Involvement of episomal hpv31 in a laryngeal carcinoma - persistent episomal maintenance of hpv DNA after passage through nude-mice.

We describe the involvement of HPV31 in a laryngeal carcinoma, a highly unusual anatomic site for this HPV subtype. In situ hybridization with a type-specific HPV probe identified infected tumor cells. Diagnostic Southern blot analysis confirmed that the HPV was type 31, and also revealed that the HPV DNA was episomal. The tumor was passaged in nude mice, and analysis of HPV DNA in the passaged tumor revealed that the viral DNA had persisted and that it had remained episomal. The status of p53 in the tumor was examined by Southern blots and by PCR analysis of a closely linked, highly polymorphic dinucleotide repeat region. There was no apparent allele loss or loss of heterozygosity at p53 or at the locus of another putative tumor suppressor gene at 17p distal to p53. To assess the integrity of the p53 gene in more detail, exons 4 through 11 were amplified by PCR, and the amplified DNA was directly sequenced. No mutations in p53 were observed, suggesting that other mechanisms such as sequestration of p53 by the E6 or E7 products may have contributed to the malignancy.