title: Preferential sites for the integration and disruption of human papillomavirus 16 in cervical lesions.
abstract: BACKGROUND
  Persistent infection with high-risk human papillomavirus (HPV) is necessary to cause cervical cancer, and integrating viral DNA into the host genome may contribute to the process of carcinogenesis. The underlying mechanisms are still unclear.
  
  
  OBJECTIVE
  In this study, we aimed to investigate the distribution of HPV 16 integration in the host genome and disrupted sites in the viral genome.
  
  
  METHODS
  The physical status of HPV 16 genomes in 46 cervical precancerous and cancerous lesions was determined via ligation-mediated chain reaction (DIPS) using 15 previously published primer sets and 12 newly designed primer sets.
  
  
  RESULTS
  A total of 60 viral-cellular junctions were identified in 31 of 46 specimens, and over 80% of the integration sites in the human genome were located in regions of repetitive elements. The proportion of LSIL-, HSIL-, and SCC-containing integration sites near cancer-relevant genes was 10%, 18.8%, and 33.3%, respectively. The frequency of viral gene disruption was significantly higher (P < 0.05) in the L2 gene than in other regions of the viral genome.
  
  
  CONCLUSIONS
  There are sites of preferential HPV 16 integration. The integration sites tend to be located in repetitive regions of the host genome, and some sites are found near cancer-relevant genes. In addition, the HPV 16 genome is more likely to be disrupted in the L2 gene locus.
authors.affiliation: Microbial Genome Research Center, CAS Key Laboratory of Pathogenic Microbiology and Immunology, Institute of Microbiology, Chinese Academy of Sciences, Beijing 100101, China.
authors.forename: Hui
authors.initials: H
authors.lastname: Li
authors.forename: Yi
authors.initials: Y
authors.lastname: Yang
authors.forename: Ruifen
authors.initials: R
authors.lastname: Zhang
authors.forename: Yupin
authors.initials: Y
authors.lastname: Cai
authors.forename: Xi
authors.initials: X
authors.lastname: Yang
authors.forename: Zhiyun
authors.initials: Z
authors.lastname: Wang
authors.forename: Yuan
authors.initials: Y
authors.lastname: Li
authors.forename: Xuemei
authors.initials: X
authors.lastname: Cheng
authors.forename: Xin
authors.initials: X
authors.lastname: Ye
authors.forename: Yang
authors.initials: Y
authors.lastname: Xiang
authors.forename: Baoli
authors.initials: B
authors.lastname: Zhu
mesh_terms: D001483:Base Sequence; D036022:Capsid Proteins / Q000235:genetics; D045744:Cell Line, Tumor; D002584:Cervix Uteri / Q000473:pathology* / Q000821:virology; D017931:DNA Primers; D005260:Female; D015894:Genome, Human; D016679:Genome, Viral; D052162:Human papillomavirus 16 / Q000235:genetics / Q000502:physiology*; D006801:Humans; D008969:Molecular Sequence Data; D009856:Oncogene Proteins, Viral / Q000235:genetics; D030361:Papillomavirus Infections / Q000821:virology*; D011995:Recombination, Genetic; D012091:Repetitive Sequences, Nucleic Acid; D017422:Sequence Analysis, DNA; D002583:Uterine Cervical Neoplasms / Q000473:pathology / Q000821:virology; D016662:Virus Integration
chemical_list: D036022:Capsid Proteins; D017931:DNA Primers; C063316:L2 protein, Human papillomavirus type 16; D009856:Oncogene Proteins, Viral