Detection of Tumor-Specific DNA in Saliva and Blood

Case ID:
C13698
Disclosure Date:
6/15/2015
Description:
Unmet Need
Head and neck squamous cell carcinomas (HNSCCs) are the seventh most common cancer worldwide, occurring in more than half a million new patients each year and in >50,000 patients in the United States alone. The incidence of certain types of HNSCC appears to be increasing, especially among young people, in part due to the increasing prevalence of human papilloma virus (HPV). Current diagnostic methods for HNSCC make challenging the detection of early disease, assessment of response to treatment, and differentiation between the adverse effects of treatment vs. persistent or recurrent disease.  The idea that the genetic alterations present in tumors can be used as biomarkers for cancer was proposed more than two decades ago. The advantage of genetic alterations over conventional bio-markers such as carcinoembryonic antigen or prostate-specific antigen is that genetic changes are exquisitely specific for neoplastic cells. One challenge in exploiting genetic alterations for this purpose is that the concentration of mutant templates is often low in bodily fluids. Over the last several years, however, technological advances have made it possible to detect such mutations even when they are rare. These advances have facilitated the detection of altered DNA sequences in plasma, stool, Pap smear fluids, sputum, and urine.  There is a continuing need in the art for more sensitive means to detect cancers.
 
Technology Overview
The inventors show that tumor-derived DNA can be detected in the saliva of patients with head and neck squamous cell carcinoma (HNSCC).  The inventors developed assays that are useful for detecting, monitoring, and predicting the course of HNSCC.  Some of the cancers are associated with HPV infection, and the cancer cells and body fluids contain HPV viral sequences.  Some of the cancers are not associated with HPV infection but rather contain somatic mutations that are specific to the cancer.  By testing both saliva and plasma of a subject, an extremely high level of sensitivity can be achieved. 
 
Stage of Development
To explore the potential of tumor-specific DNA as a biomarker for head and neck squamous cell carcinomas (HNSCC), the inventors queried DNA from saliva or plasma of 93 HNSCC patients. The inventors searched for somatic mutations or human papillomavirus genes, collectively referred to as tumor DNA. When both plasma and saliva were tested, tumor DNA was detected in 96% of 47 patients. The fractions of patients with detectable tumor DNA in early- and late-stage disease were 100% (n = 10) and 95% (n = 37), respectively. When segregated by site, tumor DNA was detected in 100% (n = 15), 91% (n = 22), 100% (n = 7), and 100% (n = 3) of patients with tumors of the oral cavity, oropharynx, larynx, and hypopharynx, respectively. In saliva, tumor DNA was found in 100% of patients with oral cavity cancers and in 47 to 70% of patients with cancers of the other sites. In plasma, tumor DNA was found in 80% of patients with oral cavity cancers, and in 86 to 100% of patients with cancers of the other sites. Thus, saliva is preferentially enriched for tumor DNA from the oral cavity, whereas plasma is preferentially enriched for tumor DNA from the other sites. Tumor DNA in saliva was found postsurgically in three patients before clinical diagnosis of recurrence, but in none of the five patients without recurrence. Tumor DNA in the saliva and plasma appears to be a valuable biomarker for detection of HNSCC.
 
Publications
Wang, Y. et al., ?Detection of somatic mutations and HPV in the saliva and plasma of patients with head and neck squamous cell carcinomas,? Sci Transl Med. 2015 June 24; 7(293): 293ra104.
 
Patent Information:
Title App Type Country Serial No. Patent No. File Date Issued Date Expire Date Patent Status
Detection of Tumor-Specific DNA in Saliva and Blood PCT: Patent Cooperation Treaty PCT PCT/US2016/037793 6/16/2016     Pending
HEAD AND NECK SQUAMOUS CELL CARCINOMA ASSAYS PCT: Patent Cooperation Treaty United States 15/739,610 12/22/2017     Pending
Inventors:
Category(s):
For Information, Contact:
Nakisha Holder
nickki@jhu.edu
410-614-0300
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