Evaluation of a new p16(INK4A) ELISA test and a high-risk HPV DNA test for cervical cancer screening: results from proof-of-concept study.

p16(INK4a), a cell cycle regulation protein, accumulates in abnormal epithelial cells infected with high-risk human papilloma virus (HPV). In immunostaining studies, p16(INK4a) has shown potential as a marker of high grade cervical intraepithelial neoplasia (CIN) and invasive cervical cancer. To evaluate its potential use in cervical cancer screening, we conducted a feasibility study to compare the performance of a new enzyme linked immunosorbant assay (ELISA) for p16(INK4a) (mtm laboratories, Heidelberg, Germany) to that of the Hybrid Capture 2 (hc2) test for high-risk HPV DNA for the detection of CIN3. Three hundred and nineteen women were referred from Western Washington Planned Parenthood clinics for colposcopy examination and cervical biopsy because of abnormal Pap test results. Cervical samples were obtained from study participants for p16(INK4a) ELISA, liquid-based cytology and hc2. The order (first and second) for obtaining samples for cervical cytology and p16(INK4a) ELISA changed with every other subject. Concentrations of p16(INK4a) protein were higher when the sample was taken before the cytology. The sensitivity of p16(INK4a) ELISA (concentration > or = 8 units/ml) taken as first sample was 90.0% for CIN3, and the sensitivity of HC2 taken as a second sample was 85%. In the same group, the specificity of p16(INK4a) ELISA (46.9%) was slightly better than hc2 (35.4%) Results from this proof-of-concept study suggest that p16(INK4a) ELISA has a similar sensitivity and slightly better specificity for CIN3 compared to hc2. These findings support proceeding with a larger study with samples from a population of women presenting for routine cytology screening.