Norwegian version

Public defence: Milan Stosic

Milan Stosic will defend his thesis "Profiling Intrahost HPV Variability – Relevance for risk stratification of cervical cancer development" for the PhD in Health Sciences.

The ordinary opponents are:

The leader of the public defense is Associate Professor Hege Tunsjø, OsloMet.

The main supervisor is Associate Professor Ole Herman Ambur, OsloMet. The co-supervisors are Professor Trine B. Rounge, University of Oslo, and PhD Irene K. Christiansen, Akershus University Hospital.

Thesis abstract

Cervical cancer, a leading cause of death among women globally, is primarily caused by long-term infections with human papillomavirus (HPV). While most HPV infections are harmless and clear up on their own, some can lead to cancer over time. Currently, it's challenging to predict which infections will become dangerous.

In this PhD research, we investigated whether tiny genetic changes within the HPV virus, occurring while it infects a person, could help identify which infections might progress to cervical cancer. This could lead to better screening methods and personalized care for women at risk.

Method

To achieve this, we improved a sequencing method called TaME-seq, allowing for a more accurate reading of the entire DNA code of different HPV types.

This helps detect subtle changes in the virus's DNA and sites where the virus integrates into human genes – a process linked to cancer development.

We then conducted a study focusing on women infected with HPV16, the most cancerous HPV type.

By analyzing how the virus's variability changed over time within these women, we discovered that specific patterns of genetic changes – especially those caused by the body's immune response through an enzyme called APOBEC3 – were associated with a lower risk of the infection leading to cancer.

To ensure that these findings were accurate and not due to technical errors in the sequencing process, we developed a computation tool called GENOMICON-Seq.

This simulator models how errors and biases can occur during DNA sequencing, helping researchers refine their methods and interpret results more reliably.

Results

Overall, our results suggest that measuring these specific genetic changes in HPV16 can serve as a biomarker to identify women at higher risk of developing cervical cancer.

While incorporating this biomarker into screening programs could improve early detection and prevention strategies, offering new hope for early detection and better care for women worldwide, further research is needed to validate the results.