Health-economic modelling of prevention strategies for HPV-related diseases in European countries

Cervical cancer is caused by a persistent infection of the human papillomavirus (HPV). There are at least fourteen HPV types that have oncogenic potential and are termed high-risk types. They are not only responsible for virtually all cervical cancer cases, but are also linked to penile cancer in men, vaginal and vulvar cancer in women, and to oropharyngeal, laryngeal, and anal cancer in both men and women. Among the oncogenic types, HPV16 and HPV18 stand out as the most important ones and are found in about 75% of the cervical cancer cases. Cervical screening programmes based on cytological testing have been implemented in several European countries. Although the incidence of cervical cancer has been substantially reduced in those countries, cervical cancer remains common and prevention needs to be further optimized. Testing for HPV DNA is currently being considered as an alternative for cytology, as it has higher sensitivity and shows less variability across populations. However, HPV DNA testing is less specific than cytology and may lead to an increase in the number of women referred for gynaecological examination and the number of detected low-grade lesions. Therefore, implementation of HPV DNA testing in the screening programme requires careful weighing of the expected costs and benefits. The aetiological link between HPV and cervical cancer has prompted the development of vaccines. In 2009 a national campaign has been initiated in the Netherlands to vaccinate all pre-adolescent girls. In large randomized trials, HPV16/18 vaccines have been shown to be nearly 100% effective in HPV16/18-naïve women against HPV16/18-positive cervical intraepithelial neoplasia grades 2 and 3 (CIN2/3), which are the major cervical cancer precursor lesions. HPV vaccination is expected to decrease the incidence of cervical cancer substantially, but screening will remain necessary also after implementation of vaccination. However, the optimal screening methods are likely to change in a population of HPV16/18-vaccinated women where abnormalities are rare. The new EC funded project 'PREHDICT' aims to determine prerequisites and strategies for vaccination in European countries and to predict the impact of vaccination on screening programmes. Because screening and vaccination trials have pre-invasive end-points and have only up to 6 years follow-up, mathematical modelling is required to predict the impact of screening and vaccination on life-years, cancer incidence, medical and non-medical costs. To achieve these goals, a multiple HPV type transmission model will be built to describe the type-specific incidence and clearance of HPV infections. This model will be linked to an individual-based simulation model used for modelling the impact of screening. For HPV-related diseases other than cervical cancer and genital warts, models will be developed after critical review of the role of HPV. To have models with strong empirical support, the PREHDICT team will collect the most updated data on HPV infection, HPV-related disease, life-style 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. Results will be pooled by meta-analytical techniques. The VUmc is the coordinator of the PREHDICT study and is involved in several work packages (WP) of the project. The VUmc is a main beneficiary in WP3 ‘Parameter estimates from European screening trials' and leads WP7 ‘Health economics’. In WP3, HPV genotype information will be collected from longitudinal screening trials. This information enables us to estimate the long-term incidence and clearance of type-specific HPV infections in European Union (EU) countries and is essential for the development of simulation models. In WP7, health economic evaluations will be done for different EU countries using an individual-based Markov simulation model. The cost-effectiveness of vaccination on the incidence of cervical cancer and other HPV-associated diseases will be estimated, and the impact of vaccination on existing cervical cancer screening programmes will be determined. Ultimately, WP7 aims to identify vaccination and screening strategies that optimize the health resources in a country-specific context. The results of the PREHDICT study will be posted on the WHO HPV information website and will be systematically disseminated to all major stakeholders, in particular to decision makers at European, national and sub-national levels. PREHDICT will aid in the improvement and standardization of prevention programmes against HPV-related diseases and fits the goals defined in the Third Prevention Programme.