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HLA Class II DRB1*1302 Allele Protects Against Progression to Cervical Intraepithelial Neoplasia Grade 3: A Multicenter Prospective Cohort Study
  1. Koji Matsumoto, MD*,
  2. Hiroo Maeda, MD,
  3. Akinori Oki, MD*,
  4. Naoyoshi Takatsuka, MD,
  5. Toshiharu Yasugi, MD§,
  6. Reiko Furuta, PhD,
  7. Ranko Hirata, BSc,
  8. Akira Mitsuhashi, MD,
  9. Takuma Fujii, MD#,
  10. Yasuo Hirai, MD**,
  11. Tsuyoshi Iwasaka, MD,,
  12. Nobuo Yaegashi, MD,,
  13. Yoh Watanabe, MD§§,
  14. Yutaka Nagai, MD∥∥,
  15. Tomoyuki Kitagawa, MD and
  16. Hiroyuki Yoshikawa, MD*
  1. * Department of Obstetrics and Gynecology, Graduate School of Comprehensive Human Science, University of Tsukuba, Tsukuba;
  2. Department of Transfusion Medicine and Cell Therapy, Saitama Medical Center, Saitama Medical University, Saitama;
  3. Department of Health Economics, Gifu University Graduate School of Medicine,Gifu;
  4. § Department of Obstetrics and Gynecology, University of Tokyo;
  5. Department of Pathology, Cancer Institute, Japanese Foundation of Cancer Research, Tokyo;
  6. Department of Reproductive Medicine, Graduate School of Medicine, Chiba University, Chiba;
  7. # Department of Obstetrics and Gynecology, Keio University School of Medicine, Tokyo;
  8. ** Departments of Gynecology and Cytopathology, Cancer Institute Hospital, Japanese Foundation of Cancer Research, Tokyo;
  9. †† Department of Obstetrics and Gynecology, Faculty of Medicine, Saga University, Saga;
  10. ‡‡ Departmentof Obstetrics and Gynecology, Tohoku University School of Medicine, Sendai;
  11. §§ Department of Obstetrics and Gynecology, Kinki University School of Medicine, Osaka; and
  12. ∥∥ Department of Obstetrics and Gynecology, Faculty of Medicine, University of the Ryukyus, Okinawa, Japan.
  1. Address correspondence and reprint requests to Koji Matsumoto, MD, Department of Obstetrics and Gynecology, Graduate School of Comprehensive Human Science, University of Tsukuba, Tsukuba 305-8575, Japan. E-mail: matsumok{at}


Objective Genetic variations in human leukocyte antigens (HLA) class II regions may influence the risk of cervical cancer by altering the efficiency of the immune responses to human papillomavirus antigens. This prospective study was designed to evaluate the effects of HLA class II alleles on the natural course of cervical precursor lesions.

Methods We followed a total of 454 Japanese women with cytological low-grade squamous intraepithelial lesion (LSIL) and histological cervical intraepithelial neoplasia grades 1 to 2 (CIN1-CIN2). Patients were tested for HLA class II alleles and cervical human papillomavirus DNA at the time of entry and then monitored by cytology and colposcopy every 4 months for a mean follow-up of 39.0 months. We analyzed cumulative probabilities of cytological regression to at least 2 consecutive negative Papanicolaou tests and histological progression to biopsy-positive CIN3.

Results During the follow-up period, 39 lesions progressed to CIN3, and 282 lesions regressed to normal cytology. Progression to CIN3 did not occur in DRB1*1302-positive women, and this protective effect of DRB1*1302 was statistically significant (P = 0.03). Low-grade squamous intraepithelial lesion regressed to normal cytology more quickly in DRB1*1302-positive women than in DRB1*1302-negative women (median time, 8.9 months vs 14.2 months), although the difference was not statistically significant (P = 0.16). The risk of LSIL persistence or progression to CIN3 within 5 years was not affected by any other HLA class II alleles.

Conclusion By using a prospective study design, we demonstrated the protective effect of the DRB1*1302 allele against progression to CIN3 among Japanese women with LSIL.

  • HLA
  • LSIL
  • HPV
  • CIN

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