Establishment of a national cervical screening programme in Ireland, CervicalCheck: the first 6 years.

The national cervical screening programme, CervicalCheck, commenced in Ireland in 2008. Free cervical smear tests are offered to over 1.2 million women aged 25-60 every 3 (aged 25-44) and 5 (aged 45-60) years. The purpose of this paper is to highlight the achievements and document the experience of the first 6 years of a new cervical screening programme. Data were extracted from the programme screening register and colposcopy management systems. SAS, version 9.4 was used for statistical analysis. Over 1.98 million smear tests were performed in over 1 million women during the first 6 years of the programme. Overall 5-year coverage at the end of the sixth year was 77.0%, where coverage is presented for the target population of women aged 25-60 years and is adjusted for hysterectomy rates. The numbers of women attending colposcopy increased significantly from 10 000 new patients attending for the first time in the first year to a peak of almost 17 500 in the third year. Increased capacity in colposcopy has delivered significant improvements in waiting times; the percentage of women referred to colposcopy offered an appointment within 8 weeks increased from 41.5% in year 1 to 93.4% in year 4 and has remained above the greater than 90% standard thereafter. The number of biopsies increased markedly, with 33 768 women being diagnosed with cervical intraepithelial neoplasia-grade 2 (CIN2), CIN3 or adenocarcinoma in situ and 860 being diagnosed with invasive cancer by the end of the sixth year. Lessons from CervicalCheck include the importance of capacity planning in programme delivery. The programme continues to evolve, particularly with the increased usage of human papillomavirus testing and planning for future testing of the human papillomavirus (HPV)-vaccinated cohort.

Increased Global DNA Methylation and Decreased TGFß1 Promoter Methylation in Glaucomatous Lamina Cribrosa Cells.

BACKGROUND: Glaucoma is an optic neuropathy that affects 60 million people worldwide. There is an underlying fibrosis associated with the lamina cribrosa (LC) in glaucoma. DNA methylation is well established in regulating fibrosis and may be a therapeutic target for glaucoma. The purpose of this study was to compare global DNA methylation levels in primary human normal (NLC) and glaucomatous (GLC) cells, and to investigate DNA methylation in driving fibrosis through regulation of transforming growth factor ß1 (TGFß1). MATERIALS AND METHODS: LC cells were cultured from normal and glaucomatous human donors. Global methylation was assessed by ELISA. qPCR was conducted for DNA methyltransferases (DNMTs), methyl-CpG-binding protein 2 (MeCP2), TGFß 1 and 2, collagen 1α1 (COL1A1), and α-smooth muscle actin (αSMA). TGFß1 and DNMT1 were examined by immunofluorescence. Methylation of the TGFß1 promoter was determined by methylation-specific PCR (MSP). RESULTS: Global DNA methylation demonstrated an increase in GLC compared with NLC cells (P<0.05). The previously mentioned methylation and matrix genes were increased in GLC compared with NLC cells (P<0.05). Immunofluorescence showed increased TGFß1 and DNMT1 in GLC compared with NLC cells. MSP showed increased unmethylated DNA in the TGFß1 promoter of GLC compared with NLC cells. CONCLUSIONS: We found increased expression of fibrotic genes in GLC cells and demonstrated an increase in global DNA methylation and in associated enzymes in GLC cells. Furthermore, we showed decreased promoter methylation of TGFß1 in GLC cells. Determining a role for methylation in glaucoma and in regulating TGFß1 may provide a novel therapeutic approach.