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- Villa, Luisa L., et al.
(författare)
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Immunologic responses following administration of a vaccine targeting human papillomavirus Types 6, 11, 16, and 18
- 2006
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Ingår i: Vaccine. - : Elsevier BV. - 1873-2518 .- 0264-410X. ; 24:27-28, s. 5571-5583
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Tidskriftsartikel (refereegranskat)abstract
- Human papillomavirus (HPV) infection causes cervical cancer and genital warts. Young women (1106) were randomized to receive one of three formulations of a quadrivalent HPV (Types 6/11/16/18) L1 virus-like particle (VLP) vaccine or one of two placebo formulations. The goal was to assess vaccine safety and immunogenicity in baseline HPV 6/11/16 or 18-naive and previously infected subjects. All three formulations were highly immunogenic. At Month 2 (postdose 1), among women with vaccine-type antibodies at baseline, vaccine-induced anti-HPV responses were similar to 12- to 26-fold higher than those observed in baseline-naive women, suggesting an anamnestic response. Following an initial, similar sized decline, anti-HPV responses plateaued and remained stable through end-of-study (3.0 years). No vaccine-related serious adverse experiences were reported. (c) 2006 Elsevier Ltd. All rights reserved.
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- Villa, Luisa L., et al.
(författare)
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Prophylactic efficacy of a quadrivalent human papillomavirus (HPV) vaccine in women with virological evidence of HPV infection
- 2007
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Ingår i: Journal of Infectious Diseases. - : Oxford University Press (OUP). - 1537-6613 .- 0022-1899. ; 196:10, s. 1438-1446
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Tidskriftsartikel (refereegranskat)abstract
- Background. A quadrivalent (types 6, 11, 16, and 18) human papillomavirus (HPV) L1 virus-like-particle (VLP) vaccine has been shown to be 95%-100% effective in preventing cervical and genital disease related to HPV-6,-11,-16, and-18 in 16-26-year-old women naive for HPV vaccine types. Because most women in the general population are sexually active, some will have already been infected with >= 1 HPV vaccine types at the time vaccination is offered. Here, we assessed whether such infected women are protected against disease caused by the remaining HPV vaccine types. Methods. Two randomized, placebo-controlled trials of the quadrivalent (types 6, 11, 16, and 18) HPV vaccine enrolled 17,622 women without consideration of baseline HPV status. Among women infected with 1-3 HPV vaccine types at enrollment, efficacy against genital disease related to the HPV vaccine type or types for which subjects were naive was assessed. Results. Vaccination was 100% effective (95% confidence interval [CI], 79%-100%) in preventing incident cervical intraepithelial neoplasia 2 or 3 or cervical adenocarcinoma in situ caused by the HPV type or types for which the women were negative at enrollment. Efficacy for preventing vulvar or vaginal HPV-related lesions was 94% (95% CI, 81%-99%). Conclusions. Among women positive for 1-3 HPV vaccine types before vaccination, the quadrivalent HPV vaccine protected against neoplasia caused by the remaining types. These results support vaccination of the general population without prescreening.
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- Paavonen, J, et al.
(författare)
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Baseline demographic characteristics of subjects enrolled in international quadrivalent HPV (types 6/11/16/18) vaccine clinical trials
- 2008
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Ingår i: Current Medical Research and Opinion. - : Informa Healthcare. - 1473-4877 .- 0300-7995. ; 24:6, s. 1623-1634
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: In Phase II/III trials, administration of quadrivalent human papillomavirus (HPV) (types 6/11/16/18) L1 virus-like-particle vaccine was highly effective in preventing HPV6/11/16/18-related cervical intraepithelial neoplasia and non-invasive cervical cancer in women aged 16-26 years who were naïve to these HPV types at enrollment. However, the makeup and extent of catch-up vaccination programs among young women is unclear, because a proportion of this population will likely already have been exposed to one or more vaccine-HPV-types. OBJECTIVE: Herein we analyze baseline data from the quadrivalent HPV vaccine clinical trial program to investigate variables which may help shape catch-up vaccine implementation policies. METHODS: Female adolescents and young adults aged 16-26 years were randomized into five clinical trials. Baseline data regarding demographics, sexual history, pregnancy history, and other characteristics were collected at enrollment. At the baseline gynecological examination during enrollment, specimens were obtained for Pap testing. Swabs of external genital, lateral vaginal, and cervical sites for HPV polymerase chain reaction (PCR) testing were taken, and serum samples were obtained for HPV serology testing. Regional analyses of data were conducted. RESULTS: Overall, 72% of subjects enrolled worldwide were naïve by both serology and PCR to all four vaccine HPV types. Few subjects were seropositive and/or PCR positive for more than two vaccine-related HPV types. Of all subjects with HSIL at enrollment, 78% were positive to at least one vaccine-related HPV type at enrollment. Regional differences in HPV and STD prevalence were evident. Study limitations included under-representation of women with >/=4 sexual partners and possible underestimation of prior HPV exposure. CONCLUSIONS: Our findings demonstrate that sexually active 16-26 year-old women with
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- Villa, L., et al.
(författare)
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Effect of prophylactic human papillomavirus L1 virus-like-particle vaccine on risk of cervical intraepithelial neoplasia grade 2, grade 3, and adenocarcinoma in situ: a combined analysis of four randomised clinical trials
- 2007
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Ingår i: The Lancet. - 1474-547X. ; 369:9576, s. 1861-1868
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Tidskriftsartikel (refereegranskat)abstract
- Background Cervical cancer and its obligate precursors, cervical intraepithelial neoplasia grades 2 and 3 (CIN2/3), and adenocarcinona in situ (AIS), are caused by oncogenic human papillomavirus (HPV). In this combined analysis of four clinical trials we assessed the effect of prophylactic HPV vaccination on these diseases. Methods 20 583 women aged 16-26 years were randomised to receive quadrivalent HPV6/11/16/18 vaccine (n=9087), its HPV16 vaccine component (n=1204), or placebo (n=10292). They underwent periodic Papanicolaou testing, with colposcopy or biopsy for detected abnormalities. The primary composite endpoint was the combined incidence of HPV16/18-related CIN2/3, AIS, or cervical cancer. These trials are registered at ClinicalTrials.gov, numbers NCT00365378, NCT00365716, NCT00092521, and NCT00092534. Findings Mean follow-up was 3.0 years (SD 0.66) after first dose. In women negative for HPV16 or HPV18 infection during the vaccination regimen (n=17129, per protocol), vaccine efficacy was 99% for the primary endpoint (95% Cl 93-100), meeting the statistical criterion for success. In an intention-to-treat analysis of all randomised women (including those who were HPV16/18 naive or HPV16/18-infected at day 1), efficacy was 44% (95% Cl 31-55); all but one case in vaccine recipients occurred in women infected with HPV16 or HPV18 before vaccination. In a second intention-to-treat analysis we noted an 18% reduction (95% CI 7-29) in the overall rate of CIN2/3 or AIS due to any HPV type. Interpretation Administration of HPV vaccine to HPV-naive women, and women who are already sexually active, could substantially reduce the incidence of HPV16/18-related cervical precancers and cervical cancer.
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| 6. |
- Villa, LL, et al.
(författare)
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Prophylactic quadrivalent human papillomavirus (types 6, 11, 16, and 18) L1 virus-like particle vaccine in young women: a randomised double-blind placebo-controlled multicentre phase II efficacy trial
- 2005
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Ingår i: The Lancet Oncology. - 1474-5488 .- 1470-2045. ; 6:5, s. 271-278
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Tidskriftsartikel (refereegranskat)abstract
- Background A randomised double-blind placebo-controlled phase II study was done to assess the efficacy of a prophylactic quadrivalent vaccine targeting the human papillomavirus (HPV) types associated with 70% of cervical cancers (types 16 and 18) and with 90% of genital warts (types 6 and 11). Methods 277 young women (mean age 20.2 years [SD 1.7]) were randomly assigned to quadrivalent HPV (20 μ g type 6, 40 μ g type 11, 40 μ g type 16, and 20 μ g type 18) L1 virus-like-particle (VLP) vaccine and 275 (mean age 20.0 years [1.7]) to one of two placebo preparations at day 1, month 2, and month 6. For 36 months, participants underwent regular gynaecological examinations, cervicovaginal sampling for HPV DNA, testing for serum antibodies to HPV, and Pap testing. The primary endpoint was the combined incidence of infection with HPV 6, 11, 16, or 18, or cervical or external genital disease (ie, persistent HPV infection, HPV detection at the last recorded visit, cervical intraepithelial neoplasia, cervical cancer, or external genital lesions caused by the HPV types in the vaccine). Main analyses were done per protocol. Findings Combined incidence of persistent infection or disease with HPV 6, 11, 16, or 18 fell by 90% (95% CI 71-97, p< 0.0001) in those assigned vaccine compared with those assigned placebo. Interpretation A vaccine targeting HPV types 6, 11, 16, 18 could substantially reduce the acquisition of infection and clinical disease caused by common HPV types.
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