This difference may be due, in part, to the low number of

disease endpoints for many types when HPV16/18 co-infections were excluded. Cross-protection against cervical disease endpoints was also observed for Gardasil® in the combined FUTURE I/II analysis [29]. Efficacy against CIN2+ associated with any one of the 10 most common oncogenic non-vaccine types was 32.5% (95% CI: 6.0–51.9). Of the 69 cases in the placebo arm, 22 (31.9%) occurred in women who also had an HPV16/18-related CIN2+. HPV31 was the only individual type for which significant protection against CIN2+ was observed, 70% (95% CI: 32.1–88.2). Efficacy against non-vaccine Selleck Ibrutinib A9 species (types find more 31,33, 35, 52, or 58) in aggregate was 35.4% (95% CI: 4.4–56.8) and, for non-vaccine A7 species (types 39, 45 or 59) in aggregate, efficacy was a nonsignificant 47.0% (95% CI: -15.0–76.9). Efficacy estimates excluding infections by vaccine types were not reported. Prior exposure to the HPV types targeted by the vaccine will be minimal in the primary focus of vaccination campaigns, 10–14 year old girls. However, vaccine safety and efficacy after HPV16/18 infection

is an issue for young women targeted by catch up vaccination programs because they are expected to have appreciable exposure at the time of vaccination. This expectation was met in the phase III clinical trials. For instance, in the PATRICIA trial, approximately

6–7% were positive for cervical HPV16 or HPV18 DNA at enrollment and 18–19% of women had serologic evidence of HPV16 and/or HPV18 infection at enrollment [32]. In a combined FUTURE I/II analysis, 19.8% of the study population was seropositive for HPV6/11/16/18 and 26.8% were either PCR DNA-positive or seropositive (-)-p-Bromotetramisole Oxalate for at least one of the vaccine types [33]. It is important to note that serologic measures of prior exposure to genital HPV infections substantially underestimate true exposure rates since many women with evidence of cervicovaginal infection will not seroconvert and some seropositive women will become seronegative over time [34]. Vaccine efficacy in PATRICIA was high for CIN2+ related to HPV16 or HPV18 in women with evidence of current infection (as measured by HPV DNA detectability) by the other vaccine type at enrollment, 90.0% (95% CI: 31.8–99.8) [32]. Among HPV16/18 DNA-negative women, vaccine efficacy against HPV16/18 infection was somewhat lower in those seropositive from natural infection than in those seronegative, 72.3% (96.1% CI: 53.0–84.5) and 90.3% (96.1% CI: 87.3–92.6), respectively. A greater probability of latent infection (susceptible to reactivation) in seropositives might explain this difference. The notably lower rate Libraries reductions in seropositives than seronegatives (2.66 vs 1.01 and 0.31 vs 0.