Try it
Pathology · Neoplasia: p16 as HPV surrogate
Sample itemA biopsy from a tonsillar squamous carcinoma in a non-smoker shows strong, diffuse nuclear and cytoplasmic p16 staining. What is the molecular explanation for this overexpression?
Original practice item, not a recalled exam question. Nothing here is recorded.
The answer and the reasoning
A. E7 inactivates Rb, removing feedback inhibition of p16
HPV E7 binds and inactivates Rb. Because p16 normally acts upstream to keep Rb active, and Rb loss removes negative feedback, p16 accumulates. Diffuse p16 staining is therefore used as a surrogate marker of high-risk HPV in oropharyngeal and cervical carcinoma.
Option by option
A. E7 inactivates Rb, removing feedback inhibition of p16 (correct)
Correct. Functional loss of Rb through E7 causes compensatory p16 overexpression.
B. Amplification of the CDKN2A gene on chromosome 9p
CDKN2A is usually deleted or methylated in tumours, not amplified.
C. E6 degrades p53, so p16 is no longer degraded
E6 degrades p53 but does not control p16 stability.
D. A germline mutation of the CDKN2A promoter silences p16
Silencing of p16 would reduce, not increase, staining.
Source note: Original NextPrep sample item — pending expert review. This item is original practice material awaiting independent expert review, so confirm important facts in a standard textbook.
More Pathology questions
- HaematopathologyBinucleate 'owl-eye' cells that stain for CD15 and CD30 are characteristic of which cond…
- NeuropathologyEosinophilic intracytoplasmic inclusions in the pigmented neurons of the substantia nigr…
- HaemodynamicsWhich of the following is NOT a component of Virchow's triad for thrombosis?
- Granulomatous diseaseNon-caseating granulomas with Schaumann bodies and asteroid bodies are typical of: