Prognostic Factors in Recent Head and Neck Squamous Cell Carcinoma of Unknown Primary Site (HNSCCUP)

Abstract

Objectives: HNSCCUP is heterogeneous and the treatment strategies remain controversial. Recently p16 overexpression may be becoming a good prognostic surrogate marker in oropharyngeal carcinoma. We investigated prognostic factors for HNSCCUP, including p16 status. Methods: Forty patients with HNSCCUP who visited our department from 1996 to 2010 were retrospectively reviewed. The nodal stage was N1, N2, and N3 in 4, 22, and 14 patients, respectively. Neck dissection alone was performed in 19 patients, neck dissection together with adjuvant irradiation in 14 patients, and chemoradiotherapy in 7 patients with unresectable nodes. We immunohistochemically assessed p16 expression in neck metastasis. As prognostic factors, we analyzed N stage, location, extracapsular spread (Ex), primary site, heavy smoking and drinking, and p16 expression. Results: The primary cancer eventually emerged in 15 patients. Eight patients were p16-positive, among whom oropharynx was the most frequent primary site ( P = 0.02). The 3-year disease-specific survival (DSS) and overall survival rates were 74% and 65%, respectively. For DDS, N3 (56% vs 84%), level IV V metastasis (50% vs 83%), Ex (59% vs 100%), and heavy smoking and drinking (55% vs 95%) were significant adverse prognostic factors. p16-negative patients had a low DSS (68% vs 100%), but it was not statistically significant. In multivariate analysis, N3 and Ex had significant correlations with prognosis. Conclusions: p16 overexpression can predict the primary site in the oropharynx and may become a positive prognostic factor. N stage, Ex, location of neck metastasis, smoking and drinking status, and p16 expression should be considered in the treatment for HNSCCUP.