title: Performance of p16INK4a/Ki-67 immunocytochemistry for identifying CIN2+ in atypical squamous cells of undetermined significance and low-grade squamous intraepithelial lesion specimens: a Japanese Gynecologic Oncology Group study.
abstract: BACKGROUND
  p16(INK4a) immunohistochemistry has revealed a high rate of positivity in cervical intraepithelial neoplasia grade 2 (CIN2) and more severe conditions (CIN2+). The Lower Anogenital Squamous Terminology Standardization project proposed p16(INK4a) immunohistochemistry as an ancillary test for CIN. Immunocytochemistry involving dual staining for p16(INK4a) and Ki-67 in the triage of atypical squamous cells of undetermined significance (ASCUS) and low-grade squamous intraepithelial lesions (LSIL) is reported to be useful in the identification of CIN2+. However, it is unclear whether p16(INK4a)/Ki-67 immunocytochemistry is of practical relevance for the triage of ASCUS and LSIL in the Japanese screening system.
  
  
  METHODS
  From 427 women fulfilling the eligibility criteria, 188 ASCUS and 239 LSIL specimens were analyzed. The accuracy of p16(INK4a)/Ki-67 immunocytochemistry and genotyping of high-risk human papillomaviruses (HPVs) in detecting CIN2+ were compared.
  
  
  RESULTS
  p16(INK4a)/Ki-67 immunocytochemistry was positive in 33.5 % (63/188) of ASCUS, and 36.8 % (88/239) of LSIL specimens. The sensitivity and specificity of p16(INK4a)/Ki-67 immunocytochemistry was 87.3 % (95 % confidence interval 78.0-93.8 %) and 76.4 % (71.6-80.8 %), respectively. The positive and negative predictive values were 45.7 % (37.6-54.0 %) and 96.4 % (93.4-98.3 %), respectively; positive and negative likelihood ratios were 3.71 and 0.17, respectively. Using the McNemar test, p16(INK4a)/Ki-67 immunocytochemistry showed equivalent sensitivity but higher specificity than the HPV genotyping test
  
  
  CONCLUSIONS
  Compared with high-risk HPV genotyping, p16(INK4a)/Ki-67 immunocytochemistry was a more accurate triage test for identifying CIN2+ in ASCUS and LSIL specimens.
authors.affiliation: Department of Obstetrics and Gynecology, School of Medicine, Keio University, 35 Shinanomachi, Shinjuku-ku, Tokyo, 160-8582, Japan, fujiit44@gmail.com.
authors.forename: Takuma
authors.initials: T
authors.lastname: Fujii
authors.forename: Miyuki
authors.initials: M
authors.lastname: Saito
authors.forename: Toshihiko
authors.initials: T
authors.lastname: Hasegawa
authors.forename: Takashi
authors.initials: T
authors.lastname: Iwata
authors.forename: Hiroyuki
authors.initials: H
authors.lastname: Kuramoto
authors.forename: Kaneyuki
authors.initials: K
authors.lastname: Kubushiro
authors.forename: Mineo
authors.initials: M
authors.lastname: Ohmura
authors.forename: Kazunori
authors.initials: K
authors.lastname: Ochiai
authors.forename: Hiroharu
authors.initials: H
authors.lastname: Arai
authors.forename: Masaru
authors.initials: M
authors.lastname: Sakamoto
authors.forename: Teiichi
authors.initials: T
authors.lastname: Motoyama
authors.forename: Daisuke
authors.initials: D
authors.lastname: Aoki
mesh_terms: D000328:Adult; D044466:Asian People; D065309:Atypical Squamous Cells of the Cervix; D019941:Cyclin-Dependent Kinase Inhibitor p16 / Q000276:immunology*; D005260:Female; D005838:Genotype; D006801:Humans; D007150:Immunohistochemistry / Q000379:methods; D019394:Ki-67 Antigen / Q000276:immunology*; D008875:Middle Aged; D027383:Papillomaviridae / Q000235:genetics; D030361:Papillomavirus Infections / Q000175:diagnosis / Q000473:pathology; D012680:Sensitivity and Specificity; D065310:Squamous Intraepithelial Lesions of the Cervix / Q000175:diagnosis* / Q000473:pathology; D002583:Uterine Cervical Neoplasms / Q000175:diagnosis* / Q000473:pathology; D055815:Young Adult; D002578:Uterine Cervical Dysplasia / Q000175:diagnosis* / Q000473:pathology
chemical_list: D019941:Cyclin-Dependent Kinase Inhibitor p16; D019394:Ki-67 Antigen
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