Rationale and design of a multicenter prospective cohort study for the eVALuation and monitoring of HPV Infections and relATEd cervical diseases in high-risk women (VALHIDATE study)

BACKGROUND: Pap screening, an effective method for cervical cancer prevention, is now supported by molecular human papillomavirus (HPV) testing. Recently commercialised preventive vaccines also provide new tools for the primary prevention of cervical cancer. To determine appropriate prevention strategies, the Health General Direction, Lombardy Region, funded a project that aims to characterize and monitor HPV infections and related cervical diseases in high-risk women. Methods/design VALHIDATE is a 5-year multicentre open prospective cohort study. It will recruit 7000 consenting women aged 13-65 years to provide information about the local biomolecular epidemiology of HPV infection and cervical diseases in high-risk women recruited from nine clinical centres and one faith-based organisation. The study will estimate the overall and type-specific prevalence of HPV infection and cervical abnormalities. It also aims to compare standard Pap screening with biomolecular screening, and to assist in the design of targeted regional prevention programs directed specifically at high-risk groups. Three groups of high-risk women: 1000 HIV-infected women (aged 26-65 years), 1000 recent migrant women (aged 26-65 years) and 3000 young women (aged 13-26 years) and 1 control group: 2000 women (aged 26-45 years) attending a spontaneous screening program, will be recruited. Sample sizes will be revised after the first year. Adult participants will undergo conventional cervical cytology, HPV DNA screening and genotyping. Paediatric participants will undergo HPV DNA testing and genotyping of urine samples. HPV DNA, cytological abnormalities and HPV types will be analysed according to demographic, epidemiological, behavioural, and clinical data collected in an electronic case report form. Overall and stratified prevalences will be estimated to analyse the associations between HPV infection and selected characteristics. Logistic regression models will be used to estimate crude and adjusted odds ratios. Cox proportional hazard models will be used to estimate hazard ratios over time and between groups. Discussion/main expected results This study will provide substantial insight into HPV infections and related cervical diseases in high-risk groups and will help determine appropriate regional cervical cancer prevention strategies. Study protocol: Sacco Hospital Ethical Committee resolution n35 (3rd Feb 2010), Sacco Hosp General Direction Resolution n174/2010 (9 March 2010).