Defining a paradigm to screen for HPV-related cancers: The next challenge for the HPV Cohort Consortium (HPVC3)
Principal Investigator
Name
Hilary Robbins
Degrees
PhD MHS MSPH
Institution
International Agency for Research on Cancer (IARC)
Position Title
Scientist
Email
About this CDAS Project
Study
PLCO
(Learn more about this study)
Project ID
2021-0006
Initial CDAS Request Approval
Sep 9, 2021
Title
Defining a paradigm to screen for HPV-related cancers: The next challenge for the HPV Cohort Consortium (HPVC3)
Summary
In the US, a growing majority of oropharyngeal cancers (OPCs) are caused by HPV. Diagnosis often occurs late, leading to extensive treatment-related morbidity. To facilitate early diagnosis, the most promising biomarker identified to date is antibodies to the HPV16-E6 oncoprotein. HPV16-E6 is easily detectable in blood, and is highly sensitive (>90%) and specific (>99%) for OPC. Less commonly, it develops prior to HPV-associated anal cancer. However, translating HPV16-E6 into clinical practice is challenging for two reasons: first, OPC and anal cancers are rare, and second, seropositivity can occur decades before cancer is detectable.
The overarching goal of our proposal is to define a paradigm to screen for HPV-related OPC and anal cancers by identifying a blood-based biomarker to use for regular follow-up among people who are HPV16-E6 seropositive. We will evaluate two promising domains of markers: circulating proteins and circulating HPV DNA. Preliminary results have demonstrated the feasibility of testing large numbers of individuals for circulating proteins, as well as the potential for circulating HPV DNA to detect very early stage disease. We will also investigate early detection markers for non-HPV-related OPC and anal cancers, and leverage these data to evaluate markers for cancer prognosis.
Evaluating early detection biomarkers among HPV16-E6 seropositive individuals requires a cohort consortium approach, due to the need for pre-diagnostic blood samples and the rarity of the HPV16-E6 biomarker. Therefore, this work will comprise the second major project of the HPV Cancer Cohort Consortium, which will include 8 cohorts from the USA, Australia, and Europe.
The overarching goal of our proposal is to define a paradigm to screen for HPV-related OPC and anal cancers by identifying a blood-based biomarker to use for regular follow-up among people who are HPV16-E6 seropositive. We will evaluate two promising domains of markers: circulating proteins and circulating HPV DNA. Preliminary results have demonstrated the feasibility of testing large numbers of individuals for circulating proteins, as well as the potential for circulating HPV DNA to detect very early stage disease. We will also investigate early detection markers for non-HPV-related OPC and anal cancers, and leverage these data to evaluate markers for cancer prognosis.
Evaluating early detection biomarkers among HPV16-E6 seropositive individuals requires a cohort consortium approach, due to the need for pre-diagnostic blood samples and the rarity of the HPV16-E6 biomarker. Therefore, this work will comprise the second major project of the HPV Cancer Cohort Consortium, which will include 8 cohorts from the USA, Australia, and Europe.
Aims
1) Determine whether circulating HPV DNA (ctDNA) predicts imminent development of cancer among people who are seropositive for HPV16-E6.
2) Identify circulating protein markers that predict imminent development of HPV-related and HPV-unrelated oropharyngeal or anal cancer.
3) Evaluate whether either circulating proteins or circulating HPV DNA predict prognosis for oropharyngeal or anal cancer.
Collaborators
Hilary Robbins (International Agency for Research on Cancer (IARC))
Paul Brennan (International Agency for Research on Cancer (IARC))
Ana Carol De Carvalho (International Agency for Research on Cancer (IARC))
Aimee Kreimer (NCI DCEG)
Mattias Johansson (International Agency for Research on Cancer (IARC))