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Markers of human papillomavirus (HPV) infection and risk of head and neck cancer- using PLCO data to contribute to cohort consortium effort

Principal Investigator
Name
Aimee Kreimer
Degrees
-
Institution
NCI, DCEG, IIB
Position Title
-
Email
About this CDAS Project
Study
PLCO (Learn more about this study)
Project ID
2011-0281
Initial CDAS Request Approval
Apr 27, 2012
Title
Markers of human papillomavirus (HPV) infection and risk of head and neck cancer- using PLCO data to contribute to cohort consortium effort
Summary
HPV is now accepted as a cause of some head and neck cancers, yet the evidence is based almost exclusively on cross-sectional case-control studies. To prospectively evaluate the risk conferred by HPV on head and neck cancer (HNC), including cancers of the oral cavity, oropharynx, and larynx, we propose to test incident cancer cases and matched controls using new serologic assays that allow measurement of anti-HPV antibodies. These assays target specific HPV proteins that are considered markers of exposure (anti-L1 antibodies) and HPV-associated disease (anti-E6/E7 antibodies). To provide preliminary data on serological data in prospective material, we recently conducted a nested case-control study within the European Prospective Investigation into Cancer and nutrition (EPIC) study. Serological analyses were performed on approximately 500 head and neck cancer cases and 850 controls in September 2011. Preliminary analysis suggests that approximately 35% of cases with oropharyngeal cancer were HPV16 E6 seropositive (and 0% of controls); ~15% of cases with oropharyngeal cancer were dual positive HPV16 E6 and E7 oncoproteins. The occurrence of HPV anti E6/E7 markers was not related to time to diagnosis, being present up to 12 years before clinical diagnosis of disease. With these initial promising results, we would like to expand the current study to PLCO and other cohorts using the cohort consortium infrastructure.
Aims

The aim of this proposal is to prospectively evaluate the risk conferred by serologic evidence HPV infection on head and neck cancer (HNC), including cancers of the oral cavity, oropharynx, and larynx, by conducting a case-control study nested within PLCO and multiple cohorts. This study will address the hypothesis that HPV causes a subset of these cancers, and address a key point in causality, that exposure precedes disease. The primary aim of the proposal is to evaluate the main effects of specific high-risk HPV types on these cancers, and determine how many years prior to head and neck cancer diagnosis these markers are present; to investigate the potential interaction between HPV and other non-infectious risk factors for HNC; and to evaluate whether there is a survival advantage among HPV-positive oropharyngeal tumors and whether this extends to HPV-associated tumors at other anatomic sites of the head and neck. Once we have preliminary HPV serology results, we would plan to submit an amendment to our proposal to additionally evaluate: 1) the velocity of antibody titers among individuals who tested HPV seropositive so that we can understand how antibody titer levels change leading up to diagnosis of head and neck cancer and how levels fluctuate when they are present in controls; and 2) HPV DNA positivity in tumor tissue, and correlate this with HPV seropositivity.

Collaborators

Paul Brennan (International Agency for Research on Cancer)
Allan Hildesheim (DCEG)
Mattias Johansson (International Agency for Research on Cancer)
Wim Quint (DDL Diagnostic Laboratory)

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