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Infectious Agents and Esophageal Adenocarcinoma: A Study from Northern Ireland

This study investigates the presence of infectious agents in Barrett's esophagus biopsy tissue from patients who progressed to high-grade dysplasia/esophageal adenocarcinoma. The preliminary results suggest that viral infections may not be involved in the progression to esophageal adenocarcinoma.

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Infectious Agents and Esophageal Adenocarcinoma: A Study from Northern Ireland

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  1. Kunzmann A, Tommasino M, Gheit T, Wilson R, Jamison J, Cardwell C, James JA, Johnston B, McManus D, Coleman HG, Anderson LA. Dr Lesley Anderson PhD MPHe BSc(Hons) PGCHET FHEA Acting Deputy Director, Northern Ireland Cancer Registry Senior Lecturer in Cancer Prevention, Queen’s University Belfast

  2. Infections and esophageal adenocarcinoma • John Cunningham virus implicated in EAC pathogenesis • Herpes simplex virus-1 (HSV-1) reported in achalasia patients. • Human papillomavirus and EAC • Aim: to investigate the presence of a range of infectious agents in Barrett's esophagusbiopsy tissue from patients who progressed to high grade dysplasia/esophagealadenocarcinoma and in a subgroup of non-progressors.

  3. Human papillomavirus and esophageal adenocarcinoma Forest plot of HPV prevalence in esophageal adenocarcinoma tissue. CI, confidence interval; HPV, human papilloma virus. Kunzmann et al. Eur J Gastro & Hepatol. 2017; 29(7):817-825.

  4. Northern Ireland Cancer Registry’s Pre-malignant Disease Registers • Barrett’s register • Colorectal polyp register • Endometrial hyperplasia register • MGUS (Monoclonal Gammopathyof Unknown Significance) register

  5. Pathology histopathology reports on new cancers- lab centre Business Services Organisation Demographic updates XRT Radiotherapy System Hospitals admissions (PAS) new cancers GRO (Death Register) Cancer deaths Multidisciplinary team meetings (CaPPS) Clinical Oncology System (COIS) / RISOH Input QARC (Quality Assurance Reference Centre Screening) Output Official Statistics Audit reports (changes in cancer care) Publish reports (cancer incidence, prevalence, survival & cancer trends) Research, education & service planning

  6. Barrett’s diagnoses and follow-up By 2010: n=13,294 incident BE (CLE), of which n=5,570 SIM positive By 2013: Almost 200 ‘progressors’ to HGD/OAC at least 1 year after index Barrett’s diagnosis

  7. Epidemiology of BE and EAC in Northern Ireland Esophageal adenocarcinoma incidence Barrett’s esophagus incidence (Coleman et al 2011 Eur J Epidemiol) Endoscopies per 100,000 population European age-standardised incidence per 100,000 EASR BE and biopsies per 100,000 population 150% Requested from Northern Ireland Cancer Registry, 2019

  8. NI Barrett’s Register • Overall mortality did not differ to general population. (Gut 2003;52(8):1081-4) • Progression to cancer lower than previously thought (0.22% per year). (JNCI 2011;103:1049-57.) • Smoking increases risk of progression to EAC. (Gastroenterol 2012;142(2):233-40) • Prior diagnosis of BE improves EAC survival. (Gut 2015;64(1):20-25)

  9. The Northern Ireland Biobank • Started 2010 • HTA licensed, HRA approved to collect, store & release samples • International standards of quality • Biosampleresources • Simple 2 tiered application system • Linked clinical & pathological data • Distribution of de-identified samples & data worldwide including industry

  10. Methods • Cases: Barrett’s esophagusesophagealadenocarcinoma • Controls: Barrett’s esophagusesophagealadenocarcinoma • Recruitment: Linkage of the NICR to the NI Barrett’s register. • Tissue: FFPE tissue from cases and controls retrospectively collected. • Processing: Non-contaminationguidelines for sectioning.Viral DNA assessed using a Luminex-based platform in the International Agency for Research on Cancer (IARC).

  11. Preliminary Results • 49 cases and 98 controls matched on age, gender are presented. • No cases or controls with JCV or HSV. Infectious Agents in 49 Barrett’s oesophagus patients who progressed to oesophageal adenocarcinoma (cases) and 98 Barrett’s oesophagus patients who did not progress (controls).

  12. Data Linkage Other data linkage possibilities: • Clinical Community Gateway (referrals from Primary to Secondary care) • Outpatients activity • Hospital Admissions and Discharges • Inpatient Waiting Lists • SOSCARE (Social Care) • NIMATS (NI Maternity System) • Primary Care Data including prescriptions

  13. Conclusions • Viral infections do not appear to be involved in the progression from Barrett’s oesophagus to oesophageal adenocarcinoma. • Premalignant registriesprovide many opportunities for informative research. • Obtaining multiple data sources improves case verification. • Linkages with a biobank enables internationally significant research.

  14. CONTACTS Northern Ireland Cancer Registry‌Centre for Public HealthSchool of Medicine, Dentistry & Biomedical ScienceQueen's University BelfastMulhouse BuildingGrosvenor RoadBelfastBT12 6BJTel: +44 (0)28 9097 6028 E-mail: nicr@qub.ac.uk

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