Barrett's oesophagus: can meaningful screening and surveillance guidelines be formulated based on new data and rejigging the old paradigm?
Gastro-oesophageal reflux disease (GORD) and Barrett's oesophagus (BO) have been considered to be the most important known risk factors for oesophageal adenocarcinoma (OAC). It has been the fastest growing cancer in the Western World and has occurred against a backdrop of progressive reduction in the risk estimate of malignancy associated with BO and no reduction in mortality from OAC using the prevailing screening and surveillance guidelines. The recently published link between high risk HPV and Barrett's dysplasia/cancer may be the 'missing' strong risk factor responsible for the significant rise of OAC since the 1970's, as has been the case with head and neck tumours, another viral associated cancer. P53 immunohistochemistry has been proposed as a good molecular marker for predicting disease progression in BD. Nevertheless, significant negative staining for this mutation in BD remains a major hurdle to widespread routine clinical use as a sole molecular marker. Recent data raises the distinct possibility of at least 2 (probably more) carcinogenic pathways operating in OAC. One is HPV mediated devoid largely of p53 mutations and the other p53 dependent. The joint use of both these markers as part of a molecular panel may represent the best bet yet of detecting the high risk group of progressors to OAC. Patients who are positive for either or both biomarkers i.e p53 or/and transcriptional markers of HPV may warrant more intensive screening. In future, genome wide technology may provide molecular signatures to aid diagnosis and risk stratification in BO.
Department of Gastroenterology & Hepatology, Bankstown-Lidcombe Hospital, South Western Sydney Local Health Network, Eldridge Road, Bankstown, Sydney, New South Wales 2200, Australia; South Western Sydney Clinical School, University of New South Wales, Kensington, Sydney, New South Wales, Australia; Gastro-Intestinal Viral Oncology Group, Ingham Institute for Applied Medical Research, Liverpool, Sydney, New South Wales 2170, Australia. Electronic address: Shan.Rajendra@sswahs.nsw.gov.au.
Shanmugarajah
S
Rajendra
D000230:Adenocarcinoma / Q000517:prevention & control* / Q000821:virology; D001471:Barrett Esophagus / Q000175:diagnosis* / Q000473:pathology / Q000821:virology*; D018450:Disease Progression; D055088:Early Detection of Cancer / Q000379:methods*; D004938:Esophageal Neoplasms / Q000517:prevention & control* / Q000821:virology; D005764:Gastroesophageal Reflux / Q000150:complications; D017408:Guidelines as Topic; D006801:Humans; D008403:Mass Screening / Q000379:methods; D030361:Papillomavirus Infections / Q000150:complications*; D011230:Precancerous Conditions / Q000175:diagnosis / Q000821:virology; D012307:Risk Factors
Barrett's oesophagus; Human papillomavirus; Oesophageal adenocarcinoma; Screening; Surveillance; p53