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

Department of Pathology, University of Liverpool, Royal Liverpool University Hospital, Liverpool L69 3GA, United Kingdom

In this study, we have demonstrated the overexpression of cyclin D1 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 D1 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 expression. These data provide in vivo evidence that low- and 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.

¹ Supported by grants from Wellbeing and the Royal College of Obstetricians and Gynecologists (H1/96) and the University of Liverpool.

² To whom requests for reprints should be addressed, at Department of Pathology, University of Liverpool, Royal Liverpool University Hospital, Daulby Street, Liverpool L69 3GA, United Kingdom. Phone: 44-151-706-4106; Fax: 44-151-706-5859; E-mail: c.s.herrington@liv.ac.uk.

Received 3/24/98. Accepted 5/29/98.

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