Sequencing HPV for biomarker discovery
Project
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HPVseq is an cross-institutional research group with three the main goals, To discover HPV biomarkers, delineate HPV evolution and develop HPV detection and characterization methods.
Background
Human papillomavirus (HPV) is the etiological agent of cervical cancer and other anogenital malignancies and cancer of the head/neck. Typically, HPV infections are transient and clear within relatively short time, typically 1-2 years. Persistent HPV infections, however, may last for years and can lead to the progressive transformation into cancer. Why typically benign infections develop into malign states remains unknown.
More than 200 HPV types are characterized. Of these, fourteen carcinogenic HPV types 16, 18, 31, 33, 35, 39, 45, 51, 52, 56, 58, 59, 66 and 68 are responsible for nearly all HPV-induced cancers.
Methodology development
High throughput HPV genotyping by NGS technology may increase sensitivity and specificity in both clinical end epidemiological contexts. We have developed a labour and cost effective genotyping protocol with improved analytical sensitivity and specificity. In addition to identifying carcinogenic and other HPV types, our protocol allows the characterization of nucleotide diversity in the target gene relevant for the study of pathogen evolution and vaccine escape.
HPV genotyping for cancer risk prediction is most often based on the gene encoding the viral capsid; the yardstick for HPV taxonomy. However, causal links between viral variants and cancer development are to be found elsewhere in the viral genome. We have therefore developed a HPV whole genome sequencing (HPV-WGS) approach for ultimate resolution in ongoing searches for associations between viral variants and cancer development.
arch group has uncovered that HPV populations within a patient is much more variable than previously known. We wish to investigate this variability, how it changes through an infection within the same patients and if some variants have a higher likelihood of developing cancer. To achieve this we will whole genome sequence high-risk HPV types from thousands of clinical cervical samples and investigate the dynamic relationship between HPV mutations, length of infection and risk of cancer.
About the project
Project leaders:
- Trine Rounge - Cancer Registry, trine.rounge@kreftregisteret.no
- Ole Herman Ambur - OsloMet, ole-herman.ambur@oslomet.no
- Irene Kraus Christiansen - Ahus, Irene.Kraus.Christiansen@ahus.no
Collaborators:
- Pekka Ellonen, Institute for Molecular Medicine Finland (FIMM)
- Racheal Mandishora, University of Zimbabwe
- Mari Nygård, CRN
- Ameli Tropé, CRN
- Audrey King, National Institute for Public Health and the Environment (RIVM)
- Pascal van der Weele, National Institute for Public Health and the Environment
- Ignacio Bravo, Le Centre national de la recherche scientifique (CNRS), France
REC: The project is approved by the regional ethics committee for medical and health research (ref: 2017/447).
Duration: April 2017 - on going