There is currently no good way to screen for early stages of head and neck cancers caused by high risk types of human papillomavirus. The objective of this proposal is to develop a screening assay for dental patients to detect HPV+ head and neck cancer ("HNC") pre-symptomatically, based on the use of viral and host gene biomarkers. The overall hypothesis of this proposal is that as the development of HPV-associated HNCs proceeds, a number of viral and cellular events occur that can be exploited as biomarkers. This combination of biomarkers creates a molecular signature for cells transformed by HPV and consequently could be used to identify individuals likely to develop cancer. More broadly, the same is true of HNC not associated with HPV infection. Furthermore, we propose that, due to the anatomical location of these tumors, the probability that cells from these cancers can be found in saliva in sufficient numbers for the detection of these biomarkers is high, though another accessible fluid for screening would be blood. Evidence for this hypothesis has been published. We will begin by profiling the gene expression changes associated with HPV+ and HPV- HNC using a new assay on a high density array platform, the qNPA" assay. In this assay, we will validate genes implicated by previous studies as putative biomarkers, and also test viral DNA and mRNA coding for genes associated with HPV, additional genes that cover cellular pathways and receptors, and miRNA. We will use tissue samples and matched blood and saliva samples to identify those candidate biomarkers that can be found (ideally) in saliva and that have the potential to distinguish between HPV-associated HNC, HNC not associated with HPV, and controls. The overall goal of this proposal is to develop a rapid, accurate and cost- effective diagnostic tool for the early identification of pre-cancerous and cancerous lesions in the head and neck area, using saliva as a sample source, with Phase I SBIR being the identification of signature genes using high-density array measurements. It is the objective of this program that the ultimate diagnostic test panel developed in a follow-on Phase II will be performed by reference laboratories on samples collected in dental offices as part of routine patient assessments to identify HPV infection and HNC. Phase I will identify putative DNA, mRNA and miRNA biomarkers for use in the diagnosis of oral HPV and the early diagnosis of HPV+ HNC. It is anticipated that, based on these results, a focused diagnostic array test (or tests) can be designed for the low-cost ArrayPlate microplate platform (Phase I, Aim 4) to be developed and validated in a Phase II grant application, which will also fund the testing of samples of an accessible fluid (expected to be saliva, but alternatively blood) from a large number of dental patients. It is anticipated that this overall program will result in validated diagnostic tests for: i) oral HPV;ii) HPV+ HNC;iii) HPV- HNC;and for iv) the pre- symptomatic identification of HNC.
Public Health Relevance: At this time, there is no good way to screen for head and neck cancers ("HNC") that are caused by Human Papillomaviruses (HPV). We propose that as the virus infects these cells and cancer begins to develop, changes in the mRNA and miRNA expressed in the affected cells occur that can be detected and used as "biomarkers" for the development of cancer, and further, that these can be detected in easily-accessible material, such as blood or saliva. This proposal is designed to develop a panel of biomarkers that could be detected in saliva, thus making it much easier to identify those individuals who are developing or are at risk for developing HNCs, especially those associated with HPV. The goal is to make it possible to quickly and accurately detect early stage HPV-associated HNC in individuals during routine dental visits.
Thesaurus Terms: Affect;Applications Grants;Area;Assay;Bio-Informatics;Bioassay;Bioinformatics;Biologic Assays;Biological Assay;Blood;Blood Sample;Blood Specimen;Body Tissues;Cancer Cause;Cancer Control;Cancer Control Science;Cancer Diagnostics;Cancer Etiology;Cancer Of Cervix;Cancer Of The Uterine Cervix;Cancerous;Cancers;Cells;Cervical Cancer;Cervix Cancer;Code;Coding System;Dna;Dna, Viral;Dental;Dental Offices;Deoxyribonucleic Acid;Detection;Development;Diagnosis;Diagnostic;Diagnostic Tests;Early Diagnosis;Early Identification;Event;Expression Profiling;Expression Signature;Formalin;Freezing;Funding;Gene Expression;Gene Expression Monitoring;Gene Expression Pattern Analysis;Gene Expression Profiling;Gene Products, Rna;Genes;Genome;Goals;Grant Proposals;Grants, Applications;Hpv;Head And Neck;Head And Neck Cancer;Head And Neck, Saliva;Head And Neck Structure;Human;Human Papillomavirus;Human Papilloma Virus Infection;Human Papillomavirus Infection;Human, General;Individual;Infectious Human Wart Virus;Laboratories;Lesion;Liquid Substance;Literature;Location;Malignant Cell;Malignant Cervical Neoplasm;Malignant Cervical Tumor;Malignant Head And Neck Neoplasm;Malignant Neoplasm Of The Cervix;Malignant Neoplasms;Malignant Oral Cavity Neoplasm;Malignant Oral Cavity Tumor;Malignant Oral Neoplasm;Malignant Tumor;Malignant Tumor Of The Cervix;Malignant Tumor Of The Cervix Uteri;Malignant Tumor Of The Head And Neck;Malignant Tumor Of The Mouth;Malignant Uterine Cervix Neoplasm;Malignant Uterine Cervix Tumor;Malignant Neoplasm Of Cervix Uteri;Malignant Neoplasm Of Mouth;Man (Taxonomy);Man, Modern;Measurement;Measures;Messenger Rna;Methods;Micro Rna;Micrornas;Molecular Fingerprinting;Molecular Profiling;Morbidity;Morbidity - Disease Rate;Mortality;Mortality Vital Statistics;Mouth Cancer;Normal Cell;Normal Range;Normal Values;Oral;Oral Cancer;Oral Diagnosis;Papilloma Virus, Human;Papillomavirus, Human;Paraffin Embedding;Pathway Interactions;Patients;Phase;Probability;Profilings, Gene Expression;Programs (Pt);Programs [publication Type];Publishing;Rna;Rna, Messenger;Rna, Non-Polyadenylated;Receptor Protein;Reproducibility;Reticuloendothelial System, Blood;Reverse Transcription;Ribonucleic Acid;Risk;Sbir;Sbirs (R43/44);Saliva;Sampling;Screening Procedure;Small Business Innovation Research;Small Business Innovation Research Grant;Source;Specificity;Staging;Testing;Time;Tissue Arrays;Tissue Chip;Tissue Microarray;Tissue Sample;Tissues;Transcript Expression Analyses;Transcript Expression Analysis;Validation;Viral;Virus;Viruses, General;Visit;Woman;Base;Biomarker;Cancer Cell;Cell Transformation;Cost;Cost Effective;Density;Design;Designing;Discovery Mining;Early Detection;Fluid;Head &Neck Cancer;Head &Neck Tumor;High Risk;Human Papillomavirus;Liquid;Literature Mining;Literature Searching;Mrna;Malignancy;Malignant Mouth Neoplasm;Men;Men's;Messenger Rna;Mirna;Molecuar Profile;Molecular Signature;Neoplasm /Cancer;Neoplasm/Cancer;Pathway;Programs;Public Health Relevance;Receptor;Screening;Screenings;Text Mining;Text Searching;Tool;Transformed Cells;Tumor;Viral Dna;Virus Dna;Wart Virus
