P16 Immunohistochemistry Interpretation by Nonpathologists as an Accurate Method for Diagnosing Cervical Precancer and Cancer

Objective: We conducted a pilot study of whether nonpathologists could accurately diagnose cervical precancer in biopsies using only a basic light microscope, evaluating p16^INK4a immunohistochemistry (p16 IHC) of biopsies, and video-based training for both. Materials and Methods: Using biopsies collected as part of a screening study conducted in rural China, we randomly selected 50 biopsies with a precancerous diagnosis of cervical intraepithelial neoplasia grade 2 (CIN2) or more severe (CIN2+) and 50 biopsies with diagnosis of CIN less severe than CIN2, and stained them for p16 using a commercial IHC kit. Twelve nonpathologists of varying educational backgrounds living in Beijing, China received video training and were assigned one of 4 sets of 25 CIN2+ and 25 CIN less severe than CIN2 for evaluation. A pathologist reviewed all 100 cases. Results: The mean sensitivity and specificity of the p16 IHC staining scored by the nonpathologists were 91.7% and 94.1%, respectively, compared to scoring by the pathologist. The readers and the pathologist agreed on p16 IHC scoring for 42 (84%) of the 50 slides of CIN less severe than CIN2 and 37 (74%) of the 50 CIN2+ slides. The mean sensitivity and specificity for consensus CIN2+ of p16 IHC as scored by the readers were 88% and 87%, respectively, versus an overall sensitivity and specificity by the pathologist of 96% and 92%, respectively. Conclusions We demonstrated that nonpathologists can accurately diagnose CIN2+ using p16 IHC alone.