Clinical relevance of copy number profiling in oral and oropharyngeal squamous cell carcinoma

Cancer Med. 2015 Oct;4(10):1525-35. doi: 10.1002/cam4.499. Epub 2015 Jul 21.

Abstract

Current conventional treatment modalities in head and neck squamous cell carcinoma (HNSCC) are nonselective and have shown to cause serious side effects. Unraveling the molecular profiles of head and neck cancer may enable promising clinical applications that pave the road for personalized cancer treatment. We examined copy number status in 36 common oncogenes and tumor suppressor genes in a cohort of 191 oropharyngeal squamous cell carcinomas (OPSCC) and 164 oral cavity squamous cell carcinomas (OSCC) using multiplex ligation probe amplification. Copy number status was correlated with human papillomavirus (HPV) status in OPSCC, with occult lymph node status in OSCC and with patient survival. The 11q13 region showed gain or amplifications in 59% of HPV-negative OPSCC, whereas this amplification was almost absent in HPV-positive OPSCC. Additionally, in clinically lymph node-negative OSCC (Stage I-II), gain of the 11q13 region was significantly correlated with occult lymph node metastases with a negative predictive value of 81%. Multivariate survival analysis revealed a significantly decreased disease-free survival in both HPV-negative and HPV-positive OPSCC with a gain of Wnt-induced secreted protein-1. Gain of CCND1 showed to be an independent predictor for worse survival in OSCC. These results show that copy number aberrations, mainly of the 11q13 region, may be important predictors and prognosticators which allow for stratifying patients for personalized treatment of HNSCC.

Keywords: 11q13; HPV; copy number aberrations; lymph node metastases; oral cavity SCC; oropharyngeal SCC.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Biomarkers, Tumor / genetics*
  • CCN Intercellular Signaling Proteins / genetics
  • Carcinoma, Squamous Cell / genetics*
  • Carcinoma, Squamous Cell / mortality*
  • Carcinoma, Squamous Cell / virology
  • Chromosome Aberrations*
  • Chromosomes, Human, Pair 11 / genetics
  • Cyclin D1 / genetics
  • DNA Copy Number Variations*
  • Disease-Free Survival
  • Female
  • Genes, Tumor Suppressor
  • Human Papillomavirus DNA Tests
  • Human papillomavirus 16 / isolation & purification
  • Humans
  • Lymphatic Metastasis
  • Male
  • Middle Aged
  • Mouth Neoplasms / genetics*
  • Mouth Neoplasms / mortality*
  • Mouth Neoplasms / virology
  • Neoplasm Staging
  • Oncogenes
  • Oropharyngeal Neoplasms / genetics*
  • Oropharyngeal Neoplasms / mortality*
  • Oropharyngeal Neoplasms / virology
  • Papillomavirus Infections / complications
  • Precision Medicine
  • Proto-Oncogene Proteins / genetics
  • Young Adult

Substances

  • Biomarkers, Tumor
  • CCN Intercellular Signaling Proteins
  • CCN4 protein, human
  • CCND1 protein, human
  • Proto-Oncogene Proteins
  • Cyclin D1