Methylation of human papillomavirus-52 and -58 is a candidate biomarker in cervical neoplasia

Isao Murakami, Takuma Fujii, Katsuaki Dan, Miyuki Saito, Akiko Ohno, Takashi Iwata, Daisuke Aoki

Research output: Contribution to journalArticle

8 Citations (Scopus)

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). Objectives: We investigated the correlation between methylation status in the L1 gene and the long control region (LCR) of HPV52/58 and CIN. Study design: 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.

Original languageEnglish
Pages (from-to)149-154
Number of pages6
JournalJournal of Clinical Virology
Volume58
Issue number1
DOIs
Publication statusPublished - 2013 Sep

Fingerprint

Methylation
Biomarkers
Cervical Intraepithelial Neoplasia
Neoplasms
Genes
Uterine Cervicitis
Human papillomavirus 18
Human papillomavirus 16
Human Genome
Genome
Polymerase Chain Reaction

Keywords

  • Biomarker
  • Cervical neoplasia
  • DNA methylation
  • Human papillomavirus 52
  • Human papillomavirus 58

ASJC Scopus subject areas

  • Virology
  • Infectious Diseases

Cite this

Methylation of human papillomavirus-52 and -58 is a candidate biomarker in cervical neoplasia. / Murakami, Isao; Fujii, Takuma; Dan, Katsuaki; Saito, Miyuki; Ohno, Akiko; Iwata, Takashi; Aoki, Daisuke.

In: Journal of Clinical Virology, Vol. 58, No. 1, 09.2013, p. 149-154.

Research output: Contribution to journalArticle

Murakami, Isao ; Fujii, Takuma ; Dan, Katsuaki ; Saito, Miyuki ; Ohno, Akiko ; Iwata, Takashi ; Aoki, Daisuke. / Methylation of human papillomavirus-52 and -58 is a candidate biomarker in cervical neoplasia. In: Journal of Clinical Virology. 2013 ; Vol. 58, No. 1. pp. 149-154.
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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). Objectives: We investigated the correlation between methylation status in the L1 gene and the long control region (LCR) of HPV52/58 and CIN. Study design: 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.",
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AU - Murakami, Isao

AU - Fujii, Takuma

AU - Dan, Katsuaki

AU - Saito, Miyuki

AU - Ohno, Akiko

AU - Iwata, Takashi

AU - Aoki, Daisuke

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N2 - 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). Objectives: We investigated the correlation between methylation status in the L1 gene and the long control region (LCR) of HPV52/58 and CIN. Study design: 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.

AB - 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). Objectives: We investigated the correlation between methylation status in the L1 gene and the long control region (LCR) of HPV52/58 and CIN. Study design: 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.

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KW - Human papillomavirus 58

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