Luciferase-Based Detection of Antibodies for the Diagnosis of HPV-Associated Head and Neck Squamous Cell Carcinoma

Burbelo, Peter D.; Chaturvedi, Adrija; Notkins, Abner L.; Gunti, Sreenivasulu

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] . Based on the unchanging survival rates of HNSCC, there is a need for better diagnostic and prognostic tools [2, 3] . 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] . In addition, human papillomavirus (HPV), particularly 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] . Particularly 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 harboring HPV-associated cancers and are not found in subjects with HPV infection alone without malignancy and healthy controls [8, 10, 11] . Interestingly, HPV-16 E6 antibodies can be detected decades before the future diagnosis of HNSCC, highlighting the potentially important role as an early biomarker for cancer screening [12, 13] .