SEQUENCING HPV FOR BIOMARKER DISCOVERY

HPV-SEQ is an cross-institutional research group with the main goals: 1) To discover HPV biomarkers 2) To delineate HPV evolution 3) To develop HPV detection and characterization methods. We take advantage of Next Generation Sequencing (NGS) Technology to reach our goals.

 Published: 26.09.2017 Last updated: 14.05.2018

Summary

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.

Sub-projects

Intra-patient HPV genetic variation - a new and specific marker for cancer development

This project aims to test the hypotheses that the level of sequence variation in HPV DNA from cervical cells can be used as a marker for cancer progression and that cancer risk can be stratified down to the level of genetic variants of HPV types.

 

 

                                                                                                                                                                                            Phd-candidate Sonja Lagström 

Genotype diversity and HPV hypervariability in screening samples from Zimbabwe.

HPV16 genome dynamics in persistent infections.

Development of high-throughput HPV genotyping by next generation sequencing.

High-throughput whole genome sequencing of HPV. 

Recent publications

Dube Mandishora RSGjøtterud KSLagström SStray-Pedersen BDuri KChin'ombe NNygård MChristiansen IKAmbur OHChirenje MZRounge TB (2018)
Intra-host sequence variability in human papillomavirus
Papillomavirus Res (in press)
PubMed 29723682

Dube Mandishora RSChristiansen IK, Chin'ombe N, Duri K, Ngara B, Rounge TB, Meisal R, Ambur OH, Palefsky JM, Stray-Pedersen B, Chirenje ZM (2017) Genotypic diversity of anogenital human papillomavirus in women attending cervical cancer screening in Harare, Zimbabwe
J Med Virol, 89 (9), 1671-1677 PubMed 28390142

Meisal R, Rounge TBChristiansen IK, Eieland AK, Worren MM, Molden TF, Kommedal Ø, Hovig E, Leegaard TM, Ambur OH (2017) HPV Genotyping of Modified General Primer-Amplicons Is More Analytically Sensitive and Specific by Sequencing than by Hybridization
PLoS One, 12 (1), e0169074 PubMed 28045981

 

 

                

 

Collaborators 

Pekka EllonenInstitute for Molecular Medicine Finland (FIMM) 

Racheal Mandishora, University of Zimbabwe

Mari Nygård, CRN

Ameli Tropé, CRN

Audrey KingNational Institute for Public Health and the Environment (RIVM)

Pascal van der WeeleRIVM

Ignacio BravoLe Centre national de la recherche scientifique (CNRS), France

 

From left: Roger Meisal, Pascal van der Weele, Irene Kraus Christiansen, Audrey King, Ole Herman Ambur, Trine Rounge, Sonja Lagström, Racheal Mandishora