Tohru Morisada1, Katsuhiro Teramoto2, Hirokuni Takano3, Ikuko Sakamoto2, Hiroshi Nishio1, Takashi Iwata1, Akihiko Hashi4, Ryohei Katoh5, Aikou Okamoto6, Hiroshi Sasaki7, Eiji Nakatani8, Satoshi Teramukai9, Daisuke Aoki10. 1. Department of Obstetrics and Gynecology, Keio University School of Medicine, Tokyo, Japan. 2. Yamanashi Prefectural Central Hospital, Yamanashi, Japan. 3. Department of Obstetrics and Gynecology, The Jikei University Kashiwa Hospital, Chiba, Japan. 4. Department of Obstetrics and Gynecology, University of Yamanashi, Yamanashi, Japan. 5. Department of Human Pathology, University of Yamanashi, Yamanashi, Japan. 6. Department of Obstetrics and Gynecology, The Jikei University School of Medicine, Tokyo, Japan. 7. Department of Gynecology, Chiba Tokushukai Hospital, Chiba, Japan. 8. Translational Research Informatics Center, Foundation for Biomedical Research and Innovation, Kobe, Japan. 9. Department of Biostatistics, Kyoto Prefectural University of Medicine Graduate School of Medical Science, Kyoto, Japan. 10. Department of Obstetrics and Gynecology, Keio University School of Medicine, Tokyo, Japan. Electronic address: aoki@z7.keio.jp.
Abstract
BACKGROUND: To assess the efficacy of screening with concurrent liquid-based cytology and human papillomavirus (HPV) testing for primary cervical cancer screening, we initiated a randomized trial entitled CervIcal cancer screening Trial by Randomization of HPV testing intervention for Upcoming Screening (CITRUS). METHODS:Between June 2013 and March 2015, women aged 30-64 years of age who participated in a regular cervical cancer screening program (every 2 years) were invited to enrollment of our study. After giving their informed consent, 18,402 women were randomly assigned to liquid-based cytology as the control group (n=9145) or to HPV DNA testing with liquid-based cytology as the intervention group (n=9257). We subsequently compared the incidence rate of cervical intraepithelial neoplasia (CIN), the rate of false positive tests and the rate of overdiagnosis, as well as assessing the risks and benefits of receiving screening for women in both groups. The primary outcome of our study was the incidence of cervical intraepithelial neoplasia grade 3 or worse (CIN3+) during the study period of around 6 years. RESULTS: In the control group, 97.9% of women were NILM, and 2.06% ASC-US or worse (ASC-US+). In the intervention group, 87.13% of women were NILM/HPV negative, 0.72% ASC-US/HPV negative, 10.34% NILM/HPV positive, 0.69% ASC-US/HPV positive, 0.90% worse than ASC-US/either HPV. Positive HPV testing was not linearly related to age in our study. CONCLUSIONS: Insights from CITRUS will provide future prospects for cervical cancer screening focused on the use of HPV testing in Japan. CLINICAL TRIAL REGISTRATION NUMBER: NCT01895517, UMIN000010843, TRIUC1312.
RCT Entities:
BACKGROUND: To assess the efficacy of screening with concurrent liquid-based cytology and human papillomavirus (HPV) testing for primary cervical cancer screening, we initiated a randomized trial entitled CervIcal cancer screening Trial by Randomization of HPV testing intervention for Upcoming Screening (CITRUS). METHODS: Between June 2013 and March 2015, women aged 30-64 years of age who participated in a regular cervical cancer screening program (every 2 years) were invited to enrollment of our study. After giving their informed consent, 18,402 women were randomly assigned to liquid-based cytology as the control group (n=9145) or to HPV DNA testing with liquid-based cytology as the intervention group (n=9257). We subsequently compared the incidence rate of cervical intraepithelial neoplasia (CIN), the rate of false positive tests and the rate of overdiagnosis, as well as assessing the risks and benefits of receiving screening for women in both groups. The primary outcome of our study was the incidence of cervical intraepithelial neoplasia grade 3 or worse (CIN3+) during the study period of around 6 years. RESULTS: In the control group, 97.9% of women were NILM, and 2.06% ASC-US or worse (ASC-US+). In the intervention group, 87.13% of women were NILM/HPV negative, 0.72% ASC-US/HPV negative, 10.34% NILM/HPV positive, 0.69% ASC-US/HPV positive, 0.90% worse than ASC-US/either HPV. Positive HPV testing was not linearly related to age in our study. CONCLUSIONS: Insights from CITRUS will provide future prospects for cervical cancer screening focused on the use of HPV testing in Japan. CLINICAL TRIAL REGISTRATION NUMBER: NCT01895517, UMIN000010843, TRIUC1312.