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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

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Abstract

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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Acknowledgments

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.

Conflict of interest

D.A. received lecture fees from Roche Diagnostics K.K. The other authors have no conflicts of interest.

Author information

Authors and Affiliations

  1. Department of Obstetrics and Gynecology, School of Medicine, Keio University, 35 Shinanomachi, Shinjuku-ku, Tokyo, 160-8582, Japan

    Takuma Fujii, Miyuki Saito, Takashi Iwata & Daisuke Aoki

  2. Department of Obstetrics and Gynecology, School of Medicine, Fujita Health University, 1-98 Dengakugakubo Kutsukakecho, Toyoake, Aichi, 470-1192, Japan

    Takuma Fujii

  3. Department of Gynecology, Tokyo Health Service Association, 1-2, Sadoharacho, Ichigaya, Shinjuku-ku, Tokyo, 162-8402, Japan

    Toshihiko Hasegawa

  4. Department of Gynecology, Kanagawa Health Service Association, 58, Nihon Ohdori, Naka-ku, Yokohama, Kanagawa, 231-0021, Japan

    Hiroyuki Kuramoto

  5. Department of Obstetrics and Gynecology, Ohashi Medical Center, Toho University School of Medicine, 2-17-6, Ohashi, Megro-ku, Tokyo, 153-8515, Japan

    Kaneyuki Kubushiro

  6. Department of Gynecology, Kokoro to Karada no Genki Plaza, 3-6-5, Iidabashi, Chiyoda-ku, Tokyo, 102-8508, Japan

    Mineo Ohmura

  7. Department of Obstetrics and Gynecology, The Jikei University School of Medicine, 3-19-18, Nishi-shinbashi, Minato-ku, Tokyo, 105-8471, Japan

    Kazunori Ochiai

  8. Department of Gynecology, National Tokyo Medical Center, 2-5-1, Higashigaoka, Meguro-ku, Tokyo, 152-8902, Japan

    Hiroharu Arai

  9. Department of Gynecology, Sasaki Foundation Kyoundo Hospital, 1-8, Surugadai, Kanda, Chiyoda-ku, Tokyo, 101-0062, Japan

    Masaru Sakamoto

  10. Department of Pathology, Yamagata University School of Medicine, 2-2-2, Iidanishi, Yamagata-city, Yamagata, 990-9585, Japan

    Teiichi Motoyama

Authors
  1. Takuma Fujii
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  2. Miyuki Saito
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  3. Toshihiko Hasegawa
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  4. Takashi Iwata
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  8. Kazunori Ochiai
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  9. Hiroharu Arai
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  11. Teiichi Motoyama
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  12. Daisuke Aoki
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Corresponding author

Correspondence to Takuma Fujii.

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Fujii, T., Saito, M., Hasegawa, T. et al. 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. Int J Clin Oncol 20, 134–142 (2015). https://doi.org/10.1007/s10147-014-0688-0

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  • DOI: https://doi.org/10.1007/s10147-014-0688-0

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