Integration of human papillomavirus type 16 DNA sequences: a possible early event in the progression of genital tumors

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Abstract
The keratinocyte line SK-v harbors only integrated human papillomavirus type 16 (HPV16) DNA sequences, although it originated from vulvar Bowenoid papules predominantly containing multiple copies of free HPV16 genomes. We have cloned a fragment of cell DNA that contains the integrated HPV16 DNA sequences and have shown that integration interrupts the HPV16 genome in open reading frames E2 and L2 and creates a deletion of 813 base pairs. This allows the expression of open reading frames E6 and E7, as actually substantiated by Northern (RNA) blot analysis of SK-v RNAs with subgenomic HPV16 RNA probes. Using a unique flanking cellular DNA sequence as the probe, we have shown that the integration of HPV16 sequences had already occurred in the premalignant lesions from which the SK-v cell line was derived.