Characterization of factors involved in human papillomavirus type 16-mediated immortalization of oral keratinocytes

We have examined intrinsic and external factors that influence human papillomavirus type 16 (HPV-16)-mediated immortalization of oral keratinocytes. The efficiency with which HPV can immortalize human oral keratinocytes was quantified and a considerable dif-ference in the transfection and immortalization com-petence of the cells was detected. The ability of HPV-16 to immortalize oral cells appeared to be linked to the age of the culture upon transfection. The addition of dexamethasone to the transfected cultures increased the efficiency of immortalization, possibly indicating a role for a critical level of HPV gene expression in initial outgrowth of immortalized colonies. We also document in detail the changes in the oral keratinocyte induced by HPV-16 immortalization. These include alterations associated with crisis and feeder independence aswell as basic changes in keratin expression and differentiation. Human papillomaviruses (HPVs) are ubiquitous patho-gens associated with both benign and malignant lesions of epithelial tissue (r viewed in zur Hausen & Schneider, 1987) This is particularly apparent in the cervix where the oncogenic HPV types 16, 18, 31 and 33 have been isolated from cervical carcinoma tissue (Boshart et al., 1984; Diirst et al., 1983; Lorincz et al., 1987; Syrjanen et al., 1985). In contrast, HPV types 6 and 11 are predominantly associated with benign lesions of the oral and genital mucosa (Gissmann et al., 1983). Immortal-ization of foreskin and cervical keratinocytes with the oncogenic HPV types has been well documented (Pirisi e