BACKGROUND: Cervical screening using primary human papilloma virus (HPV) testing and cytology is being implemented in several countries. Cytology as triage for colposcopy referral suffers from several shortcomings. HPV testing overcomes some of these but lacks specificity in women under 30. Here, we aimed to develop and validate an automatable triage test that is highly sensitive and specific independently of age and sample heterogeneity, and predicts progression to CIN3+ in HPV+ patients. RESULTS: The WIDTM-qCIN, assessing three regions in human genes DPP6, RALYL, and GSX1, was validated in both a diagnostic (case-control) and predictive setting (nested case-control), in a total of 761 samples. Using a predefined threshold, the sensitivity of the WIDTM-qCIN test was 100% and 78% to detect invasive cancer and CIN3, respectively. Sensitivity to detect CIN3+ was 65% and 83% for women < and ≥ 30 years of age. The specificity was 90%. Importantly, the WIDTM-qCIN test identified 52% of ≥ 30-year-old women with a cytology negative (cyt-) index sample who were diagnosed with CIN3 1-4 years after sample donation. CONCLUSION: We identified suitable DNAme regions in an epigenome-wide discovery using HPV+ controls and CIN3+ cases and established the WIDTM-qCIN, a PCR-based DNAme test. The WIDTM-qCIN test has a high sensitivity and specificity that may outperform conventional cervical triage tests and can in an objective, cheap, and scalable fashion identify most women with and at risk of (pre-)invasive cervical cancer. However, evaluation was limited to case-control settings and future studies will assess performance and generalisability in a randomised controlled trial.

• MeSH
• Alphapapillomavirus * MeSH
• časná detekce nádoru MeSH
• dospělí MeSH
• dysplazie děložního hrdla * diagnóza   genetika   MeSH
• infekce papilomavirem * diagnóza   genetika   MeSH
• lidé MeSH
• metylace DNA MeSH
• nádory děložního čípku * diagnóza   genetika   MeSH
• Papillomaviridae genetika   MeSH
• Check Tag
• dospělí MeSH
• lidé MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH

The incidence of cancer is continuing to rise and risk-tailored early diagnostic and/or primary prevention strategies are urgently required. The ideal risk-predictive test should: integrate the effects of both genetic and nongenetic factors and aim to capture these effects using an approach that is both biologically stable and technically reproducible; derive a score from easily accessible biological samples that acts as a surrogate for the organ in question; and enable the effectiveness of risk-reducing measures to be monitored. Substantial evidence has accumulated suggesting that the epigenome and, in particular, DNA methylation-based tests meet all of these requirements. However, the development and implementation of DNA methylation-based risk-prediction tests poses considerable challenges. In particular, the cell type specificity of DNA methylation and the extensive cellular heterogeneity of the easily accessible surrogate cells that might contain information relevant to less accessible tissues necessitates the use of novel methods in order to account for these confounding issues. Furthermore, the engagement of the scientific community with health-care professionals, policymakers and the public is required in order to identify and address the organizational, ethical, legal, social and economic challenges associated with the routine use of epigenetic testing.

• MeSH
• epigenomika trendy   MeSH
• genom lidský genetika   MeSH
• hodnocení rizik * MeSH
• lidé MeSH
• metylace DNA genetika   MeSH
• nádory epidemiologie   genetika   MeSH
• rizikové faktory MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• přehledy MeSH

BACKGROUND/AIMS: Peginterferon plus ribavirin is the state-of-the-art antiviral therapy for prevention of serious complications of hepatitis C. Our aim was to compare market uptake of and access to these drugs across Europe. METHODS: We collected launch and sales data for peginterferons for 21 countries in the WHO European region and compared country-specific sales rates. Additionally, we converted sales figures into patient numbers and related those to country-specific hepatitis C prevalence, taking into account genotype distribution, patient characteristics and practice patterns. RESULTS: Peginterferon sales rates differed considerably across countries. The earliest, most rapid and highest adoption rates were in EU founder states, followed by EU members that joined after foundation, and EU non-member states. Most new member states showed a marked increase in sales. By the end of 2005, approximately 308,000 patients had been treated with peginterferons in the 21 countries evaluated. The number of patients ever treated ranged from 16% of prevalent cases in France to less than 1% of cases in Romania, Poland, Greece and Russia. CONCLUSIONS: Peginterferon market uptake and access differed considerably across Europe, suggesting unequal access to optimised therapy. Besides budget restrictions, national surveillance and treatment policies should be considered as reasons for market access variation.

• MeSH
• antivirové látky ekonomika   terapeutické užití   MeSH
• disparity zdravotní péče ekonomika   MeSH
• Evropská unie MeSH
• hepatitida C farmakoterapie   ekonomika   MeSH
• interferon alfa-2 MeSH
• interferon alfa ekonomika   terapeutické užití   MeSH
• lékařská praxe - způsoby provádění ekonomika   MeSH
• lidé MeSH
• marketing zdravotnických služeb ekonomika   MeSH
• náklady na zdravotní péči MeSH
• polyethylenglykoly ekonomika   terapeutické užití   MeSH
• rekombinantní proteiny MeSH
• ribavirin ekonomika   terapeutické užití   MeSH
• Světová zdravotnická organizace MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• srovnávací studie MeSH
• Geografické názvy
• Česká republika MeSH
• Kanada MeSH