Numerical aberrations of chromosome 1 in cervical intraepithelial neoplasia are strongly associated with infection with high‐risk human papillomavirus types

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Abstract
The aims of this study were to assess the relationships between numerical aberrations of chromosome 1 and the presence of high‐risk human papillomavirus (HPV). Five normal samples, 11 CIN1, 13 CIN2, 18 CIN3, and nine carcinomas were studied by in situ hybridization (ISH), using a DNA probe for the centromere of chromosome 1 (cen#1) and a DNA probe cocktail for HPV types 16 and 18. A short fragment polymerase chain reaction hybridization line probe assay (SPF‐PCR‐LiPA) technique was used to detect 25 HPV types. The mean number of cen#1 per nucleus (chromosome index, CI) was measured, and the fractional areas of dysplastic epithelium with HPV16/18 infection and with cen#1 aneusomy were estimated. Disomy was found in all normal epithelium and in 36% of CIN1. Tetrasomy was observed in 64% of CIN1, 15% of CIN2, and 17% of CIN3. Hyper‐tetrasomy was observed in 77% of CIN2, 83% of CIN3, and 100% of invasive carcinomas. High‐risk HPVs were present in 20%, 75%, and 94% of disomic, tetrasomic, and hyper‐tetrasomic lesions, respectively. The mean CI value was significantly higher in the lesions infected with high‐risk HPV than in the lesions not infected by high‐risk HPV (p < 0.001), due to the significantly higher prevalence of hyper‐tetrasomy. The ISH study disclosed that HPV16/18 was exclusively found within dysplastically altered epithelium. The area with aneusomy is mostly enclosed within the area infected with HPV. In 83% of the HPV16/18‐positive CIN lesions, the fractional area of HPV‐infected epithelium was equal to, or larger than, the fractional area with aneusomy. In conclusion, aneusomy for chromosome 1 is strongly associated with high‐grade CIN lesions and infection with high‐risk HPV; it is likely that the occurrence of numerical aberrations of chromosome 1 is preceded by infection with high‐risk HPV. Copyright © 2002 John Wiley & Sons, Ltd.

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