Head and neck cancers are the fifth most common cancer type in the United States, with an overall survival rate lower than 50%. Although the incidence of other sub-sites of head and neck cancer has decreased steadily in past decades, the number of oropharyngeal squamous cell carcinoma (OPSCC) cases has increased significantly. Most OPSCC patients receive standard cancer therapy.4 However, the clinical outcomes vary significantly and are difficult to predict. Predicting early in treatment whether a tumor is likely to respond to treatment is one of the most difficult yet important tasks in providing individualized cancer care. Human papillomavirus (HPV) is a known driving oncogenic factor in oropharyngeal cancer, as well as a significant prognostic biomarker for patient survival. Retrospective studies conducted by the International Head and Neck Cancer Epidemiology Consortium (INHANCE) have demonstrated that clinical biomarkers have prognostic value in helping stratify OPSCC patients into groups with differing risks of death or disease progression. However, HPV-positive oropharyngeal cancer patients have similar rates of metastatic spread to HPV-negative patients. The same is true for patient groups stratified with other clinical biomarkers. More robust prognostic biomarkers are needed to accurately stratify patients for optimally effective treatment. MicroRNAs (miRNAs) are a family of small non-coding RNA molecules that collectively control the expression of thousands of protein-coding genes. Multiple studies indicate that miRNAs are promising cancer biomarkers and play critical regulatory roles in oropharyngeal cancer. Imaging features extracted from medical images are an exciting new class of cancer biomarkers for characterizing tumor habitats. For several tumor sites, imaging biomarkers have shown promise in accurately separating favorable and unfavorable prognosis patients. However, current efforts to utilize high-dimensional multimodal biomarkers for treatment outcome prediction have been compromised by small patient numbers relative to the feature space dimensionality; feature redundancy, heterogeneity, and uncertainty; and patient cohorts with unbalanced outcomes. The correlation, independence, and complementary nature of multimodal biomarkers (imaging, miRNA, HPV, clinical, and histopathologic biomarkers) remains unexplored as well. The major goal of this research is to develop a multimodal biomarker-based model that can reliably predict subsets of OPSCC patients with low and high risks for treatment failure. The model will serve as a clinical decision-making tool. Specifically, we propose a novel principle and systematic machine learning-based strategy to effectively identify and seamlessly combine prognostic information carried by multimodal biomarkers.
Aim 1 : Identify prognostic multimodal biomarkers, given OPSCC patient data.
Aim 2 : Develop and test a comprehensive multimodal biomarker-based model for predicting OPSCC treatment outcomes.
Aim 3 : Assess the clinical benefit of the model for OPSCC patient stratification and individualized treatment.

Public Health Relevance

The achievement of this project forms a basis of combining non-invasive imaging biomarkers with miRNAs, HPV, clinical, and histopathologic biomarkers for accurate cancer prognosis and discovering the correlation with genetic mechanisms leading to specific tumor phenotypes. This clinical decision-making tool can provide useful information to support patient stratification and individualized treatment. We anticipate that many of the methodological improvements established in this proposal will improve oropharyngeal squamous cell carcinoma treatment and tumor response assessment and treatment in other disease sites as well.

Agency
National Institute of Health (NIH)
Institute
National Cancer Institute (NCI)
Type
Research Project (R01)
Project #
5R01CA233873-02
Application #
9994253
Study Section
Biomedical Computing and Health Informatics Study Section (BCHI)
Project Start
2019-08-12
Project End
2024-07-31
Budget Start
2020-08-01
Budget End
2021-07-31
Support Year
2
Fiscal Year
2020
Total Cost
Indirect Cost
Name
University of Illinois Urbana-Champaign
Department
Type
DUNS #
041544081
City
Champaign
State
IL
Country
United States
Zip Code
61820