Background: The inability of current diagnostic tools to detect small lymph node metastases in patients with Head and Neck Squamous Cell Carcinoma (HNSCC) leads to a rate of undetected metastases that is too high to refrain from elective neck treatment, resulting in overtreatment. The aim of this study is validation of a gene expression signature for distinguishing metastasizing from non-metastasizing HNSCC on a large multi-center cohort.

Material and methods: Samples of oral cavity and oropharyngeal cancer were collected from all head and neck oncological centers in the Netherlands. Gene expression was analyzed with a DNA microarray representing 696 previously reported predictive genes. The negative predictive value (NPV) was assessed on the whole cohort (n=222), on a subset including only clinically node negative (cN0) tumors (n=143) and on the most relevant subset that included T1 and T2, cN0 oral cavity tumors (n=101). Histological examination was used as gold standard for nodal status.

Results: Overall, the NPV of the signature was 72 %. The signature performed better on the cN0 subset (NPV 85%) and very well in the clinically most relevant subset of T1 and T2, cN0, oral cavity SCC (NPV 89%).

Conclusion: Combining the results of clinical and radiological examination with the gene expression signature decreases the rate of undetected nodal metastasis to 11 % in the relevant group of early stage cancers of the oral cavity. This result should be considered sufficient to refrain from elective neck treatment in these patients.

Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 4122. doi:10.1158/1538-7445.AM2011-4122