title: Variability of pathologists' utilization of p16 and ki-67 immunostaining in the diagnosis of cervical biopsies in routine pathology practice and its impact on the frequencies of cervical intraepithelial neoplasia diagnoses and cytohistologic correlations.
abstract: BACKGROUND
  The use of p16 in cervical biopsies improves the accuracy of cervical intraepithelial neoplasia (CIN) diagnosis and grading and decreases its interpathologist variability.
  
  
  OBJECTIVE
  To determine the impact of the frequency of use of p16 immunostains in cervical biopsies on pathologists' diagnoses of CIN grade 1 and grade 2 or above (CIN1 and CIN2+) and on cytohistologic correlations.
  
  
  METHODS
  We identified all cervical biopsy specimens with cytologic correlations subjected or not to p16 staining from January 1, 2005, to September 30, 2010; calculated each pathologist's percentage of p16 use; and correlated it with their major cytohistologic discrepancy rates, CIN2+ diagnoses, and CIN1/CIN2+ ratios.
  
  
  RESULTS
  During the study period, each of the 23 pathologists interpreted 59 to 1811 (mean, 518) of 11 850 cervical biopsy specimens, used p16 for 0% to 21.31% (mean, 10.14%) of these, had CIN2+ detection rates of 9.5% to 24.1% (mean, 18.9%), and CIN1/CIN2+ ratios of 0.7 to 4.5 (mean, 1.5). Compared to the 12 "low users" of p16, who used p16 fewer times than the institution's mean for p16 use, the 11 "high users" of p16 diagnosed more biopsies (8391 versus 3459), had a lower rate of major cytohistologic discrepancies (12.62% versus 14.92%, P < .001), a higher rate of CIN2+ diagnoses (19.9% versus 16.4%, P < .001), a lower range of CIN2+ rates (15.0%-23.1% versus 9.5%-24.1%), and lower CIN1/CIN2+ ratios (1.2 versus 2.3).
  
  
  CONCLUSIONS
  We found a high intrainstitutional variability of p16 use in cervical biopsies, CIN2+ rates, and CIN1/CIN2+ ratios. Use of p16 for greater than 10% of cervical biopsies was associated with improved cytohistologic correlation rates and with lower variability in the frequencies of histologic diagnoses.
authors.affiliation: From the Department of Laboratory Medicine and Pathology, University of Minnesota Medical School (Drs Singh, Truskinovsky, Thyagarajan, Gulbahce, Manivel, and Pambuccian); the School of Nursing, University of Minnesota (Ms Savik); and the Cytology Laboratory, University of Minnesota Medical Center-Fairview (Mr Amirouche and Ms Holler), Minneapolis. Dr Pambuccian is now at the Department of Pathology, Loyola University Medical Center, Maywood, Illinois.
authors.forename: Charanjeet
authors.initials: C
authors.lastname: Singh
authors.forename: J Carlos
authors.initials: JC
authors.lastname: Manivel
authors.forename: Alexander M
authors.initials: AM
authors.lastname: Truskinovsky
authors.forename: Kay
authors.initials: K
authors.lastname: Savik
authors.forename: Samy
authors.initials: S
authors.lastname: Amirouche
authors.forename: Jana
authors.initials: J
authors.lastname: Holler
authors.forename: Bharat
authors.initials: B
authors.lastname: Thyagarajan
authors.forename: H Evin
authors.initials: HE
authors.lastname: Gulbahce
authors.forename: Stefan E
authors.initials: SE
authors.lastname: Pambuccian
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D014408:Biomarkers, Tumor / Q000032:analysis; D001706:Biopsy; D019941:Cyclin-Dependent Kinase Inhibitor p16 / Q000032:analysis*; D003581:Cytodiagnosis / Q000379:methods; D005260:Female; D006801:Humans; D007150:Immunohistochemistry / Q000379:methods / Q000706:statistics & numerical data*; D019394:Ki-67 Antigen / Q000032:analysis*; D008875:Middle Aged; D002583:Uterine Cervical Neoplasms / Q000175:diagnosis* / Q000378:metabolism; D055815:Young Adult; D002578:Uterine Cervical Dysplasia / Q000175:diagnosis* / Q000378:metabolism
chemical_list: D014408:Biomarkers, Tumor; D019941:Cyclin-Dependent Kinase Inhibitor p16; D019394:Ki-67 Antigen