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: Takuma Fujii, Miyuki Saito, Toshihiko Hasegawa, Takashi Iwata, Hiroyuki Kuramoto, Kaneyuki Kubushiro, Mineo Ohmura, Kazunori Ochiai, Hiroharu Arai, Masaru Sakamoto, Teiichi Motoyama, Daisuke Aoki
• Journal: International journal of clinical oncology (Int J Clin Oncol) Vol. 20 Issue 1 Pg. 134-42 (Feb 2015) ISSN: 1437-7772 [Electronic] Japan
• PMID: 24744261 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Cyclin-Dependent Kinase Inhibitor p16
• Ki-67 Antigen

Topics

• Adult
• Asian People
• Atypical Squamous Cells of the Cervix
• Cyclin-Dependent Kinase Inhibitor p16 (immunology)
• Female
• Genotype
• Humans
• Immunohistochemistry (methods)
• Ki-67 Antigen (immunology)
• Middle Aged
• Papillomaviridae (genetics)
• Papillomavirus Infections (diagnosis, pathology)
• Sensitivity and Specificity
• Squamous Intraepithelial Lesions of the Cervix (diagnosis, pathology)
• Uterine Cervical Neoplasms (diagnosis, pathology)
• Young Adult
• Uterine Cervical Dysplasia (diagnosis, pathology)