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- Villa, Luisa L., et al.
(författare)
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Quadrivalent vaccine against human papillomavirus to prevent high-grade cervical lesions
- 2007
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Ingår i: New England Journal of Medicine. - 0028-4793 .- 1533-4406. ; 356:19, s. 1915-1927
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Tidskriftsartikel (refereegranskat)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. |
- Wilking, N., et al.
(författare)
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Long-term follow-up of the SBG 9401 study comparing tailored FEC-based therapy versus marrow-supported high-dose therapy
- 2007
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Ingår i: Annals of Oncology. - : Elsevier BV. - 0923-7534 .- 1569-8041. ; 18:4, s. 694-700
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Tidskriftsartikel (refereegranskat)abstract
- Background: The purpose was to investigate adjuvant marrow-supportive high-dose chemotherapy compared with an equitoxicity-tailored comparator arm. Patients and methods: Five hundred and twenty-five women below theage of 60 years with operated high-risk primary breast cancer were randomised to nine cycles of granulocyte colony-stimulating factor supported and individually tailored FEC (5-fluorouracil, epirubicin, cyclophosphamide), (n = 251) or standard FEC followed by marrow-supported high-dose therapy with CTCb (cyclophosphamide, thiotepa, carboplatin) therapy (n = 274), followed by locoregional radiotherapy and tamoxifen for 5 years. Results: There were 104 breast cancer relapses in the tailored FEC group versus 139 in the CTCb group (double triangular method by Whitehead, P = 0.046), with a median follow-up of all included patients of 60.8 months. The event-free survival demonstrated 121 and 150 events in the tailored FEC- and CTCb group, respectively [P = 0.074, hazard ratio (HR) 0.804, 95% confidence interval (CI) 0.633-1.022]. Ten patients in the tailored FEC regimen developed acute myeloid leukaemia (AML)/myelodysplasia (MDS). One hundred deaths occurred in the tailored FEC group and 121 in the CTCb group (P = 0.287, HR 0.866, 95% CI 0.665-1.129). Conclusion: The update of this study shows an improved outcome linked to the tailored FEC treatment in relation to breast cancer relapse, but also an increased incidence of AML/MDS. © 2007 Oxford University Press.
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| 3. |
- Kulmala, M., et al.
(författare)
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General overview: European Integrated project on Aerosol Cloud Climate and Air Quality interactions (EUCAARI) - integrating aerosol research from nano to global scales
- 2011
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Ingår i: Atmospheric Chemistry And Physics. - : Copernicus GmbH. - 1680-7316 .- 1680-7324. ; 11:24, s. 13061-13143
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Tidskriftsartikel (refereegranskat)abstract
- In this paper we describe and summarize the main achievements of the European Aerosol Cloud Climate and Air Quality Interactions project (EUCAARI). EUCAARI started on 1 January 2007 and ended on 31 December 2010 leaving a rich legacy including: (a) a comprehensive database with a year of observations of the physical, chemical and optical properties of aerosol particles over Europe, (b) comprehensive aerosol measurements in four developing countries, (c) a database of airborne measurements of aerosols and clouds over Europe during May 2008, (d) comprehensive modeling tools to study aerosol processes fron nano to global scale and their effects on climate and air quality. In addition a new Pan-European aerosol emissions inventory was developed and evaluated, a new cluster spectrometer was built and tested in the field and several new aerosol parameterizations and computations modules for chemical transport and global climate models were developed and evaluated. These achievements and related studies have substantially improved our understanding and reduced the uncertainties of aerosol radiative forcing and air quality-climate interactions. The EUCAARI results can be utilized in European and global environmental policy to assess the aerosol impacts and the corresponding abatement strategies.
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| 4. |
- 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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| 5. |
- 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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| 10. |
- Luostarinen, T, et al.
(författare)
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Joint effects of different human papillomaviruses and Chlamydia trachomatis infections on risk of squamous cell carcinoma of the cervix uteri
- 2004
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Ingår i: European Journal of Cancer. - : Elsevier BV. - 1879-0852 .- 0959-8049. ; 40:7, s. 1058-1065
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Tidskriftsartikel (refereegranskat)abstract
- This case-control study based in Nordic serum banks evaluated the joint effects of infections with genital human papillomavirus (HPV) types, and Chlamydia trachomatis in the aetiology of cervical squamous cell carcinoma. Through a linkage with the cancer registries, 144 cases were identified and 420 controls matched to them. Exposure to past infections was defined by the presence of specific IgG antibodies. The odds ratio (OR) for the second-order interaction of HPV16, HPV6/11 and C. trachomatis was small (1.0) compared to the expected multiplicative OR, 57, and the additive OR, 11. The interactions were not materially different among HPV16 DNA-positive squamous cell carcinomas. When HPV16 was replaced with HPV18/33 in the analysis of second-order interactions with HPV6/11 and C. trachomatis, there was no evidence of interaction, the joint effect being close to the expected additive OR. Possible explanations for the observed antagonism include misclassification, selection bias or a true biological phenomenon with HPV6/11 and C. trachomatis exposures antagonizing the carcinogenic effects of HPV16. (C) 2004 Elsevier Ltd. All rights reserved.
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