There are more than 40,000 new cases of head and neck squamous cell carcinoma (HNSCC) in the United States each year, with a mortality rate of 12,000 U.S. deaths annually. In recent decades, little progress has been achieved in terms of survival for patients with head and neck malignancies despite advances in radiologic imaging, surgical and anesthetic technique and chemotherapy and radiotherapy. Knowledge of the genetic basis of these HNSCC tumors is needed to develop new strategies for early diagnosis and effective therapy.
Promoter hypermethylation is a process that alters cells (cell differentiation) by which tumor suppressor genes may be inactivated (transcriptional inactivation). This process can be detected using methods that quantify DNA methylation potentially leading to the determination of a threshold value of this methylation. A threshold value could serve to improve sensitivity and specificity in detection of tumor-specific signals. Detecting DNA methylation in body fluids has the potential to identify patients at higher-risk for cancer. Among the higher risks that may be better identified are occult cancers where the cells have spread to the lymph nodes and the primary site (the site where the cancer initially formed) is unknown; or, patients who are at an even higher risk to develop cancer.
Patterns of cell differentiation resulting from promoter hypermethylation have been found between primary tumors and saliva or serum obtained from patients with HNSCC. Further, our studies have shown differential promoter hypermethylation in HNSCC patients in comparison to normal individuals in body fluids.
The purpose is two-fold. One is to develop an accurate, sensitive and specific test for early detection of head and neck (H&N) cancer using tumor specific promoter hypermethylation markers. The second is to evaluate aberrant promoter hypermethylation of candidate tumor suppressor genes as a means to detect epigenetic alterations specific to solid tumors, including head and neck squamous cell carcinoma (HNSCC).
Risks and Discomforts
All specimens will be obtained in the course of routine medical care and will not involve any additional risk other than the risk of venipuncture in the rare instance in which blood is drawn solely for study purposes. The removal of tumor from surgical resection specimens will be supervised by surgeon and/or pathologist to ensure that there is no negative effect on diagnostic assessment by the pathologist.
Information about historical use of alcohol and tobacco, as well as diagnostic information about cancer, and molecular alterations present in tumors are to be collected. This data might impact decisions about employability or insurability of subjects.
The use of molecular markers in body fluids in molecular detection has been explored with the intent to improve screening accuracy and cost-effectiveness. Body fluids can potentially carry whole cells as well as protein, DNA, and RNA species that allow for detection of cellular alterations related to cancer.