Infectious agents and progression from Barrett’s oesophagus to oesophageal adenocarcinoma: a nested case-control study

Background
A causal role of high-risk HPV in oesophageal adenocarcinoma development has been hypothesised, but longitudinal evidence is limited. This study aims to investigate a potential causal role of infectious agents in the malignant progression of Barrett’s oesophagus.

Methods
Using a retrospective nested case-control study design, index Barrett’s biopsies were retrieved for individuals within the Northern Ireland Barrett’s oesophagus register who subsequently progressed to oesophageal adenocarcinoma (n = 150) and matched non-progressors (n = 298). Index Barrett’s biopsies were assessed for the presence of 142 infectious agents by multiplex polymerase chain reaction using the Luminex platform. RNA in-situ hybridisation assessed persistent transcriptional activity in subsequent tissue samples, for infectious agents detected more frequently in progressors.

Results
High-risk HPV genotypes (HPV16 and HPV18) were only identified in the index biopsies of progressors but not non-progressors (4% [5/150] versus 0% [0/298], P = 0.004), though no signs of persistence or transcriptional activity were observed in subsequent tissue. Prevalence of infections did not differ between progressors and non-progressors for any other infectious agents, including Helicobacter Pylori and Herpes.

Conclusion
Despite a higher prevalence of high-risk HPV in progressors than non-progressors, no evidence of transcriptionally active high-risk HPV was observed in subsequent samples, indicating presence in Barrett’s is likely non-causal.