title: Methylation of human papillomavirus-52 and -58 is a candidate biomarker in cervical neoplasia.
abstract: BACKGROUND
  Previous studies of human papillomavirus (HPV)16/18 genome methylation have concluded that methylation status of the L1 gene might act as a biomarker for cervical intraepithelial neoplasia (CIN).
  
  
  OBJECTIVE
  We investigated the correlation between methylation status in the L1 gene and the long control region (LCR) of HPV52/58 and CIN.
  
  
  METHODS
  Exfoliated cervical cells were taken from 54 HPV52-positive and 41 HPV58-positive women. The HPV genome was examined using bisulfite modification, polymerase chain reaction amplification, and sequencing.
  
  
  RESULTS
  The CpGs were unmethylated or hypomethylated in the HPV52/58 LCR. In contrast, the methylation status of the HPV52 L1 gene was correlated with the severity of cervical neoplasia, with average percentages of 15%, 34%, and 52% for cervicitis/CIN1, CIN2, and CIN3, respectively (P<0.05). Methylation status of the HPV52 L1 gene was also correlated with the prognosis of CIN1/2, with median percentages of 15% and 35% for regression and persistence/progression, respectively (P<0.05). The methylation status of the HPV58 L1 gene was correlated with the severity of cervical neoplasia, with average percentages of 12%, 38%, and 61% for cervicitis/CIN1, CIN2, and CIN3, respectively (P<0.05).
  
  
  CONCLUSIONS
  The increased methylation at the CpG sites in the HPV52/58 L1 gene was correlated with the severity of cervical neoplasia, similar to HPV16/18 in previous studies. These data suggest that HPV methylation status of the L1 gene is a candidate biomarker of CIN for detecting CIN2 and CIN3.
authors.affiliation: Department of Obstetrics and Gynecology, School of Medicine, Keio University, 35 Shinanomachi, Shinjuku-ku, Tokyo 160-8582, Japan.
authors.forename: Isao
authors.initials: I
authors.lastname: Murakami
authors.forename: Takuma
authors.initials: T
authors.lastname: Fujii
authors.forename: Katsuaki
authors.initials: K
authors.lastname: Dan
authors.forename: Miyuki
authors.initials: M
authors.lastname: Saito
authors.forename: Akiko
authors.initials: A
authors.lastname: Ohno
authors.forename: Takashi
authors.initials: T
authors.lastname: Iwata
authors.forename: Daisuke
authors.initials: D
authors.lastname: Aoki
mesh_terms: D015415:Biomarkers / Q000032:analysis*; D036022:Capsid Proteins / Q000235:genetics*; D019175:DNA Methylation; D004279:DNA, Viral / Q000737:chemistry* / Q000302:isolation & purification; D005260:Female; D006801:Humans; D025202:Molecular Diagnostic Techniques / Q000379:methods*; D009856:Oncogene Proteins, Viral / Q000235:genetics*; D012720:Severity of Illness Index; D002583:Uterine Cervical Neoplasms / Q000175:diagnosis* / Q000473:pathology / Q000821:virology
chemical_list: D015415:Biomarkers; D036022:Capsid Proteins; D004279:DNA, Viral; C114580:HPV L1 protein, Human papillomavirus; C574671:L1 protein, human papillomavirus type 52; D009856:Oncogene Proteins, Viral
keywords: Biomarker; CIN; Cervical neoplasia; DNA methylation; HPV; Human papillomavirus 52; Human papillomavirus 58; LCR; PCR; cervical intraepithelial neoplasia; human papillomavirus; long control region; polymerase chain reaction