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Cervical Cancer Screening With Human Papillomavirus DNA and Cytology in Japan
  1. Yuri Sasaki, MD*,,
  2. Osamu Iwanari, MD, PhD,
  3. Ichiro Arakawa, PhD§,
  4. Takuya Moriya, MD, PhD,
  5. Yoshiki Mikami, MD, PhD,
  6. Kuniko Iihara, MD, PhD# and
  7. Ryo Konno, MD, PhD*
  1. *Department of Obstetrics and Gynecology, Jichi Medical University Saitama Medical Center, Saitama-city, Saitama;
  2. Department of Obstetrics and Gynecology, Iwate Medical University, Morioka-city, Iwate;
  3. Department of Obstetrics and Gynecology, Shimane Prefectural Central Hospital, Izumo-city, Shimane;
  4. §Faculty of Pharmaceutical Sciences, Teikyo Heisei University, Nakano-ku, Tokyo;
  5. Department of Pathology, Kawasaki Medical School, Kurashiki-city, Okayama;
  6. Department of Pathology, Kumamoto University Hospital, Kumamoto-city, Kumamoto; and
  7. #Department of Diagnostic Pathology, Tokyo Yamate Medical Center, Shinjyuku-ku, Tokyo, Japan.
  1. Address correspondence and reprint requests to Ryo Konno, MD, PhD, Department of Obstetrics and Gynecology, Jichi Medical University Saitama Medical Center, 1-847, Amanuma, Omiya, Saitama-city, Saitama, 330-8503, Japan. E-mail:


Objective The aim of this study was to determine the value of human papillomavirus (HPV) testing for primary cervical cancer screening in Japan.

Methods In total, 5065 women who underwent primary screening with cytology and HPV between January 2005 and December 2006 were enrolled. In the baseline phase, these women were stratified by age, and the rates of HPV-positive and abnormal cytology were compared between women younger than and older than 30 years. In the follow-up phase, women aged 20 to 69 years and cytology negative for intraepithelial lesions or malignancy at baseline were followed up until December 2011 (n = 2383). Progression to grade 2/3 cervical intraepithelial neoplasia or worse (CIN2+/CIN3+) was compared between the HPV-positive and HPV-negative groups.

Results In the baseline phase, HPV-positive rates were significantly higher in women younger than 30 years at 20.7% (95% confidence interval [CI], 18.4–22.9; 255/1234) compared with women 30 years or older at 7.2% (95% CI, 6.4%–8.0%; 275/3831; P < 0.001). However, there was no statistical difference for high-grade squamous intraepithelial lesion or worse rates between them, at 2.7% (95% CI, 1.8%–3.6%; 33/1234) and 2.4% (95% CI, 1.9%–2.9%; 91/3831), respectively, P = 0.55. In the follow-up phase, the rate of progression to CIN2+/CIN3+ was significantly higher in the HPV-positive group than in the HPV-negative group (P < 0.001). Moreover, relative risk of progression to CIN2+ was 15.9 times higher in the HPV-positive group, and that of progression to CIN3+ was 16.1 times higher in the HPV-positive group.

Conclusions Human papillomavirus testing is a useful test for predicting progression to CIN and is recommended as a primary screening tool. However, screening with cytology alone is still appropriate for younger women, younger than 30 years, because HPV testing yields more false-positive results in younger women.

  • Cervical cancer screening
  • Cytology
  • Disease progression
  • Human papillomavirus

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  • The human papillomavirus test, Hybrid Capture 2 (Qiagen, Germantown, MD), used to test for high-risk human papillomavirus types in this study, was donated by Qiagen. Qiagen played no role in the research design, analysis, or interpretation of the data.

  • R.K. has received lecture fees from Qiagen, BD, Roche Diagnostics, GSK, MSD and Chugai Pharmaceutical, Co, Ltd. His institute received research funding from Chugai Pharmaceutical, Co, Ltd and Roche Diagnostics outside the submitted work. Those lecture fees and funding have no influence on the manuscript. All other authors declare no conflicts of interest.

  • This is an open-access article distributed under the terms of the Creative Commons Attribution-Non Commercial-No Derivatives License 4.0 (CCBY-NC-ND), where it is permissible to download and share the work provided it is properly cited. The work cannot be changed in any way or used commercially without permission from the journal.