Clinical history: 56 year old male with tonsillar mass.
What is the most probable diagnosis?
Non-keratinizing squamous cell carcinoma of the tonsil
The tonsil is the most common site of intra-oral squamous cell carcinoma. Oral non-keratinizing tumours are frequently related to human papilloma virus (HPV) infection and are positive for p16 by immunohistochemistry as a surrogate marker for HPV infection.
As you will recall, part of the HPV genome expresses two genes that encode proteins E6 and E7. The E6 protein product disrupts the function of the p53 protein and the E7 protein disrupts the function of the Rb protein, both important tumour suppressor genes.
p16, or CDKN2A, essentially functions as an inhibitor of the Rb protein by inactivating kinases that inactivate Rb and therefore allow cell division (active Rb prevents cells division). In the absence of Rb inhibition, a cell can potentially divide without normal control, e.g. in malignancy.
p16 is unregulated in response to attempt to inhibit Rb, and is therefore detectable by immunohistochemistry as a surrogate for HPV infection.
HPV is associated with carcinomas of the cervix, vulva, vagina, penis, oropharynx and anus.