High risk human papilloma virus related head and neck squamous cell carcinoma (HPVHNSCC) incidence is rapidly increasing, and will soon surpass the incidence of cervical carcinoma in the US. There are no effective ways to detect preclinical or early HPVHNSCC, screen populations at increased risk for HPVHNSCC development, or even assay for microscopic persistence of HPVHNSCC after therapy. However, epigenetic alterations have been detected in body fluids from premalignant and early stage cancers and multiplex tests have shown promise for identification of patients with oral premalignancy. Our primary hypothesis is that multiplex testing of plasma and salivary rinses based on HPVHNSCC specific epigenetic alterations combined with high risk HPV DNA presence has potential as useful test for presence of HPVHNSCC. This project will serve as a discovery and diagnostic validation biomarker development trial for HPVHNSCC detection with potential application for assessment of disease response and development of a population based screening test.

Public Health Relevance

Human papilloma virus related head and neck cancer (HPVHNSCC) incidence is increasing rapidly in the United States, but has no available method for screening and no methods to define subclinical recurrent or persistent disease. Recent data indicate that methylation changes in DNA can be used for disease detection and that HPVHNSCC is well suited to these approaches. This project uses whole genome DNA methylation discovery techniques in combination with HPV DNA detection in salivary rinse and plasma to define a panel of biomarkers for HPVHNSCC detection.

Agency
National Institute of Health (NIH)
Institute
National Institute of Dental & Craniofacial Research (NIDCR)
Type
Research Project (R01)
Project #
5R01DE023347-05
Application #
9043726
Study Section
Clinical Oncology Study Section (CONC)
Program Officer
Venkatachalam, Sundaresan
Project Start
2015-12-14
Project End
2018-03-31
Budget Start
2016-04-01
Budget End
2017-03-31
Support Year
5
Fiscal Year
2016
Total Cost
Indirect Cost
Name
University of California San Diego
Department
Surgery
Type
Schools of Medicine
DUNS #
804355790
City
La Jolla
State
CA
Country
United States
Zip Code
92093
Fukusumi, T; Califano, J A (2018) The NOTCH Pathway in Head and Neck Squamous Cell Carcinoma. J Dent Res 97:645-653
Fukusumi, Takahito; Guo, Theresa W; Sakai, Akihiro et al. (2018) The NOTCH4-HEY1 Pathway Induces Epithelial-Mesenchymal Transition in Head and Neck Squamous Cell Carcinoma. Clin Cancer Res 24:619-633
Afsari, Bahman; Guo, Theresa; Considine, Michael et al. (2018) Splice Expression Variation Analysis (SEVA) for inter-tumor heterogeneity of gene isoform usage in cancer. Bioinformatics 34:1859-1867
Kelley, Dylan Z; Flam, Emily L; Izumchenko, Evgeny et al. (2017) Integrated Analysis of Whole-Genome ChIP-Seq and RNA-Seq Data of Primary Head and Neck Tumor Samples Associates HPV Integration Sites with Open Chromatin Marks. Cancer Res 77:6538-6550
Gaykalova, Daria A; Zizkova, Veronika; Guo, Theresa et al. (2017) Integrative computational analysis of transcriptional and epigenetic alterations implicates DTX1 as a putative tumor suppressor gene in HNSCC. Oncotarget 8:15349-15363
Guo, Theresa; Sakai, Akihiro; Afsari, Bahman et al. (2017) A Novel Functional Splice Variant of AKT3 Defined by Analysis of Alternative Splice Expression in HPV-Positive Oropharyngeal Cancers. Cancer Res 77:5248-5258
Guo, Theresa; Gaykalova, Daria A; Considine, Michael et al. (2016) Characterization of functionally active gene fusions in human papillomavirus related oropharyngeal squamous cell carcinoma. Int J Cancer 139:373-82
Gaykalova, Daria A; Manola, Judith B; Ozawa, Hiroyuki et al. (2015) NF-?B and stat3 transcription factor signatures differentiate HPV-positive and HPV-negative head and neck squamous cell carcinoma. Int J Cancer 137:1879-89
Gaykalova, Daria A; Vatapalli, Rajita; Wei, Yingying et al. (2015) Outlier Analysis Defines Zinc Finger Gene Family DNA Methylation in Tumors and Saliva of Head and Neck Cancer Patients. PLoS One 10:e0142148
Sun, Wenyue; Califano, Joseph A (2014) Sequencing the head and neck cancer genome: implications for therapy. Ann N Y Acad Sci 1333:33-42