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Human Papillomavirus's Physical State and Cyclin A1 Promoter Methylation in Cervical Cancer
  1. Pattamawadee Yanatatsaneejit, PhD*,
  2. Apiwat Mutirangura, PhD and
  3. Nakarin Kitkumthorn, PhD
  1. *Department of Botany, Faculty of Science,
  2. Center of Excellence in Molecular Genetics of Cancer and Human Diseases, Department ofAnatomy, Faculty of Medicine, Chulalongkorn University; and
  3. Department of Oral and Maxillofacial Pathology, Faculty of Dentistry, Mahidol University, Bangkok, Thailand.
  1. Address correspondence and reprint requests to Nakarin Kitkumthorn, PhD, Department of and Maxillofacial Oral Pathology, Faculty of Dentistry, Mahidol University, Bangkok 10400, Thailand. E-mail: Nakarinkit{at}


Background: Cervical cancer is the second biggest cause of death among human female cancers. Human papillomavirus (HPV) is the main factor in this cancer, especially HPV types 16 and 18, which constitute the high-risk group. There are 2 physical states of HPV in host cells: integrated and episomal forms. Our previous study explored the very high degree of cyclin A1 (CCNA1) promoter methylation in invasive cervical cancer in which all cases were infected by HPV.

Objective: From previous evidence, it seemed that HPV might affect CCNA1 promoter methylation. Therefore, both the quantity and physical state of HPV were investigated in this study for their effects on CCNA1 promoter methylation.

Materials and Methods: To determine the correlation of HPV quantity and CCNA1 methylation, the proportion of HPV L1/HAT (histone acetyltransferase, which is a human housekeeping gene) and the percentage intensity of CCNA1 promoter methylation were observed. CCNA1 promoter methylation was detected by methylation-specific primer polymerase chain reaction. To investigate the physical state, the HPV E2 region was amplified. The effect of the physical state on CCNA1 methylation was observed.

Results: No correlation was found between the quantity of HPV and CCNA1 promoter methylation. Interestingly, the physical state of HPV had the potential to affect methylation of this gene. The integrated form of HPV had a significantly higher impact on CCNA1 methylation than HPV in episomal form (P = 0.001; 95% confidence interval, 11.96-38.44).

Conclusion: We suggest that the integrated form of HPV might lead to CCNA1 promoter methylation in cervical cancer by some mechanisms.

  • HPV
  • Episome
  • Integrated
  • CCNA1 promoter methylation
  • Cervical cancer

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  • This work was supported by the Center of Excellence in Molecular Genetics of Cancer and Human Diseases, Department of Anatomy, Faculty of Medicine, Chulalongkorn University, TRF-MRG Young Scientific Researcher Grant Nos. MRG 5180006 and MRG 5380010 and research funds from the Faculty of Science, Chulalongkorn University.