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- Villa, Luisa L., et al.
(author)
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Quadrivalent vaccine against human papillomavirus to prevent high-grade cervical lesions
- 2007
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In: New England Journal of Medicine. - 0028-4793 .- 1533-4406. ; 356:19, s. 1915-1927
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Journal article (peer-reviewed)abstract
- BACKGROUND: Human papillomavirus types 16 (HPV-16) and 18 (HPV-18) cause approximately 70% of cervical cancers worldwide. A phase 3 trial was conducted to evaluate a quadrivalent vaccine against HPV types 6, 11, 16, and 18 (HPV-6/11/16/18) for the prevention of high-grade cervical lesions associated with HPV-16 and HPV-18. METHODS: In this randomized, double-blind trial, we assigned 12,167 women between the ages of 15 and 26 years to receive three doses of either HPV-6/11/16/18 vaccine or placebo, administered at day 1, month 2, and month 6. The primary analysis was performed for a per-protocol susceptible population that included 5305 women in the vaccine group and 5260 in the placebo group who had no virologic evidence of infection with HPV-16 or HPV-18 through 1 month after the third dose (month 7). The primary composite end point was cervical intraepithelial neoplasia grade 2 or 3, adenocarcinoma in situ, or cervical cancer related to HPV-16 or HPV-18. RESULTS: Subjects were followed for an average of 3 years after receiving the first dose of vaccine or placebo. Vaccine efficacy for the prevention of the primary composite end point was 98% (95.89% confidence interval [CI], 86 to 100) in the per-protocol susceptible population and 44% (95% CI, 26 to 58) in an intention-to-treat population of all women who had undergone randomization (those with or without previous infection). The estimated vaccine efficacy against all high-grade cervical lesions, regardless of causal HPV type, in this intention-to-treat population was 17% (95% CI, 1 to 31). CONCLUSIONS: In young women who had not been previously infected with HPV-16 or HPV-18, those in the vaccine group had a significantly lower occurrence of high-grade cervical intraepithelial neoplasia related to HPV-16 or HPV-18 than did those in the placebo group.
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| 2. |
- Brown, Darron R., et al.
(author)
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The Impact of Quadrivalent Human Papillomavirus (HPV; Types 6, 11, 16, and 18) L1 Virus-Like Particle Vaccine on Infection and Disease Due to Oncogenic Nonvaccine HPV Types in Generally HPV-Naive Women Aged 16-26 Years
- 2009
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In: Journal Of Infectious Diseases. - : Oxford University Press (OUP). - 0022-1899 .- 1537-6613. ; 199:7, s. 926-935
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Conference paper (peer-reviewed)abstract
- Background. Human papillomavirus (HPV)-6/11/16/18 vaccine reduces the risk of HPV-6/11/16/18-related cervical intraepithelial neoplasia (CIN) 1-3 or adenocarcinoma in situ (AIS). Here, its impact on CIN1-3/AIS associated with nonvaccine oncogenic HPV types was evaluated. Methods. We enrolled 17,622 women aged 16-26 years. All underwent cervicovaginal sampling and Pap testing at regular intervals for up to 4 years. HPV genotying was performed for biopsy samples, and histological diagnoses were determined by a pathology panel. Analyses were conducted among subjects who were negative for 14 HPV types on day 1. Prespecified analyses included infection of >= 6 months' duration and CIN1-3/AIS due to the 2 and 5 most common HPV types in cervical cancer after HPV types 16 and 18, as well as all tested nonvaccine types. Results. Vaccination reduced the incidence of HPV-31/45 infection by 40.3% (95% confidence interval [CI], 13.9% to 59.0%) and of CIN1-3/AIS by 43.6% (95% CI, 12.9% to 64.1%), respectively. The reduction in HPV-31/33/45/52/58 infection and CIN1-3/AIS was 25.0% (95% CI, 5.0% to 40.9%) and 29.2% (95% CI, 8.3% to 45.5%), respectively. Efficacy for CIN2-3/AIS associated with the 10 nonvaccine HPV types was 32.5% (95% CI, 6.0% to 51.9%). Reductions were most notable for HPV-31. Conclusions. HPV-6/11/16/18 vaccine reduced the risk of CIN2-3/AIS associated with nonvaccine types responsible for similar to 20% of cervical cancers. The clinical benefit of cross-protection is not expected to be fully additive to the efficacy already observed against HPV-6/11/16/18-related disease, because women may have >1 CIN lesion, each associated with a different HPV type.
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| 3. |
- Wheeler, Cosette M., et al.
(author)
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The Impact of Quadrivalent Human Papillomavirus (HPV; Types 6, 11, 16, and 18) L1 Virus-Like Particle Vaccine on Infection and Disease Due to Oncogenic Nonvaccine HPV Types in Sexually Active Women Aged 16-26 Years
- 2009
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In: Journal Of Infectious Diseases. - : Oxford University Press (OUP). - 0022-1899 .- 1537-6613. ; 199:7, s. 936-944
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Conference paper (peer-reviewed)abstract
- Background. We evaluated the impact of a quadrivalent human papillomavirus (HPV) vaccine on infection and cervical disease related to 10 nonvaccine HPV types (31, 33, 35, 39, 45, 51, 52, 56, 58, and 59) associated with >20% of cervical cancers. The population evaluated included HPV-naive women and women with preexisting HPV infection and/or HPV-related disease at enrollment. Methods. Phase 3 efficacy studies enrolled 17,622 women aged 16-26 years. Subjects underwent cervicovaginal sampling and Pap testing on day 1 and then at 6-12-month intervals for up to 4 years. HPV typing was performed on samples from enrollment and follow-up visits, including samples obtained for diagnosis or treatment of HPV-related disease. All subjects who received >= 1 dose and returned for follow-up were included. Results. Vaccination reduced the rate of HPV-31/33/45/52/58 infection by 17.7% (95% confidence interval [CI], 5.1% to 28.7%) and of cervical intraepithelial neoplasia (CIN) 1-3 or adenocarcinoma in situ (AIS) by 18.8% (95% CI, 7.4% to 28.9%). Vaccination also reduced the rate of HPV-31/58/59-related CIN1-3/AIS by 26.0% (95% CI, 6.7% to 41.4%), 28.1% (95% CI, 5.3% to 45.6%), and 37.6% (95% CI, 6.0% to 59.1%), respectively. Although a modest reduction in HPV-31/33/45/52/58-related CIN2 or worse was observed, the estimated reduction was not statistically significant. Conclusions. These cross-protection results complement the vaccine's prophylactic efficacy against disease associated with HPV-6, -11, -16, and - 18. Long-term monitoring of vaccinated populations are needed to fully ascertain the population-based impact and public health significance of these findings.
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