HPV episomal copy number closely correlates with cell size in keratinocyte monolayer cultures

W12E keratinocytes maintaining episomal copies of HPV DNA were separated according to size by centrifugal elutriation. HPV DNA copy number was greatly increased in the largest, most differentiated cells of the population. The large cells with the highest HPV copy number also showed evidence of endoreduplication of host cell DNA. Other cell lines maintaining episomal copies of HPV18 and HPV31 were also tested with all lines showing similar results. The results demonstrate that increase in HPV DNA copy number correlates well with increased cell size, a fundamental marker of keratinocyte differentiation. The results also indicate that simple monolayer cultures may be useful for studying the relationship between differentiation, HPV DNA replication, and cell-cycle events.