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.

Public Health Relevance

Biomarkers of human papillomavirus (HPV) infection and risk of two increasing cancers Project narrative Human papillomavirus infection is causing an increasing number of oropharynx and anal cancers in the US. We have recently found that blood biomarkers of HPV infection (HPV16 E6) are detectable many years before diagnosis in a large proportion of oropharynx and anal cancer cases, and because this biomarker was also rare among healthy controls (about 0.5%), it may be possible to use it as a highly specific biomarker of these two increasing cancers. To further evaluate the potential of HPV biomarkers we propose to bring together 10 cohorts, including an additional 252 oropharynx and 180 anal cancer cases with pre-diagnostic blood samples available for analysis. We will also collect and analyze 150 tumor samples to validate that the blood biomarker indicate 'HPV-driven' cancers. This project has the potential of providing a pre-diagnostic biomarker for both oropharynx and anal cancers caused by HPV, allowing for earlier diagnosis and improved survival.

Agency
National Institute of Health (NIH)
Institute
National Cancer Institute (NCI)
Type
Research Project--Cooperative Agreements (U01)
Project #
5U01CA195603-02
Application #
9135267
Study Section
Special Emphasis Panel (ZRG1)
Program Officer
Krueger, Karl E
Project Start
2015-09-01
Project End
2019-08-31
Budget Start
2016-09-01
Budget End
2017-08-31
Support Year
2
Fiscal Year
2016
Total Cost
Indirect Cost
Name
International Agency for Research on Cancer
Department
Type
DUNS #
279551881
City
Lyon
State
Country
France
Zip Code
69008
Kreimer, Aimée R; Johansson, Mattias; Yanik, Elizabeth L et al. (2017) Kinetics of the Human Papillomavirus Type 16 E6 Antibody Response Prior to Oropharyngeal Cancer. J Natl Cancer Inst 109: