  The incidence of HPV infection is very high among sexually active women [56–58]. Therefore, vaccination before SPTLC1 initiation of sexual contacts is the safest strategy for complete protection. However, vaccination programmes targeting 12-year-olds will, compared to programmes targeting 15-year-olds, delay the cancer prevention gains by 3 years [59]. The highest HPV incidences are between 16 and 20 years of age, with a peak incidence at 18 years [59]. ‘Catch-up’ vaccination programmes that target the age groups that are spreading the infection most actively will be required for effective infection control. Large cancer-preventive gains are expected from catch-up vaccination up to 18 years of age and diminishing, but still noteworthy, gains are seen up to 24 years of age [59,60]. In the vaccination trials, women who were vaccine-type HPV DNA- or seropositive at enrolment or who became HPV DNA-positive during the vaccination period were not part of the per-protocol population.