Finding a cure for HPV with basic research

Nova Gorica, 31 January - Slovenian researcher Martina Bergant Marušič is doing basic research on human papillomavirus (HPV), hoping to contribute to finding an active substance preventing infection with what is a common cause of cervical cancer and several other types of cancer both in women and men.

Viruses are special biological entities. They are very small and usually consist of nucleic acids (DNA or RNA) and a protein shell. Since they do not have their own metabolism, they cannot reproduce on their own and require a host cell which provides them with the infrastructure required to produce new virus parts.

Nova Gorica
Researcher Martina Bergant Marušič.
Photo: Anže Malovrh/STA

Like other viruses, HPV invades host cells by attaching to the cell membrane and entering the cell. Once successfully inside, it releases hereditary material from the protein shell. The material then travels to the nucleus and starts reproducing. New viruses exit the cell to find a new host, usually destroying the cell.

When the infection lasts for a long time, the DNA of the virus integrates itself into human DNA and duplicates along with it. A long-term release of HPV oncogenes causes malign changes in host cells, leading to cancer.

Human papillomavirus

There are thousands of different viruses in the world and they are mainly known for causing disease. They can infect all kinds of living beings. HPVs are among viruses that infect humans. In fact, they are the most common sexually transmitted infection. They cause genital warts as well as various cancers, most commonly cervical cancer.

Martina Bergant Marušič, a researcher at the Nova Gorica University Laboratory for Environmental and Life Sciences, is researching HPVs to find missing information about the process of viral infection and details about molecular mechanisms that transmit virus DNA into nuclei where the virus starts to reproduce.

Her team are trying to discern how the virus attaches to the cell, how it enters the cell, how it travels inside the cell and which proteins are included in the process, and how it avoids being destroyed by the human immune system.

This would help them better understand viruses and find new antiviral substances that would prevent infection with HPV. "Condoms already contain some chemical components and we could add additional substances that impede HPV viruses. They would be present but they would be unable to infect the cells," Bergant Marušič told the STA.

Almost everyone gets infected with HPV

Researchers know about 200 types of HPV, which are roughly divided into skin and mucous, and low- and high-risk types. Almost everybody gets infected with HPV at one point in their life, but mostly the infection passes without notice. The highest prevalence is in teenagers and young adults aged between 15 and 25 years.

Like other viral infections, HPV is in most cases expelled from the body over time, as the immune system discovers the infection and eliminates it. But in the event they are not expunged and discovered, long-term infection can lead to cancer.

Cervical cancer

Cervical cancer, which can be caused by HPV, is a major health issue in the world, in particular in countries with lower quality of healthcare. In Europe this is not such a problem because of good screening systems which help detect problems at an early stage.

In Slovenia, the incidence of cervical cancer has nearly halved from 200 to 120 per year since the Zora screening programme for battling cervical cancer was introduced in 2003.

According to Zora data, around 200 people in Slovenia get sick because of HPV infection, of which 120 cases are cervical cancers and the rest are penile, anal, throat and other cancers.

Nova Gorica
Researcher Martina Bergant Marušič.
Photo: Anže Malovrh/STA

Vaccination is the most effective prevention

To prevent infection from various types of HPV that can lead to cervical cancer, three very effective vaccines have been available for some years now. The only problem with the vaccines is that they have only been developed for some of the most common types of the virus, whereas HPV has more than 200 types.

The vaccine with the broadest protection has been developed for nine types of HPV. It is very effective and safe and is said to reduce the risk of cancer by 70%. It is almost 100% effective against the nine types it has been developed for and it remains effective for at least ten years, according to Bergant Marušič.

People should be vaccinated before becoming sexually active, because vaccines are not effective against the types that the individual has already been infected with. Nevertheless, it will protect against those types the individual has not been exposed to before.

"Despite having the HPV vaccines, we believe that the positive effects will only show in 50 years. Until then, cervical cancer will continue to be one of the most common cancers in women. We need the medicine and we're still trying to figure out how the virus works and the mechanisms it uses to infect cells so that we can use it in other infections. The more we know about the virus the easier it is to battle it. Despite the existence of vaccines, we have not stopped the research," she said.

Immunization coverage a broader problem

Vaccination against HPV is not mandatory in Slovenia and the vaccination rate is below the desired threshold. But this is not only a problem with HPV, it is a broader problem, Bergant Marušič said.

She says that the benefits of vaccination outweigh all potential side effects. "It's my belief that vaccination is not just a personal decision, it is also about social responsibility. Diseases are not limited to us. Because we live in society we have to take care not to spread these diseases. If vaccination coverage for a certain disease drops, it will begin to crop up," Bergant Marušič said.

"We have measles outbreaks and it can be a serious disease in some cases. But because of the debates about the side effects, because of people's fears, a lack of information or over-information, immunization coverage has been dropping in the developed world.

"We'll likely hit a threshold where the consequences of absence of vaccination win over the fears and coverage will again rise. Vaccination is needed and it is one of the best ways to prevent diseases," she stressed.

While it may seem that the number of viruses is growing, their existence has been even throughout evolution. However, they are spreading faster because of better and faster transport. And because of the shrinking of animals' living space, they are more often transmitted from animals to humans.

Martina Bergant Marušič

Martina Bergant Marušič is a virus biology researcher at the Nova Gorica University Laboratory for Environmental and Life Sciences. She also gives lecture on fundamental biological subjects and heads the doctoral studies on molecular biology and biotechnology.