Laryngeal papillomatosis is associated with a defect in cellular differentiation

The effects of human papillomavirus infection, which can cause laryngeal papillomas, were studied in vitro in laryngeal stratified squamous epithelial cells. Interferon exposure had only minor effects on the outgrowth of primary cells from tissue fragments and the incorporation of tritiated amino acids by first-passage cells. There was a marked decrease in tritiated thymidine incorporation by papilloma cells when cultured in the presence of interferon, but no effect on thymidine incorporation by normal cells. Differentiation of laryngeal papillomas appears to be abnormal. Sodium dodecyl sulphate-polyacrylamide gel electrophoresis of keratins showed that the keratins of high relative molecular mass (Mr 51,000 and 59,000) associated with normal laryngeal differentiation were absent from papilloma tissue. Rather, both papilloma tissue and cultured papilloma cells contained a keratin of Mr 53,000 not normally present. Binding of the fluoresceinated lectin peanut agglutinin to cell surfaces suggested that there were alterations in the normal distribution of glycoproteins or glycolipids on papilloma tissues. Filaggrin, a protein synthesized by differentiating cells, was not detectable in most superficial papilloma cells after immunohistochemical staining. These studies strongly suggest that papilloma cells do not differentiate normally. We propose that this defect may be responsible for the hypertrophy of the tissue.