Principal Investigator

Paul Joseph
Brennan
Awardee Organization

International Agency For Res On Cancer
United States

Fiscal Year
2018
Activity Code
U01
Project End Date

Biomarkers of human papillomavirus (HPV) infection and risk of two increasing cancers

Biomarkers of human papillomavirus (HPV) infection and risk of two increasing cancers Summary Oropharyngeal cancer and anal cancer have been recently highlighted in the annual `Report to the Nation on the Status of Cancer' as ebing the two cancers in the US that are increasing among both men and women. Our proposal focuses on these two cancers. Our pilot data from the European Prospective Investigation into Nutrition and Cancer (EPIC) cohort indicate that circulating HPV16 E6 antibodies are present over 10 years before diagnosis in a large proportion of people who develop oropharyngeal cancer (35%), whilst being rare among controls (0.6%). We have subsequently identified HPV16 E6 antibodies in 29% of anal cancers and, again, being extremely rare among a separate group of controls (0.6%). These results are noteworthy as they indicate that a HPV-driven neoplastic process is present many years prior to diagnosis for both of these cancers, and raises the possibility that HPV16 E6 antibodies can be used as a highly specific biomarker to predict cancer onset. We have already established a cohort consortium in order to evaluate the sensitivity, specificity, and true latent period of HPV16 E6 antibody response before diagnosis, as well as survival outcome among all head and neck cancers for those who test positive. By bringing together 10 prospective cohorts from the US and Northern Europe, two populations where HPV infection now being recognized as the predominant cause of oropharynx cancer, we plan to identify 252 new oropharyngeal cancers and 180 anal cancer cases with pre-diagnostic blood samples available for analysis. We will also collect tumor tissue from 100 oropharynx cancer cases and 50 anal cases to evaluate the correlation between serology and tumor biomarkers of HPV infection.

Publications

  • D'Souza G, Tewari SR, Troy T, Waterboer T, Struijk L, Castillo R, Wright H, Shen M, Miles B, Johansson M, Robbins HA, Fakhry C. Prevalence of oral and blood oncogenic human papillomavirus biomarkers among an enriched screening population: Baseline results of the MOUTH study. Cancer. 2023 Aug 1;129(15):2373-2384. Epub 2023 Apr 9. PMID: 37032449
  • Robbins HA, Ferreiro-Iglesias A, Waterboer T, Brenner N, Nygard M, Bender N, Schroeder L, Hildesheim A, Pawlita M, D'Souza G, Visvanathan K, Langseth H, Schlecht NF, Tinker LF, Agalliu I, Wassertheil-Smoller S, Ness-Jensen E, Hveem K, Grioni S, Kaaks R, Sánchez MJ, Weiderpass E, Giles GG, Milne RL, Cai Q, Blot WJ, Zheng W, Weinstein SJ, Albanes D, Huang WY, Freedman ND, Kreimer AR, Johansson M, Brennan P. Absolute Risk of Oropharyngeal Cancer After an HPV16-E6 Serology Test and Potential Implications for Screening: Results From the Human Papillomavirus Cancer Cohort Consortium. Journal of clinical oncology : official journal of the American Society of Clinical Oncology. 2022 Nov 1;40(31):3613-3622. Epub 2022 Jun 14. PMID: 35700419
  • Kreimer AR, Johansson M, Yanik EL, Katki HA, Check DP, Lang Kuhs KA, Willhauck-Fleckenstein M, Holzinger D, Hildesheim A, Pfeiffer R, Williams C, Freedman ND, Huang WY, Purdue MP, Michel A, Pawlita M, Brennan P, Waterboer T. Kinetics of the Human Papillomavirus Type 16 E6 Antibody Response Prior to Oropharyngeal Cancer. Journal of the National Cancer Institute. 2017 Aug 1;109. (8). PMID: 28376197
  • Waterboer T, Brenner N, Klussmann JP, Brennan P, Wieland U, Robbins HA. Study results and related evidence do not support use of HPV16 L1 DRH1 antibodies as a cancer screening test. EBioMedicine. 2020 Dec;62:103143. Epub 2020 Nov 27. PMID: 33249381
  • 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. Timing of HPV16-E6 antibody seroconversion before OPSCC: findings from the HPVC3 consortium. Annals of oncology : official journal of the European Society for Medical Oncology. 2019 Aug 1;30(8):1335-1343. PMID: 31185496