AS374 - Biomarkers of HPV infection and risk of two increasing cancers

Investigator Names and Contact Information

Paul Brennan [ brennanp@iarc.fr] and Nicolas Schlecht [nicolas.schlecht@einstein.yu.edu]

Introduction/Intent

Pilot data from the European Prospective Investigation into Nutrition and Cancer (EPIC) study indicate that circulating HPV16 E6 antibodies were present in a large proportion of oropharyngeal cancer (34.8% of 135 cases) up to 12 years before diagnosis, while the proportion was rare among controls (0.6% of 1599 controls). This result was noteworthy as it raises the possibility that HPV16 E6 antibodies can be used as a highly specific biomarker to predict oropharyngeal cancer many years prior to diagnosis. Lifetime risk or oropharyngeal cancer for those testing positive approached 50%. We propose to establish a head and neck cancer cohort consortium initiative in order to specifically evaluate the sensitivity, specificity, true latent period, and implications for those who test HPV16 positive. By bringing together as many cohorts as possible, we plan to identify over 2000 head and neck cancer cases, including over 300 oropharynx cancer cases, and comparable controls. We will investigate residual effects for other head and neck cancer sites, as well as possible additional effects for other HPV types. Where feasible, we will also collect tumor tissue to identify the correlation between serology and tumor DNA markers for HPV infection. Finally, we will establish the infrastructure for a head and neck cancer cohort consortium that will subsequently be available for additional molecular epidemiology studies.

Specific Aims

• Explore the extent to which HPV16 E6 serology can predict additional HPV‐related anogenital cancers for which preliminary data are limited, including cancers of the vagina.
• Evaluate the validity of HPV16 E6 serology as a biomarker for early detection of oropharyngeal cancer using pre-diagnostic blood samples. In particular, evaluate the utility of the biomarker in predicting oropharyngeal cancer in US populations and that it has a very high specificity of 99.8% in healthy populations.
• Estimate the sensitivity of HPV16 E6 serology of predicting HPV driven head and neck cancers by evaluating its concordance with HPV tumor status in prevalent cases determined using comprehensive state-of-the-art molecular techniques.
• Confirm preliminary findings that HPV16E6 may also be informative marker additional HPV related cancers, in particular for anal cancer.
• Optimize the HPV16 E6 serology biomarker for potential clinical use by further evaluating its reproducibility, confirming the optimal titer threshold for defining HPV seropositive subjects, evaluate and whether additional HPV16 antibodies (e.g. E1, E2, E4, and E5)
• Provide risk prediction models within the US cohorts regarding the probability of HPV related tumor based on the HPV antibody serology results, age, sex, and tobacco exposure and alcohol intake.