Background: The low sensitivity of cytology and low specificity of human papillomavirus testing prompts searching for more accurate cervical cancer screening strategies. Our goal was to evaluate an ELISA-based test for p16(INK4a).
Methods: 1,781 women undergoing routine screening provided cervical specimens for p16(INK4a) ELISA (original and enhanced versions of a prototype), liquid-based cytology, and Hybrid Capture II (hc2) testing. All women with a positive result and a random sample of those with negative results on all tests were referred for histologic diagnosis. Cervical intraepithelial neoplasia grade >or=3 (>or=CIN3) was the main outcome. The original analysis included all >or=CIN3 outcomes (n = 28). The a posteriori analysis was used to represent clinically relevant results with >or=CIN3 as outcomes only when detected after a positive screening test (n = 27).
Results: Participants had a median age of 23 years. The prevalence of high-risk human papillomavirus DNA was 30.6%. In a posteriori analyses, the sensitivity and specificity for p16(INK4a) ELISA (>or=8 pg/mL cut-point), cytology, and hc2 were 50.9%, 58.1%, and 100.0%, respectively, and 90.4%, 89.3%, and 69.2%, respectively. Referral to colposcopy of women with positive results for hc2 and p16(INK4a) (enhanced ELISA, >or=6 pg/mL cut-point) had a sensitivity of 91.8% (95% confidence interval, 79.1-100.0%) and specificity of 86.0% (95% confidence interval, 82.0-89.0%). Results of the original analyses had similar specificity but substantially lower sensitivity due to the strong influence of the single CIN3 case with completely negative screening results.
Conclusions: An enhanced version of this prototypic p16(INK4a) ELISA showed promise in screening, particularly when combined with hc2.