TY - JOUR
T1 - Performance of p16INK4a/Ki-67 immunocytochemistry for identifying CIN2+ in atypical squamous cells of undetermined significance and low-grade squamous intraepithelial lesion specimens
T2 - a Japanese Gynecologic Oncology Group study
AU - Fujii, Takuma
AU - Saito, Miyuki
AU - Hasegawa, Toshihiko
AU - Iwata, Takashi
AU - Kuramoto, Hiroyuki
AU - Kubushiro, Kaneyuki
AU - Ohmura, Mineo
AU - Ochiai, Kazunori
AU - Arai, Hiroharu
AU - Sakamoto, Masaru
AU - Motoyama, Teiichi
AU - Aoki, Daisuke
N1 - Funding Information:
We thank Drs. T. Abe and R. Roberts, Center for Clinical Research, Keio University School of Medicine, for conducting biostatistical analysis. We also thank Dr. Tsuda, Department of Pathology and Clinical Laboratories, National Cancer Center Hospital, Tokyo, Japan and Dr. Fukunaga, Department of Pathology, The Jikei University, School of Medicine, Daisan Hospital, Tokyo, Japan for conducting central pathology. The protocol JGOG-1073 was sponsored by the Japanese Gynecologic Oncology Group.
Publisher Copyright:
© 2014, Japan Society of Clinical Oncology.
PY - 2015/2
Y1 - 2015/2
N2 - Background: p16INK4a 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 p16INK4a immunohistochemistry as an ancillary test for CIN. Immunocytochemistry involving dual staining for p16INK4a 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 p16INK4a/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 p16INK4a/Ki-67 immunocytochemistry and genotyping of high-risk human papillomaviruses (HPVs) in detecting CIN2+ were compared. Results: p16INK4a/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 p16INK4a/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, p16INK4a/Ki-67 immunocytochemistry showed equivalent sensitivity but higher specificity than the HPV genotyping test Conclusions: Compared with high-risk HPV genotyping, p16INK4a/Ki-67 immunocytochemistry was a more accurate triage test for identifying CIN2+ in ASCUS and LSIL specimens.
AB - Background: p16INK4a 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 p16INK4a immunohistochemistry as an ancillary test for CIN. Immunocytochemistry involving dual staining for p16INK4a 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 p16INK4a/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 p16INK4a/Ki-67 immunocytochemistry and genotyping of high-risk human papillomaviruses (HPVs) in detecting CIN2+ were compared. Results: p16INK4a/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 p16INK4a/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, p16INK4a/Ki-67 immunocytochemistry showed equivalent sensitivity but higher specificity than the HPV genotyping test Conclusions: Compared with high-risk HPV genotyping, p16INK4a/Ki-67 immunocytochemistry was a more accurate triage test for identifying CIN2+ in ASCUS and LSIL specimens.
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U2 - 10.1007/s10147-014-0688-0
DO - 10.1007/s10147-014-0688-0
M3 - Article
C2 - 24744261
AN - SCOPUS:84939873782
VL - 20
SP - 134
EP - 142
JO - International Journal of Clinical Oncology
JF - International Journal of Clinical Oncology
SN - 1341-9625
IS - 1
ER -