title: Human papillomavirus's physical state and cyclin A1 promoter methylation in cervical cancer.
abstract: 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.
  
  
  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).
  
  
  CONCLUSIONS
  We suggest that the integrated form of HPV might lead to CCNA1 promoter methylation in cervical cancer by some mechanisms.
authors.affiliation: Department of Botany, Faculty of Science, Center of Excellence in Molecular Genetics of Cancer and Human Diseases, Chulalongkorn University, Bangkok, Thailand.
authors.forename: Pattamawadee
authors.initials: P
authors.lastname: Yanatatsaneejit
authors.forename: Apiwat
authors.initials: A
authors.lastname: Mutirangura
authors.forename: Nakarin
authors.initials: N
authors.lastname: Kitkumthorn
mesh_terms: D000465:Algorithms; D052685:Alphapapillomavirus / Q000235:genetics / Q000502:physiology*; D056750:Cyclin A1 / Q000235:genetics* / Q000502:physiology; D019175:DNA Methylation / Q000502:physiology*; D005260:Female; D005838:Genotype; D052162:Human papillomavirus 16 / Q000235:genetics / Q000302:isolation & purification / Q000502:physiology; D052161:Human papillomavirus 18 / Q000235:genetics / Q000302:isolation & purification / Q000502:physiology; D006801:Humans; D030361:Papillomavirus Infections / Q000150:complications / Q000821:virology; D011401:Promoter Regions, Genetic / Q000502:physiology; D002583:Uterine Cervical Neoplasms / Q000209:etiology / Q000235:genetics / Q000473:pathology / Q000821:virology; D016662:Virus Integration / Q000235:genetics / Q000502:physiology; D002578:Uterine Cervical Dysplasia / Q000209:etiology / Q000235:genetics / Q000473:pathology / Q000821:virology
chemical_list: C503745:CCNA1 protein, human; D056750:Cyclin A1