Immunohistochemical examination of the proliferative activity of cells was made investigating the expression of Ki-67 protein and the location of proteins associated with epithelial cell papillomavirus infection involving Р16INK4а and HPV16 proteins in different cell areas of the intact mucosa, in leukoplakia with the signs of hyperplasia and dysplasia, and in squamous cell carcinoma. There was a positive correlation between the proliferative activity of cells in the parabasal cell areas and the expression of Р16INK4а protein in oral leukoplakia with the signs of hyperplasia (rs=0.397; р=0.018). In oral leukoplakia with dysplastic changes, there was a positive correlation between the proliferation of cells in the parabasal and prickle cell layers and the location of HPV type 16 antigens (rs=0.515; р=0.041 and rs=0.651; р=0.006). Detection of papillomavirus infection in leukoplakia can solve not only the problems with its genesis, but this is also a morphological basis for the effective prevention and treatment of this common oral mucosal disease.