Correction between p16ink4a expression and human papillomavirus in atypical glandular cells of undetermined significance-categorized pap smears with follow-up biopsies

Objective. This study was to correlate high-risk human papillomavirus (HR-HPV) viral load to p16INK4A (p16) expression in atypical glandular cells (AGC)-categorized Pap smears with follow-up biopsies for elucidating their relationships. Methods. We enrolled 36 AGC-categorized Pap smears with subsequent follow-up biopsies. HR-HPV viral load was determined by Hybrid Capture II assay in each AGC-diagnosed Pap smear. Both smears and biopsies were immunostained with a primary anti-p16 antibody, clone E6H4. Correlations between HR-HPV viral load in each AGC-diagnosed Pap smear and p16 expression of smears with follow-up biopsies were performed. Results. Comparative analysis of two tests disclosed both consistencies and discrepancies. There were significant differences (p = 0.02) between negative or weak p16 expression of Pap smears with the presence of reactive lesion or LSILs/CIN1s in follow-up biopsies and negative HR-HPV viral load. However, no significant difference (p = 0.317) was found between p16 expression of Pap smears with the presence of HSIL/CIN2, 3 and AIS or adenocarcinoma in follow-up biopsies and high HR-HPV viral load. In addition, there were significant differences (p = 0.012) in specificity, but no significant differences were found in sensitivity (p = 0.604), positive and negative predictive value (p = 0.066, and 0.264) between p16 immunoexpression and HR-HPV viral load. Conclusions. Pathogenic activity of HR-HPV was indicated by p16 expression on smears and tissue sections, which appears to be a better strategy than HR-HPV viral load test for the detection of clinically insignificant lesions from AGC-categorized Pap smears.