Impact of p16INK4a Immunohistochemistry Staining on Interobserver Agreement on the Diagnosis of Cervical Intraepithelial Neoplasia

Objectives: This study aimed to compare the interobserver Cohen kappa on H&E staining and on H&E plus p16(INK4a) staining of all cervical biopsy specimens in a population-based screening program. Methods: All the colposcopy-guided biopsies generated by the routine screening of 23,258 women aged 25 to 64 years were stained with H&E and H&E plus p16. Biopsy specimens were reviewed by six external experts. Results: The four diagnoses were available in 441 cases. The interobserver kappa values were 0.52 (95% confidence interval [CI], 0.45-0.58) and 0.48 (95% CI, 0.42-0.56) with H&E and H&E + p16, respectively, when using a five-group classification (normal, GIN 1, GIN 2, GIN 3, and cancer); adopting a two-group classification (<= CIN 1 and >= CIN 2), the values were 0.75 (95% CI, 0.66-0.82) and 0.70 (95% CI, 0.61-0.79), respectively. Conclusions: The use of p16 on all cervical biopsy specimens in a screening program showed virtually no effect on reproducibility of the histologic diagnosis.