Genomics is transforming how we understand and treat gynaecological cancers. In this blog, Dr Amudha Thangavelu and Dr Katie Snape explore some of the most exciting developments.
Over the past quarter-century, genomic medicine has transformed the way we understand and manage cancer. From early sequencing breakthroughs to nationwide screening programmes, genomics now underpins prevention, diagnosis, and treatment strategies across multiple cancer types.
Following the publication of ‘The Human Genome Project’ in 2001 [1], international scientific efforts have focused on identifying and understanding genetic alterations impacting cancer development. The establishment of ‘The Cancer Genome Atlas (TCGA) Program’ in 2005 (The Cancer Genome Atlas Program (TCGA) - NCI) and ‘The 100000-genome project’ in 2012 (100,000 Genomes Project | Genomics England) has not only changed the way we understand cancer but has also revolutionised the way cancer can now be prevented, diagnosed, and treated.
Advances in genomic technology and a better understanding of the viral genome have led to the development of the Human Papilloma Virus (HPV) vaccine, a recombinant DNA vaccine. It is the first vaccine that is aimed at preventing specific types of cancer (cervix, vagina, anus, penis, throat, and mouth). Long-term follow-up data from the HPV vaccination programme in England has shown it to be highly effective in reducing the incidence of cervical cancer and high grade pre-invasive disease in the vaccinated cohort [2].
Building on this, genomic technology has now transformed the NHS Cervical Screening Programme, leading to the roll out of Primary HPV screening in England in 2019. With high-risk HPV (hr HPV) contributing to more than 95% of cervical cancers, patients are now tested for the presence or absence of the viral DNA in their smear sample. The high sensitivity of these tests and the low false positive rates has allowed the screening programme to extend the screening interval from 3 to 5 years from 1st July 2025.
While HPV has transformed cervical cancer prevention, genomic testing is also reshaping how we approach ovarian and endometrial cancers. Ovarian cancer was the first gynaecological cancer to be studied as part of the TCGA program. All patients diagnosed with any high grade non-mucinous epithelial ovarian cancer in the UK are eligible for mainstreamed germline testing for a panel of ovarian cancer susceptibility genes including BRCA1/2 irrespective of their family history [3]. This enables identification of patients with germline pathogenic variation (GPV) and cascade testing of family members, thereby opening avenues for cancer screening and prevention.
Lynch Syndrome is an autosomal dominant condition caused by a GPV in one of the 4 mismatch repair (MMR) genes. Patients with Lynch Syndrome have an increased risk of colorectal, endometrial, gastric, ovarian, pancreas, ureter and renal pelvis, bladder, prostate, biliary tract, brain, and small intestinal cancers, as well as sebaceous gland adenomas and keratoacanthomas. Identification and subsequent screening of patients with Lynch Syndrome will aid prevention and early diagnosis of several cancers. In 2020, The National Institute of Clinical Excellence (NICE) recommended Lynch Syndrome testing using MMR immunohistochemistry for all four mismatch repair proteins (MLH1, MSH2, MSH6 and PMS2) in all patients diagnosed with endometrial cancer [4]. Mainstreamed germline genetic testing is now available to all patients diagnosed with endometrial cancer under the age of 40, in addition to those with unexplained MMRd.
In addition to germline testing, tumour testing for somatic pathogenic variants of cancer predisposition genes had led to an increase in the use of targeted therapies in ovarian cancer (e.g. PARP inhibitors for BRCA deficient cancers), and immunotherapy for MMRd endometrial cancers.
The rapid pace with which genomics has been incorporated into clinical medicine over the last decade has been exciting but also challenging. In an effort to address these challenges and to ensure that genomics education and training is relevant and accessible to its members, the RCOG has created open access resources and a learning plan (Genomics at RCOG | RCOG). The NHS England Genomics Education Programme (Welcome to Genomics Education Programme - Genomics Education Programme) has also created a broad range of educational opportunities for healthcare professionals.
As more patients with genetic mutations are identified, the healthcare system must evolve to support patients and families identified with genetic predispositions. Establishing clear surveillance pathways and multidisciplinary services including nurse specialists, genetic counsellors, psychologists, primary and secondary care clinicians is imperative to provide holistic, patient centred care and improve long-term outcomes.
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Authors:
- Dr Amudha Thangavelu, Consultant Gynaecological Oncologist, Leeds Teaching Hospitals NHS Trust and
- Dr Katie Snape, Lead Consultant for Cancer Genetics, South West Thames Centre for Genomics, St George’s University Hospitals NHS Foundation Trust
References:
- International Human Genome Sequencing Consortium, Initial sequencing and analysis of the human genome. Nature 409, 860–921 (2001).
- Falcaro M, Soldan K, Ndlela B, Sasieni P. Effect of the HPV vaccination programme on incidence of cervical cancer and grade 3 cervical intraepithelial neoplasia by socioeconomic deprivation in England: population based observational study BMJ 2024;
- Ovarian cancer: identifying and managing familial and genetic risk (2024). www.nice.org.uk/guidance/ng241
- Testing strategies for Lynch syndrome in people with endometrial cancer (2020). www.nice.org.uk/guidance/dg42