de Oliveira Talita H A, Anderson Lesley A, Craig Stephanie G, Coleman Helen G, Gheit Tarik, McKay-Chopin Sandrine, Jamison Jacqueline, McManus Damian T, Cardwell Christopher R, Bingham Victoria, Johnston Brian T, James Jacqueline A, Kunzmann Andrew T
Patrick G. Johnston Centre for Cancer Research, Queen's University Belfast, Belfast, Antrim, United Kingdom.
Aberdeen Centre for Health Data Science, University of Aberdeen, Aberdeen, United Kingdom.
Br J Cancer. 2025 Apr 8. doi: 10.1038/s41416-025-03003-7.
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.
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.
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.
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.
已有研究推测高危型人乳头瘤病毒（HPV）在食管腺癌发生过程中起因果作用，但纵向证据有限。本研究旨在调查感染因子在巴雷特食管恶性进展中的潜在因果作用。
采用回顾性巢式病例对照研究设计，从北爱尔兰巴雷特食管登记册中检索出索引性巴雷特活检样本，这些个体随后进展为食管腺癌（n = 150），并与未进展者（n = 298）进行匹配。使用Luminex平台通过多重聚合酶链反应评估索引性巴雷特活检样本中142种感染因子的存在情况。RNA原位杂交评估后续组织样本中持续的转录活性，用于在进展者中更频繁检测到的感染因子。
高危型HPV基因型（HPV16和HPV18）仅在进展者的索引活检样本中被鉴定出来，而在未进展者中未被鉴定出（4% [5/150] 对0% [0/298]，P = 0.004），尽管在后续组织中未观察到持续存在或转录活性的迹象。对于任何其他感染因子，包括幽门螺杆菌和疱疹病毒，进展者和未进展者之间的感染患病率没有差异。
尽管进展者中高危型HPV的患病率高于未进展者，但在后续样本中未观察到转录活性高危型HPV的证据，表明其在巴雷特食管中的存在可能无因果关系。
