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HPV and p16 Testing in Oropharyngeal Squamous Cell Carcinoma

Methodology, Interpretation, and Significance


Slide 17

March 2012

p16 is a cyclin-dependent kinase inhibitor. When the HPV E7 oncoprotein inactivates retinoblastoma, p16 expression increases dramatically. It is worth noting that p16 overexpression is not exclusive to this mechanism and can be seen in 10-20% of cases of oropharyngeal squamous cell carcinoma in the absence of confirmed HPV infection. In other words, p16 expression is not a perfect surrogate marker for HPV infection because it lacks a certain degree of specificity.

However, recent studies have suggested that p16 expression is an independent prognostic factor of improved locoregional control and disease free survival in oropharyngeal squamous cell carcinoma. These studies point to the finding that HPV-negative cases that are strongly and diffusely immunoreactive for p16 show better outcome than p16 negative patients, regardless of their HPV status. This remains an area of interest as knowing the answer to this question is paramount to future testing practices in oropharyngeal squamous cell carcinoma. If p16 positive/HPV positive patients perform differently than p16 positive/HPV negative patients, it will be worthwhile to test both p16 and HPV. On the other hand, if the distinction in outcome can be forecasted by p16 immunohistochemistry alone then HPV testing is essentially futile.



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