TY - JOUR
T1 - Methylation of human papillomavirus-52 and -58 is a candidate biomarker in cervical neoplasia
AU - Murakami, Isao
AU - Fujii, Takuma
AU - Dan, Katsuaki
AU - Saito, Miyuki
AU - Ohno, Akiko
AU - Iwata, Takashi
AU - Aoki, Daisuke
N1 - Funding Information:
The authors received a Grant-in-Aid for Scientific Research from the Ministry of Education, Culture, Sports, Science and Technology, Japan ( 23791855 , 23592462 ).
PY - 2013/9
Y1 - 2013/9
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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U2 - 10.1016/j.jcv.2013.06.026
DO - 10.1016/j.jcv.2013.06.026
M3 - Article
C2 - 23871162
AN - SCOPUS:84881551339
SN - 1386-6532
VL - 58
SP - 149
EP - 154
JO - Journal of Clinical Virology
JF - Journal of Clinical Virology
IS - 1
ER -
