Universal immunisation with human papillomavirus (HPV) vaccine among females aged 12-17 recommended in Germany Y Deleré (firstname.lastname@example.org), C Meyer, S Reiter Immunisation Division, Department for Infectious Disease Epidemiology, Robert Koch-Institut, Berlin, Germany In March 2007, vaccination against human papillomavirus (HPV) was added to the recommended routine immunisation schedule in Germany . Primary immunisation is recommended for females aged 12 to 17. It involves three separate 0.5 mL doses of the vaccine according to the following schedule: first dose at elected date; second dose two months after the first; third dose six months after the first. Unlike many other European countries, Germany does not have a nationwide vaccination programme. The Standing Committee on Vaccination at the Robert Koch-Institut (Ständige Impfkommission, STIKO) gives general recommendations, which are the basis for recommendations in the federal lands (Länder) and put into practice by individual physicians. STIKO has strongly recommended the implementation of a coordinated immunisation programme regarding HPV vaccination between physicians, pediatricians, gynaecologists and public health practitioners to assure the immunisation of 12. to 17 year old girls before their first sexual intercourse. The primary aim of introducing the HPV vaccine into the routine immunisation schedule is the reduction of morbidity and mortality due to cervical cancer. An estimated 6,500 cases of cervical cancer are diagnosed in Germany every year, with an estimated 1,600 deaths . Infections with carcinogenic HPV types (mainly HPV type 16 and 18) can result in cervical cancer precursor lesions, which can progress to cervical carcinoma if left untreated . Studies have shown that HPV-DNA is detectable in 90% of cervical cancer tissue [4,5]. HPV 16 accounts for approximately 50-60% and HPV 18 for 10-20% of cervical carcinomas . The available vaccine is a mixture of different HPV type-specific VLPs (virus-like particles) prepared from the L1 protein of different HPV types. Clinical trials have shown high efficacy of available vaccines in preventing persistent HPV infection and cervical cancer precursor lesions among females without HPV infections at the time of vaccination (95.2%; (95%, KI: 87.2-98.7)) . Genital HPV infection is a common sexually transmitted disease. In one study of adolescents and young women aged 13 to 21 years, 70% had evidence of HPV infection within five to seven years of onset of sexual activity . To achieve optimal effectiveness of the vaccination, it is recommended that immunisation should be completed before onset of sexual activity. In Germany, according to national survey data, 12% of females report being sexually active by age 14 years, 23% by age 15 years and 47% by age 16 years . Vaccination will be free of charge for patients and will be provided by paediatricians, general practitioners and gynaecologists (by age 16 years, 72% of females have consulted a gynaecologist ). STIKO’s task is to recommend immunisation on an epidemiological risk benefit analysis, so no comparisons of health technologies in prevention were undertaken. Nevertheless, the committee stressed the need for the continuation and modification of the screening programme. Its recommendations also made it clear that the programme must be monitored and that vaccination and screening are synergistic strategies; the latter should be taken into account by all institutions responsible for the structure of the health system in Germany. References: 1. Robert Koch-Institut, Berlin. Impfung gegen humane Papillomaviren (HPV) für Mädchen von 12 bis 17 Jahren – Empfehlung und Begründung. Epidemiol Bull 12/2007. Available from: http://www.rki.de/cln_048/nn_205760/DE/Content/Infekt/EpidBull/Archiv/2007/12__07,templateId=raw,pro perty=publicationFile.pdf/12_07.pdf 2. Bertz J, Giersiepen K, Haberland J, Hentschel S, Kaatsch P, Katalinic A, Stabenow R, Stegmaier C, Ziegler H. Krebs in Deutschland. 5.überarbeitete, aktualisierte Ausgabe. Gesellschaft der epidemiologischen Krebsregister in Deutschland e.V. und das RKI. Saarbrücken, 2006. 3. zur Hausen H. Papillomavirus causing cancer: Evasion from host-cell control in early events in carcinogenesis. J Natl Cancer Inst 2000; 92: 690-698. 4. Munoz N, Bosch FX, de Sanjose S, Herrero R, Castellsague X, Shah KV, Snijders PJ, Meijer CJ; International Agency for Research on Cancer Multicenter Cervical Cancer Study Group. Epidemiologic classification of human papillomavirus types associated with cervical cancer. N Engl J Med. 2003;348:518-27. 5. Walboomers JM, Jacobs MV, Manos MM, Bosch FX, Kummer JA, Shah KV, Snijders PJ, Peto J, Meijer CJ, Munoz N. Human papillomavirus is a necessary cause of invasive cervical cancer worldwide. J Pathol 1999; 189: 12–19. 6. Munoz N, Bosch FX, Castellsagué X, Diaz M, de Sanjose S, Hammouda D, Shah KV, Meijer CJ. Against which human papillomavirus types shall we vaccinate and screen? The international perspective. Int J Cancer 2004; 111: 278-285. 7. Villa LL, Costa RL, Petta CA, Andrade RP, Ault KA, Giuliano AR, Wheeler CM, Koutsky LA, Malm C, Lehtinen M, Skjeldestad FE, Olsson SE, Steinwall M, Brown DR, Kurman RJ, Ronnett BM, Stoler MH, Ferenczy A, Harper DM, Tamms GM, Yu J, Lupinacci L, Railkar R, Taddeo FJ, Jansen KU, Esser MT, Sings HL, Saah AJ, Barr E. 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. Lancet Oncol. 2005; 6:271-8. 8. Moscicki AB, Hills N, Shiboski S et al. Risks for incident human papillomavirus infection and low-grade squamous intraepithelial lesion development in young females. JAMA 2001; 285: 2995-3002. 9. Jugendsexualität. Repräsentative Wiederholungsbefragung von 14- bis 17-Jährigen und ihren Eltern. 2005. Hrsg.: BZgA Köln, 2006. Available from: http://www.sexualaufklaerung.de/index.php?docid=962 Human papillomavirus vaccination: the United Kingdom’s recommendation and update on European licensure and efficacy data R Howell-Jones (Rebecca.Howell-Jones@hpa.org.uk), Health Protection Agency, London, United Kingdom Introduction The United Kingdom (UK) has announced that it will introduce a Human papillomavirus (HPV) vaccination programme for all 12- to 13-year-old girls starting in 2008, and will implement a catch- up campaign for girls up to 18 years old [1,2,3]. This strategy was recommended by the Joint Committee on Vaccination and Immunisation (JCVI), which provides independent expert advice to the British government on publicly funded immunisation. The JCVI’s recommendations follow extensive review of the evidence on the potential impact of HPV vaccination in the UK and assessment of the cost-effectiveness of HPV vaccination as an additional measure – besides cervical screening – to prevent cervical cancers and pre-cancers. There are currently around 2,500 cases of cervical cancer in the UK annually, and around 1,000 deaths . The UK will start to vaccinate 12-13 year old girls (school year 8) in September 2008. The age of around 12 years has been identified as an appropriate target age from available data on sexual activity  and HPV infection . Furthermore, some work has indicated that 12 years is considered an acceptable age for HPV vaccination . Primary Care Trusts will plan how to deliver the vaccine programme locally, but the JCVI has advised that HPV vaccination would be most efficiently delivered through schools. The UK will also conduct a catch-up campaign targeting those up to the age of 18 years. In England and Wales, the intention is to conduct the catch-up campaign during the secondand third years of vaccination by offering vaccination to girls in school years 12 and 13 (school years in which girls turn 17 years and 18 years respectively) in the autumn of 2009, and to girls in school years 11 and 12 (school years in which girls turn 16 years and 17 years respectively) in the autumn of 2010 [1,2]. In Scotland, the catch-up campaign will be carried out over the two-three- year period following the start of routine immunisation, and will target all younger than 18 years in September 2008 . Delivery plans are likely to include the involvement of general practitioners and others in enabling routine and catch-up vaccinations that are not delivered through educational settings. Decisions are still awaited on which of the two licensed vaccines (bivalent from GlaxoSmithKline or quadrivalent from Sanofi Pasteur MSD) will be used in the UK national vaccination programme and how the vaccine should be made available to some women aged 18 years or older at the start of the vaccination programme who might benefit from vaccination. As a decline in cervical cancers and pre-cancers is not expected to be seen for over 10 years, the impact of the vaccination programme will be measured initially by monitoring vaccine coverage, conducting surveys of type-specific HPV DNA and seroprevalence (among both vaccinated females and unvaccinated females and males) and the enhanced surveillance of warts incidence (if appropriate). The British government’s decision follows decisions to introduce HPV vaccination in several other European countries, including Austria, Belgium, Denmark, France, Germany, Italy, Luxembourg, Norway, Spain, Sweden, and Switzerland [8,9]. Licensure in Europe Two HPV vaccines are now licensed by the European Medicines Agency (EMEA). In September 2007, Cervarix, a bivalent HPV 16 and 18 vaccine from GlaxoSmithKline was licensed for the prevention of high-grade cervical intraepithelial neoplasia (CIN) grades 2 and 3 and cervical cancer causally related to HPV 16 and 18 . This follows licensure by EMEA one year previously of Gardasil, a quadrivalent HPV 6, 11, 16 and 18 vaccine from Sanofi Pasteur MSD . Latest findings from clinical trials Phase III efficacy data The latest data for Gardasil and Cervarix, published this year, show efficacy of over 90% in HPV- naïve women for both vaccines [12,13]. Gardasil has also been shown to have similar efficacy against warts caused by HPV 6 and HPV 11 . Table 1 summarises these Phase III efficacy data. Data on the two vaccines are not directly comparable, as analyses of different sub-groups of the study population have been reported. There are also differences in follow-up periods. Published efficacy data from Phase II trials have been summarised previously in Eurosurveillance . Cross-protection data Data, albeit limited, in support of some cross protection against non-vaccine HPV types have also been presented this year for both HPV vaccines. The potential for additional benefit due to cross- protection is due to the closely related nature of many of the high-risk oncogenic HPV types. HPV 16 is part of the A9 HPV species that includes HPV types 33, 31, 58, 52 and 35 : 15.6% of cervical cancers worldwide are attributed to these five types . The contribution of each of these types to cervical cancer worldwide is 4.4%, 3.5%, 3.4%, 2.5% and 1.8% respectively . HPV 18 is a member of the HPV A7 species: a group that also includes HPV types 45, 59, 39 and 68 : 6% of cervical cancers worldwide are attributed to these five types, with each type associated with 3.7%, 1.1%, 0.7%, and 0.5% respectively . Analyses for the two vaccines have reported different end points and reported on slightly different groupings of HPV types. Efficacy against persistent infection, CIN1+ and CIN2+ related to groups of HPV types composed of types 31, 33, 45, 52, 58 and related to any of 10 non-vaccine oncogenic types have been reported for the quadrivalent vaccine ; while efficacy against incident infection  and persistent infection with individual HPV types 31, 33, 45, 52, 58 and with any of 12 non- vaccine HPV types  have been reported for the bivalent vaccine. Recently reported data on evidence of cross-protection are summarised in Table 2. References: 1. Department of Health. Press release: HPV vaccine recommendation for NHS immunisation programme. 26 October. Government News Network. http://www.gnn.gov.uk/environment/fullDetail.asp?ReleaseID=325799&NewsAreaID=2&NavigatedFromDepa rtment=False [Accessed 29 October 2007]. 2. Health of Wales Information Service. News: Vaccination against Cervical Cancer to be introduced in Wales. Welsh Assembly Government. 26 October 2007. http://www.wales.nhs.uk/newsitem.cfm?contentid=7808 [Accessed 30th October 2007]. 3. The Scottish Government. News: Cervical cancer vaccine. 26 October 2007. http://www.scotland.gov.uk/News/Releases/2007/10/26114714 [Accessed 30 October 2007]. 4. Cancer Research UK. Cervical Cancer: UK Cervical Cancer Statistics. August 2007. http://info.cancerresearchuk.org/cancerstats/types/cervix/?a=5441 [Accessed 2 November 2007]. 5. Wellings K, Nanchahal K, Macdowall W, McManus S, Erens B, Mercer CH, et al. Sexual behaviour in Britain: early heterosexual experience. Lancet 2001;358:1843-50. 6. Jit M, Vyse A, Borrow R, Pebody R, Soldan K and Miller E. Prevalence of human papillomavirus antibodies in young female subjects in England. Br J Cancer 2007; doi:10.1038/sj.bjc.6603955. 7. Noakes K, Yarwood J, Salisbury D. Parental response to the introduction of a vaccine against human papilloma virus. Hum Vaccin. 2006;2:243-48. 8. Kudjawu Y, Lévy-Bruhl D, Pastore Celentano L, O’Flanagan D, Salmaso S, Lopalco P, et al. The current status of HPV and rotavirus vaccines in national immunisation schedules in the EU – preliminary results of a VENICE survey. Euro Surveill. 2007;12(4):E070426.1. Available from: http://www.eurosurveillance.org/ew/2007/070426.asp#1 9. Medical News Today. Two more European countries recommend free human papillomavirus vaccination for pre-adolescent girls to prevent cervical cancer. 16 October 2007. http://www.medicalnewstoday.com/articles/85624.php [Accessed 14 November 2007]. 10. European Medicines Agency (EMEA). EPARs for authorised medicinal products for human use: Cervarix. 3 October 2007. http://www.emea.europa.eu/humandocs/Humans/EPAR/cervarix/cervarix.htm [Accessed 30 October 2007]. 11. European Medicines Agency (EMEA). EPARs for authorised medicinal products for human use: Gardasil. Revision 4. 7 September 2007. http://www.emea.europa.eu/humandocs/Humans/EPAR/gardasil/gardasil.htm [Accessed 30 October 2007]. 12. Paavonen J, Jenkins D, Bosch FX, Naud P, Salmerón J, Wheeler CM, et al. for the HPV PATRICIA study group. Efficacy of a prophylactic adjuvanted bivalent L1 virus-like-particle vaccine against infection with human papillomavirus types 16 and 18 in young women: an interim analysis of a phase III double-blind, randomised controlled trial. Lancet 2007;369:2161-70. 13. The Future II Study Group. 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. Lancet 2007; 369:1861–68. 14. Garland SM, Hernandez-Avila M, Wheeler CM, Perez G, Harper DM, Leodolter S, et al. for the Females United to Unilaterally Reduce Endo/Ectocervical Disease (FUTURE) I Investigators. Quadrivalent vaccine against human papillomavirus to prevent anogenital diseases. N Engl J Med 2007;356:1928-43. 15. Editorial team. Mounting evidence of the efficacy of human papillomavirus vaccines. Euro Surveill. 2006;11(5):E060511.3. Available from: http://www.eurosurveillance.org/ew/2006/060511.asp#3 16. Muñoz N, Castellsagué X, de González AB, Gissmann L. Chapter 1: HPV in the etiology of human cancer. Vaccine 2006; 24(S3):1-10. 17. Clifford G, Franceschi S, Diaz M, Muñoz N, Villa LL. Chapter 3: HPV type-distribution in women with and without cervical neoplastic diseases. Vaccine 2006; 24(S3):26-34. 18. Brown D, for the FUTURE Study Group. HPV Type 6/11/16/18 Vaccine: First analysis of cross-protection against persistent infection, cervical intraepithelial neoplasia (CIN), and adenocarcinoma in situ (AIS) caused by oncogenic HPV types in addition to 16/18. ICAAC Chicago. September 2007. 19. Harper DM, Franco EL, Wheeler CM, Moscicki A-B, Romanowski B, Roteli-Martins CM, et al. on behalf of the HPV Vaccine Study Group. Sustained efficacy up to 4.5 years of a bilvalent L1 virus-like particle vaccine against human papillomavirus types 16 and 18: follow up from a randomised control trial. Lancet; 2006; 367:1247-55. Eurosurveillance, Volume 12, Issue 17, 26 April 2007 Articles Citation style for this article: Kudjawu Y, Lévy-Bruhl D, Pastore Celentano L, O’Flanagan D, Salmaso S, Lopalco PL, Mullins N, Bacci S. The current status of HPV and rotavirus vaccines in national immunisation schedules in the EU – preliminary results of a VENICE survey. Euro Surveill. 2007;12(17):pii=3181. Available online: http://www.eurosurveillance.org/ViewArticle.aspx?ArticleId=3181 The current status of HPV and rotavirus vaccines in national immunisation schedules in the EU – preliminary results of a VENICE survey Y Kudjawu1, D Lévy-Bruhl (email@example.com)1, L Pastore Celentano2,3, D O’ Flanagan4, S Salmaso2, P Lopalco3, N Mullins4, S Bacci2 on behalf of the VENICE working group* 1. Institut de Veille Sanitaire (National Institute of Public Health, INVS), Paris, France 2. Istituto Superiore di Sanità (National Institute of Health, ISS), Rome, Italy 3. European Centre for Disease Prevention and Control (ECDC), Stockholm, Sweden 4. Health Protection Surveillance Centre, Dublin, Ireland In the second half of 2006, two vaccines against rotavirus infections and one against human papillomavirus (HPV) infection were granted licensing authorisations by the European Medicines Agency (EMEA). A second HPV vaccine is currently under evaluation by EMEA and is expected to be licensed this year. With the availability of these new vaccines, European countries are facing one question: should they be integrated into the national or, where applicable, regional immunisation schedules? Although the products were shown to be safe and effective in phase II and III randomised clinical trials, the decision to adopt a universal immunisation strategy is not an easy one. The alleged added benefit of the HPV vaccination in the prevention of cervical cancer when compared with high coverage regular screening is questionable. Diarrhoea due to rotavirus infections is very common in infants and young children, with an estimated 80% cumulative risk of developing the disease before the age of five years . However, rotavirus-related deaths are very rare. In 2005, it was estimated that 231 deaths due to rotavirus had occurred in the then-25 European Union Member States’ total population of 23,598,000 children aged five years and under . The decision to include these vaccines in the national immunisation programmes should therefore be based on thorough epidemiological and economical analyses – ideally, modelling exercises. With the aim of promoting the exchange of information, tools and expertise, the Vaccine European New Integrated Collaboration Effort (VENICE)* working group carried out a survey to monitor the decision-making process across the EU. After a pilot survey had been completed in five volunteer countries, two questionnaires, one for each vaccine, were posted in January 2007 on a secured section of the VENICE website. Questions covered the availability of relevant epidemiological data as well as studies or analyses already carried out or planned to support the decision on the vaccines’ introduction. Among these, the development of mathematical models or economic assessments was considered. The willingness of the participating countries to exchange developed tools was also investigated. In each country, a ‘gatekeeper’ (appointed to act as a national contact point for the VENICE project) was asked to fill in both questionnaires or have them filled in by the relevant experts. All EU Member States (except Malta and Estonia for the HPV survey and only Malta for the rotavirus survey) and two EEA/EFTA countries (Iceland and Norway) completed both questionnaires. The full analysis is still ongoing, but some conclusions regarding the decision process can already be highlighted, keeping in mind the rapidly evolving situation. HPV vaccination As of the end of March 2007, the decision to include the HPV vaccination in the immunisation programme had already been taken in four countries: Austria, Germany, France and Italy. In Italy, the vaccine will be given to 12-year-old girls. In France, 14-year-old females are targeted and a catch-up is recommended for those up to 23 years of age who are not yet sexually active or have only recently started their sexual life. In Germany, the target population consists of girls aged 12 to 17 years . In Austria, the target population includes females, preferably before the beginning of sexual activity, but the vaccination of persons of both sexes is seen as being useful in principle . In Italy, the vaccine is offered free of charge to the targeted population, whereas in the three other countries the decision regarding the reimbursement of the vaccine is still pending. In two countries (Greece and Slovakia), an expert advisory committee has recommended including HPV vaccination in the national immunisation schedule but no formal decision has yet been taken by the national authorities. Nine countries answered that the issue was currently under examination by their national immunisation advisory body. In seven states, such investigation is planned for the future, while in the remaining five the question was not under consideration at all. Rotavirus vaccination As of the end of March 2007, five countries have taken a decision regarding the rotavirus vaccination. In Austria, Belgium and Luxembourg, the vaccine has been included in the national immunisation schedule, although in Austria the decision to offer the vaccine free of charge has not yet been taken. France and Germany, on the other hand, decided not to recommend universal infant immunisation. In Slovakia, an expert advisory body recommended including the vaccination in the national programme, but no decision has yet been taken by the national authorities. In Spain, the advisory body recommended not to include the vaccine in the national immunisation programme. In Poland, the decision is currently under examination by the national immunisation advisory body. In 11 countries, such investigations are planned for the future, while in nine states the question is not under consideration at all. To our knowledge, this survey is the first to investigate prospectively the decision-making process regarding the integration of a newly available vaccine into the European national immunisation schedules. It is therefore impossible to compare the current situation with what happened with previous vaccines. Nevertheless, the fact that few countries have, by the end of March, chosen universal immunisation for HPV or rotavirus vaccines may indicate that these are difficult decisions. Further analysis of the questionnaires and follow-up of the situation will help to understand this process and to identify the main constraints in integrating the new vaccines into the universal immunisation schedules. * The Vaccine European New Integrated Collaboration Effort (VENICE, http://venice.cineca.org) project, supported by the European Commission’s Directorate General for Health and Consumer Protection (DG SANCO), was launched in January 2006 with the aim of establishing a European network of experts involved in national immunisation programmes . Its main objective is to encourage the use of standard approaches to the monitoring and evaluation of immunisation programmes. Acknowledgements We thank all national experts who filled in the questionnaires and we are especially grateful to Eva Appelgren (ISS, Roma) and Luca De Mattè (Cineca, Italy) for their contribution to the implementation of the survey. References: 1. Parashar UD, Alexander JP, Glass RI. Prevention of Rotavirus gastroenteritis among infants and children. Recommendations of the ACIP. MMWR. 2006; 55; (RR-12):1-13. 2. Soriano-Gabarro M, Mrukowicz J, Vesikari T, Verstraeten T. Burden of rotavirus disease in European Union countries. Pediatr Infect Dis J. 2006 Jan;25(Suppl):S7-S11. 3. Deleré Y, Meyer C, Reiter S. Universal immunisation with human papillomavirus (HPV) vaccine among females aged 12-17 recommended in Germany. Euro Surveill 2007;12(4):E070405.2. Available from: http://www.eurosurveillance.org/ew/2007/070405.asp#2 4. Austrian Vaccination Plan 2007. Available from: http://www.bmgfj.gv.at/cms/site/detail.htm?thema=CH0016&doc=CMS1038913010412 5. Pastore Celentano L, Lopalco PL, O'Flanagan D, Levy-Bruhl D, Ferro A, Tridente, G, Appelgren E, Salmaso S. VENICE: Europe's new network for vaccination. Euro Surveill. 2007 Jan 18;12(1):E070118.3. Available from: http://www.eurosurveillance.org/ew/2007/070118.asp#3 Eurosurveillance, Volume 10, Issue 37, 15 September 2005 Articles Citation style for this article: Lehtinen M. Preparations for implementing human papillomavirus vaccination should begin. Euro Surveill. 2005;10(37):pii=2791. Available online: http://www.eurosurveillance.org/ViewArticle.aspx?ArticleId=2791 Preparations for implementing human papillomavirus vaccination should begin Matti Lehtinen (Matti.Lehtinen@uta.fi) National Public Health Institute, Oulu, Finland The World Health Organization held a meeting in Geneva on 14-15 April 2005 on the latest developments in human papillomavirus (HPV) vaccination . The leading theme that emerged was how to implement within national programmes the concept of vaccinating adolescents both against a common sexually transmitted infection (STI) and against a chronic disease. HPV is the most common (often asymptomatic) STI in young people. The worst outcome occurs when infection with high risk (hr) HPVs progresses over about 20 years to anogenital cancer in 1/100 of infected individuals. This is the most important known cause of mortality from cancer among women worldwide (there are 239 000 deaths annually from cervical cancer alone). Fortunately, the incidence of other HPV-associated anogenital cancers is not very high, and most HPV-associated cancers can probably be prevented by HPV vaccination. The first generation of virus-like particle (VLP) vaccines against the most common hrHPVs (types 16 and 18) will probably be licensed in 2006 or 2007. The fact that infection with hrHPVs (types 16,18,31,33,35,39,45,51,52,56,58,59,66) is the major and necessary cause of cervical cancer and many anogenital cancers was underlined at the meeting in a presentation by Professor Harald zur Hausen (Deutsches Krebsforschungszentrum, Heidelberg), who also discussed the carcinogenic action of hrHPVs. The increase in sexual risk- taking behaviour since the 1970s has increased the prevalence of hrHPVs in women <25 years of age to 30% . The ongoing work of assessing HPV type-distribution in young and old women and in cervical neoplasia cases on five continents was introduced by Dr Nubia Munoz and Dr Silvia Franceschi (International Agency for Research on Cancer, Lyon). The proportion of cervical cancer preventable by HPV16/18 vaccine was 80% in developed countries and 60%-65% in the developing countries. Developing countries might benefit from inclusion of some of the other hrHPV types (31,33,45,52,58) in the vaccines. Tetravalent (HPV6/11/16/18, Merck & Co. Inc.) and bivalent (HPV16/18, GlaxoSmithKline Biologicals) vaccines are administrated in three doses during a conventional six month schedule. In phase II trials, both vaccines have induced 100-fold higher antibody levels than natural infections, and ≥90% vaccine efficacy (VE) against persistent HPV16 and HPV18 infections as outlined by Dr Elaine Esber (Merck) and Dr Gary Dubin (GlaxoSmithKline). Ongoing phase III trials will determine vaccine efficacy against HPV16/18 positive cervical intraepithelial neoplasia grade 2+ (CIN2+) and probably enable licensure of both the vaccines in 2006/7. Dr Matti Lehtinen (Finland) described the enrolment of 7000 girls aged 16 and 17 years, in a population study of 20% of all the 15 to 25 year old women who have received the tetravalent or the bivalent HPV vaccine in the phase III trials. To assess direct, indirect and total long term effects of the intervention, 18 000 non-vaccinated women aged 18 and 19 years were also enrolled. Passive follow up of all 25 000 young women by the Finnish Cancer Registry will assess vaccine efficacy of the different HPV vaccines against cervical carcinoma in situ by 2015. The effectiveness of hrHPV vaccination against cervical cancer in the developed and developing countries was considered by Dr Sue Goldie (Harvard University) and Dr Ewan Myers (Duke University). The duration of protection of HPV vaccination in adolescence is especially important if women acquire new infections later in life. In the worst case scenario, waning of immunity in 5 years would result in low or no reduction of cervical cancer incidence. On the other hand, assuming 10 to 30 year protection from HPV vaccines, a combination of HPV16/18 vaccination at the age of 12 years and a single lifetime hrHPV screening would most cost effectively decrease the incidence of cervical cancer by almost half, compared with no intervention or different (hrHPV screening or cervical smear screening) interventions. In summary, even affluent societies do not offer many health services that adolescents recognise to be related to their health and wellbeing. Soon to be licensed HPV vaccines probably pave the way for a variety of interventions against common STIs in the young. In this context, promotion of condom use, and screening for Chlamydia trachomatis and hrHPVs in young adults can be highly synergistic with the herd immunity induced by HPV vaccination of the new birth cohorts entering sexually active life. It is clear that the appropriate ages for these interventions vary by continent, country and even within countries. New work must be done to find out how not only the various stakeholders at the societal level but also adolescents and their parents can best become committed to the promotion of the sexual wellbeing of the young. Finland is starting a series of community randomised trials (preventive HPV vaccination, condom promotion and C. trachomatis screening) among 13 to 15 year olds, 15 to 17 year olds and 17 to 19 year olds in 2007, with the aim of tackling the silent STI epidemics of the young, most notably hrHPV. The author is the Finnish principal investigator of both Merck and GSK phase III HPV vaccination trials. References: 1. WHO. WHO consultation on human papiloomavirus vaccines. Wkly Epidemiol Rec 2005; 80(35): 299-301. (http://www.who.int/wer/2005/wer8035.pdf) 2. Laukkanen P, Koskela P, Pukkala E, Dillner J, Laara E, Knekt P, Lehtinen M. Time trends in incidence and prevalence of human papillomavirus type 6, 11 and 16 infections in Finland. J Gen Virol. 2003 Aug;84(Pt 8):2105-9. (http://vir.sgmjournals.org/cgi/content/full/84/8/2105) Eurosurveillance, Volume 8, Issue 48, 25 November 2004 Articles Citation style for this article: Evidence that HPV vaccine may be effective in preventing cervical cancer. Euro Surveill. 2004;8(48):pii=2593. Available online: http://www.eurosurveillance.org/ViewArticle.aspx?ArticleId=2593 Evidence that HPV vaccine may be effective in preventing cervical cancer Editorial team (firstname.lastname@example.org), Eurosurveillance editorial office and Catherine Lowndes, Health Protection Agency Centre for Infections, Commmunicable Disease Surveillance Centre, London, United Kingdom Recently published results of a randomised, double-blind, multi-centre, placebo-controlled trial involving 1113 women from North America and Brazil indicate that a vaccine against the two most common human papillomavirus (HPV) types causing cervical cancer, is highly effective at preventing recipients from viral infection and subsequent pre-cancerous abnormalities resulting from infection . The most commonly occurring oncogenic HPV types are HPV-16 and HPV-18. The evidence that these viruses are a cause of cervical cancer has been clearly established . Worldwide, HPV-16 accounts for more than 60% of invasive cervical cancers, and HPV-18 about 10%. The vaccine used in the trial contained HPV 16 and HPV 18 L1 virus-like particles (VLPs), which induced specific HPV antibody titres 80-100 fold greater than those seen in natural infections. The trial participants, aged between 15-25 years of age, received either the vaccine or a placebo at month 0, 1 month and 6 months. They were followed up over a period of 27 months. The groups receiving vaccine or placebo in the United States, Canada and Brazil were demographically similar. Also, similar proportions smoked, had multiple partners, and began sexual activity between 15-19 years of age. Women seropositive for HPV-16 or HPV-18, or high-risk HPV DNA-positive, were excluded from the according-to-protocol (ATP) analyses. In the ATP analyses, the vaccine was found to be 91.6% (95% Confidence Interval: 64.5-98.0) effective at preventing incident infection with the virus and 100% effective at preventing persistent infection. According to the intention-to-treat analyses, the vaccine was 95.1% effective against persistent cervical infection with HPV-16/18 and 92.9% effective against cervical cytological abnormalities associated with HPV infection. No serious adverse events occurred in either the vaccine or placebo groups and similar numbers of reports of fatigue and headaches were reported in both groups. The creation of HPV virus-like particle (VLP) vaccines in the 1990's was breakthrough, as HPV VLPs mimic HPV well, and induce a strong immunogenic response on vaccination. This study is further evidence of the efficacy of HPV VLP vaccines in prevention of incident and persistent cervical infections with HPV-16 and HPV-18, and associated cytological abnormalities and lesions [3,4,5]. Given the proven link between infection with high-risk HPV types and invasive cervical cancer, the study findings indicate that the vaccine could contribute substantially to reduction of rates of cervical cancer worldwide. However, as the authors state: ‘large-scale trials with long-term follow- up are needed to extend the findings and confirm that vaccination prevents cervical cancer.’ In Europe, despite extensive population-based Pap screening efforts in many countries, official estimates for 2002 were that approximately 60 000 new cases of cervical cancer were diagnosed and 30 000 women died from the disease that year . References: 1. Harper D, Franco E, Wheeler C, Ferris D, Jenkins D, Schuind A et al. Efficacy of a bivalent L1 virus-like particle vaccine in prevention of infection with human papillomavirus types 16 and 18 in young women: a randomised controlled trial. Lancet 2004: 364: 1757 2. Bosch FX, Lorincz A, Munoz N, Meijer CJ, Shah KV. The causal relation between human papillomavirus and cervical cancer. J Clin Pathol 2002; 55(4):244-65. 3. Harro CD, Susana Pang Y-Y, Roden R, et al. Safety and immunogenicity trial in adult volunteers of a human papillomavirus 16 L1 virus-like-particle vaccine. J Natl Cancer Inst 2001; 93: 284-92. 4. Koutsky LA, Ault KA, Wheeler CM, for the Proof of Principle Study Investigators. A controlled trial of a human papillomavirus type 16 vaccine. N Engl J Med 2002; 347: 1645-51. 5. Lowndes C. Promising results from trials of vaccines against human papillomavirus (HPV) and herpes simplex virus type 2 (HSV-2) genital infections. Eurosurveillance Weekly 2002; 6(51): 19/12/2002 (http://www.eurosurveillance.org/ew/2002/021219.asp#3) 6. GLOBOCAN 2002: Cancer Incidence, Mortality and Prevalence Worldwide. WHO International Agency for Research on Cancer. (http://www-depdb.iarc.fr/globocan/GLOBOframe.htm) associazione vaccinare informati doc./immagini news Novità del Piano nazionale Vaccinazioni 2008-2010 "Dal 1°Gennaio 2008 è entrato in vigore il nuovo piano nazionale per le vaccinazioni che in Italia coprirà il biennio 2008-2010. Già alla fine dello scorso anno avevamo avuto notizie dell’iter che la nuova regolamentazione avrebbe avuto. Ora ci siamo. Donato Greco, direttore generale del dipartimento prevenzione e comunicazione del ministero della Salute e direttore del Centro nazionale per la prevenzione e il controllo delle malattie aveva infatti anticipato alla fine del mese di novembre 2007 le nuove regolamentazioni con l’obiettivo di superare le differenze regionali su questa materia. Aveva assicurato Greco: ” Siamo quasi pronti e certi che il Piano diventi un Lea (i livelli essenziali di assistenza, dunque a carico del Ssn), e quindi si superino le differenze geografiche nell’offerta, che ancora esistono oggi in Italia”. Ma che cosa cambia in concreto in materia di vaccini? Innanzi tutto dalle attuali 9 vaccinazioni (quattro obbligatorie e cinque consigliate) si passerà a 12 e si cercherà di eliminare l’obbligatorietà lasciandole invece come consigliate ma sempre gratuite. In sostanza al piano nazionale 2005-2007 si affiancheranno altre 4 nuove vaccinazioni. Ma vediamo nel dettaglio le novità del piano: dal primo gennaio 2008 è stato introdotta la vaccinazione gratuita contro il papilloma virus a tutte le ragazze (circa 13.000) nel corso del dodicesimo anno di vita (ne avevamo parlato in questo articolo), per prevenire l’insorgere delle lesioni cancerose o pre-cancerose al collo dell’utero. La vaccinazione in questa fascia di età garantisce l’immunità prima dell’inizio dell’attività sessuale, elemento di importanza fondamentale dato che l’infezione da Hpv si trasmette proprio sessualmente. A partire dal primo luglio 2008 la vaccinazione antipneumococco verrà invece offerta gratuitamente per tutti i neonati, con l’obiettivo di raggiungere una copertura dell’80%. Ed ancora il «vecchio» vaccino trivalente contro il morbillo, la parotite e la rosolia diventa quadrivalente con l’aggiunta del vaccino contro la varicella (tra il tredicesimo e il quindicesimo mese e a 5-6 anni). Anche in questo caso la modifica sarà lanciata a partire dal luglio 2008. Il calendario prevede inoltre l’offerta attiva e gratuita della vaccinazione antivaricella anche a tutti gli adolescenti tra i 12 e i 14 anni...." Dal sito: http://www.medicinalive.com/sesso-fertilita/ostetricia-e-ginecologia/nuovo-piano-nazionale-vaccini-2008-2010-informarsi-per-prevenire/ Human papillomavirus (HPV) Human papillomaviruses are common throughout the world. Although most infections with HPV cause no symptoms, persistent genital HPV infection can cause cervical cancer in women. HPV can also cause other types of anogenital cancer, head and neck cancers, and genital warts, in both men and women. HPV are transmitted through sexual contact. HPV are estimated to cause about half a million cases of cervical cancer every year, and are the leading cause of death from cancer for women in the developing world. For many years, the main way to prevent cervical cancer has been through screening programmes. Unfortunately, these have not been successfully implemented in most low-resource settings. There are two HPV vaccines now being marketed in many countries throughout the world. Both vaccines are highly efficacious in preventing infection with virus types 16 and 18, which are together responsible for approximately 70% of cervical cancer cases globally. They are also highly efficacious in preventing precancerous cervical lesions caused by these types. One vaccine is also highly efficacious in preventing anogenital warts, a common genital disease which is virtually always caused by infection with HPV types 6 and 11. The primary target group in most of the countries recommending HPV vaccination is young adolescent girls. Data from clinical trials and initial post-marketing surveillance conducted in several continents show both vaccines to be safe. As of mid-2008, HPV vaccines had been recommended for use in females through the national immunization programmes of more than 15 high-income countries and at least two middle-income countries. Related links - Cervical cancer, human papillomavirus (HPV), and HPV vaccines. Key points for policy-makers and health professionals [pdf 174mb] - Preparing for the introduction of HPV vaccines: policy and programme guidance for countries - Human papillomavirus and HPV vaccines: technical information for policy-makers and health professionals - Cancer Control. Knowledge into action. WHO guide for effective programmes. Prevention [pdf 1.95Mb] - Comprehensive cervical cancer control. A guide to essential practice - WHO/ICO (Institut Català d’Oncologia) Information Centre on Human Papillomavirus (HPV) and Cervical Cancer - Sexually transmitted diseases and other reproductive tract infections - a guide to essential practice Netherlands Selects Glaxo Cervical Cancer Vaccine AP Online - Nov. 20, 2008 LONDON_British drug maker GlaxoSmithKline PLC said Thursday that the Dutch government has selected its cervical cancer vaccine Cervarix for a nationwide vaccination program. Glaxo did not disclose financial terms of the deal, which is a win for the London-based company over its rival Merck & Co.'s Gardasil vaccine. Both products vaccinate against human papillomavirus, a common cause of cervical cancer. Under the Dutch National Immunization Program, due to start in Sept. 2009, more than 350,000 girls aged between 12 and 13 will be vaccinated in the first year. Cervarix, which is already marketed in 67 countries across Europe and Asia, is still awaiting U.S. approval. Glaxo said in June that it had responded to questions raised by the U.S. Food and Drug Administration about the vaccine and that it will provide the agency with more complete late-stage study data in 2009. FDA action on the application is then expected to take up to six months.