HIGH-RISK HUMAN-PAPILLOMAVIRUS INFECTION AND E6 PROTEIN EXPRESSION INLESIONS OF THE UTERINE CERVIX

Pathologic and epidemiologic investigations carried out over the past several years have provided evidence that carcinogenesis in the uterin e cervix is a multi-step process involving discreet preinvasive stages , Molecular epidemiologic data also indicate that human papillomavirus (HPV) infection is a critical factor in the tumor progression process , In vitro studies have shown that for the initiation and maintenance of the malignant phenotype, the expression of the HPV-transforming pro tein E6 is required, The E6 protein produced by the high-risk HPV type s 16 and 18 can bind to and inactivate the tumor suppressor protein p5 3 leading to deregulated proliferation and defective apoptosis, thus f acilitating tumor progression, Therefore, determination of the HPV gen otype alone may not be sufficient in assessing tumor progression in th e uterine cervix, In the present study, a total of 623 cervical tissue samples at various phases of tumor progression were assessed for HPV infection by nonisotopic in situ hybridization (NISH) and for HPV 16/1 8 E6 protein expression by immunocytochemistry, There was significant correlation between the extent of histological abnormality and HPV inf ection. Significant correlation (r = 0.707, p = 0.000) was observed be tween the presence of HPV 16 and high-grade squamous intraepithelial l esions (SILs) and invasive cancer, The odds ratio of a cervical tissue infected with HPV 16 falling into these two categories was 44.57 (95% CI: 27.10, 73.30), The E6 protein also was mostly detected in high-gr ade SILs and cervical cancer tissue expressing either HPV 16 or 18, It was less frequent in low-grade SILs infected with HPV 16/18 and was a bsent in benign cervical tissue infected with HPV 16, The odds ratio o f an HPV-16/18-infected cervical tissue positive for E6 being a high-g rade SIL or invasive cancer was 16.20 (95% CI: 6.06, 43.33). These res ults thus show the clinical utility of HPV characterization along with the analysis of the transforming protein E6 in the assessment of tumo r progression in the uterine cervix.