Role of Human papilloma virus Infection and Altered Methylation of Specific Genes in Esophageal Cancer

Abstract

<b>Background:</b> Evaluation of Human papilloma virus (HPV) and its association with promoter methylationof candidate genes, p53 and Aurora A in esophageal cancer. Materials and <br/><b>Methods</b>: One hundred forty-oneesophageal tissue samples from different pathologies were evaluated for HPV infection by PCR, while thepromoter methylation status of p53 and Aurora A was assessed by methylation-specific restriction based PCRassay. Statistical analyses were performed with MedCalc and MDR software. <br/><b>Results</b>: Based on endoscopy andhistopathology, samples were categorized: cancers (n=56), precancers (n=7), esophagitis (n=19) and normals(n=59). HPV infection was found to be less common in cancers (19.6%), whereas its prevalence was relativelyhigh in precancers (71.4%), esophagitis (57.8%) and normals (45.7%). p53 promoter methylation did notshow any significant difference between cancer and normal tissues, whereas Aurora A promoter methylationdemonstrated significant association with disease (p=0.00016, OR:5.6452, 95%CI:2.18 to 14.6) when comparedto normals. Aurora A methylation and HPV infection was found in a higher percentages of precancer (66.6%),esophagitis (54.5%) and normal (45.2%) when compared to cancers (14.2%). <br/><b>Conclusions</b>: Aurora A promotermethylation is significantly associated with esophageal cancer, but the effect of HPV infection on this epigeneticalteration is not significant. However MDR analysis showed that the hypostatic effect of HPV was nullified whenthe cases had Aurora methylation and tobacco exposure. Further HPV sub-typing may give an insight into itsreduced prevalence in esophageal cancer verses normal tissue. However, with the present data it is difficult toassign any significant role to HPV in the etiopathology of esophageal cancer.