Biomarkers for human papilloma virus-associated cancers

Patent metadata

Field	Value
Publication number	US-9790553-B2
Application number	US-201113194624-A
Country	US
Kind code	B2
Filing date	Jul 29, 2011
Priority date	Jul 24, 2007
Publication date	Oct 17, 2017
Grant date	Oct 17, 2017

Abstract

Cervical cancer cells and HPV + head and neck cancer cells express three testis-specific genes not normally expressed in somatic cells: testicular cell adhesion molecule 1 (TCAM1), synaptonemal complex protein 2 (SYCP2) and stromal antigen 3 (STAG3). Among the three markers, TCAM1 and SYCP2 are early detection markers. Various methods for identifying a human or non-human animal as a candidate for further examination for cervical cancer, preneoplastic lesion for cervical cancer, head and neck cancer, or preneoplastic lesion for head and neck cancer are disclosed. Methods of detecting said cancers and preneoplastic lesions, methods of screening for drugs for treating said cancers and preneoplastic lesions, methods for monitoring the effectiveness of a treatment for said cancers, and methods of treating said cancers are also disclosed. Further disclosed are kits that can be used to practice the above methods.

First claim

We claim:

1. A method for identifying a human or non-human animal as having a preneoplastic lesion for human papillomavirus positive (HPV+) head and neck cancer comprising the steps of:
measuring the expression of a member selected from testicular cell adhesion molecule 1 (TCAM1) and synaptonemal complex protein 2 (SYCP2) protein in cells of a body fluid sample comprising exfoliated epithelial cells, wherein TCAM1 and SYCP2 are co-expressed in the exfoliated epithelial cells, wherein the body fluid sample is selected from the group consisting of a saliva specimen, mouth rinse, throat rinse, mouth swab, and throat swab, and wherein measuring comprises
(i) binding the member to an antibody having specificity for the member, wherein the antibody has specificity for a TCAM1 or SYCP2 polypeptide expressed on exfoliated epithelial cells;
(ii) detecting the binding of the member and the antibody; and
(iii) quantifying an expression level of the member TCAM1 or SYCP2 on the exfoliated epithelial cells by comparing the detected binding level to a normal non-neoplastic control, wherein a higher expression of one member in exfoliated epithelial cells of the body fluid tissue sample relative that of a non-neoplastic control indicates that cells in the body fluid sample are preneoplastic for HPV+ head and neck cancer;
identifying the human or non-human animal as having a preneoplastic lesion for HPV+head and neck cancer in a head or neck region from which the body fluid sample is obtained; and
administering to the identified human or non-human animal having a preneoplastic lesion for HPV+ head and neck cancer a chemotherapeutic agent operably linked to an antibody having specificity for TCAM1.

2. The method of claim 1 , wherein the member is TCAM1 and the antibody has specificity to at least a portion of a polypeptide encoded by the nucleotide sequence of SEQ ID NO:3.

3. The method of claim 1 , wherein the member is SYCP2 and the antibody has specificity to at least a portion of a polypeptide having the sequence of SEQ ID NO: 6.

4. The method of claim 1 , wherein the binding is detected by an immunological protein detection method.

5. A method for detecting a preneoplastic lesion for HPV+ head and neck cancer in a human or non-human animal comprising the steps of:
detecting an expression level of a member in cells of a body fluid sample of a human or non-human animal comprising exfoliated epithelial cells, wherein the body fluid sample is selected from the group consisting of a saliva specimen, mouth rinse, throat rinse, mouth swab, and throat swab, and wherein detecting comprises, in order, the steps of:
(i) binding a member selected from the group consisting of testicular cell adhesion molecule 1 (TCAM1) and synaptonemal complex protein 2 (SYCP2) protein to an antibody having specificity for the member, wherein TCAM1 and SYCP2 are co-expressed in exfoliated epithelial cells, wherein the antibody has specificity for a TCAM1 or SYCP2 polypeptide expressed on the exfoliated epithelial cells of the body fluid sample;
(ii) detecting the binding of the member and the antibody by an immunological protein detection method; and
(iii) quantifying an expression level of the member TCAM1 or SYCP2 on the exfoliated epithelial cells by comparing the detected binding level to a normal non-neoplastic control, wherein a higher expression in exfoliated epithelial cells of the body fluid tissue sample relative that of a non-neoplastic control indicates that cells of the body fluid sample are preneoplastic for HPV+ head and neck cancer in the head or neck region from which the body fluid sample is obtained and the human and non human animal has a preneoplastic lesion for HPV+ head and neck cancer; and

administering to a human or non-human animal having a preneoplastic lesion for HPV+ head and neck cancer a chemotherapeutic agent operably linked to an antibody having specificity for TCAM1.

Assignees

• Pyeon Dohun
• Lambert Paul F
• Newton Michael A
• Ahlquist Paul G
• Wisconsin Alumni Res Found

Inventors

• Pyeon Dohun
• Lambert Paul F
• Newton Michael A
• Ahlquist Paul G

Classifications

• C12Q1/6886 Primary

  for cancer (immunoassay for cancer G01N33/575) · CPC title

• C12Q2600/112

  Disease subtyping, staging or classification · CPC title

• C12Q1/708

  for papilloma · CPC title

• A61P35/00

  Antineoplastic agents · CPC title

• C12Q2600/136

  Screening for pharmacological compounds · CPC title