Human papillomavirus 16 E6 antibodies in individuals without diagnosed cancer: A pooled analysis

Krystle A. Lang Kuhs, 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.A.S. 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 journalArticlepeer-review

49 Scopus citations


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 againstHPV16 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 observedwithmoderateHPV16 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 diagnosedHPV-drivencancer,especiallythosewithseropositivityagainst other HPV16 proteins, may harbor a biologically relevant HPV16 infection. Cancer Epidemiol Biomarkers Prev; 24(4); 683-9.

Original languageEnglish
Pages (from-to)683-689
Number of pages7
JournalCancer Epidemiology Biomarkers and Prevention
Issue number4
StatePublished - Apr 1 2015

Bibliographical note

Publisher Copyright:
© 2015 AACR.

ASJC Scopus subject areas

  • Epidemiology
  • Oncology


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