Reconstruction of human papillomavirus type 16-mediated early-stage neoplasia implicates E6/E7 deregulation and the loss of contact inhibition in neoplastic progression

J Virol. 2012 Jun;86(11):6358-64. doi: 10.1128/JVI.07069-11. Epub 2012 Mar 28.


Infection with human papillomavirus type 16 (HPV-16) can lead to low- or high-grade squamous intraepithelial lesions (LSIL or HSIL). Here we show that these in vivo disease states can be replicated in raft cultures of early-pass HPV-16 episomal cell lines, at both the level of pathology and the level of viral gene expression. A reduced responsiveness to cell-cell contact inhibition and an increase in E6/E7 activity correlated closely with phenotype. Similar deregulation is likely to underlie the appearance of LSIL or HSIL soon after infection.

MeSH terms

  • Carcinoma in Situ / virology*
  • Cells, Cultured
  • Contact Inhibition*
  • Female
  • Human papillomavirus 16 / pathogenicity*
  • Humans
  • In Vitro Techniques
  • Oncogene Proteins, Viral / metabolism*
  • Papillomavirus E7 Proteins / metabolism*
  • Repressor Proteins / metabolism*
  • Uterine Cervical Neoplasms / virology*
  • Virulence Factors / metabolism*


  • E6 protein, Human papillomavirus type 16
  • Oncogene Proteins, Viral
  • Papillomavirus E7 Proteins
  • Repressor Proteins
  • Virulence Factors
  • oncogene protein E7, Human papillomavirus type 16