Sequencing HPV for biomarker discovery

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.

Last updated: 2019.03.09

HPV infections and cancer development

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.

Read more about HPV research at the cancer registry here. 

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.

 

 

                                                                                                                                                                                                                                                             

The dynamic HPV genome and cancer
 
The aim of this project is to investigate how the genomes of human papillomaviruses (HPVs) changes through an infection. While HPVs are evolutionary stable and slowly evolving viruses, previous studies conducted by our research 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.

 

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. 

News and events:

HPV genomic workshop 7-9 September 2017

 

Selected publications:

Lagström S, Umu SU, Lepistö M, Ellonen P, Meisal R, Christiansen IK, Ambur OH, Rounge TB (2019)  TaME-seq: An efficient sequencing approach for characterisation of HPV genomic variability and chromosomal integration Sci Rep, 9 (1), 524

DOI 10.1038/s41598-018-36669-6, PubMed 30679491

 

Dube Mandishora RS, Gjøtterud KS, Lagström S, Stray-Pedersen B, Duri K, Chin'ombe N, Nygård M, Christiansen IK, Ambur OH, Chirenje MZ, Rounge TB (2018)
Intra-host sequence variability in human papillomavirus
Papillomavirus Res, 5, 180-191
DOI
10.1016/j.pvr.2018.04.006
, PubMed 29723682

 

Dube Mandishora RS, Christiansen 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
DOI
10.1002/jmv.24825
, PubMed 28390142

 

Meisal R, Rounge TB, Christiansen 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
DOI
10.1371/journal.pone.0169074
, 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 WeeleNational Institute for Public Health and the Environment 

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