Dr Lesley Anderson PhD MPHe BSc(Hons) PGCHET FHEA USING CANCER REGISTRY INFRASTRUCTURE AND LINKAGE TO BIOBANK FACILITIES TO INVESTIGATE THE ROLE OF INFECTIOUS AGENTS IN THE PROGRESSION FROM ESOPHAGEAL PREMALIGNANCY TO CANCER 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

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 esophagus biopsy tissue from patients who progressed to high grade dysplasia/esophageal adenocarcinoma and in a subgroup of non-progressors.

Human papillomavirus and esophageal adenocarcinoma 8,099 records 6,191 titles and abstracts screened in duplicate 170 full text articles assessed in duplicate 30 eligible studies 1,908 duplicates 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.

Northern Ireland Cancer Registry’s Pre-malignant Disease Registers Barrett’s register Colorectal polyp register Endometrial hyperplasia register MGUS (Monoclonal Gammopathy of Unknown Significance) register Barretts incidence 62.0/100,000 during 2002–2005. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3541934/ We estimate that the annual incidence of MGUS in men is 120 per 100,000 population at the age of 50 years and increases to 530 per 100,000 population at the age of 90 years. The rates for women are 60 per 100,000 population at the age of 50 years and 370 per 100,000 population at the age of 90 years.

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

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

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

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)

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

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

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).

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 So some examples of the datasets we hold – outpatients activity, admissions and discharges, prescriptions, patient registrations and so on.

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

CONTACTS Northern Ireland Cancer Registry‌ Centre for Public Health School of Medicine, Dentistry & Biomedical Science Queen's University Belfast Mulhouse Building Grosvenor Road Belfast BT12 6BJ Tel: +44 (0)28 9097 6028 E-mail: nicr@qub.ac.uk