The aim of this study was to reveal whether 3
biomarkers (p16INK4a, ProEx C, and human papilloma virus
DNA) are useful in the diagnosis of
cervical intraepithelial neoplasia and whether they could predict
disease progression of cervical intraepithelial neoplasia-1. We analyzed 252 cervical specimens: nondysplastic mucosa (n = 9),
cervical intraepithelial neoplasia (n = 229), and
squamous cell carcinoma (n = 14). Immunostaining for p16INK4a and ProEx C, and the hybridcapture II assay for human papilloma virus
DNA were performed. Expression of p16INK4a and staining for ProEx C were significantly higher in intraepithelial
neoplasia 2/3 (96%-100%) than in nondysplastic mucosa (11%) or intraepithelial
neoplasia 1 (40%-53%). Human papilloma virus
DNA was detected in 69% of intraepithelial neoplasia-1, 95% of intraepithelial neoplasia-2, and 100% of intraepithelial
neoplasia 3. Of 99 patients with intraepithelial
neoplasia 1 for whom follow-up data was available, 62 (73%) showed
spontaneous regression, 17 (20%) demonstrated persistent low-grade lesion, and 7 (7%) progressed to intraepithelial
neoplasia 2/3. Expressions of p16INK4a and staining with ProEx C were significantly higher in the progression group than in the regression group. Testing for p16INK4a and ProEx C was sensitive (86%) and moderately specific (60% and 61%, respectively) in predicting the progression of
cervical intraepithelial neoplasia 1. Human papilloma virus
DNA testing was highly sensitive (100%) but less specific (37%). In conclusion, this study revealed that p16INK4a and ProEx C are useful
biomarkers for the diagnosis of
cervical intraepithelial neoplasia, and have potential as predictors of progression of low-grade lesions.