An interview with Professor Attila Lorincz from Queen Mary University of London (QMUL), discussing the development of a new cervical cancer test that is able to identify cervical cancer and pre-cancer in 100% cases.
How do we currently screen for cervical cancer in the UK?
The main method of cervical cancer screening is the Pap cytology (smear) test, however, we are now slowly transitioning to HPV screening. The cytology test is gradually being replaced and transitioned to a follow-up, or triage test.
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What are the limitations of the Pap smear and HPV-based cervical cancer screening?
The Pap smear has a poor ability to detect cervical cancer and pre-cancer. The sensitivity of the cytology test is in the range of 50 to 60%, therefore the cytology test produces a lot of false negatives. The HPV test has a very good detection ability with a sensitivity for picking up 90 to 95% of cervical cancers and pre-cancers. However, very few women with HPV infection develop cervical cancer, therefore the HPV test produces a lot of false positives.
Please describe the cervical cancer test you recently developed.
My new test measures DNA methylation, which is a chemical change on one of the four base letters that make up the human genetic code. These base letters are A C T G. Methylation adds a methyl group (CH3) to the cytosine or C base, a change that has profound effects on the way the DNA is decoded.
The variable presence of a methyl group on C can be imagined as a set of punctuation marks that tell how to interpret the genetic code. For example, if every word in a dictionary was run together into one very long string it would be difficult to interpret what was there. By adding spaces, periods and commas etc. the words become interpretable. Similarly, methylation on C provides the interpretational guidelines for the human genome.
My test detects the levels of methylation in specific target regions of human and HPV DNA, which is an indicator of disease state. For example, the genes in my test that are measured start out with very low levels of methylation in normal people and as the methylation increases so too does the risk of cancer.
What are the major benefits of this test?
The DNA methylation test is more accurate than the cytology test or the HPV test for identifying women at risk of cervical cancer. It can detect all cervical cancers and can predict the development of the cancers up to five years in advance.
The cytology test misses most of the cancers and is very poor at predicting cervical cancers. The HPV test is better at predicting the cancers but because so many women are infected by HPV it is difficult to know which ones will develop the cancer.
A big downside of HPV testing is that a huge number of women are alarmed by being told they are carrying a cancer-causing virus, when in fact very few of them are actually at risk of cancer.
The methylation test is easy to do, is less error-prone, is fully molecular and suffers much less from problems of human errors or inaccuracies. It will also be less expensive than either cytology or HPV testing when fully established in large volumes.
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Do you think that epigenetic profiling will become a routine part of cancer screening?
Yes. Epigenetic profiling is one of the most important discoveries of the decade and it will revolutionize the way we understand and the way we detect and treat cancers. Abnormal epigenetic patterns appear to be the drivers of pre-cancers and early cancers at many body sites, with cervical cancer being a prime example.
It is likely that researchers will discover a major role of epigenetic changes in almost all human cancers. Epigenetic changes can be detected in a variety of bodily fluids including blood which will further expand the use of DNA methylation testing into a major and perhaps a universal diagnostic modality.
What are the next steps for your research?
I am in the process of helping to make my DNA methylation test routinely available to women worldwide. I am also looking to make new methylation tests for other cancers. Additionally, I am doing studies to further validate my tests and identify new uses for DNA methylation testing beyond cancer.
Where can readers find more information?
- Cook DA, Krajden M, Brentnall AR, Gondara L, Chan T, Law JH, Smith LW, van Niekerk DJ, Ogilvie GS, Coldman AJ, Warman R, Reuter C, Cuzick J, Lorincz AT. (2018). Evaluation of a validated methylation triage signature for human papillomavirus-positive women in the HPV FOCAL cervical cancer screening trial. Int J Cancer. 2018 Nov 9.
- Lorincz A. 2016. The virtues and weaknesses of DNA methylation as a test for cervical cancer prevention. Acta Cytologica. 60:501-512.
About Professor Attila Lorincz
Professor Attila Lorincz is a molecular biologist and epidemiologist with formal training in genetics, microbiology, and diverse aspects of human disease.
Professor Lorincz has made many seminal discoveries that have been published in leading journals. His scientific career spans 35 years, with ~300 published papers. He was also the Winner of THE TIMES Award for Research Project of the Year UK in 2012.
In his current research studies, Professor Lorincz is focusing on the role of epigenetics in cancer. He recently discovered and developed a new DNA methylation test for cervical cancer. This novel test is simple to run and has remarkable clinical performance, it is likely to substantially improve screening for cervical cancer in the next 5 to 10 years in places where barriers are not imposed by the existence of entrenched systems.