EXPRESSION OF HUMAN PAPILLOMAVIRUS TYPE-16 E6-E7 OPEN READING FRAME VARIES QUANTITATIVELY IN BIOPSY-TISSUE FROM DIFFERENT GRADES OF CERVICAL INTRAEPITHELIAL NEOPLASIA

The proteins encoded by the human papillomavirus type 16 E6-E7 open re ading frame are essential for transformation of the host cell. Two mRN A species, E6I and E6*II, generated by alternative splicing of a poly cistronic pre-mRNA, encode truncated E6 proteins and the E7 protein. O ur investigation assessed whether or not the level of expression of E6 I and E6*II varies quantitatively in relation to the grade of cervica l intraepithelial neoplasia (CIN). We used a quantitative reverse tran scription PCR assay to quantify these transcripts in concurrently coll ected biopsy tissue and exfoliated cervical cells from 22 women with a normal cervix or various grades of CIN. We evaluated transcription pr ofiles in relation to CIN grade and specimen type. The expression leve ls of E6I and E6*II in exfoliated cervical cells did not vary signifi cantly in relation to the grade of CIN. However, expression of E6II w as significantly diminished or absent in biopsy tissue obtained from C IN grade II and III lesions (P = 0.014). Our findings suggest that qua ntification of E6I and E6*II expression in biopsy tissue may be more clinically relevant than analysis of exfoliated cells. The identificat ion of distinct patterns of expression in association with low- and hi gh-grade CIN suggests that quantification of E6I and E6*II expression in biopsy tissue may have prognostic value as an indicator of CIN pro gression.