Timing of HPV16-E6 antibody seroconversion before OPSCC: Findings from the HPVC3 consortium

A. R. Kreimer, A. Ferreiro-Iglesias, M. Nygard, N. Bender, L. Schroeder, A. Hildesheim, H. A. Robbins, M. Pawlita, H. Langseth, N. F. Schlecht, L. F. Tinker, I. Agalliu, S. W. Smoller, E. Ness-Jensen, K. Hveem, G. D'Souza, K. Visvanathan, B. May, G. Ursin, E. WeiderpassG. G. Giles, R. L. Milne, Q. Cai, W. J. Blot, W. Zheng, S. J. Weinstein, D. Albanes, N. Brenner, J. Hoffman-Bolton, R. Kaaks, A. Barricarte, A. Tjønneland, C. Sacerdote, A. Trichopoulou, R. C.H. Vermeulen, W. Y. Huang, N. D. Freedman, P. Brennan, T. Waterboer, M. Johansson

Research output: Contribution to journalArticle

2 Citations (Scopus)

Abstract

Background: Human papillomavirus type 16 (HPV16)-E6 antibodies are detectable in peripheral blood before diagnosis in the majority of HPV16-driven oropharyngeal squamous cell carcinoma (OPSCC), but the timing of seroconversion is unknown. Patients and methods: We formed the HPV Cancer Cohort Consortium which comprises nine population cohorts from Europe, North America and Australia. In total, 743 incident OPSCC cases and 5814 controls provided at least one pre-diagnostic blood sample, including 111 cases with multiple samples. Median time between first blood collection and OPSCC diagnosis was 11.4 years (IQR = 6-11 years, range = 0-40 years). Antibodies against HPV16-E6 were measured by multiplex serology (GST fusion protein based Luminex assay). Results: HPV16-E6 seropositivity was present in 0.4% of controls (22/5814; 95% CI 0.2% to 0.6%) and 26.2% (195/743; 95% CI 23.1% to 29.6%) of OPSCC cases. HPV16-E6 seropositivity increased the odds of OPSCC 98.2-fold (95% CI 62.1-155.4) in whites and 17.2-fold (95% CI 1.7-170.5) in blacks. Seropositivity in cases was more frequent in recent calendar periods, ranging from 21.9% pre-1996 to 68.4% in 2005 onwards, in those with blood collection near diagnosis (lead time <5 years). HPV16-E6 seropositivity increased with lead time: 0.0%, 13.5%, 23.7%, and 38.9% with lead times of >30 years (N = 24), 20-30 years (N = 148), 10-20 years (N = 228), and <10 years (N = 301 cases) (p-trend < 0.001). Of the 47 HPV16-E6 seropositive cases with serially-collected blood samples, 17 cases seroconverted during follow-up, with timing ranging from 6 to 28 years before diagnosis. For the remaining 30 cases, robust seropositivity was observed up to 25 years before diagnosis. Conclusions: The immune response to HPV16-driven tumorigenesis is most often detectable several decades before OPSCC diagnosis. HPV16-E6 seropositive individuals face increased risk of OPSCC over several decades.

Original languageEnglish (US)
Pages (from-to)1335-1343
Number of pages9
JournalAnnals of Oncology
Volume30
Issue number8
DOIs
StatePublished - Aug 1 2019

Fingerprint

Human papillomavirus 16
Squamous Cell Carcinoma
Antibodies
Seroconversion
Serology
North America
Carcinogenesis

Keywords

  • HPVC3
  • OPCSCC
  • oropharyngeal squamous cell carcinoma

ASJC Scopus subject areas

  • Hematology
  • Oncology

Cite this

Kreimer, A. R., Ferreiro-Iglesias, A., Nygard, M., Bender, N., Schroeder, L., Hildesheim, A., ... Johansson, M. (2019). Timing of HPV16-E6 antibody seroconversion before OPSCC: Findings from the HPVC3 consortium. Annals of Oncology, 30(8), 1335-1343. https://doi.org/10.1093/annonc/mdz138

Timing of HPV16-E6 antibody seroconversion before OPSCC : Findings from the HPVC3 consortium. / Kreimer, A. R.; Ferreiro-Iglesias, A.; Nygard, M.; Bender, N.; Schroeder, L.; Hildesheim, A.; Robbins, H. A.; Pawlita, M.; Langseth, H.; Schlecht, N. F.; Tinker, L. F.; Agalliu, I.; Smoller, S. W.; Ness-Jensen, E.; Hveem, K.; D'Souza, G.; Visvanathan, K.; May, B.; Ursin, G.; Weiderpass, E.; Giles, G. G.; Milne, R. L.; Cai, Q.; Blot, W. J.; Zheng, W.; Weinstein, S. J.; Albanes, D.; Brenner, N.; Hoffman-Bolton, J.; Kaaks, R.; Barricarte, A.; Tjønneland, A.; Sacerdote, C.; Trichopoulou, A.; Vermeulen, R. C.H.; Huang, W. Y.; Freedman, N. D.; Brennan, P.; Waterboer, T.; Johansson, M.

In: Annals of Oncology, Vol. 30, No. 8, 01.08.2019, p. 1335-1343.

Research output: Contribution to journalArticle

Kreimer, AR, Ferreiro-Iglesias, A, Nygard, M, Bender, N, Schroeder, L, Hildesheim, A, Robbins, HA, Pawlita, M, Langseth, H, Schlecht, NF, Tinker, LF, Agalliu, I, Smoller, SW, Ness-Jensen, E, Hveem, K, D'Souza, G, Visvanathan, K, May, B, Ursin, G, Weiderpass, E, Giles, GG, Milne, RL, Cai, Q, Blot, WJ, Zheng, W, Weinstein, SJ, Albanes, D, Brenner, N, Hoffman-Bolton, J, Kaaks, R, Barricarte, A, Tjønneland, A, Sacerdote, C, Trichopoulou, A, Vermeulen, RCH, Huang, WY, Freedman, ND, Brennan, P, Waterboer, T & Johansson, M 2019, 'Timing of HPV16-E6 antibody seroconversion before OPSCC: Findings from the HPVC3 consortium', Annals of Oncology, vol. 30, no. 8, pp. 1335-1343. https://doi.org/10.1093/annonc/mdz138
Kreimer AR, Ferreiro-Iglesias A, Nygard M, Bender N, Schroeder L, Hildesheim A et al. Timing of HPV16-E6 antibody seroconversion before OPSCC: Findings from the HPVC3 consortium. Annals of Oncology. 2019 Aug 1;30(8):1335-1343. https://doi.org/10.1093/annonc/mdz138
Kreimer, A. R. ; Ferreiro-Iglesias, A. ; Nygard, M. ; Bender, N. ; Schroeder, L. ; Hildesheim, A. ; Robbins, H. A. ; Pawlita, M. ; Langseth, H. ; Schlecht, N. F. ; Tinker, L. F. ; Agalliu, I. ; Smoller, S. W. ; Ness-Jensen, E. ; Hveem, K. ; D'Souza, G. ; Visvanathan, K. ; May, B. ; Ursin, G. ; Weiderpass, E. ; Giles, G. G. ; Milne, R. L. ; Cai, Q. ; Blot, W. J. ; Zheng, W. ; Weinstein, S. J. ; Albanes, D. ; Brenner, N. ; Hoffman-Bolton, J. ; Kaaks, R. ; Barricarte, A. ; Tjønneland, A. ; Sacerdote, C. ; Trichopoulou, A. ; Vermeulen, R. C.H. ; Huang, W. Y. ; Freedman, N. D. ; Brennan, P. ; Waterboer, T. ; Johansson, M. / Timing of HPV16-E6 antibody seroconversion before OPSCC : Findings from the HPVC3 consortium. In: Annals of Oncology. 2019 ; Vol. 30, No. 8. pp. 1335-1343.
@article{0958983d57764fb2b5d2f81c36f7ea21,
title = "Timing of HPV16-E6 antibody seroconversion before OPSCC: Findings from the HPVC3 consortium",
abstract = "Background: Human papillomavirus type 16 (HPV16)-E6 antibodies are detectable in peripheral blood before diagnosis in the majority of HPV16-driven oropharyngeal squamous cell carcinoma (OPSCC), but the timing of seroconversion is unknown. Patients and methods: We formed the HPV Cancer Cohort Consortium which comprises nine population cohorts from Europe, North America and Australia. In total, 743 incident OPSCC cases and 5814 controls provided at least one pre-diagnostic blood sample, including 111 cases with multiple samples. Median time between first blood collection and OPSCC diagnosis was 11.4 years (IQR = 6-11 years, range = 0-40 years). Antibodies against HPV16-E6 were measured by multiplex serology (GST fusion protein based Luminex assay). Results: HPV16-E6 seropositivity was present in 0.4{\%} of controls (22/5814; 95{\%} CI 0.2{\%} to 0.6{\%}) and 26.2{\%} (195/743; 95{\%} CI 23.1{\%} to 29.6{\%}) of OPSCC cases. HPV16-E6 seropositivity increased the odds of OPSCC 98.2-fold (95{\%} CI 62.1-155.4) in whites and 17.2-fold (95{\%} CI 1.7-170.5) in blacks. Seropositivity in cases was more frequent in recent calendar periods, ranging from 21.9{\%} pre-1996 to 68.4{\%} in 2005 onwards, in those with blood collection near diagnosis (lead time <5 years). HPV16-E6 seropositivity increased with lead time: 0.0{\%}, 13.5{\%}, 23.7{\%}, and 38.9{\%} with lead times of >30 years (N = 24), 20-30 years (N = 148), 10-20 years (N = 228), and <10 years (N = 301 cases) (p-trend < 0.001). Of the 47 HPV16-E6 seropositive cases with serially-collected blood samples, 17 cases seroconverted during follow-up, with timing ranging from 6 to 28 years before diagnosis. For the remaining 30 cases, robust seropositivity was observed up to 25 years before diagnosis. Conclusions: The immune response to HPV16-driven tumorigenesis is most often detectable several decades before OPSCC diagnosis. HPV16-E6 seropositive individuals face increased risk of OPSCC over several decades.",
keywords = "HPVC3, OPCSCC, oropharyngeal squamous cell carcinoma",
author = "Kreimer, {A. R.} and A. Ferreiro-Iglesias and M. Nygard and N. Bender and L. Schroeder and A. Hildesheim and Robbins, {H. A.} and M. Pawlita and H. Langseth and Schlecht, {N. F.} and Tinker, {L. F.} and I. Agalliu and Smoller, {S. W.} and E. Ness-Jensen and K. Hveem and G. D'Souza and K. Visvanathan and B. May and G. Ursin and E. Weiderpass and Giles, {G. G.} and Milne, {R. L.} and Q. Cai and Blot, {W. J.} and W. Zheng and Weinstein, {S. J.} and D. Albanes and N. Brenner and J. Hoffman-Bolton and R. Kaaks and A. Barricarte and A. Tj{\o}nneland and C. Sacerdote and A. Trichopoulou and Vermeulen, {R. C.H.} and Huang, {W. Y.} and Freedman, {N. D.} and P. Brennan and T. Waterboer and M. Johansson",
year = "2019",
month = "8",
day = "1",
doi = "10.1093/annonc/mdz138",
language = "English (US)",
volume = "30",
pages = "1335--1343",
journal = "Annals of Oncology",
issn = "0923-7534",
publisher = "Oxford University Press",
number = "8",

}

TY - JOUR

T1 - Timing of HPV16-E6 antibody seroconversion before OPSCC

T2 - Findings from the HPVC3 consortium

AU - Kreimer, A. R.

AU - Ferreiro-Iglesias, A.

AU - Nygard, M.

AU - Bender, N.

AU - Schroeder, L.

AU - Hildesheim, A.

AU - Robbins, H. A.

AU - Pawlita, M.

AU - Langseth, H.

AU - Schlecht, N. F.

AU - Tinker, L. F.

AU - Agalliu, I.

AU - Smoller, S. W.

AU - Ness-Jensen, E.

AU - Hveem, K.

AU - D'Souza, G.

AU - Visvanathan, K.

AU - May, B.

AU - Ursin, G.

AU - Weiderpass, E.

AU - Giles, G. G.

AU - Milne, R. L.

AU - Cai, Q.

AU - Blot, W. J.

AU - Zheng, W.

AU - Weinstein, S. J.

AU - Albanes, D.

AU - Brenner, N.

AU - Hoffman-Bolton, J.

AU - Kaaks, R.

AU - Barricarte, A.

AU - Tjønneland, A.

AU - Sacerdote, C.

AU - Trichopoulou, A.

AU - Vermeulen, R. C.H.

AU - Huang, W. Y.

AU - Freedman, N. D.

AU - Brennan, P.

AU - Waterboer, T.

AU - Johansson, M.

PY - 2019/8/1

Y1 - 2019/8/1

N2 - Background: Human papillomavirus type 16 (HPV16)-E6 antibodies are detectable in peripheral blood before diagnosis in the majority of HPV16-driven oropharyngeal squamous cell carcinoma (OPSCC), but the timing of seroconversion is unknown. Patients and methods: We formed the HPV Cancer Cohort Consortium which comprises nine population cohorts from Europe, North America and Australia. In total, 743 incident OPSCC cases and 5814 controls provided at least one pre-diagnostic blood sample, including 111 cases with multiple samples. Median time between first blood collection and OPSCC diagnosis was 11.4 years (IQR = 6-11 years, range = 0-40 years). Antibodies against HPV16-E6 were measured by multiplex serology (GST fusion protein based Luminex assay). Results: HPV16-E6 seropositivity was present in 0.4% of controls (22/5814; 95% CI 0.2% to 0.6%) and 26.2% (195/743; 95% CI 23.1% to 29.6%) of OPSCC cases. HPV16-E6 seropositivity increased the odds of OPSCC 98.2-fold (95% CI 62.1-155.4) in whites and 17.2-fold (95% CI 1.7-170.5) in blacks. Seropositivity in cases was more frequent in recent calendar periods, ranging from 21.9% pre-1996 to 68.4% in 2005 onwards, in those with blood collection near diagnosis (lead time <5 years). HPV16-E6 seropositivity increased with lead time: 0.0%, 13.5%, 23.7%, and 38.9% with lead times of >30 years (N = 24), 20-30 years (N = 148), 10-20 years (N = 228), and <10 years (N = 301 cases) (p-trend < 0.001). Of the 47 HPV16-E6 seropositive cases with serially-collected blood samples, 17 cases seroconverted during follow-up, with timing ranging from 6 to 28 years before diagnosis. For the remaining 30 cases, robust seropositivity was observed up to 25 years before diagnosis. Conclusions: The immune response to HPV16-driven tumorigenesis is most often detectable several decades before OPSCC diagnosis. HPV16-E6 seropositive individuals face increased risk of OPSCC over several decades.

AB - Background: Human papillomavirus type 16 (HPV16)-E6 antibodies are detectable in peripheral blood before diagnosis in the majority of HPV16-driven oropharyngeal squamous cell carcinoma (OPSCC), but the timing of seroconversion is unknown. Patients and methods: We formed the HPV Cancer Cohort Consortium which comprises nine population cohorts from Europe, North America and Australia. In total, 743 incident OPSCC cases and 5814 controls provided at least one pre-diagnostic blood sample, including 111 cases with multiple samples. Median time between first blood collection and OPSCC diagnosis was 11.4 years (IQR = 6-11 years, range = 0-40 years). Antibodies against HPV16-E6 were measured by multiplex serology (GST fusion protein based Luminex assay). Results: HPV16-E6 seropositivity was present in 0.4% of controls (22/5814; 95% CI 0.2% to 0.6%) and 26.2% (195/743; 95% CI 23.1% to 29.6%) of OPSCC cases. HPV16-E6 seropositivity increased the odds of OPSCC 98.2-fold (95% CI 62.1-155.4) in whites and 17.2-fold (95% CI 1.7-170.5) in blacks. Seropositivity in cases was more frequent in recent calendar periods, ranging from 21.9% pre-1996 to 68.4% in 2005 onwards, in those with blood collection near diagnosis (lead time <5 years). HPV16-E6 seropositivity increased with lead time: 0.0%, 13.5%, 23.7%, and 38.9% with lead times of >30 years (N = 24), 20-30 years (N = 148), 10-20 years (N = 228), and <10 years (N = 301 cases) (p-trend < 0.001). Of the 47 HPV16-E6 seropositive cases with serially-collected blood samples, 17 cases seroconverted during follow-up, with timing ranging from 6 to 28 years before diagnosis. For the remaining 30 cases, robust seropositivity was observed up to 25 years before diagnosis. Conclusions: The immune response to HPV16-driven tumorigenesis is most often detectable several decades before OPSCC diagnosis. HPV16-E6 seropositive individuals face increased risk of OPSCC over several decades.

KW - HPVC3

KW - OPCSCC

KW - oropharyngeal squamous cell carcinoma

UR - http://www.scopus.com/inward/record.url?scp=85072607506&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=85072607506&partnerID=8YFLogxK

U2 - 10.1093/annonc/mdz138

DO - 10.1093/annonc/mdz138

M3 - Article

C2 - 31185496

AN - SCOPUS:85072607506

VL - 30

SP - 1335

EP - 1343

JO - Annals of Oncology

JF - Annals of Oncology

SN - 0923-7534

IS - 8

ER -