Susceptibility of various human tissues to transformation in vivo with human papillomavirus type 11

Human papillomaviruses (HPVs) are associated with proliferative lesions in a variety of human epithelial types. In some cases, the associations are highly specific in that a certain papillomavirus type may infect only one human epithelial cell phenotype. In other cases, one papillomavirus apparently infects several tissue types and not others. Further, HPV replication capacity varies considerably in different epithelia. Due to the lack of a suitable method, it has not been possible, until now, to define the role of the host cell phenotype in determining the outcome of infection with an HPV. We recently developed a system in which human epithelium was exposed to HPV-II and transplanted to athymic mice. Cervix and skin grafts developed into typical condylomata. We now test the hypothesis that the outcome of infection of diverse epithelial types with a single human papillomavirus is largely determined by the phenotype of the original epithelial cell. For example, skin obtained from a number of disparate sites from a single patient varied dramatically in its capacity for morphological transformation with HPV-II. Skin from penis was highly susceptible, but skin from abdomen did not transform. Vocal cord from 3 children and 2 adults responded to HPV-II infection by producing typical laryngeal papillomata. A variety of tissues were obtained from II donor infants and infected with HPV-II. Foreskin and cervical tissues of these children were transformed at a frequency of 100%. Vocal cord was transformed at an incidence of 88% and urethra at 73%. Only 37% of esophagus samples were transformed and both abdominal skin and urinary bladder from the same infants were totally resistant to morphological transformation. In a separate study, ureteral tissues from a child and an adult were completely resistant to HPV-II infection. Papillomavirus replication was readily detected as capsid antigen in foreskin, cervix, and urethra, but was poorly expressed in morphologically-transformed esophagi and vocal cords. In the last two tissues HPV-II DNA and RNA were demonstrated in cells by in situ hybridization techniques. We conclude that the epithelial cell phenotype is a major determinant of HPV-II infection, controlling both morphological transformation and viral replication.