Differential Cell Cycle Regulation by Low- and High-Risk Human Papillomaviruses in Low-Grade Squamous Intraepithelial Lesions of the Cervix1

In this study, we have demonstrated the overexpression of cyclin Dl protein in 24 (92%) of 26 low-grade squamous intraepithelial lesions infected with low-risk human papillomaviruses (HPV 6, 11,42,43, and 44) and the absence of cyclin Dl expression in 25 (87%) of 29 lesions infected with high-risk HPVs (HPV 16, 18, 31, 33, 39, 45, 51, 52, 56, 58, and 66). The expression of cyclins E, A, and B proteins was increased in both low-risk and high-risk HPV infections. Tetrasomy of chromosomes 1, 3, 11, 17, 18, and X was present in nine lesions, all of which were infected with high-risk HPVs, but was not related to the pattern of cyclin expres sion. These data provide in vivo evidence that lowand high-risk HPV types alter cell cycle control by different mechanisms and that cell cycle checkpoint abnormalities are induced by high-risk, but not low-risk, HPV infection.