Diagnostic accuracy of serum antibodies to human papillomavirus type 16 early antigens in the detection of human papillomavirus-related oropharyngeal cancer

Cancer. 2017 Dec 15;123(24):4886-4894. doi: 10.1002/cncr.30955. Epub 2017 Sep 12.

Abstract

Background: Because of the current epidemic of human papillomavirus (HPV)-related oropharyngeal cancer (OPC), a screening strategy is urgently needed. The presence of serum antibodies to HPV-16 early (E) antigens is associated with an increased risk for OPC. The purpose of this study was to evaluate the diagnostic accuracy of antibodies to a panel of HPV-16 E antigens in screening for OPC.

Methods: This case-control study included 378 patients with OPC, 153 patients with nonoropharyngeal head and neck cancer (non-OPC), and 782 healthy control subjects. The tumor HPV status was determined with p16 immunohistochemistry and HPV in situ hybridization. HPV-16 E antibody levels in serum were identified with an enzyme-linked immunosorbent assay. A trained binary logistic regression model based on the combination of all E antigens was predefined and applied to the data set. The sensitivity and specificity of the assay for distinguishing HPV-related OPC from controls were calculated. Logistic regression analysis was used to calculate odds ratios with 95% confidence intervals for the association of head and neck cancer with the antibody status.

Results: Of the 378 patients with OPC, 348 had p16-positive OPC. HPV-16 E antibody levels were significantly higher among patients with p16-positive OPC but not among patients with non-OPC or among controls. Serology showed high sensitivity and specificity for HPV-related OPC (binary classifier: 83% sensitivity and 99% specificity for p16-positive OPC).

Conclusions: A trained binary classification algorithm that incorporates information about multiple E antibodies has high sensitivity and specificity and may be advantageous for risk stratification in future screening trials. Cancer 2017;123:4886-94. © 2017 American Cancer Society.

Keywords: head and neck neoplasms; human papillomavirus; oropharyngeal cancer; papillomavirus oncogene proteins; serum antibodies.

MeSH terms

  • Academic Medical Centers
  • Adult
  • Age Distribution
  • Aged
  • Antibodies, Viral / blood*
  • Biopsy, Needle
  • Case-Control Studies
  • Enzyme-Linked Immunosorbent Assay
  • Female
  • Human papillomavirus 16 / genetics*
  • Human papillomavirus 16 / isolation & purification
  • Humans
  • Immunohistochemistry
  • In Situ Hybridization
  • Incidence
  • Logistic Models
  • Male
  • Middle Aged
  • Oropharyngeal Neoplasms / diagnosis*
  • Oropharyngeal Neoplasms / epidemiology
  • Oropharyngeal Neoplasms / virology*
  • Papillomavirus Infections / complications
  • Papillomavirus Infections / diagnosis*
  • Prognosis
  • Reference Values
  • Risk Assessment
  • Sensitivity and Specificity
  • Sex Distribution
  • Texas

Substances

  • Antibodies, Viral