SUMMARY: Certain viruses commonly infect and cause cancer in poultry. Human exposure to these viruses is virtually universal, and occurs through: 1) contact with live poultry, their blood, secretions, feces, raw meat, and eggs; 2) through ingestion of raw or inadequately cooked poultry meat and eggs; 3) inoculation with vaccines manufactured by growing the vaccine virus in chicken eggs contaminated with these viruses, such as measles, mumps, and yellow-fever vaccines; 4) occupationally in jobs such as raising, slaughtering, and sale of raw poultry products; veterinarians; cooks; etc. It is known that the viruses can infect human cells in vitro and transform them into cancerous cells, and can infect and cause tumors in primates. Serological tests in humans indicate widespread infection of the general population. However, definitive proof that the viruses cause cancer in humans is lacking partly because of the absence of analytic epidemiologic studies of cancer risk in exposed individuals. We hypothesize that if these viruses cause cancer in humans, it will be most readily evident in workers in poultry slaughtering & processing plants who have the highest human exposures to these agents. Accordingly, we conducted cancer mortality studies in three separate cohorts of these workers. The results indicate an excess occurrence of deaths from 10 cancer sites. We are currently conducting a NIOSH-funded RO1 case-cohort study of seven of these cancer sites (lung, pancreas, liver, brain, ovary, buccal & nasal cavities & pharynx, and hemopoietic & lymphatic systems). This application is an extension of this study in which we plan to investigate the role of these poultry oncogenic viruses in the occurrence of two of the remaining three sites, viz., esophagus and cervix. It is important to study these two cancers separately also, because of their known association with HPV infection that is abnormally highly prevalent in poultry workers. For controls we will utilize the same control group that is being used in the ongoing case-cohort study. Thus this proposal will permit investigation of these two cancer sites at much reduced costs. The purpose of the proposed study is 4-fold: 1) to investigate the link between tasks associated with high exposure to poultry oncogenic viruses, HPV, and occupational chemical carcinogenic exposures (polycyclic aromatic hydrocarbons, heterocyclic amines, nitrosamines, benzene, etc.) and the occurrence of these two cancer sites, while adjusting for and concurrently investigating the roles of other potential occupational and non-occupational risk factors; 2) to assist in providing the critical epidemiologic evidence linking avian oncogenic viruses with cancer occurrence in humans; 3) to examine the high occurrence of warts in different parts of the body of poultry workers as a risk factor for these cancers; 4) to identify prime biopsy samples of these two cancers that could be used in future laboratory-based studies to confirm the ro...