1. 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

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

3. 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):

4. 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–
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.

5. 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)

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
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

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: )
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
Biosample resources
Simple 2 tiered application system
Linked clinical & pathological data
Distribution of de-identified samples & data worldwide including industry

10. 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).

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

13. 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.

14. 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)