It is unclear what exactly determines who clears an infection and who doesn’t, although certain characteristics like age and whether they smoke play a role. In our recent research, now published in the International Journal of Cancer, we investigated further, how the body deals with the HPV infection on a molecular level and what distinguishes women who do and women who do not successfully clear the infection and progress to developing cancer. We do so by looking at differences in the epigenome of cervical cells collected from women with and without HPV infection.
The epigenome (Greek for ‘on top of the genome’) is the cells’ ‘software’. It defines which of the inherited genes, from our mother and father, take action, when they take action and how strongly. In contrast to the ‘hardwired’ genetics of our cells, the epigenome is ever-changing and altered by age and experiences. It records the footprint (DNA methylation) of someone’s exposure to external factors throughout their lifetime, starting before birth. The epigenome is also sensitive to factors that negatively impact on health and contribute to the risk of developing cancer, such as viral infections, diet and smoking. By measuring this epigenetic footprint, we can predict not only the age of an individual, but also their health status and risk for developing disease.
Cervical cancer develops through different stages, with several ‘precancerous’ stages where we can detect changes to the cells to varying degrees, from cervical intraepithelial neoplasia 1 (or CIN1) to CIN3. Most cases of CIN1 and CIN2 clear and only a small portion of women go on to develop CIN3 or cervical cancer. Our research team had access to a large collection of samples from cervical screening tests, including samples across various stages of HPV infection and CIN progression.
Our research shows that in healthy women the presence of HPV in cells changes the epigenome and the cells die (called ‘programmed cell death’ or apoptosis). Because the cells containing the virus die, the virus itself cannot survive and so is cleared. In women with CIN3, the cervical cells appear to have an impaired ability to die after HPV infection. In these cells, HPV leads to misprogramming of the epigenome and genome, which eventually leads to cancer development.
We looked at the reasons why cells die after HPV infection in some women but not in others. We found that factors driving faster cell divisions in the cells responsible for maintaining healthy tissues (called stem cells or progenitor cells) are linked with the cells’ inability to die after HPV infection. Known factors driving faster cell divisions include chronic infections and lifestyle behavior such as smoking. Our research strongly supports the view that HPV vaccination, which protects against chronic HPV infection, and other factors reducing the speed of cell divisions, such as not smoking, may help increase the body’s self-defense against the virus and reduce the chances of cervical cancer developing.
You can read the paper in full on the International Journal of Cancer