Illustration of HP virus infecting epithelial cells in the cervix.
A new study by scientists from the University of Innsbruck provides detailed insights into the development of cervical cancer as a result of HPV infection. Epigenetic research decodes the molecular mechanisms behind this process, expanding the body of knowledge regarding HPV and confirming previous assumptions.
A new study has looked at the molecular level of how the body fights off human papillomavirus (HPV) infection and what factors can lead to women developing cervical cancer following being infected with HPV. The results of the research project led by Martin Widschwendter, Professor of Cancer Prevention and Screening at the University of Innsbruck, were published yesterday in the International Journal of Cancer. Molecular medicine specialist Chiara Herzog and bioinformatician Charlotte Vavourakis were also significantly involved in the project. Herzog and Vavourakis conduct research at the European Translational Oncology Prevention & Screening Institute (EUTOPS), which is headed by Widschwendter.
errors in programmed cell death
Persistent human papillomavirus (HPV) infection is the most common cause of cervical cancer – over 90% of cervical cancer cases are caused by HPV. The virus is widespread, more than 80% of all women will be infected with HPV at least once in their lifetime. When infected, the virus invades epithelial cells, which are the cells that line the cervix.
The researchers found that in the majority of women, HPV leads to finely timed epigenetic changes that initiate a “cell death program” in affected cells. Since the virus can only survive inside human cells, it is thus eliminated by the death of infected cells. The new study shows that in some women, the cells in the cervix have lost this ability and programmed cell death does not occur following an HPV infection. HPV infection no longer seems to trigger the normal cell death program, particularly in “aged” stem and progenitor cells that have already undergone many cell divisions. Accordingly, the virus can survive in these cells, continue to multiply and subsequently cause cell damage that leads to cancer.
“Environmental factors can also lead to stem and progenitor cells dividing faster and thus ‘aging’ faster,” explains Chiara Herzog. “It can be a chronic infection, but it can also be a harmful habit like smoking. Our results confirm that HPV vaccination not only protects once morest infection with the virus, but also once morest cervical cancer. But quitting smoking can also prevent cervical cancer.”
The footprint in the epigenome
For the study, the epigenome of cervical cells with and without HPV infection was examined. “In a way, the epigenome is the cell’s software,” explains Martin Widschwendter. “It defines which genes are used in a cell and how intensively they do so. In contrast to the ‘hardware’ of our DNA, the epigenome is greatly altered by age and external influences.”
Research shows that in healthy women, the epigenome is programmed so that the presence of HPV in epithelial cells triggers cell death—thus clearing the infection. In women whose stem cells have already undergone frequent division and have undergone a corresponding change in the epigenome, HPV can damage the cells further and trigger genetic changes that lead to the development of cervical cancer over months and years.
“So if we examine the epigenome, we can not only infer a person’s age, but also their state of health and the risk of developing the disease,” says Widschwendter.
A English language blog post The study was published on The Eve Appeal website. The Eve Appeal is a UK not-for-profit organization that raises awareness and funds research into the five gynecological cancers of the ovary, uterus, cervix, vagina and vulva.
Study:
Herzog, C., Vavourakis, C.D., Barrett, J.E., Karbon, G., Villunger, A., Wang, J., Sundström, K., Dillner, J. and Widschwendter, M. (2023), HPV-induced host epigenetic reprogramming is lost upon progression to high-grade cervical intraepithelial neoplasia. Int. J. Cancer. https://doi.org/10.1002/ijc.34477