[Detection of high-risk human papillomavirus (HPV) E6 and E7 oncogene transcripts increases the specificity of the detection of a cervical intraepithelial neoplasia (CIN)]

Abstract

Aims: The oncogenic potential of the high-risk human papillomavirus (HR-HPV) genotypes depends on the expression of the viral oncogenes E6 and E7. Thus, the detection of these transcripts could serve as a factor in the evaluation of a woman's risk of development of cervical intraepithelial neoplasia (CIN).

Methods: A nested RT-PCR assay for the detection of E6/E7 oncogene transcripts of all known HR-HPV genotypes was established. Cervical scrapes of 779 HR-HPV-DNA-positive women exhibiting all grades of CIN were examined.

Results: Spliced E6/E7 oncogene transcripts of all the HR-HPVs were detected in numerous samples. In 459 cases with agreement between the cytologic and histologic findings, the prevalence increased with lesion severity: CIN 0, 18%; CIN I, 58%; CIN II, 77%; CIN III, 84%. While sensitivity and negative predictive value of HR-HPV DNA-positivity for the detection of a CIN lesion were significantly (p < 0.0001) higher than those of E6/E7 mRNA positivity (90.3% vs. 65.5% and 93% vs. 83.1%), the opposite was true for the specificity and positive predictive value (72.8 % vs. 95.2%) and 65.1% vs. 88.5%, p < 0.0001). Preliminary follow-up data in 120 initially HPV-16 DNA-positive women revealed the development, persistence or progression of a CIN lesion in 33% (8/24) of HR-HPV DNA-positive and E6/E7 mRNA-negative women, compared to 93% (66/71, p < 0.0001) in women in whom transcriptional activity of the E6/E7 oncogenes was detectable.

Conclusions: Besides the identification of HPV DNA, the detection of HR-HPV E6/E7 oncogene transcripts may serve as a valuable tool in increasing the specificity of HPV testing.