title: HLA class II DRB1*1302 allele protects against progression to cervical intraepithelial neoplasia grade 3: a multicenter prospective cohort study.
abstract: 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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Department of Obstetrics and Gynecology, Graduate School of Comprehensive Human Science, University of Tsukuba, Tsukuba, Japan. matsumok@mui.biglobe.ne.jp
authors.forename: Koji
authors.initials: K
authors.lastname: Matsumoto
authors.forename: Hiroo
authors.initials: H
authors.lastname: Maeda
authors.forename: Akinori
authors.initials: A
authors.lastname: Oki
authors.forename: Naoyoshi
authors.initials: N
authors.lastname: Takatsuka
authors.forename: Toshiharu
authors.initials: T
authors.lastname: Yasugi
authors.forename: Reiko
authors.initials: R
authors.lastname: Furuta
authors.forename: Ranko
authors.initials: R
authors.lastname: Hirata
authors.forename: Akira
authors.initials: A
authors.lastname: Mitsuhashi
authors.forename: Takuma
authors.initials: T
authors.lastname: Fujii
authors.forename: Yasuo
authors.initials: Y
authors.lastname: Hirai
authors.forename: Tsuyoshi
authors.initials: T
authors.lastname: Iwasaka
authors.forename: Nobuo
authors.initials: N
authors.lastname: Yaegashi
authors.forename: Yoh
authors.initials: Y
authors.lastname: Watanabe
authors.forename: Yutaka
authors.initials: Y
authors.lastname: Nagai
authors.forename: Tomoyuki
authors.initials: T
authors.lastname: Kitagawa
authors.forename: Hiroyuki
authors.initials: H
authors.lastname: Yoshikawa
mesh_terms: D000293:Adolescent; D000328:Adult; D000465:Algorithms; D000483:Alleles; D044466:Asian People / Q000235:genetics; D015331:Cohort Studies; D018450:Disease Progression; D005260:Female; D005500:Follow-Up Studies; D020022:Genetic Predisposition to Disease; D006681:HLA-D Antigens / Q000235:genetics; D059811:HLA-DRB1 Chains / Q000235:genetics* / Q000502:physiology; D006801:Humans; D008875:Middle Aged; D060787:Neoplasm Grading; D011446:Prospective Studies; D002583:Uterine Cervical Neoplasms / Q000208:ethnology / Q000235:genetics* / Q000473:pathology*; D055815:Young Adult; D002578:Uterine Cervical Dysplasia / Q000208:ethnology / Q000235:genetics* / Q000473:pathology*
chemical_list: D006681:HLA-D Antigens; D059811:HLA-DRB1 Chains