THE ROLE OF THE HUMAN PAPILLOMA-VIRUS IN ESOPHAGEAL CANCER

Esophageal squamous cell carcinoma (ESCC) demonstrates wide regional v ariation in incidence and causal associations. Human papillomavirus (H PV) has been implicated in ESCC, particularly the sub-types 16 and 18. Transforming proteins E6 and E7 from these high risk sub-types, inter act with p53 protein and Rb protein respectively, leading to loss of f unction of these tumor suppressor gene products. These interactions fu rther lead to inactivation of the growth suppressive effects of the p5 3 and Rb proteins, resulting in abnormal proliferative states. p53 pro tein expression has been found in both HPV-positive and -negative tumo rs, indicating that HPV and p53 protein expression are not mutually ex clusive and can occur together in the same tumor. It has been observed that HPV plays a more significant role in esophageal carcinogenesis i n geographic areas with a high prevalence of the disease. A variation in the association between HPV and ESCC worldwide may be due to enviro nmental and geographic factors, or to genetic susceptibility to esopha geal HPV infections. Variations in the sensitivity of techniques used in the detection of the virus and in the methodology for processing th e tumor tissues, may also be responsible for global differences. Esoph ageal carcinogenesis is a complex multistep process with a multifactor ial etiology. Infection with oncogenic HPV types may be an integral pa rt in a multistep process that leads to ESCC.