HPV and p16 Testing in Oropharyngeal Squamous Cell Carcinoma
Methodology, Interpretation, and Significance
In the pathology literature, E6 and E7 receive the most attention by a landslide.
The E6 protein binds p53 and, in concert with E6-associated protein (E6AP), which is a cellular ubiquitin ligase, marks it for degradation by way of a proteosome-dependent pathway. This is assumed to play a role in the evasion of cell death, a form of cellular immortalization if you will. E6 is also thought to work outside of the p53 pathway by activating telomerases.
The E7 protein, on the other hand, binds and inactivates proteins of the retinoblastoma gene family of tumor suppressors. This family includes retinoblastoma, p130, and p107. In the normal state, retinoblastoma protein is hypophosphorylated and then binds and becomes a regulator of E2F, a transcription factor that modulates activity of other factors involved in cell cycle progression. E7 essentially binds and inactivates the hypophosphorylated retinoblastoma protein and permits E2F to proceed with cell cycle progression. Retinoblastoma will also modify the activity of other tumor suppressor proteins such as p16, a cyclin-dependent kinase inhibitor.
p16, the cell cycle regulatory protein, is up-regulated by HPV oncoproteins. To this end, as you well know, p16 is widely considered a surrogate marker for HPV infection.
HPV in OPSCC — Pathways
Jump to section:
- Oropharyngeal Squamous Cell Carcinoma in Review
- Oropharynx Anatomy
- Epidemiology of OPSCC — Demographics
- Epidemiology of OPSCC — Incidence
- Management Strategies in OPSCC
- The Role of HPV and p16 in Oropharyngeal Squamous Cell Carcinoma
- Human Papillomavirus (HPV)
- HPV in OPSCC Oncogenesis — Genome
- HPV in OPSCC Oncogenesis — Pathways
- HPV in OPSCC Oncogenesis — Detection
- Indications for HPV and p16 Testing in Oropharyngeal Squamous Cell Carcinoma
- Interpretation of HPV and p16 Testing in Oropharyngeal Squamous Cell Carcinoma
- Interpret the Presence or Absence of HPV
- Don't Jump the Gun
- Polymerase Chain Reaction (PCR)
- DNA In Situ Hybridization
- E6/E7 Messenger Ribonucleic Acid (mRNA)
- P16 Immunohistochemistry
- HPV and p16 Testing in Oropharyngeal Squamous Cell Carcinoma in Review
- Contact Information