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PREHDICT Report Summary

Project reference: 242061
Funded under: FP7-HEALTH
Country: Netherlands

Periodic Report Summary - PREHDICT (Health-economic modelling of prevention strategies for HPV-related diseases in European countries)

Project context and objectives:

The goals of the PREHDICT study are to determine prerequisites and strategies for vaccination in European countries and to predict the impact of vaccination on screening programmes. To achieve these goals, Human papillomavirus (HPV) type transmission models will be built to describe the transmission of HPV types between males and females and to describe the type-specific incidence and clearance of HPV infections. These models will be linked to an individual-based simulation model used for modelling the impact of screening. For HPV-related diseases other than cervical cancer, the impact of vaccination will be assessed after critical review of the role of HPV.

In the PREHDICT study, country-specific cost-effective analyses will be performed for the vaccination and include determination of the vaccination age, the number of doses, the vaccination population, and the optimal catch-up vaccination age. Furthermore, the impact of vaccination on screening programmes will be assessed. This involves determination of the screening technology, screening frequency, and follow-up management of test-positive women. Special attention will be given to screening attendance and its relation to vaccination attendance.

To have models with strong empirical support, the PREHDICT team will collect the most updated data on HPV infection, HPV-related disease, lifestyle factors, and demographics. Furthermore, HPV-type specific analyses will be performed on the outcomes of a vaccination trial, three large screening trials, and one self-sampling trial for screening non-attenders. By meta-analytical techniques, results will be pooled. The costs involved in the calculations will include the costs of organising, running, and monitoring a vaccination and/or screening programme.

The results of the PREHDICT study will be published in international peer-reviewed journals, posted on the World Health Organisation (WHO) HPV information centre website and will also be systematically disseminated to all major stakeholders, in particular to decision makers at European, national and sub-national levels.

Project results:

Epidemiological data on HPV infection, HPV-associated diseases, life style factors, and cancer prevention strategies

The objectives for these first 18 months of the project were to select, process and compile the data to be delivered in modules 2 and 5 of the European HPV epidemiological database (HPV-associated disease burden and socio-demographic indicators, respectively). During this period, data were compiled and datasets created, achieving the delivery of modules 2 and 5 as scheduled. Furthermore, the objectives of the project and performed work were to select, process and compile the data to be delivered in modules 3 and 4 of the European HPV epidemiological database (data on risk factors and cofactors for HPV exposure and cervical carcinogenesis, and on preventative strategies respectively). In addition, the data to be delivered in Module 1 of the European HPV epidemiological database (data on HPV prevalence and genotype distribution in subjects with and without cancer-related lesions) was selected, processed and compiled.

Parameter estimates from European screening trials

Samples from the NTCC trial (Italy), the POBASCAM trial (Netherlands), and the samples from the intervention arm of the Swedescreen trial have been typed. The typing data, together with cytological, and histological outcomes have been stored in a database. In tasks 3.1 and 3.2, estimates should be provided of the occurrence of new HPV infections by genotype and by age and of time- and age-specific clearance of HPV infection by type. For these tasks, the datasets were prepared and the preliminary analyses were performed. A similar approach was followed for task 3.6, in which an estimate has to be made for the predictive value of biomarkers in women with vaccine and non-vaccine HPV types and the need for new tests in these women.

Meta-analytical pooling of data providing parameters for modelling

The aim of the first 18 months period of Work package five (WP5) is to list-up study questions related to primary and secondary prevention of cervical cancer through HPV vaccination and HPV-based screening which can be addressed through meta-analyses. Moreover, the WP aims to conduct new meta-analyses and to update previous ones related to new screening methods, management of screen-positive women and prophylactic HPV vaccination. Specific activities were to continue updating previous reviews and to start new reviews on the accuracy of triage of women with atypical or low-grade cytological abnormalities using repeat cytology, high-risk HPV Deoxyribonucleic acid (DNA) testing, p16 immuno-testing and messenger Ribonucleic acid (mRNA) testing. Furthermore, new meta-analyses we set up comparing triage of women with ASCUS or LSIL cervical cytology using the new APTIMA assay versus the established HC2 test, and comparing p16 immunostaining vs HC2. The incidence of cervical intraepithelisal neoplasia and cervical cancer was also assessed among women with a negative HPV result versus a negative cytology at base line screening in randomised trials. Finally, work was continued related to the assessment of the accuracy of punch biopsies to detect cervical cancer precursors, using subsequent wide excision of cervical tissue as the gold standard.

HPV transmission modelling

In the first 18 months three dynamic HPV vaccination models were developed and brought to 'production' level. In addition a comprehensive statistical analysis plan for the community randomised (phase IV) trial on the effectiveness of HPV vaccination is shaping up.

The three models are:

- The Finnish Nation Institute of Health and Welfare (THL) / University of Tampere model (by Dr S-P Vänskä) has been used in modelling the various outcomes and cost-effectiveness impact of a national HPV vaccination program integrated or not integrated with the existing or changed / evolved national HPV screening model. Finnish national expert report on the implementation of HPV mass vaccination in Finland was based on this model.
- At the Imperial College London (ICL) the dynamic transmission model developed by dr. I. Baussano (under the supervision of Prof. Geoff Garnett) was accepted as a doctoral thesis (see list of scientific publications). It is being used e.g. in power calculations for the ongoing community randomised trial on the effectiveness of different HPV vaccination strategies.
- The third model at the London School of Hygiene and Tropical Medicine (LSHTM) is developed by Drs Helen Johnson and John Edmunds.

The models were brought to production level to be used in work linked to vaccination programme recommendation and the phase IV trial, continuing the work on parameterisation, developing, analysing, and comparing the results models produce with similar parameters (UTa & THL, ICL).

Health economics

The goal of WP7 is to evaluate the cost-effectiveness of prevention measures against HPV-related diseases in European countries. Besides, software tools need to be developed that enable local modelling. The goal of month 1-6 is to start the construction of a simulation model that describes the natural disease history based on HPV-type specific infections. This programme needs to be programmed in C++ (task 7.1). Furthermore, country-specific costs and utilities need to be collected.

The activities in Month 6-18 included the development of a module for evaluating prevention strategies by vaccination and screening and to provide a simulation model suitable for general consumption by other modellers. A microsimulation natural history model for 14 HPV types has been developed and programmed for studying the impact of vaccination and screening in a country-specific setting. The programme has an easy interface and can be connected to the transmission models developed in WP6. Furthermore, a flexible screening and vaccination module has been developed for assessment of the cost-effectiveness of several vaccination and screening strategies. To assess treatment costs, a questionnaire has been developed. The microsimulation model was applied to study the effect of differential vaccine pricing on the cost-effectiveness of adults in the Netherlands.


The overall objectives of WP8 are to disseminate information about the PREHDICT project goals and outcomes to the general public and to relevant professional audiences. For dissemination of information about the PREHDICT project to the general public, a section dedicated to the PREHDICT project was created on the ECCA website ( and the PREHDICT logo was placed on the homepage with a link to the PREHDICT section to facilitate access. A non-technical summary of the project was prepared and placed in the PREHDICT section of the ECCA website together with a summary of the project's objectives and partners. The design of a media briefing pack was started with delivery scheduled for month 36. The design of the web-based application for professional dissemination of results was started. A dedicated domain ( has been settled for the project, but access will be restricted until month 33 (see deliverable D8.4).

Potential impact:

The expected final results will be the following:

1. The European epidemiological HPV database will be accessible on the web and contains information on HPV prevalence, incidence of disease, lifestyle, screening efforts, and sociodemographics. These data are useful for stakeholders, epidemiologists, and modelers aiming at taking well-informed decisions about future prevention of HPV related diseases.
2. A European screening database will be constructed and analyses from this pooled database will appear in peer-reviewed journals.
3. Meta-analyses on the performance of cytological and molecular screening tests and the performance of colposcopy and biopsy will appear in in peer-reviewed journals.
4. Predictions from transmission models on the impact of vaccination will be available for several European countries.
5. Predictions on integrated vaccination and screening based on microsimulation modelling will be available for several European countries.
6. A (simplified) model will be accessible on the Web the purpose of which is to encourage local modelling efforts and to contribute to capacity building across the European countries.

The expected results of the project are essential for local governments in order to take well-informed decisions about future prevention of HPV-related diseases. Firstly, these results support decisions to be taken with regard to vaccination (the age of vaccination, the targeted vaccination population, and the catch-up vaccination age range). Secondly, for countries with a screening programme, the results will support health decision makers to decide on future screening instruments and the intensity of screening. Thirdly, the results enable health decision makers to have an informed discussion with industries that manufacture vaccines or screening tests about the pricing of their products. This ensures that both governments and industries can take the responsibility of enhancing preventive health care in Europe by cost-effective implementation of prevention strategies. Fourthly, the results will inform decision makers to be informed about changes to be made in the allocation of the health resources required to implement new prevention programmes. By offering a web-accessible version of the model, local modelling efforts are also stimulated. This may contribute to capacity building within the different European countries and further stimulates health-decision makers to take informed model-based decisions.

The PREHDICT study will further lead to an enhancement of the awareness and knowledge of the general public about HPV-related disease. Partner 9 (ECCA) is specialised in this field and has an excellent network to reach the general public in Europe. The improvement in knowledge among the audience is likely to lead to a better participation in European vaccination and screening programmes. This will eventually lead to a better women's health in Europe.

Project website:


Berkhof, Johannes (Head Unit Biostatistics)
Tel.: +31 20 4444909
Fax: +31 20 4444475

De Boelelaan, 1117

Record Number: 55310 / Last updated on: 2013-01-18
Information source: SESAM
Collaboration sought: N/A