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p16 in Head and Neck Squamous Cancer

Posted on June 02 2014

Pathology Update

HPVā€associated head and neck squamous carcinomas have only been recently recognized. These malignancies are predominantly oropharyngeal, and their incidence is increasing.

NCCN guidelines recommend p16 by immunohistochemistry (IHC) in the workup of oropharynx cancer.

MPLN recommends p16 by IHC as the optimal test method for determining HPV status in head and neck squamous cancer. P16 and HPV positivity are strong, independent and favorable prognostic factors in patients treated with chemo-radiation therapy and surgery (although not by accelerated radiotherapy). Tumor HPV and p16 status (positive or negative) are the strongest predictors of survival in head and neck squamous carcinoma patients treated with radiotherapy.

Immunohistochemical staining for p16 is an excellent surrogate marker for HPV status and has the advantage of being independent of HPV subtype. Many in situ hybridization assays for HPV have undetermined sensitivities for non-HPV 16 subtypes, which may explain why p16 by immunohistochemistry is better associated with favorable response to radiation, chemotherapy and surgery than HPV status determined by ISH or PCR.

Current investigations are designed to determine how p16 (HPV) status can more specifically guide therapy. Therefore, p16 (HPV) status should be part of all clinical trials for head and neck squamous carcinoma. Ongoing trials are investigating whether p16 (HPV) positive cancers benefit from less intense radiotherapy, intensity-modulated radiation therapy, targeted therapies including anti-EGFR drugs cetuximab and erlotinib, or histone deacetylase inhibition.

Kian Ang K et al. (2010).Human Papillomavirus and Survival of Patients with Oropharyngeal Cancer. N Engl J Med 363:24-35.

Lewis J,S et al. (2010). p16 Positive Oropharyngeal Squamous Cell Carcinoma: An Entity With a Favorable Prognosis Regardless of Tumor HPV Status. Am J Surg Pathol 34:1088–1096

Schlecht N, F et al.(epub 13 May 2011). A Comparison of Clinically Utilized Human Papillomavirus Detection Methods in Head and Neck Cancer. Modern Pathology.

Rischin D e al. (2010). Prognostic Significance of p16INK4A and Human Papillomavirus in Patients With Oropharyngeal Cancer Treated on TROG 02.02 Phase III Trial. J.Clin Oncol. 2010 Sep 20;28(27):4142-8