A non-invasive test to detect cervical pre-cancer by analysing urine and vaginal samples collected by women themselves is likely to improve participation in cervical cancer screening programmes according to a new study.

The study, presentated at the 2019 NCRI Cancer Conference, is the largest to test a methylation classifier, called S5, in urine and self-collected cervical samples to detect pre-cancer lesions in women who have been referred for further investigation. 

Cervical cancer is the fourth most frequently occurring cancer in women in the world. In 2018, there were an estimated 570,000 new cases of cervical cancer and 310,000 women died from the disease. Infection with human papilloma virus (HPV) is the main cause of cervical cancer. 

The cervical screening programme in the UK has been very successful but there has been also a decline in its uptake, particularly in some areas in the UK and specific ethnic groups. The current gold-standard pap smear test is taken in the clinic and often follows a positive test for HPV. 

Woman prefer doing cervical cancer tests at home

“The initial use of self-sampling is likely to be for women who do not attend clinic after a screening invitation and in countries without a cervical cancer screening programme. In the longer term, self-sampling could become the standard method for all screening tests. The study indicated that women much preferred doing a test at home than attending a doctor’s surgery,” said Dr Nedjai, who is Senior Research Fellow and Director of the Molecular Epidemiology Lab at Queen Mary University of London, UK.

“HPV testing is rapidly becoming the primary screening method for cervical cancer worldwide. It is a very sensitive method, very good at detecting true positives, but lacks specificity – in other words, a second test is needed to exclude HPV positive women that are not at increased risk of developing cancer. The choice of an appropriate strategy for high-risk HPV positive women is a key issue.”

The S5 test developed by Dr Nedjai and her colleagues at Queen Mary, measures DNA methylation – a chemical change to one of the four DNA base letters that make up the human genetic code. S5 looks at DNA methylation of four HPV types most strongly associated with cancer – HPV16, HPV18, HPV31 and HPV33 – and the human gene EPB41L3 to produce a score that indicates the level of risk. If the score is above a selected cut-off it indicates an increased risk of a pre-cancer lesion, and the higher the score the higher the risk of cancer. They had discovered in earlier research that when S5 was used on cervical samples collected by health care professionals, it was 100% accurate at detecting invasive cervical cancer, and 93% accurate at detecting pre-cancer in women who had an HPV positive test.

In the future, Dr Nedjai said the samples could be collected at home for both HPV and S5 methylation analysis without the need to go to the clinic.

She added: “We are currently working on new markers to try to improve the accuracy of the classifier even further, but these findings represent an advance in cervical cancer screening, especially for women who do not attend the clinic, such as older women, or women who find the smear test too painful or who do not have access to a screening programme in their country. We think it’s promising.”

Vital that further research is conducted

Robert Music, Chief Executive at Jo's Cervical Cancer Trust: “The findings from this research could be a game-changer. It could mean those requiring treatment are identified faster and reduce the number of women having to go for potentially unnecessary investigations at colposcopy.

"This would also save the NHS precious funds. It is vital that further research is conducted on larger groups of women however the findings are exciting and could mean that new methods for cervical screening are getting closer to reality. For women who find the current methods of cervical screening difficult, including those with a physical disability or who have experienced trauma, it could mean they can access screening in a far more acceptable and accessible way.”