incidence of 2.95 per 100,000 might be considered one of the low incidence areas. Esophageal carci- noma is among the most common gastrointestinal (GI) cancers in the province.2 There are significant differences in the epidemiology of ESCCs, which strongly implicate dietary and environmental fac- tors as well as an ill-defined contribution from genetic predisposition involved in etiology and pathogenesis of esophageal carcinomas.3 It has been shown that human papilloma virus (HPV) DNA is found frequently in ESCCs from high incidence areas. Its presence is infrequent, how- ever, in cancer-bearing patients of North America,4 and many other low incidence regions. Human papiloma virus particles are about 55 nm in diam- eter, and contain a circular ds DNA molecule of 7.2-8.0 Kbp. Human papiloma virus with more than 200 genotypes is implicated in the genesis of several cancers, particularly squamous cell carcinoma of the cervix, and anogenital, oral and laryngeal regions.5 Molecular analyses reveal that in benign and preneoplastic lesions, the HPV genome is maintained in an episomal (non integrated) form, whereas in cancers the viral DNA is usually inte- grated into the host cell genome. This suggests that the integration of viral DNA is important in malignant transformation. The site, at which the viral DNA is interrupted in the process of integra- tion, is fairly constant. It is almost always within E1/E2 open reading frame of the viral genome. Because the E2 region of the viral DNA normally represses the transcription of the E6 and E7 early viral genes, its interruption causes over expres- sion of the E6 and E7 proteins of the HPV-16 and HPV-18.6 Oncogenic potential of these HPVs may be related to these two early viral gene products.7,8 The E7 protein binds to the underphosphorylated form of the tumor-suppressor protein pRb and displaces the E2F transcription factors that are normally bound by pRb. The E6 protein binds to and facilitates the degradation of p53 gene product. The E6 and E7 proteins derived from high-risk HPVs (types 16, 18 and 31) bind to pRb and p53 with high affinity, whereas those of low- risk viruses (types 6 and 11) bind with low affinity. Thus, it seems that the E6 and E7 proteins of the high-risk HPVs disable two important tumor suppressor proteins that regulate the cell cycle. It has been reported that one particular allele of p53 with an arginine rather than a proline at a certain position is much more susceptible to degrada- tion by E6. Correspondingly, individuals with the “arginine form” of p53 have a seven fold higher risk of developing cervical cancer than those who do not posses this allele of p53.8,9 Although, these observations implicate Iran J Med Sci June 2012; Vol 37 No 2 Papilloma virus in esophageal squamous cell carcinoma certain HPV types in the pathogenesis of human cancer, it seems most likely that infection with HPV acts as an initiating event and that additional somatic mutations are essential for full malignant transformation. There are conflicting reports on the effects of formalin fixation on DNA quality. While a number of reports indicate that the use of formalin for tissue fixation causes DNA degradation and reduces DNA solubility, a number of others suggest that formalin fixation does not have significant effect on the successful amplification of DNA.10-12 de Villiers and colleagues studied 117 samples of esophageal carcinoma originating from the high incidence areas of china, and showed that HPV DNA was present in 20 out of 117 samples (17.1%). Only three of Mucosotropic HPVs were of the high risk types (HPV-16, 18 and 33).13 Li and colleagues evaluated specimens of balloon cytol- ogy examination from volunteers in two regions with significantly different incidence of esophageal carcinoma. Specimens were evaluated using both PCR and in situ hybridization (ISH) protocols. The results of PCR showed that the prevalence of HPV-16 E6 gene in the high incidence area was 1.9 fold higher than that of low incidence area (72% and 37% respectively, P<0.01). Simi- lar results were obtained with HPV-16 E7 gene using ISH. They suggested that HPV-16 plays a causative role in the pathogenesis of esophageal cancer, especially in the high incidence area of China.14 Si and colleagues evaluated some HPV-16 positive cases of ESCC in order to determine physical status of HPV-16 in these cases. They showed a predominance of integrated form of viral genes in HPV-16 positive ESCCs from china implying the HPV infection may play a role in the pathogenesis of ESCC.15 Shen and colleagues used a reliable model for studying the cellular and molecular mecha- nisms involved in carcinogenesis of esophageal carcinomas. In order to demonstrate the effect of viruses and tumor promoters on the tumorigenicity, human embryonic esophageal cells were infected with HPV-18 E6 E7-AAV in synergy with exposure to 12-o-tetradecanoyl phorbol 13-acetate (TPA). Malignant transformation of human embryonic epithelial cells was induced in vitro by HPV-18 E6E7 in synergy with TPA. This is a good evidence for the close relationship between HPV-18 as an etiologic factor and pathogenesis of esophageal carcinoma.16 In contrast to the above mentioned studies, there are several reports originating mainly from western European countries and United States of America that show the absence of HPV DNA in ESCCs. Some of these studies show only rare 127