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Can we use saliva to detect cancer?

    One in two people in the UK will be diagnosed with cancer during their lifetime. These findings, published by Cancer Research UK, can be extrapolated to any European country given the progressive ageing of the population. In this context, it will be essential to have new methods for the early diagnosis of cancer with the aim of improving the effectiveness of treatments.

    Research published in the International Journal of Oral Science suggests that saliva is a promising biomarker source. Being able to detect a disease using this biological sample would, firstly, provide us with an inexpensive and non-invasive diagnostic method. As such, cost-effectiveness analyses support the use of saliva for detecting diseases such as cancer. Furthermore, saliva studies have certain advantages over conventional blood tests such as simplicity in obtaining the sample, safety (e.g. saliva has factors that inhibit HIV infectivity) and ease in storing these samples. 

 

Soft Power (Flickr)

 

    But what is the composition of saliva? Can it vary over time and hence influence the results of possible diagnosis methods? A paper published in Physiology Research explained that saliva is more than just a fluid produced by the salivary glands. In addition to its high water content, it also contains proteins, hormones, lipids, sugars and ions, whose concentration can be affected based on the type and duration of the gland stimuli, the flow rate and our circadian rhythm. But saliva also contains epithelial cells, bacteria and food debris, which affect the proteome of saliva. Today we know that amylase, carbonic anhydrase, mucins and cystatins are some of the most important enzymes found in saliva, although the complete list would amount to over three thousand proteins.

    Proteomics research has made it possible to prepare a first profile of the biological molecules that can be found in saliva, so we can now compare healthy people and cancer patients. Knowing which molecules can act as biomarkers is a very important first step. Scientists at the University of California have set up the first saliva proteome knowledge base, a significant advance in a new discipline better known as salivaomics. As shown in the figure below, over the past six years a number of biomolecules have been identified in saliva that can be used to detect local and systemic diseases. They include diabetes, dental problems, breast cancer and AIDS. 

 

Majem et al. Int J Mol Sci. 2015 Apr; 16(4): 8676–8698

 

Source: Majem et al. Int J Mol Sci. 2015 Apr; 16(4): 8676–8698

    What biomarkers could be used to diagnose cancer using saliva? Preliminary studies have evaluated the differential expression of microRNAs such as miR-21 and miR-141 in patients with prostate cancer by using nanographene biosensors, a faster and more effective technique than detection by qPCR. Another study, published in Biomed Research International, pointed to the possible use of a panel of three microRNAs (miR-17, miR-21, miR-181b) for the early diagnosis of pancreatic cancer. These advances could be key to treating the disease as there are currently no useful tests for the early detection of tumours of this kind.

    Another type of analysis that can be performed with saliva is to study the microbiome, which could also be crucial. A paper published in Clinical Microbiology Reviews showed an interesting correlation between peripheral diseases such as pancreatic cancer and oral microbiota. In particular, the Neisseria elongata and Streptococcus mitis bacteria were proposed as good candidates since their levels were significantly reduced (p<0.05 in qPCR studies) in cancer patients compared with healthy people. Although this study is too preliminary to be transferred to clinical practice, its conclusions show the importance of finding good biomarkers in saliva which allow diseases to be diagnosed. In the case of oral cancer, other microorganisms have been identified that could serve as “clues” for early diagnosis, such as Capnocytophaga gingivalis, Prevotella melaninogenica and the abovementioned Streptococcus mitis.

    Although the detection of cancer using saliva sounds promising, the fact is that it has to overcome several challenges before it can be used in clinical practice. They include the heterogeneity of different tumours and biological samples, the use of mathematical models to improve the sensitivity and specificity of testing and the standardisation of protocols for the extraction, handling and analysis of these biological samples. In any case, saliva is considered the “holy grail” of diagnostic tests, meaning that these studies could be key to the early detection of cancer in the medium and long term.