Wendell Yarbrough, MD, MMHC, FACS

Professor of Surgery (Otolaryngology) and of Pathology; Section Chief, Otolaryngology; Co-Director Molecular Virology Research Program; Director, Head & Neck Cancer Program, Smilow Cancer Hospital

Research Interests

DNA Damage; Head and Neck Neoplasms; Salivary Gland Neoplasms; NF-kappa B; Tumor Suppressor Proteins; Human papillomavirus 16; Human Papillomavirus DNA Tests; Diseases

Research Organizations

Surgery: Otolaryngology Surgery: Head & Neck Cancer Surgery Program

Pathology

Faculty Research

HPV

Virology laboratories

Yale Cancer Center: Virus and Other Infection-associated Cancers

Research Summary

Identification of tumor suppressors in head and neck cancers; Understanding of tumor growth; Association between viruses and the development of cancer, particularly the link between the human papillomavirus and head and neck cancers.

Specialized Terms: Head and neck oncology; Salivary oncology; Mouse modeling of human cancer; Human-in-mouse cancer models; Tumor suppressor activity; Molecular defects in cancer; NF-kappa B; NF-kB; Signaling; DNA damage; Human papilloma virus; HPV

Extensive Research Description

I am a surgeon-scientist active in head & neck cancer research for more than two decades. In 2012, I was appointed Chief of Otolaryngology, Director of the Head & Neck Disease Center and Co-Director of the Molecular Virology Program at Yale. Since my arrival, Dr. Issaeva (Co-PI) and I have worked to established a translational research program at Yale focused on head and neck squamous cell carcinoma (HNSCC) with particular interest in HPV-associated cancers. Priorities have been to better understand defects in HPV-associated HNSCC and to identify molecular characteristics that may be essential for tumor formation or maintenance. While prioritizing projects, we took advantage of hypermethylation of HPV+ cancers to explore demethylating drugs and found that these tumors are very responsive to 5-azacytidine (5-aza). We found that 5-aza decreased expression of HPV genes, restored p53 levels and activity, and caused DNA damage, particularly double strand breaks (DSB). Cytotoxicity of 5-aza toward HPV-positive (HPV+) HNSCC was partially attributable to p53 and partially due to DNA damage. Mechanistic studies found that 5-aza-induced DSB required transcription, replication and APOBEC3B, a cytidine deaminase active in virally infected cells.These studies led to an investigator-initiated window trial at Yale Cancer Center. The desire to translate our discoveries for the benefit of patients drives our research. Although we have only relatively recently focused on HPV(+) HNSCC, our research team has made key discoveries and created the infrastructure that has great potential to advance understanding of mechanisms of tumorigenesis and tumor maintenance in HPV-associated HNSCC.

Selected Publications

  • Untreated oral cavity cancer: Long-term survival and factors associated with treatment refusal. Cheraghlou S, Kuo P, Mehra S, Yarbrough WG, Judson BL. Untreated oral cavity cancer: Long-term survival and factors associated with treatment refusal. Laryngoscope. March 2018. doi: 10.1002/lary.26809.
  • Salvage Surgery after Radiation Failure in T1/T2 Larynx Cancer: Outcomes following Total versus Conservation Surgery. Cheraghlou S, Kuo P, Mehra S, Yarbrough WG, Judson BL. Salvage Surgery after Radiation Failure in T1/T2 Larynx Cancer: Outcomes following Total versus Conservation Surgery. Otolaryngology Head Neck Surgery. December 2017. 194599817742596. doi: 10.1177/0194599817742596.
  • Treatment deintensification in human papillomavirus-positive oropharynx cancer: Outcomes from the National Cancer Data Base. Cheraghlou S, Yu PK, Otremba MD, Park HS, Bhatia A, Zogg CK, Mehra S, Yarbrough WG, Judson BL. Treatment deintensification in human papillomavirus-positive oropharynx cancer: Outcomes from the National Cancer Data Base. Cancer. December 2017. doi: 10.1002/cncr.31104.
  • Demethylation Therapy as a Targeted Treatment for Human Papillomavirus-Associated Head and Neck Cancer. Biktasova A, Hajek M, Sewell A, Gary C, Bellinger G, Deshpande HA, Bhatia A, Burtness B, Judson B, Mehra S, Yarbrough WG, Issaeva N. Demethylation Therapy as a Targeted Treatment for Human Papillomavirus-Associated Head and Neck Cancer. Clinical Cancer Research, December 2017. 23(23):7276-7287. doi: 10.1158/1078-0432.CCR-17-1438
  • A Comparison of Prognostic Ability of Staging Systems for Human Papillomavirus-Related Oropharyngeal Squamous Cell Carcinoma. Husain ZA, Chen T, Corso CD, Wang Z, Park H, Judson B, Yarbrough WG, Deshpande H, Mehra S, Kuo P, Decker RH, Burtness BA. A Comparison of Prognostic Ability of Staging Systems for Human Papillomavirus-Related Oropharyngeal Squamous Cell Carcinoma. JAMA Oncol, 2017, 3(3):358-365.
  • Response Bledsoe TJ, Park HS, Stahl JM, Yarbrough WG, Burtness BA, Decker RH, Husain ZA. Response. Journal of National Cancer Institute. November 2017. doi: 10.1093/jnci/djx230.
  • Hypofractionated Radiotherapy for Patients with Early-Stage Glottic Cancer: Patterns of Care and Survival. Bledsoe TJ, Park HS, Stahl JM, Yarbrough WG, Burtness BA, Decker RH, Husain ZA. Hypofractionated Radiotherapy for Patients with Early-Stage Glottic Cancer: Patterns of Care and Survival. Journal of National Cancer Institute, October 2017. 109(10). doi: 10.1093/jnci/djx042.
  • TRAF3 and CYLD Gene Defects in HPV-Associated Head and Neck Cancer: Biomarker of Response and Indicator of Targets for New Therapies. Issaeva N, Burtness B, Yarbrough WG. TRAF3 and CYLD Gene Defects in HPV-Associated Head and Neck Cancer: Biomarker of Response and Indicator of Targets for New Therapies. Journal of Cancer Clinical Trials. October 2017. J Cancer Clin Trials 3: 1000142.
  • Treatment guidelines and patterns of care in oral cavity squamous cell carcinoma: Primary surgical resection vs. nonsurgical treatment. Fujiwara RJT, Burtness B, Husain ZA, Judson BL, Bhatia A, Sasaki CT, Yarbrough WG, Mehra S. Treatment guidelines and patterns of care in oral cavity squamous cell carcinoma: Primary surgical resection vs. nonsurgical treatment. Oral Oncology, August 2017. 71:129-137. doi: 10.1016/j.oraloncology.2017.06.013
  • MYB fusions and CD markers as tools for authentication and purification of cancer stem cells from salivary adenoid cystic carcinoma. Panaccione A, Zhang Y, Ryan M, Moskaluk CA, Anderson KS, Yarbrough WG*, Ivanov SV. MYB fusions and CD markers as tools for authentication and purification of cancer stem cells from salivary adenoid cystic carcinoma. Stem Cell Research, May 2017, 21:160-166.
  • Treatment delays in oral cavity squamous cell carcinoma and association with survival. Fujiwara RJ, Judson BL, Yarbrough WG, Husain Z, Mehra S. Treatment delays in oral cavity squamous cell carcinoma and association with survival. Head Neck, April 2017, 39(4):639-646.
  • Loss of LZAP inactivates p53 and regulates sensitivity of cells to DNA damage in a p53-dependent manner. Wamsley JJ, Gary C, Biktasova A, Hajek M, Bellinger G, Virk R, Issaeva N, Yarbrough WG*. Loss of LZAP inactivates p53 and regulates sensitivity of cells to DNA damage in a p53-dependent manner. Oncogenesis, April 2017, 6(4):e314.
  • Randomized, placebo-controlled window trial of EGFR, Src, or combined blockade in head and neck cancer. Bauman JE, Duvvuri U, Gooding WE, Rath TJ, Gross ND, Song J, Jimeno A, Yarbrough WG, Johnson FM, Wang L, Chiosea S, Sen M, Kass J, Johnson JT, Ferris RL, Kim S, Hirsch FR, Ellison K, Flaherty JT, Mills GB, Grandis JR. Randomized, placebo-controlled window trial of EGFR, Src, or combined blockade in head and neck cancer. JCI Insight, March, 2017, 2(6):e90449.
  • Chromosomal abnormalities and molecular landscape of metastasizing mucinous salivary adenocarcinoma Panaccione A, Zhang Y, Mi Y, Mitani Y, Yan G, Prasad ML, McDonald WH, El-Naggar AK, Yarbrough WG*, Ivanov SV. Chromosomal abnormalities and molecular landscape of metastasizing mucinous salivary adenocarcinoma. Oral Oncology, March 2017, 66:38-45.
  • The risk of level IB nodal involvement in oropharynx cancer: guidance for submandibular gland sparing irradiation. Lee N.C., J.R Kelly., H.S. Park, W.G. Yarbrough, B.A. Burtness, and Z.A. Husain. The risk of level IB nodal involvement in oropharynx cancer: guidance for submandibular gland sparing irradiation. Practical Radiation Oncology, February 2017, pii: S1879-8500(17)30047-4.
  • Loss of LZAP Inactivates p53 and Regulates Sensitivity of Cells to DNA Damage in a p53-dependent Manner. Wamsley J. J., C. Gary, A. Biktasova, M. Hajek, G. Bellinger, R. Virk, N. Issaeva, and W.G. Yarbrough*. Loss of LZAP Inactivates p53 and Regulates Sensitivity of Cells to DNA Damage in a p53-dependent Manner. Oncogenesis, February 2017, 6(4):e314.
  • The Prognostic Value of Extranodal Extension in Human Papilloma Virus-associated Oropharyngeal Squamous Cell Carcinoma. An, Y., Park, H., Kelly, J., Stahl, J., W.G. Yarbrough, Burtness, B.A., Contessa, J., Decker, R., Koshy, M., Husain, Z.A. The Prognostic Value of Extranodal Extension in Human Papilloma Virus-associated Oropharyngeal Squamous Cell Carcinoma. Cancer 2017, 123(14):2762-2772.
  • Novel role of the mitochondrial protein Fus1 in protection from premature hearing loss via regulation of oxidative stress and nutrient and energy sensing. W. Tan, L. Song, M. Graham, A. Schettino, D. Navaratnam, W.G. Yarbrough, J. Santos-Sacchi, and A.V., Ivanova. Novel role of the mitochondrial protein Fus1 in protection from premature hearing loss via regulation of oxidative stress and nutrient and energy sensing. Antioxidants & Redox Signaling. January 2017. doi:10.1089/ars.2016.6851.
  • LZAP is a novel Wip1 binding partner and positive regulator of its phosphatase activity in vitro. Wamsley J., N. Issaeva, H. An, X. Lu, L. Donehower & W.G. Yarbrough*. LZAP is a novel Wip1 binding partner and positive regulator of its phosphatase activity in vitro. Cell Cycle, 2017 Jan 17; 16(2):213-223.
  • Expression Profiling of Clinical Specimens Supports the Existence of Neural Progenitor-Like Stem Cells in Basal Breast Cancers. A. Panaccione, Y. Guo, W.G. Yarbrough, S.V. Ivanov. Expression Profiling of Clinical Specimens Supports the Existence of Neural Progenitor-Like Stem Cells in Basal Breast Cancers. Clinical Breast Cancer, January 2017, (4):298-306.e7.
  • TRAF3/CYLD Mutations Identify a Distinct Subset of Human Papilloma Virus-Associated Head and Neck Squamous Cell Carcinoma. M. Hajek, A. Sewell, S. Kaech, B. Burtness, W.G. Yarbrough*, N. Issaeva. TRAF3/CYLD Mutations Identify a Distinct Subset of Human Papilloma Virus-Associated Head and Neck Squamous Cell Carcinoma. Cancer, January 2017, 123(10):1778-1790.
  • Comparison of Survival Outcomes Among Human Papillomavirus–Negative cT1-2 N1-2b Patients with Oropharyngeal Squamous Cell Cancer Treated with Upfront Surgery vs Definitive Chemoradiation Therapy. J.R. Kelly, H.S. Park, Y. An, J.N. Contessa, W.G. Yarbrough, B. A. Burtness, R. Decker, Z. Husain. Comparison of Survival Outcomes Among Human Papillomavirus–Negative cT1-2 N1-2b Patients with Oropharyngeal Squamous Cell Cancer Treated with Upfront Surgery vs Definitive Chemoradiation Therapy. JAMA Oncology, January, 2017. doi:10.1001/jamaoncol.2016.5769.
  • Pathogenesis and Progression of Squamous Cell Carcinoma of the Head and Neck. Aronberg, R., N. Issaeva, W.G. Yarbrough. Pathogenesis and Progression of Squamous Cell Carcinoma of the Head and Neck. Cancer of Head and Neck, 2016, pp. 4-29.
  • Clinical and Molecular Insights Into Adenoid Cystic Carcinoma: Neural Crest-Like Stemness as a Target. Yarbrough, W.G., A.Panaccione, M.T. Chang, S. Ivanov. Clinical and Molecular Insights Into Adenoid Cystic Carcinoma: Neural Crest-Like Stemness as a Target. Laryngoscope Investigative Otolaryngology; 60-77, August 2016.
  • Pretreatment Predictors of Adjuvant Chemoradiation in Patients Receiving Transoral Robotic Surgery for Squamous Cell Carcinoma of the Oropharynx: A Case Control Study. Subramanian, H.E., Park, H.S., Barbieri, A., Mahajan, A., Judson, B.L., Mehra, S., W.G. Yarbrough, Burtness, B.A., Husain, Z.A. Pretreatment Predictors of Adjuvant Chemoradiation in Patients Receiving Transoral Robotic Surgery for Squamous Cell Carcinoma of the Oropharynx: A Case Control Study. Cancers of the Head and Neck. July 2016. DOI: 10.1186/s41199-016-0008-7

Full List of PubMed Publications

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Contact Info

Wendell Yarbrough, MD, MMHC, FACS
Patient Care Locations
Head & Neck Cancer ProgramSmilow Cancer Hospital at Yale New Haven
35 Park Street

New Haven, CT 06511
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Park Avenue Medical CenterPark Avenue Medical Center
5520 Park Avenue

Trumbull, CT 06611
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Mailing Address
Otolaryngology SurgeryPO Box 208062
New Haven, CT 06520-8062

Curriculum Vitae

Yarbrough Laboratory for Head and Neck Oncology