HPV HANDBOOK - Zervita

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THE POTENTIAL PUBLIC HEALTH IMPACT OF VACCINES AGAINST HPVprogrammes to ensure all benefits are realized, because the effects ofvaccination on women already exposed to HPV infection are not yetknown. Adding therapeutic properties to a prophylactic vaccine couldmake it a more attractive option to decision makers, because someshort-term gains would be possible. These considerations highlightthe importance of identifying suitable clinical trial endpoints.Implications for clinical trial endpointsTable 2 summarizes the efficacy trials for prophylactic vaccines thatare currently planned (2004).Table 2 Current stage of candidate HPV vaccine developmentVaccine type(prophylactic ortherapeutic)ProphylacticVLPProphylacticVLPProphylacticVLPGroup Antigen(s) Adjuvant Safety andimmunogenicitytrial results(Phase I–II)GSK L1 HPV16 & 18MerckL1 HPV16 & 18Clinical trialendpoints(Phase III–IV)Alum-based Ongoing PlannedAlum Ongoing In Phase III• Genital wartsrelated toHPV 6/11• CIN 1 relatedto HPV6/11/16/18• CIN 2/3related toHPV 16/18NCI L1 HPV 16 No adjuvant Ongoing Planned (CostaRica)• Persistentcervical HPV16 DNA• HPV 16positive LSIL(CIN 1)The choice of clinical endpoints for vaccine efficacy trials is animportant issue. Because clinical trials cannot ethically consider CC asa trial endpoint, other stages in disease pathogenesis, such aspersistent HPV infection or SIL, should be used as surrogate endpointsof vaccine efficacy. 2 However, using HSIL or LSIL as endpoints is73
3: HPV AND CERVICAL CANCER: PUBLIC HEALTH PERSPECTIVESproblematic. While 30% of women with persistent oncogenic HPVinfections were observed to develop cervical dysplasia, only 5–8% ofthose women developed HSIL. 18 Few cases of HSIL develop into CC,so if HSIL were used as an endpoint, large, extended clinical trialswould be required, and a possibly effective prophylactic vaccine wouldbe beyond the reach of women who could have benefited from it.Using LSIL as an endpoint could introduce significant inter-observerand inter-laboratory variation and, since LSIL can resolvespontaneously, vaccine efficacy might not be accurately recorded. Asshown in Table 2, another endpoint is persistent HR HPV DNApositivity,as this can be reliably and consistently determined and is anecessary step in disease pathogenesis.Figure 7 shows the modelled impact of vaccination on LSIL, HSIL andCC on the HPV types vaccinated against over the first 25 years. Thedecrease in type-specific LSIL is earlier and of greater magnitude,compared with HSIL. Thus, the model results support the use of typespecificLSIL as a trial endpoint, because it is a surrogate for thedecrease in CC incidence that follows the LSIL incidence decrease.The introduction of an HPV vaccine based on reduction in typespecificLSIL has the potential to save lives because the time-intervalbefore a reduction in HSIL would be many more years.Annual SIL incidenceper 100 000 women500 5045LSIL – novaccination400405530030252001000520 35 50 65 80Years after vaccination20151050Annual ICC incidenceper 100 000 womenLSIL – 80%vaccinationHSIL – novaccinationHSIL – 80%vaccinationCervical cancerno vaccinationCervical cancer80% vaccinationFigure 7 The effect of vaccination on the incidence of LSIL, HSIL and CC:implications for trial endpoints74
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THE HEALTH PROFESSIONAL’SHPV HAND
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ContentsList of contributors 7Intro
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Introduction to the HPV Handbook se
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3: HPV AND CERVICAL CANCER: PUBLIC
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Page 80 and 81: Indexadenocarcinoma,detection by HP
Page 82 and 83: INDEXuse in ASCUS 53use to confirm
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HPV HANDBOOK - Zervita

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