Barrett's oesophagus: Can meaningful screening and surveillance guidelines be formulated based on new data and rejigging the old paradigm?

Risk factors for esophageal cancer: emphasis on infectious agents

“…Previously published studies using PCR techniques that showed negative results were due to poor tissue classification, suboptimal testing methodology exacerbated by low viral load, old specimen samples susceptible to DNA/RNA degradation, as well as ethnic and regional variations . Instead of fresh frozen material, almost all of these retrospective investigations used paraffin‐embedded tissue, which yields a significant false negative HPV PCR DNA result . Some studies misclassified as negative used only nondysplastic BE.…”

“…Moreover, persistent hr‐HPV infection and p53 overexpression predicted treatment failure after endoscopic ablation of BD and EAC . The vast majority of BD and EAC specimens containing biologically active hr‐HPV were shown to have wild‐type TP53 , which is typical of HPV‐driven cancers . Recently, it was demonstrated that HPV‐associated EAC harbors a distinct profile of molecular aberrations/genomic abnormalities compared with HPV‐negative EAC, indicating different biological mechanisms of tumor formation .…”

“…GERD and BE have traditionally been considered the most important risk factors for EAC, the fastest growing cancer in the Western world and occurring against a backdrop of progressive reduction in the risk of malignancy associated with BE but no reduction in mortality from EAC, using the prevailing screening and surveillance guidelines. 68 The recently published link between high risk HPV and Barrett's dysplasia (BD)/cancer may be one of the missing strong risk factors responsible for the significant rise of EAC since the 1970s, as has been the case with head and neck squamous cell carcinomas, a significant minority of which are also virally associated. 69,70 Previously published studies using PCR techniques that showed negative results were due to poor tissue classification, suboptimal testing methodology exacerbated by low viral load, old specimen samples susceptible to DNA/RNA degradation, as well as ethnic and regional variations.…”

“…[71][72][73][74][75] Instead of fresh frozen material, almost all of these retrospective investigations used paraffin-embedded tissue, which yields a significant false negative HPV PCR DNA result. 68 Some studies misclassified as negative used only nondysplastic BE. Barrett's metaplastic tissue has never been shown to be HPV-associated.…”

“…80 The vast majority of BD and EAC specimens containing biologically active hr-HPV were shown to have wild-type TP53, which is typical of HPV-driven cancers. 60,68,81 Recently, it was demonstrated that HPV-associated EAC harbors a distinct profile of molecular aberrations/genomic abnormalities compared with HPV-negative EAC, indicating differ- ent biological mechanisms of tumor formation. 82 HPV-positive EAC was shown to have half the number of nonsilent somatic mutations than HPVnegative esophageal cancers.…”