Human Papillomavirus 16 E6 Antibodies in Individuals Without Diagnosed Cancer: A Pooled Analysis

Cancer Epidemiol Biomarkers Prev. 2015 Apr;24(4):683-9. doi: 10.1158/1055-9965.EPI-14-1217. Epub 2015 Jan 26.

Abstract

Background: The increasing incidence of oropharyngeal cancer in many developed countries has been attributed to human papillomavirus type 16 (HPV16) infections. Recently, HPV16 E6 serology has been identified as a promising early marker for oropharyngeal cancer. Therefore, characterization of HPV16 E6 seropositivity among individuals without cancer is warranted.

Methods: A total of 4,666 controls were pooled from several studies of cancer and HPV seropositivity, all tested within the same laboratory. HPV16 E6 seropositive controls were classified as having (i) moderate [mean fluorescent intensity (MFI) ≥ 484 and <1,000] or (ii) high seroreactivity (MFI ≥ 1,000). Associations of moderate and high HPV16 E6 seroreactivity with (i) demographic risk factors; and seropositivity for (ii) other HPV16 proteins (E1, E2, E4, E7, and L1), and (iii) E6 proteins from non-HPV16 types (HPV6, 11, 18, 31, 33, 45, and 52) were evaluated.

Results: Thirty-two (0.7%) HPV16 E6 seropositive controls were identified; 17 (0.4%) with moderate and 15 (0.3%) with high seroreactivity. High HPV16 E6 seroreactivity was associated with former smoking [odds ratio (OR), 5.5; 95% confidence interval (CI), 1.2-51.8], and seropositivity against HPV16 L1 (OR, 4.8; 95% CI, 1.3-15.4); E2 (OR, 7.7; 95% CI, 1.4-29.1); multiple HPV16 proteins (OR, 25.3; 95% CI, 2.6-119.6 for three HPV16 proteins beside E6) and HPV33 E6 (OR, 17.7; 95% CI, 1.9-81.8). No associations were observed with moderate HPV16 E6 seroreactivity.

Conclusions: High HPV16 E6 seroreactivity is rare among individuals without diagnosed cancer and was not explained by demographic factors.

Impact: Some HPV16 E6 seropositive individuals without diagnosed HPV-driven cancer, especially those with seropositivity against other HPV16 proteins, may harbor a biologically relevant HPV16 infection.

Publication types

  • Research Support, N.I.H., Intramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Antibodies, Viral / blood*
  • Carcinoma, Squamous Cell / immunology
  • Carcinoma, Squamous Cell / virology*
  • Case-Control Studies
  • Cohort Studies
  • Enzyme-Linked Immunosorbent Assay
  • Female
  • Human papillomavirus 16 / immunology
  • Humans
  • Male
  • Middle Aged
  • Oncogene Proteins, Viral / immunology*
  • Oropharyngeal Neoplasms / immunology
  • Oropharyngeal Neoplasms / virology*
  • Papillomavirus Infections / immunology
  • Repressor Proteins / immunology*
  • Risk Factors
  • Young Adult

Substances

  • Antibodies, Viral
  • E6 protein, Human papillomavirus type 16
  • Oncogene Proteins, Viral
  • Repressor Proteins