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 reading frame are essential for transformation of the host cell. Two mRNA species, E6I and E6II, generated by alternative splicing of a polycistronic pre-mRNA, encode truncated E6 proteins and the E7 protein. Our investigation assessed whether or not the level of expression of E6I and E6II varies quantitatively in relation to the grade of cervical intraepithelial neoplasia (CIN). We used a quantitative reverse transcription PCR assay to quantify these transcripts in concurrently collected biopsy tissue and exfoliated cervical cells from 22 women with a normal cervix or various grades of CIN. We evaluated transcription profiles in relation to CIN grade and specimen type. The expression levels of E6I and E6II in exfoliated cervical cells did not vary significantly in relation to the grade of CIN. However, expression of E6II was significantly diminished or absent in biopsy tissue obtained from CIN grade II and III lesions (P = 0.014). Our findings suggest that quantification of E6I and E6II expression in biopsy tissue may be more clinically relevant than analysis of exfoliated cells. The identification of distinct patterns of expression in association with low- and high-grade CIN suggests that quantification of E6I and E6*II expression in biopsy tissue may have prognostic value as an indicator of CIN progression.