Liquid Biopsy for Head and Neck Cancer

Liquid biopsy is when a simple blood draw is performed in order to detect cancer cells (CTC) or mutated DNA fragments (ctDNA) free floating in the bloodstream that has been shed from the cancer's primary or secondary sites. This test has been heralded as an alternative way to make a diagnosis instead of an invasive surgical biopsy whether by needle or excision.

Liquid biopsy has been developed mainly for detecting cancers of the breast, prostate, colon, ovarian, lung, and melanoma. Liquid biopsy for such cancers are also the basis for media reports including the widely read New York Times article published in June 4, 2016.

Unfortunately, liquid biopsy to detect cancers of the head and neck (HNC) has not been as fully researched and has a limited if any role at this time.

According to studies done to date, the following mutations were found in the blood of HNC patients (percentage noted in parentheses). Please note that these values were obtained from patients who have known advanced head and neck cancer (HNC):

• PIK3CA195 (30%)
• TP53 (50%-72%)
• BRAF (10%)
• AKAP9 (10%)
• PIK3CA(21%)
• FAT1 (23%)
• CDKN2A (22%)
• Other mutations include TRAF3, CASP8, NOTCH1, NSD1, HRAS, NRAS, AJUBA, MLL2, TGFRBR2, HLA-A, NFE2I2, FAT1, NFE2L2, and amplification of 3q26/28 and 11q13/22

Given these numbers have been obtained from patients with known advanced head and neck cancer, the percentages are probably much lower in the early stages.

Such numbers are far from the 90%+ detection levels quoted in media reports like the New York Times.

However, detection levels are much better when the saliva is also analyzed in combination with blood, especially for cancers originating in the oral cavity such as the tongue and tonsil. When both blood and saliva is checked for TP53, PIK3CA, CDKN2A, HRAS, NRAS as well as HPV (HPV-16,-18), cancer detection rates increased up to around 90% [link]. In fact, for early stage cancer, saliva had a significantly higher detection level compared with blood.

However, mutant DNA fragments were shown to be 10 times more prevalent in plasma than in saliva which could influence treatment regimens.

As such, when liquid biopsies become formally available for HNC, it will probably involve testing both blood and saliva for maximal accuracy and cancer detection from both a diagnostic as well as therapeutic reasons.

Before patients get too excited however, keep in mind that these results are based on very low numbers of patients and at this time, may only be used to monitor the cancer and suggest treatment regimens... not to diagnose it. Before such testing can be used with confidence and reliability for patients with head and neck cancer, further research with larger numbers of patients need to be undertaken.

As such, tissue biopsies are still required to diagnose head and neck cancers. Another thing to keep in mind is that current research for HNC liquid biopsies generally check for only one specific type of cancer called squamous cell carcinoma; granted, it is the most common type. However, there are many other head and neck cancers that current investigational liquid biopsies do not address including mucoepidermoid carcinoma, acinic cell carcinoma, adenocarcinoma, neuroendocrine carcinoma, thyroid carcinoma, etc.

In any case, for those interested, commercial testing is available for HPV in the saliva as well as most genetic mutations in the blood by private labs like Guardant Health. Testing for genetic mutations in the saliva is still not commercially available at this time.

Furthermore, blood genetic mutation testing is ONLY indicated for advanced solid tumors at this time.


Sources:
‘Liquid’ Cancer Test Offers Hope for Alternative to Painful Biopsies. NYT 6/4/16

References:
A liquid biopsy for head and neck cancers. Expert Rev Mol Diagn. 2016;16(2):165-72. doi: 10.1586/14737159.2016.1127758. Epub 2016 Jan 18.

Detection of somaticmutations and HPV in the saliva and plasma of patients with head and neck squamous cell carcinomas. Cancer.2015;7(293):1–7

Detection of circulating tumour DNA in early- and late-stage human malignancies. Sci Transl Med. 2014 Feb 19;6(224):224ra24. doi: 10.1126/scitranslmed.3007094.

Comprehensive genomic characterisation of head and neck squamous cell carcinoma. Nature. 2015;17:576–82.

The mutational spectrum of squamous-cell carcinoma of the head and neck: targetable genetic events and clinical impact. Ann Oncol. 2014 Oct;25(10):1889-900. doi: 10.1093/annonc/mdu143. Epub 2014 Apr 8.

Detection of somatic mutations and HPV in the saliva and plasma of patients with head and neck squamous cell carcinomas. Science Translational Medicine 24 Jun 2015: Vol. 7, Issue 293, pp. 293ra104 DOI: 10.1126/scitranslmed.aaa8507