Abstract
Point-of-care tests are needed for the screening of head and neck squamous cell carcinoma (HNSCC) and other malignancies. Luciferase immunoprecipitation systems (LIPS), employing light-emitting proteins, were used to examine serum antibodies against several cancer-associated targets in blood donor controls and subjects with colon cancer (CC) and HNSCC. The assessment of antibodies against the wild type p53 tumor antigen showed that approximately 25% of the CC and 20% of the HNSCC patients were seropositive. In addition, humoral responses against two p53 mutants, p53-R175H and p53-R273H, generally tracked the antibody responses seen against wild type p53. Analysis of antibodies against highly specific biomarkers of HPV-16-associated malignancy, E2, E6, and E7 oncoproteins, revealed no seropositivity in blood donors and CC patients. However, 45% (9/20) of the HNSCC patients showed E6 seropositivity, which overlapped all the detectable E2 (40%; 8/20) and E7 seropositive subjects (35%; 7/20). Using neodymium magnets, ultrarapid LIPSTICKS testing of HPV-16 E6 antibodies in <60 s per HNSCC sample demonstrated almost the same diagnostic performance (40% sensitivity and 100% specificity) as LIPS testing in 2.5 h. While additional improvements and standardization are needed, these results highlight the possibility of using these approaches for the diagnosis of HPV-16-associated HNSCC.
Highlights
There is an interest in developing point-of-care tests in the oral health setting for the clinical detection of head and neck squamous cell carcinoma (HNSCC) [1]
We describe studies using the luciferase immunoprecipitation systems (LIPS) assay to detect cancer-associated antibody responses against the tumor antigens including p53 and human papillomavirus (HPV)-16 E2, E6 and E7 proteins
Using the LIPS technology, antibodies against wild type p53 were evaluated in serum samples from a cohort that included Healthy volunteer (HV) (n = 20), and CC (n = 20) and HNSCC (n = 20)
Summary
There is an interest in developing point-of-care tests in the oral health setting for the clinical detection of head and neck squamous cell carcinoma (HNSCC) [1]. One potential approach exploits the patient’s antibody responses directed against tumor antigens. Cancer-related antibodies against these tumor antigens are thought to arise by protein overexpression, altered spliced forms, mutations, protein modifications and/or represent viral oncogenes [4]. Studies in HNSCC and other cancers have detected antibodies against p53, a well-characterized tumor antigen that is commonly mutated in cancer [5]. Human papillomavirus (HPV), the HPV-16 and HPV-18 genotypes, are directly involved in causing cancer in a subset of HNSCC patients [6,7,8], as well as in cervical cancer and anal cancer [9]. Relevant is the finding that serum antibodies against the HPV-16 E6 and HPV-16 E7 oncoproteins are highly specific biomarkers for the presence of HPV-driven tumors. Antibodies against HPV-16 E6 and E7 proteins are only found in patients
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