Several studies have detected human papilloma virus (HPV) DNA in squamous cell carcinoma of the oesophagus (OSCC). In this study, we analysed OSCC specimens from 114 patients for the presence of HPV DNA, and p53 and p73 expression. HPV DNA was detected in 44.7% of cases, with the low risk HPV11 occurring most frequently. p53 and p73 expression was detected in 70% and 61.4% of cases, respectively. There was no correlation between expression of p53, p73 or HPV infection and tumour grade, or between p53 expression and the presence of HPV DNA. There was, however, significant correlation between p73 expression and the presence of HPV DNA (p<0.01) and p53 and p73 co-expression (p<0.001), as well as co-expression of p53 and p73 with HPV status (p<0.05). These data support previous studies suggesting a role for HPV infection in OSCC and also indicate that HPV infection and p53 and p73 overexpression are not mutually exclusive. In addition, the data implicate a role for p73 in OSCC and suggest a complex interaction between p53, p73 and HPV in the aetiology of the disease.