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HPV and p16 Testing in Oropharyngeal Squamous Cell Carcinoma

Methodology, Interpretation, and Significance


Slide 27

March 2012

We reviewed the anatomy of the oropharynx; if you refuse to remember the anatomic borders of the oropharynx, simply remember that it includes the base of tongue and bilateral palatine tonsils.

The distribution of oropharyngeal squamous cell carcinoma cases is no longer exclusive to those with long-term carcinogen exposure. It now includes the so-called HPV-associated cases of oropharyngeal squamous cell carcinoma. These patients are typically younger, lack a history of significant tobacco and/or alcohol exposure, and have engaged in “high-risk” sexual behavior.

The incidence of oropharyngeal squamous cell carcinoma is rising even though cigarette use is declining. Again, this is thought to primarily be a function of the HPV-associated cases of oropharyngeal squamous cell carcinoma.

HPV is an encapsulated, nonenveloped, double-stranded DNA virus, with over 100 known genotypes. These genotypes are broken into low- and high-risk categories. High-risk genotypes, especially HPV-16, are commonly associated with oropharyngeal squamous cell carcinoma. HPV can be detected in 50-80% of cases of oropharyngeal squamous cell carcinoma.

E6 and E7 oncoproteins are expressed in low- and high-risk genotypes; however, these proteins bind tumor suppressor proteins with greater affinity when expressed by high-risk genotypes. It appears that E6 and E7 must be derived from high-risk genotypes to actually induce and transform cells in vitro.

What questions should you ask yourself when you evaluate HPV testing and what lies ahead for the management of oropharyngeal squamous cell carcinoma?

The presence of HPV DNA tells us nothing about transcription. Transcription tells us nothing about posttranscriptional regulation. To this end, what have the aforementioned assays told us?

Is p16 a better predictive biomarker than HPV? This has yet to be clarified definitively.

Will HPV or p16 status be incorporated into current staging practices? Deescalating treatment intensity may be an option given the less aggressive behavior of HPV-associated oropharyngeal squamous cell carcinoma.

Questions regarding the HPV vaccine, Gardasil, as a means of preventing head and neck squamous cell carcinoma are beginning to surface. Naturally, this makes the need to clarify HPV’s role in oropharyngeal squamous cell carcinoma imperative.



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