FORECEE

Overview

The FORECEE project is focused on the implementation of omics based methods into wide scale clinical practice for the stratification and risk prediction of cancers that are hormone-associated and specific to women (breast, ovarian, endometrial and cervical cancers). These represent more than 47% of all cancers in women and amongst them are cancers with a 5-year survival rate of less than 40%.

This project originates from cutting edge research, conducted by several members of this consortium, which has identified a novel and exciting opportunity to exploit omics methods in the prevention of female specific cancers.

A critical factor in the prevention of cancer is access to the cell of origin (Figure 1). Cervical screening, through application of the Papanicolaou test (or Pap smear) and/or human papilloma virus (HPV) testing assesses which women are at risk of developing an invasive cervical cancer and would benefit from a preventive procedure (ie excision of the cervical area at risk). Widespread introduction of the Pap test has reduced both the incidence of cervical cancer and associated deaths by up to 80%¹. The accessibility of the cancer’s cell of origin from the uterine cervix and recognition of risk markers reflecting an individual’s interaction and response to environmental exposure, in this case to HPV, are integral to this success.

In sharp contrast, breast, endometrial and ovarian cancers continue to pose considerable challenges in terms of risk prediction. Access to the cell of origin for these cancers can only be achieved with fully invasive methods such as a random breast biopsy, a hysteroscopy and endometrial biopsy or a laparoscopy under general anaesthesia. These options are definitely not feasible for the general population and hence our ability up to date to stratify and identify high risk groups is severely restricted.

We posit that the epigenome is the ideal surrogate which records the individual response to environmental disease-triggering factors. The epigenome is known (1) to vary across tissues and (2) depend on sensors (i.e. hormone receptors) to record individual responses to cancer-promoting factors (i.e. a large component in all women’s cancer is aberrant exogenous and endogenous hormonal exposure). Cells from the uterine cervix are the only cell type which (i) is both epithelial (hence same cell type as the cell of origin for all four women specific cancers) and responsive to hormones and (ii) can be easily accessed. These cells can also be used to analyse the genetic component of the risk (i.e. analysis of single nucleotide polymorphisms) and microbial factors (HPV and vaginal microbiome) which contribute to the development of female genital tract cancers.

Hence we have identified the possibility of utilising cervical cells, which remain abundant in the clinical setting [97% of cells in a cervical liquid based cytology (LBC) sample are not required for the cervical cancer screen], combined with a multi-omics enabled analysis pipeline to provide a bridge for the prevention of all major female specific cancers (Figure 1). The FORECEE project is aligned with the novel concept of “P4 Medicine” (predictive, preventive, personalized, and participatory) seeking to develop a multi-omics enabled risk prediction tool and translate the tool’s output into recommendations for new clinical pathways for screening and prevention of all female cancers that can be implemented on a national/international scale. The multi-disciplinary FORECEE team present leading expertise in epigenetics, genetics, metagenomics, health economics, risk prediction, communication, Health Technology Assessment as well as population health and is uniquely placed to develop and specify the future strategy and policy for the prevention of female specific cancers. 

Figure 1. The FORECEE Vision – the use of cervical cells and omics-based analysis to predict the risk of all women specific cancers