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Head & Neck Cancers


Oral Cancer: Molecular Profiles & Clinical Outcomes (Oralchip)

Oral squamous cell carcinoma (OSCC) is associated with considerable mortality and morbidity. We have been conducting a hospital-based clinical study to discover biomarkers that may improve diagnosis and prognosis of oral cancer. Our ultimate goals are to address the following clinically important questions.

  • What determines which OSCC patients go on to develop local recurrence and/or second primary tumors, so that more aggressive medical treatment and/or surveillance can be offered selectively to these patients?
  • How can we identify those clinically node-negative OSCC patients who harbor occult nodal metastasis, patients who should undergo neck dissection while those without can be spared unnecessary surgery?
  • To what degree can molecular markers improve upon the prediction of survival based on the current staging system so that physicians can better individualize patients’ treatments?

Oralchip Publications

2) Lohavanichbutr P, Houck J, Fan W, Yueh B, Mendez E, Futran N, Doody DR, Upton MP, Farwell DG, Schwartz SM, Zhao LP, Chen C. Genome-wide gene expression profiles of HPV-positive and HPV-negative oropharyngeal cancer: potential implications for treatment choices. Arch Otolaryngol Head Neck Surg, 135:180-188, 2009. PMCID: PMC2761829.

3) Mendez E, Houck J, Doody D, Lohavanichbutr P, Fan W, Rue TC, Yueh B, Futran ND, Upton M, Farwell DG, Heagerty PJ, Zhao LP, Schwartz SM, Chen C. A genetic expression profile associated with oral cancer identifies a group of patients at high-risk of poor survival. Clin Cancer Res, 15:1353-1361, 2009. PMCID: PMC2683360.

4) Xu C, Liu Y, Wang P, Fan W, Rue TC, Upton MP, Houck JR, Lohavanichbutr P, Doody DR, Futran ND, Zhao LP, Schwartz SM, Chen C, Méndez E. Integrative analysis of DNA copy number and gene expression in metastatic oral squamous cell carcinoma identifies genes associated with survival. Mol Cancer, 9:143, 2010. PMCID: PMC2884331.

5) Mendez E, Lohavanichbutr P, Fan W, Houck JR, Rue TC, Doody DR, Futran ND, Upton MP, Yueh B, Zhao LP, Schwartz SM, Chen C. Can a metastasis gene expression profile outperform tumor size as a predictor of occult lymph node metastasis in oral cancer patients? Clin Cancer Res, 17(8):2466-73, 2011. PMCID: PMC3078996.

6) Stott-Miller M, Houck JR, Lohavanichbutr P, Mendez E, Upton MP, Futran ND, Schwartz SM, Chen C. Tumor and salivary matrix metalloproteinase levels are strong diagnostic markers of oral squamous cell carcinoma. Cancer Epidemiol Biomarkers Prev, 20(12):2628-36, 2011. PMCID: PMC3237810. NIHMSID: NIHMS328479.

7) Sharma A, Mendez E, Yueh B, Lohavanichbutr P, Houck J, Doody DR, Futran ND, Upton MP, Schwartz SM, Chen C. Human Papillomavirus-positive oral cavity and oropharyngeal cancer patients do not have better quality-of-life trajectories. Otolaryngol Head Neck Surg. 2012; 146(5):739-45. PMID: 22275190, PMCID: PMC3535430.

8) Lohavanichbutr P, Houck J, Doody DR, Wang P, Mendez E, Futran N, Upton MP, Holsinger FC, Schwartz SM and Chen C. Gene expression in uninvolved oral mucosa of OSCC patients facilitates identification of markers predictive of OSCC outcomes. PLoS One. 2012; 7(9):e46575. PMID: 23029552, PMCID: PMC3460916.]

9) Serrano NA, Xu C, Liu Y, Wang P, Fan W, Upton MP, Houck JR, Lohavanichbutr P, Kao  M,  Zhao LP, Schwartz SM, Chen C, Méndez E. Integrative analysis in oral squamous cell carcinoma reveals DNA copy number-associated miRNAs dysregulating target genes. Otolarygol-Head Neck Surg, 2012 Apr 2. [Epub ahead of print]. In press. PMID: 22470160.

10) Lohavanichbutr P, Méndez E, Holsinger FC, Rue TC, Zhang Y, Houck J, Upton MP, Futran N, Schwartz SM, Wang P, Chen C. A 13-gene signature prognostic of HPV-negative oral cavity cancer: discovery and external validation. Clin Cancer Res. 2013; 19(5):1197-203. PMID:23319825, PMCID: PMC3593802.].

11) Chen C, Zhang Y, Loomis MM, Upton MP, Lohavanichbutr P, Houck JR, Doody DR, Mendez E, Futran N, Schwartz SM, Wang P. Genome-wide loss of heterozygosity and DNA copy number aberration in HPV-negative oral squamous cell carcinoma and their associations with oral cancer-specific survival. GEO Data Repository: GSE68717. PLoS One. 2015; 10(8):e0135074. PMID: 26247464; PMCID: PMC4527746.


International Head and Neck Cancer Epidemiology Consortium (INHANCE)

Dr. Chen is a member of the INHANCE Consortium, which was established in 2004 and is comprised of groups performing large molecular epidemiology studies of head and neck cancer. Through collaborations with investigators throughout the world, this group hopes to address the role of single nucleotide polymorphisms (SNPs) and their interactions with environmental factors, the etiology in rare subgroups of individuals (including young age at onset, nonsmokers and nondrinkers), and the effects of human papillomavirus (HPV) with respect to cancer subsite.

Selected Publications with Investigators in INHANCE

1) Heck JE et al. Int J Epidemiol. 2010 Feb;39(1):166-81. doi: 10.1093/ije/dyp350. Sexual behaviours and the risk of head and neck cancers: a pooled analysis in the International Head and Neck Cancer Epidemiology (INHANCE) consortium.

2) Lubin JH et al. Am J Epidemiol. 2010 Jun 15;171(12):1250-61. doi: 10.1093/aje/kwq088. Body mass index, cigarette smoking, and alcohol consumption and cancers of the oral cavity, pharynx, and larynx: modeling odds ratios in pooled case-control data.

3) Gaudet MM et al, Int J Epidemiol. 2010 Aug;39(4):1091-102. doi: 10.1093/ije/dyp380. Body mass index and risk of head and neck cancer in a pooled analysis of case-control studies in the International Head and Neck Cancer Epidemiology (INHANCE) Consortium.

4) McKay JD et al. PLoS Genet. 2011 Mar;7(3):e1001333. doi: 10.1371/journal.pgen.1001333. A genome-wide association study of upper aerodigestive tract cancers conducted within the INHANCE consortium.

5) Chen D et al. Cancer Epidemiol Biomarkers Prev. 2011 Apr;20(4):658-64. doi: 10.1158/1055-9965.EPI-10-1008. A sex-specific association between a 15q25 variant and upper aerodigestive tract cancers.

6) Chuang SC et al. Front Oncol. 2011 Jul 12;1:13. doi: 10.3389/fonc.2011.00013. eCollection 2011. Sequence Variants and the Risk of Head and Neck Cancer: Pooled Analysis in the INHANCE Consortium.

7) Chuang SC et al. Cancer Causes Control. 2012 Jan;23(1):69-88. doi: 10.1007/s10552-011-9857-x. Diet and the risk of head and neck cancer: a pooled analysis in the INHANCE consortium.

8) Stott-Miller M et al. Cancer Epidemiol Biomarkers Prev. 2012; 21(2):294-304. History of Diabetes and risk of head and neck cancer: a pooled analysis from the International Head and Neck Cancer Epidemiology (INHANCE) Consortium.

9) Wyss A et al. Am J Epidemiol. 2013 Sep 1;178(5):679-90. doi: 10.1093/aje/kwt029. Cigarette, cigar, and pipe smoking and the risk of head and neck cancers: pooled analysis in the International Head and Neck Cancer Epidemiology Consortium.

10) Marks MA et al. Cancer Epidemiol Biomarkers Prev. 2014 Jan;23(1):160-71. doi: 10.1158/1055-9965.EPI-13-0181. Association of marijuana smoking with oropharyngeal and oral tongue cancers: pooled analysis from the INHANCE consortium.

11) Leoncini E et al. Eur J Epidemiol. 2014 Jan;29(1):35-48. doi: 10.1007/s10654-013-9863-2. Adult height and head and neck cancer: a pooled analysis within the INHANCE Consortium.

12) Toporcov TN et al. Int J Epidemiol. 2015 Feb;44(1):169-85. doi: 10.1093/ije/dyu255. Risk factors for head and neck cancer in young adults: a pooled analysis in the INHANCE consortium.