The EVOLPROOF project was conceived to develop a multi-level approach to the evolution of oncoviruses, spanning from the cellular level to the population level. It focused in particular on genital infections by human papillomaviruses (HPV), which are the most oncogenic viruses known to humans. Furthermore, safe and efficient vaccines targeting some genotypes of these DNA viruses had been implemented for approximately 10 years at the beginning of the project. This made it an opportunity to explore the selective pressure that vaccination exerts on viral populations.
This project aimed to use data and concepts from ecology and evolutionary biology to tackle issues in clinical microbiology. From a methodological point of view, it combined mathematical modelling with the setting up of a clinical study.
Overall, the project's main achievement was to set up a longitudinal cohort (PAPCLEAR) of 149 healthy young women, who were followed for a median duration of 290 days. This resulted in hundreds of gynaecological visits and thousands of biological samples. The value of the PAPCLEAR cohort resides in the density of the follow-up (clinical visits every 2 months on average and weekly self-samples) and in the quality of the data generated. Indeed, we collected detailed microbiological, immunological, and behavioural data that offer a unique opportunity to paint a dynamic picture of HPV infections, but also the vaginal microbiota. Building on evolutionary ecology theory, one goal, in particular, was to investigate the genetic diversity of the three actors (the human host, the virus, and the microbiota) to identify potential interactions.
To improve epidemiological investigations, we planned to combine this longitudinal cohort with a cross-sectional cohort of a similar size. However, due to the COVID-19 pandemic, this second part of the clinical study had to be stopped prematurely resulting in only 40 inclusions out of 150 planned. Nevertheless, the resulting overall cohort size (189 women) was sufficient to test some clinical hypotheses.
Mathematical models were developed during the project that can be used to interpret the data. All of the clinical data required for the analyses have also been collected and, in part, published. Investigations are still ongoing to characterise in detail HPV infection and vaginal microbiota dynamics.
As illustrated with the recent SARS-CoV-2 pandemic, understanding how viral infections unfold within hosts and how public health interventions, such as vaccination campaigns, impact and are impacted by virus evolution is a critical societal issue in terms of public health.
