Interobserver Reproducibility in Determining p16 Overexpression in Cervical Lesions : Use of a Combined Scoring Method

Objectives : To evaluate interobserver reproducibility of a combined scoring method for immunohistochemicalinterpretation of p16 overexpression in cervical lesions. Materials and methods : p16 immunostaining wasperformed in cervical samples from 183 patients, including 69 normal, 42 low grade squamous intraepitheliallesions(LSIL), 36 high grade SIL (HSIL), and 36 squamous cell carcinomas(SCCAs). Each case was evaluatedby a combined scoring method based on the percentage of positive cells (score 0-3), the intensitiy of staining(score 0-3), and the distribution pattern (score 0-2). Immunoexpression for p16 was considered as positive whenthe combined score was 4-8 and negative with a score of 0-3. Ten pathologists with varied experience ininterpretating p16 immunostains evaluated each slide independently. Results : All normal cervical squamousepithelia (69/69) were uniformly negative for p16. All HSILs (36/36), all SCCAs (100/100), and all but one of theLSILs (40/41, 97.62%) showed positive expression. In 172 of 183 cases (93.99%), p16 interpretation wasconcordant with all pathologists. Eleven cases with discordant results included 10 LSILs and 1 normal mucosasample. Percentage of agreement of each pathologist pair ranged from 96.7-100% (mean 98.1 ± 0.96%) withmean kappa value of 0.96 ± 0.0201 (range 0.93-1.000). Conclusion : The proposed combined scoring methodshows good reproducibility among the participating pathologists and good correlation with the histologicdiagnosis. This method may be a useful guide in the interpretation of p16 expression in cervical epithelial lesions.