Predicting Residual Neck Disease in Patients With Oropharyngeal Squamous Cell Carcinoma Treated With Radiation Therapy: Utility of p16 Status | Cancer Biomarkers | JAMA Otolaryngology–Head & Neck Surgery | JAMA Network
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Original Article
November 16, 2009

Predicting Residual Neck Disease in Patients With Oropharyngeal Squamous Cell Carcinoma Treated With Radiation Therapy: Utility of p16 Status

Author Affiliations

Author Affiliations: Departments of Otolaryngology–Head and Neck Surgery (Drs Shonka, Reibel, Levine, and Jameson), Radiation Oncology (Drs Shoushtari and Read), Internal Medicine, Division of Hematology/Oncology (Dr Thomas), and Pathology (Dr Moskaluk), University of Virginia Heath System, Charlottesville.

Arch Otolaryngol Head Neck Surg. 2009;135(11):1126-1132. doi:10.1001/archoto.2009.153

Objective  To identify factors that predict complete response of cervical nodal disease to radiation therapy (RT) in patients with oropharyngeal squamous cell carcinoma (OP-SCCA).

Design  Histologic analysis of prospectively collected specimens and retrospective medical chart review.

Setting  Tertiary referral center.

Subjects  Sixty-nine patients with OP-SCCA treated from January 1, 2002, through June 1, 2008.

Intervention  Definitive RT, with or without chemotherapy and with or without neck dissection (ND).

Main Outcome Measure  Presence of a viable tumor in post-RT ND specimen.

Results  Tissue specimens from 69 patients with OP-SCCA treated primarily with RT, with or without chemotherapy, were evaluated. Of these, 47 (68.1%) were strongly and diffusely positive for p16 expression by immunohistochemical analysis, signifying human papillomavirus positivity. Patients with p16-positive and p16-negative tumors (hereinafter, p16+ and p16−, respectively) had similarly sized primary tumors on presentation, but p16+ primary tumors were associated with more advanced neck disease (nodal stages N2c-N3; 31.9% vs 4.5% for p16− tumors) and more contralateral nodes (27.7% vs 4.5% for p16− tumors). Forty-seven patients (59.0%) underwent planned posttreatment ND (a total of 55 NDs). The NDs performed for p16− tumors were significantly more likely to have viable tumor in the specimen (50.0% vs 18.0% for p16+ tumors;  = .02). In addition, p16+ necks with residual viable cancer were characterized by incomplete response on post-RT imaging, tobacco and alcohol use, and extracapsular spread on pretreatment imaging.

Conclusions  In conjunction with other clinical parameters, p16 status can help predict the need for post-RT ND in patients with OP-SCCA. Although close observation may be warranted in selected patients with p16+ tumors, patients with p16− tumors are at much higher risk for residual neck disease, even when initial nodal disease is less advanced.