Purpose: Therapeutic vaccination with human papillomavirus type 16 (HPV16) E6 and E7 synthetic long peptides (SLP) is effective against HPV16-induced high-grade vulvar and vaginal intraepithelial neoplasia (VIN/VaIN). However, clinical nonresponders displayed weak CD8 þ T-cell reactivity. Here, we studied if imiquimod applied at the vaccine site could improve Results: Forty-three patients were assigned to either ISA101 with imiquimod (n ¼ 21) or ISA101 only (n ¼ 22). Imiquimod did not improve the outcomes of vaccination. However, vaccineinduced clinical responses were observed in 18 of 34 (53%; 95% CI, 35.1-70.2) patients at 3 months and in 15 of 29 (52%; 95% CI, 32.5-70.6) patients, 8 of whom displayed a complete histologic response, at 12 months after the last vaccination. All patients displayed vaccine-induced T-cell responses, which were significantly stronger in patients with complete responses. Importantly, viral clearance occurred in all but one of the patients with complete histologic clearance.Conclusions: This new study confirms that clinical efficacy of ISA101 vaccination is related to the strength of vaccine-induced HPV16-specific T-cell immunity and is an effective therapy for HPV16-induced high-grade VIN/VaIN.

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Not only HPV vaccination of girls before sexual debut is a highly effective and cost-effective strategy for prevention of cervical cancer, but also vaccination of women until the age of 25 years is generally cost-effective.

BackgroundIn the Netherlands, human papillomavirus (HPV) vaccination is part of a national program equally accessible for all girls invited for vaccination. To assess possible inequalities in vaccine uptake, we investigated differences between vaccinated and unvaccinated girls with regard to various characteristics, including education and ethnicity, (both associated with non-attendance to the national cervical screening program), sexual behaviour and knowledge of HPV.MethodsIn 2010, 19,939 nationwide randomly-selected 16–17 year-old girls (2009 vaccination campaign) were invited to fill out an online questionnaire. A knowledge scale score and multivariable analyses identified variables associated with vaccination status.Results2989 (15%) of the selected girls participated (65% vaccinated, 35% unvaccinated). The participants were comparable with regard to education, ethnicity, most sexual risk behaviour and had similar knowledge scores on HPV transmission and vaccination. However, unvaccinated girls lived in more urbanised areas and were more likely to have a religious background. Irrespective of vaccination status, 81% of the girls were aware of the causal relationship between HPV and cervical cancer, but the awareness of the necessity of cervical screening despite being vaccinated was limited.ConclusionsHPV vaccine uptake was not associated with knowledge of HPV and with factors that are known to be associated with non-attendance to the cervical cancer screening program in the Netherlands. Furthermore, most sexual behaviour was not related to vaccination status meaning that teenage unvaccinated girls were not at a disproportionally higher risk of being exposed to HPV. Routine HPV vaccination may reduce the social inequity of prevention of cervical cancer.