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

Krystle A Lang Kuhs (Lead / Corresponding author), Devasena Anantharaman, Tim Waterboer, Mattias Johansson, Paul Brennan, Angelika Michel, Martina Willhauck-Fleckenstein, Mark P Purdue, Ivana Holcátová, Wolfgang Ahrens, Pagona Lagiou, Jerry Polesel, Lorenzo Simonato, Franco Merletti, Claire M Healy, Kristina Kjaerheim, David I Conway, Tatiana V Macfarlane, Peter Thomson, Xavier CastellsaguéAriana Znaor, Amanda Black, Wen-Yi Huang, Vittorio Krogh, Antonia Trichopoulou, H B As Bueno-de-Mesquita, Françoise Clavel-Chapelon, Elisabete Weiderpass, Johanna Ekström, Elio Riboli, Anne Tjønneland, María-José Sánchez, Ruth C Travis, Allan Hildesheim, Michael Pawlita, Aimée R Kreimer

Research output: Contribution to journalArticle

33 Citations (Scopus)

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.

Original languageEnglish
Pages (from-to)683-9
Number of pages7
JournalCancer Epidemiology, Biomarkers & Prevention
Volume24
Issue number4
Early online date26 Jan 2015
DOIs
Publication statusPublished - Apr 2015

Keywords

  • Adult
  • Aged
  • Aged, 80 and over
  • Antibodies, Viral
  • Carcinoma, Squamous Cell
  • Case-Control Studies
  • Cohort Studies
  • Enzyme-Linked Immunosorbent Assay
  • Female
  • Human papillomavirus 16
  • Humans
  • Male
  • Middle Aged
  • Oncogene Proteins, Viral
  • Oropharyngeal Neoplasms
  • Papillomavirus Infections
  • Repressor Proteins
  • Risk Factors
  • Young Adult
  • Journal Article
  • Research Support, N.I.H., Intramural
  • Research Support, Non-U.S. Gov't

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  • Cite this

    Lang Kuhs, K. A., Anantharaman, D., Waterboer, T., Johansson, M., Brennan, P., Michel, A., Willhauck-Fleckenstein, M., Purdue, M. P., Holcátová, I., Ahrens, W., Lagiou, P., Polesel, J., Simonato, L., Merletti, F., Healy, C. M., Kjaerheim, K., Conway, D. I., Macfarlane, T. V., Thomson, P., ... Kreimer, A. R. (2015). Human Papillomavirus 16 E6 Antibodies in Individuals without Diagnosed Cancer: A Pooled Analysis. Cancer Epidemiology, Biomarkers & Prevention, 24(4), 683-9. https://doi.org/10.1158/1055-9965.EPI-14-1217