Biomarkers for detection and diagnosis of head and neck squamous cell carcinoma

Abstract

Novel, sensitive and specific markers and methods for diagnostics and monitoring of head and neck squamous cell carcinoma (HNSCC) are provided. Kits and methods for the use of hyaluronic acid, hyaluronidase and CD44 to diagnose HNSCC are described.

1 - 32 . (canceled) 
     
     
         33 . A method of treating a subject diagnosed with cancer, the method comprising:
 a. measuring the level of total protein and the level of CD44 in a biological sample comprising a bodily fluid obtained from said subject subsequent to receiving the treatment and combining these levels;   b. comparing the combined levels to combined total protein and CD44 levels detected prior to treatment in the same subject, wherein a change in combined levels of total protein and CD44 in the biological sample obtained from said subject subsequent to receiving the treatment compared to combined total protein and CD44 levels detected prior to treatment in the same subject is indicative of effectiveness of treatment;   c. changing the course of treatment of the subject according to the results of step (b).   
     
     
         34 . The method of  claim 33 , wherein the cancer is squamous cell carcinoma. 
     
     
         35 . The method of  claim 33 , wherein head and neck squamous cell carcinoma (HNSCC). 
     
     
         36 . The method of  claim 33 , wherein the subject's score has increased during treatment, indicating an aggressive tumor. 
     
     
         37 . The method of  claim 36 , wherein the subject is exposed to surgery, radiation, or chemotherapy, or a combination thereof, based on the comparison of the score with prior values, wherein the subject was not previously exposed to surgery, radiation, or chemotherapy, or a combination thereof. 
     
     
         38 . The method of  claim 37 , wherein the subject is exposed to different levels of surgery, radiation, or chemotherapy based on the comparison of the score with prior values. 
     
     
         39 . The method of  claim 37 , wherein the subject's score decreases during treatment, indicating a non-aggressive tumor. 
     
     
         40 . The method of  claim 37 , wherein treatment is stopped based on the comparison of the score. 
     
     
         41 . The method of  claim 33 , further comprising analyzing the subject's sample for the presence of and measuring the level of at least one of: hyaluronic acid (HA) and hyaluronidase (HAase), and using the level of at least one of: HA and HAse in multivariate analysis to determine a score, and comparing the score with prior values obtained from the subject, whereby comparing the score indicates effectiveness of treatment; and treating the subject accordingly. 
     
     
         42 . The method of  claim 41 , wherein HA, HAase, total protein and CD44 are measured. 
     
     
         43 . The method of  claim 33 , wherein the bodily fluid is selected from the group consisting of oral rinse, saliva, sputum, breath condensate, blood, blood plasma, serum, and urine. 
     
     
         44 . The method of  claim 33 , wherein the subject's sample is saliva or an oral rinse. 
     
     
         45 . The method of  claim 33 , wherein CD44 is soluble CD44 and isoforms thereof. 
     
     
         46 . The method of  claim 33 , wherein the presence of total protein and CD44 is detected using a binding assay. 
     
     
         47 . The method of  claim 46 , wherein the binding assay is an immunoassay. 
     
     
         48 . The method of  claim 33 , further comprising assessing the subject for at least one risk factor or demographic factor selected from the group consisting of: tobacco exposure, alcohol exposure, race, ethnicity, dental health, gender, level of education, and age. 
     
     
         49 . The method of  claim 48 , wherein the assessment of the at least one risk factor or demographic factor combined with elevated levels of CD44 and total protein in the subject's sample compared to normal levels of CD44 and total protein in a control population is used to determine future course of treatment subsequent to initial course of treatment. 
     
     
         50 . A method of detecting cancer in a subject, comprising:
 collecting a biological sample from a subject;   using a kit to detect cancer, wherein the kit comprises a reference sample of at least one biomarker selected from the group consisting of CD44 and total protein, and means for detecting/measuring said biomarker(s); and   detecting said biomarkers.   
     
     
         51 . The method of  claim 50 , wherein the cancer is squamous cell carcinoma. 
     
     
         52 . The method of  claim 50 , wherein head and neck squamous cell carcinoma (HNSCC). 
     
     
         53 . The method of  claim 50 , wherein the biological sample is an oral sample. 
     
     
         54 . The method of  claim 50 , wherein the kit additionally comprises a reference sample of hyaluronic acid (HA) and hyaluronidase (HAase) and a means for detecting/measuring hyaluronic acid (HA) and hyaluronidase (HAase). 
     
     
         55 . The method of  claim 50 , wherein the kit additionally comprises a substrate or container for holding a biological sample from a subject. 
     
     
         56 . The method of  claim 50 , wherein the kit further comprises at least one colorimetric agent for the detection of a biomarker. 
     
     
         57 . The method of  claim 50 , wherein detecting cancer is done to measure treatment success after an initial course of treatment. 
     
     
         58 . The method of  claim 50 , wherein detecting cancer is done to predict recurrence of cancer after treatment.