HUMAN PAPILLOMAVIRUS TYPE-18 AND INTRAEPITHELIAL LESIONS OF THE CERVIX

The conventional perception of HPV type 18 is that it is associated pr incipally with invasive cancer of the cervix. However, in precursor le sions it is frequently identified in lesions of lower grade morphology , in contrast to the typical high grade lesions associated with HPV 16 . To better characterize this uncommon relationship of low grade morph ology and high risk virus, we studied four low grade and two high grad e intraepithelial lesions of the cervix which were shown to contain HP V 18 by polymerase chain reaction/restriction fragment length polymorp hism analysis. Immunohistochemistry and in situ hybridization identifi ed capsid proteins and viral DNA in an epithelial distribution charact eristic of episomal replication and late gene expression. Sequencing o f the E2, E6, E7, and upstream regulatory regions revealed four silent mutations within these precursor lesions. Two of these sequence alter ations were also noted in three of four HPV 18 positive squamous carci nomas, suggesting a viral subtype which was not unique to cervical pre cursors. The bland morphology of many HPV 18 related precursors contra sts with the high grade morphology of HPV 18 associated cancers. Howev er, this diversity cannot be linked to functional differences in seque nces encoding in vitro transforming potential, transcriptional regulat ion or transactivation functions. Whether these differences in lesion phenotype relate to unique host variables remains to be determined.