Human papillomaviruses are the causative agent of cancers in stratified epithelial surfaces. They replicate in the upper parts of the epithelium, where cells would normally be dying to produce a cornified layer.

Therefore, they need to inhibit or delay differentiation and stimulate cell cycle progression to create an environment conducive for replication of the viral genome.

The alterations both in differentiation and in the cell cycle are achieved by the viral proteins E6 and E7, which modulate cellular transcription mainly through their effects on p53 and the retinoblastoma family.

Subtypes

 high-risk HPV

• HPV16

Pathology

 cervical squamous cell carcinoma
 tonsillar squamous cell carcinoma
 laryngeal squamous cell carcinoma

Tumorigenesis

 HPV E6 and E7 oncoproteins are able to inactivate the tumor suppressor functions of p53 and Rb

• HPV E6 protein
• HPV E7 protein

References

 McCance DJ. Transcriptional regulation by human papillomaviruses. Curr Opin Genet Dev. 2005 Oct;15(5):515-9. PMID: #16099158#

 Wentzensen N, Vinokurova S, von Knebel Doeberitz M. Systematic review of genomic integration sites of human papillomavirus genomes in epithelial dysplasia and invasive cancer of the female lower genital tract. Cancer Res. 2004 Jun 1;64(11):3878-84. PMID: #15172997#

 Storey A. Papillomaviruses: death-defying acts in skin cancer. Trends Mol Med. 2002 Sep;8(9):417-21. PMID: #12223312#