A new diagnostic technique tested in the United States for head and neck cancer (caused by human papilloma virus - HPV) makes it possible to measure the risk of recurrence with greater accuracy and therefore to better tailor treatment.
The approach to the treatment of head and neck cancer caused by human papilloma virus (HPV) infection – but also the future treatment of other types of cancer – could be significantly improved by a new method of liquid biopsy based not on blood analysis, as is traditional, but on the analysis of lymphatic fluid. A liquid biopsy consists of the search for traces of DNA or other molecules “leaked” from cancerous cells within body fluids.
A study published in the scientific journal Clinical Cancer Research by oncologists from Washington University in Saint Louis (USA) showed the technique to be extremely reliable in predicting the risk of recurrence and, therefore, in identifying the best strategies to adopt following surgery.
What is lymphatic fluid? It is a transparent fluid that circulates in the lymphatic system with different functions: it collects excess fluids, transports useful substances even to the remotest parts of the body, and enables white blood cells to move from tissues to the lymphatic nodules, where they are activated to fight infections or other threats.
Cancer that is difficult to identify and remove
The cases of head and neck cancer are on the increase for a number of reasons and, in around 25% of cases, they originate from an HPV infection. The main target of the virus is actually the genital area (in particular the uterus), but HPV can also affect the oropharynx area, above all as a result of oral sex.
Normally surgery is performed to remove the tumour, but deciding what to do next isn’t straightforward, because the sampling of tissue fragments with the aim of verifying if any malignant cells still remain can be affected by the skill of the operator or simply may identify affected cells in one area but not “see” those present in another.
Liquid biopsy as an alternative to the traditional biopsy?
For some time, researchers have tried to understand if a liquid biopsy (up to now based, as we said, on the search for certain indicators in the blood) can be used alongside, if not replace, the traditional biopsy, but the results have been rather uncertain.
Now, however, the results obtained in Saint Louis could represent an undoubted step forward. The idea of the US researchers was to analyse the drainage fluid that is always collected following surgery for at least 24 hours in order to make sure there are no complications. Normally it is thrown away but, above all in the case of these types of cancer, it contains, according to the researchers, extremely valuable material such as the HPV genetic code, which helps understand if the infection is still present and, therefore, if the patient is still at risk.
Post-surgery drainage fluid
To check its potential, the US doctors collected the drainage fluid of 100 patients immediately after surgery over a period of 24 hours, and also took a blood sample from all of them. They analysed both for circulating virus DNA, finding it in 78% of the lymphatic fluid samples, but only in 12% of the blood samples: a difference that, on its own, would justify the adoption of this technique.
Furthermore, the concentration of DNA in the lymphatic fluid was thousands of times higher than in the blood samples, and this too presents a unique opportunity. The liquid biopsy of the lymphatic fluid can also be quantitative, as well as qualitative, while with blood it is very difficult to perform an assay, given the scarcity of the material.
The presence of virus DNA in the lymphatic fluid should come as no surprise. Lymphatic fluid passes through the lymph nodes, which are the biological filters in which virus particles are concentrated. Drainage removes the residues present, which can then be studied. On the contrary, only traces of viruses are found in blood.
And the confirmation has come from patients: two of them, apparently, based on the histopathology report, no longer had malignant cells, but suffered a relapse one year after surgery. In both cases, following the relapse, the blood tests showed nothing, but the lymphatic fluid, on the other hand, was positive for HPV. On the contrary, another three patients, who were directed towards chemotherapy/radiotherapy, temporarily suspended their treatment to undergo additional tests given that the lymphatic fluid was completely free of virus DNA. The liquid biopsy of the lymphatic fluid could therefore be very beneficial, and also costs very little and is virtually painless.
Interpretations with artificial intelligence
But there’s more. The authors have also developed an artificial intelligence programme that helps interpret the results and predicts the likelihood of recurrence and survival by processing, as well as data from the liquid biopsy of the lymphatic fluid, also the blood liquid biopsy, traditional histopathology and clinical data.
As well as being found to be specific and reliable, the programme has confirmed the extremely important role of the lymphatic fluid test. Further data on a wider range of cases is expected, while researchers are trying to optimise the tests that indicate the absence of HPV viruses so that the test can become even more specific and sensitive.
