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

Cancer Prev Res (Phila). 2019 Oct;12(10):689-700. doi: 10.1158/1940-6207.CAPR-19-0185. Epub 2019 Aug 16.


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.

Publication types

  • Comparative Study
  • Evaluation Study
  • Research Support, N.I.H., Extramural

MeSH terms

  • Adult
  • Aged
  • Antibodies, Viral / blood
  • Biomarkers / analysis*
  • Body Fluids / virology
  • Cell Transformation, Viral / physiology
  • Cohort Studies
  • Female
  • Humans
  • Male
  • Middle Aged
  • Oropharyngeal Neoplasms / blood
  • Oropharyngeal Neoplasms / diagnosis*
  • Oropharyngeal Neoplasms / epidemiology
  • Oropharyngeal Neoplasms / etiology
  • Papillomaviridae / immunology*
  • Papillomaviridae / isolation & purification*
  • Papillomavirus Infections / blood
  • Papillomavirus Infections / complications
  • Papillomavirus Infections / diagnosis*
  • Papillomavirus Infections / epidemiology
  • Predictive Value of Tests
  • Prevalence
  • Risk Factors
  • Saliva / virology*
  • Sensitivity and Specificity
  • Seroepidemiologic Studies
  • Serologic Tests*
  • Therapeutic Irrigation


  • Antibodies, Viral
  • Biomarkers