title: Human papillomavirus genotype distribution in cervical intraepithelial neoplasia grade 2/3 and invasive cervical cancer in Japanese women.
abstract: OBJECTIVE
  Human papillomavirus vaccines are being introduced worldwide and are expected to reduce the incidence of cervical cancer. Here we report a cross-sectional study using a validated human papillomavirus genotyping method to reveal the human papillomavirus prevalence and genotype distribution in Japanese women with cervical intraepithelial neoplasia Grade 2/3 and invasive cervical cancer.
  
  
  METHODS
  Cervical exfoliated cells were collected from 647 patients with abnormal cervical histology (cervical intraepithelial neoplasia Grade 2, n = 164; cervical intraepithelial neoplasia Grade 3, n = 334; and invasive cervical cancer, n = 149), and subjected to the PGMY-PCR-based genotyping assay. The association between human papillomavirus infection and lesion severity was calculated using a prevalence ratio.
  
  
  RESULTS
  Overall, the prevalence of human papillomavirus deoxyribonucleic acid was 96.3% in cervical intraepithelial neoplasia Grade 2, 98.8% in cervical intraepithelial neoplasia Grade 3 and 88.0% in invasive cervical cancer (97.8% in squamous cell carcinoma and 71.4% in adenocarcinoma). The three most prevalent types were as follows: human papillomavirus 16 (29.3%), human papillomavirus 52 (27.4%) and human papillomavirus 58 (22.0%) in cervical intraepithelial neoplasia Grade 2; human papillomavirus 16 (44.9%), human papillomavirus 52 (26.0%) and human papillomavirus 58 (17.4%) in cervical intraepithelial neoplasia Grade 3; and human papillomavirus 16 (47.7%), human papillomavirus 18 (23.5%) and human papillomavirus 52 (8.7%) in invasive cervical cancer. The prevalence ratio of human papillomavirus 16 was significantly higher in cervical intraepithelial neoplasia Grade 3 compared with cervical intraepithelial neoplasia Grade 2 (prevalence ratio, 1.62; 95% confidence interval, 1.26-2.13) and in squamous cell carcinoma compared with cervical intraepithelial neoplasia Grade 3 (prevalence ratio, 1.55; 95% confidence interval, 1.25-1.87). Multiple infections decreased from cervical intraepithelial neoplasia Grade 2/3 (38.4/29.6%) to invasive cervical cancer (14.1%), whereas co-infections with human papillomavirus 16/52/58 were found in cervical intraepithelial neoplasia Grade 2/3.
  
  
  CONCLUSIONS
  The results of this study provide pre-vaccination era baseline data on human papillomavirus type distribution in Japanese women and serve as a reliable basis for monitoring the future impact of human papillomavirus vaccination in Japan.
authors.affiliation: WHO HPV LabNet Regional Reference Laboratory, WHO Western Pacific Region, Pathogen Genomics Center, National Institute of Infectious Diseases, Tokyo.
authors.forename: Yukari
authors.initials: Y
authors.lastname: Azuma
authors.affiliation: WHO HPV LabNet Regional Reference Laboratory, WHO Western Pacific Region, Pathogen Genomics Center, National Institute of Infectious Diseases, Tokyo.
authors.forename: Rika
authors.initials: R
authors.lastname: Kusumoto-Matsuo
authors.affiliation: WHO HPV LabNet Regional Reference Laboratory, WHO Western Pacific Region, Pathogen Genomics Center, National Institute of Infectious Diseases, Tokyo.
authors.forename: Fumihiko
authors.initials: F
authors.lastname: Takeuchi
authors.affiliation: Department of Obstetrics and Gynecology, NTT Medical Center Tokyo, Tokyo.
authors.forename: Asami
authors.initials: A
authors.lastname: Uenoyama
authors.affiliation: Department of Obstetrics and Gynecology, NTT Medical Center Tokyo, Tokyo.
authors.forename: Kazunari
authors.initials: K
authors.lastname: Kondo
authors.affiliation: Department of Obstetrics and Gynecology, NTT Medical Center Tokyo, Tokyo.
authors.forename: Hajime
authors.initials: H
authors.lastname: Tsunoda
authors.affiliation: Department of Obstetrics and Gynecology, Graduate School of Medicine, The University of Tokyo, Tokyo.
authors.forename: Kazunori
authors.initials: K
authors.lastname: Nagasaka
authors.affiliation: Department of Obstetrics and Gynecology, Graduate School of Medicine, The University of Tokyo, Tokyo.
authors.forename: Kei
authors.initials: K
authors.lastname: Kawana
authors.affiliation: Department of Obstetrics and Gynecology, Keio University School of Medicine, Tokyo, Japan.
authors.forename: Tohru
authors.initials: T
authors.lastname: Morisada
authors.affiliation: Department of Obstetrics and Gynecology, Keio University School of Medicine, Tokyo, Japan.
authors.forename: Takashi
authors.initials: T
authors.lastname: Iwata
authors.affiliation: Department of Obstetrics and Gynecology, Keio University School of Medicine, Tokyo, Japan.
authors.forename: Daisuke
authors.initials: D
authors.lastname: Aoki
authors.affiliation: WHO HPV LabNet Regional Reference Laboratory, WHO Western Pacific Region, Pathogen Genomics Center, National Institute of Infectious Diseases, Tokyo ikuki@nih.go.jp.
authors.forename: Iwao
authors.initials: I
authors.lastname: Kukimoto
mesh_terms: D000230:Adenocarcinoma / Q000821:virology; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D044466:Asian People / Q000706:statistics & numerical data*; D002294:Carcinoma, Squamous Cell / Q000821:virology; D003430:Cross-Sectional Studies; D004279:DNA, Viral / Q000302:isolation & purification; D005260:Female; D005838:Genotype; D006801:Humans; D015994:Incidence; D007564:Japan / Q000453:epidemiology; D008875:Middle Aged; D060787:Neoplasm Grading; D027383:Papillomaviridae / Q000235:genetics* / Q000302:isolation & purification; D030361:Papillomavirus Infections / Q000150:complications* / Q000821:virology; D015995:Prevalence; D002583:Uterine Cervical Neoplasms / Q000473:pathology* / Q000821:virology*; D002578:Uterine Cervical Dysplasia / Q000473:pathology* / Q000821:virology*
chemical_list: D004279:DNA, Viral
keywords: cervical cancer; genotyping; human papillomavirus; prevalence ratio