Evaluating the Utility and Prevalence of HPV Biomarkers in Oral Rinses and Serology for HPV-related Oropharyngeal Cancer

Abstract

Performance of commercially available human papillomavirus (HPV) assays (approved for cervical HPV detection) is unknown for detecting HPV-related oropharyngeal cancer (HPV-OPC). Assays for detection of HPV DNA [ELISA (DEIA) and Cobas], and RNA (Aptima) in oral rinse samples, and serum HPV oncogene antibodies were evaluated. Sensitivity and specificity of each test was explored among HPV-OPC cases and controls. Biomarker prevalence was evaluated among 294 "at-risk" people (screening) and 133 "high-risk" people [known to previously have oral oncogenic HPV (oncHPV) DNA and/or HPV16 E6/E7 antibodies detected]. HPV16 E6 antibodies had the best overall test performance with sensitivity of 88%, compared with oral HPV16 DNA sensitivity of 51% by DEIA and 43% by Cobas (each P < 0.001). Specificity was comparable in each of these tests (≥98%). When positivity for any oncHPV type was compared with HPV16 for the same test, sensitivity was comparable (60% vs. 51%, 40% vs. 43%, and 92% vs. 88% for DEIA, Cobas, and E6 antibodies, respectively), but specificity was reduced (93%-97%). Aptima had poor sensitivity (23%). Sensitivity decreased when cotesting HPV16 oral rinse DNA and E6 antibodies (37%-48%), or multiple E antibodies (69%-72%). HPV16 DNA were detected in ∼2% of the at-risk by either DEIA or Cobas and up to 15% of the high-risk population. HPV16 E6 seroprevalence was 2.3% and 2.4% in the at-risk and high-risk populations, respectively. Oral rinse HPV testing had moderate-to-poor sensitivity for HPV-OPC, suggesting many true positives would be missed in a potential screening scenario. HPV16 E6 serum antibody was the most promising biomarker evaluated.

Conflict of interest statement

Disclosure of Potential Conflicts of Interest

D.J. Wiley reports receiving other commercial research support from Copan Italia (specimen swabs), Roche Molecular Systems (Cobas HPV test kits), Hologic, Inc (HPV-APTIMA kits), and Qiagen, Inc. (HPV HC2 kits). R.I. Haddad has unpaid consultant/advisory board relationship with BMS, MERCK, PFIZER, GENENTECH, LOXO, BAYER, IMMUNOMIC, NANOBIOTIX, GSK. No potential conflicts of interest were disclosed by the other authors.

©2019 American Association for Cancer Research.

Figures

Figure 1.

Flowchart of sample dilution and testing, by sample type (oral rinse and serum) and study population (HOTSPOT and MOUTH).

Figure 2.

Pattern of HPV biomarker detection among subjects positive to at least one of the following 5 biomarkers in the at-risk (MOUTH screening population, A) and high-risk (MACS/WIHS population, B), with color indicating a positive result to each assay, including: (i) DEIA oncogenic oral HPV DNA (yellow), (ii) Cobas oncogenic oral HPV DNA (orange), (iii) HPV16 E7 serum antibodies (pink), (iv) HPV16 E6 serum antibodies (bright red), (v) Aptima oncogenic HPV RNA (dark red). Shaded gray areas represent biomarker results not tested/available.