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

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

Tertiary referral center.

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

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

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

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; P = .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.

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.