New Research Reveals Link Between HPV and Breast, Labia, and Anal Cancer Risk

Human papillomavirus (HPV) can cause breast, labia and anal cancer. Despite the fact that there is a vaccination program in children, many unvaccinated people will still be at risk of cancer due to HPV in the coming decades. In this group the chance of HPV infection is very high (80%). If the virus is not cleared by the immune system, precancerous lesions can develop which can progress to cancer. In the Netherlands, more than 10,000 patients are diagnosed with pre-cancer due to HPV each year. These patients are now often treated, which causes a lot of complaints, damage and stress. Many treatments are also not needed, as most pre-cancerous stages (70-90%) do not develop into cancer.

Research guidelines

To better determine who does and who does not need treatment to prevent cancer, it is important to understand the biological changes that take part in the progression of precancerous lesions to cancer. “Growing without anchor” is an important factor for this. Healthy cells need to attach to a substrate to divide, while cancer cells can divide without an anchor. To study “unanchored growth”, the researchers have developed new methods with previous funding from KWF to determine whether all known genes (~25,000) are actively involved in this process . This has resulted in 6 genes that play an important role in “anchorless growth”.

Research purpose

This project aims to prove that the 6 genes are important for the progression of precancerous lesions to cancer. For this purpose, the researchers use three-dimensional culture methods that allow them to closely simulate the pre-cancerous stages: organotypic raft cultures and organoids.

Research design

• In work package 1, the genes will be tested in organotypic raft cultures of cell lines with HPV and it will be determined which genes are important for growth.
• In work package 2, organoids are grown from normal tissue, pre-cancerous tissue, cancerous tissue of the cervix, anus and labia. These organoids are extensively characterized and compared to tissues to determine their representativeness.
• In work package 3, the genes tested in work package 1 will be tested in the organoids from work package 2.

With the long-term collaboration between the laboratory and the clinic of this research group, their unique model systems and the recent development of breast cancer organoids, they are well positioned to successfully carry out this project. . Furthermore, organoids of HPV precancerous cells have not been created before.

Expected result

The genes that have been functionally tested in these preclinical models are the basis for developing a treatment pathway for patients with precancerous lesions caused by HPV. This will lead to fewer unnecessary treatments and therefore less unnecessary complaints, damage and stress. The products and organoids also lead to better treatment of precancerous lesions that require treatment, as well as cancer.

Steps to implementation

The genes will first be tested as prognostic disease markers in tissues and smears that we have collected over the past 25 years. Confirmation will follow in ongoing prospective studies with patients with precancerous lesions of breast cancer, anal cancer and labia cancer. Collaboration with pharmaceutical companies is sought for the therapeutic application.