Background: Head and neck squamous cell carcinoma (HNSCC) is a heterogeneous disease evolving through multistep carcinogenesis, one of the steps being genetic alterations. Noninvasive identification of HNSCC-specific genetic alterations using saliva would have immense potential in early diagnosis and screening, particularly among high-risk patients.
Design: In this exploratory study, a prospective cohort of 27 HNSCC and 10 healthy controls was examined to determine whether genetic alterations (losses and gains) in saliva DNA differentiated HNSCC patients from normal controls. Saliva DNA was interrogated by a candidate gene panel comprising 82 genes using the multiplex ligation-dependent probe amplification assay.
Results: Eleven genes showed some predictive ability in identifying HNSCC cases from normal controls: PMAIP1, PTPN1, ERBB2, ABCC4, UTY, DNMT1, CDKN2B, CDKN2D, NFKB1, TP53, and DCC. Statistical analysis using the Classification and Regression Tree (CART) identified 2 genes, PMAIP1 and PTPN1, which correctly discriminated all 27 HNSCC patients (100%) from normal controls. Results were validated using the leave-one-out validation approach.
Conclusions: Noninvasive high-throughput multiplex ligation-dependent probe amplification identified discrete gene signatures that differentiated HNSCC patients from normal controls providing proof-of-concept for noninvasive HNSCC detection.