32. HPV type and strain variant concordance between anal cancers and their preceding high-grade squamous intraepithelial lesions

Abstract

Background: Anal high-grade squamous intraepithelial lesions (HSIL) are frequently found overlying anal cancer on histology, and anal cancer has been observed to develop in the same location as previously diagnosed anal HSIL. These observations support the role of HSIL as the direct precursor lesion to anal cancer. To further investigate a direct pathogenetic relationship between anal HSIL and cancer, we typed and sequenced HPV DNA in anal HSIL and the cancers that subsequently developed in the same location. Methods: Tissues samples were analysed from 15 HIV-infected men followed at UCSF in whom anal cancer developed at a previously biopsied site of HSIL. Formalin-fixed paraffin-embedded pairs of HSIL and cancer were typed for HPV DNA using L1 PCR. HPV 16-positive samples underwent E6-based strain variant analysis. Results: Nine matched pairs for which DNA from both HSIL and cancer were available were analysed. Eight pairs (89%) contained HPV 16 DNA. One (11%) contained both HPV 18 and 51 in both samples. Of the eight HPV 16-positive pairs, each pair contained the same HPV 16 strain variant. Four contained the Eur-350T variant alone, and one contained Eur-350T in both the HSIL and cancer, with an additional 426T variant in the cancer. One pair contained both Eur-350T and 457C in both the HSIL and the cancer. Two pairs contained the Eur-350G variant alone. Conclusions: Concordance of both the HPV type and strain variant in anal cancers and their site-matched preceding HSIL further supports the role of anal HSIL as an anal cancer precursor.