Early cancer detection saves lives! A salivary RNA test for oral and throat cancer

Cheryl is a vibrant 56-year-old woman managing hypertension with determination. Recently, during her routine visit to the dentist, Cheryl’s hygienist noticed some inflammation in her gums and decided to take a proactive approach to Cheryl’s persistent oral health issues. The hygienist ordered a saliva-based molecular test, which provides a comprehensive picture of oral health, along with detecting a biomarker associated with oral malignancies. With ease and convenience, Cheryl collected a simple saliva sample from the comfort of her own home and sent it off for analysis. Unexpectedly, the test came back positive for detection of markers of oral or throat cancer, with several markers out of the expected range!

Cheryl’s dentist, equipped with this valuable information, delved deeper into her medical history and lab data. Recognizing the significance of the positive result, he didn't waste any time and promptly referred Cheryl to an expert otolaryngologist. The otolaryngologist, skilled and meticulous, conducted a thorough examination followed by an endoscopy, and there it was—a small lesion in the pharynx, unseen to the naked eye during the routine oral exam. Acting swiftly, the otolaryngologist performed a biopsy, and the results confirmed their suspicions. Cheryl had localized oropharyngeal squamous cell carcinoma (OPSCC), a discovery that might have remained hidden without the aid of this innovative test. Armed with this early detection, Cheryl's medical team swiftly planned a curative resection, targeting the cancerous cells before they had a chance to spread. The surgery was a success, thanks to the timely intervention made possible by this salivary test!

The underestimated challenge of oral and throat cancer detection

Cheryl's success story serves as a testament to the power of advancements in medical technology. This test not only overcame the challenges of the standard screening methods but also gave Cheryl the gift of early detection, saving her from a more arduous and uncertain battle. Her story reminds us of the profound impact that innovative healthcare solutions can have in transforming lives and paving the way for brighter, healthier futures.

While medical advances are making it easier to live longer and better lives, we still fail to detect oral cancer early. Shocking statistics reveal a staggering 62% surge in global oral cancer cases by 2035 due to different factors, including a lack of new diagnostic and detection tools in clinical practice in the last 40 years. 

In current clinical practice, diagnosing oral cancer relies on the expertise of various healthcare providers (dentists, dental hygienists, primary physicians). Screening for oral and throat cancer involves a visual and tactile check. However, assessing the oral cavity and throat this way is akin to exploring the ocean's depths with only a flashlight and hands. While you might glimpse prominent features and feel surfaces, a world of complexity and hidden details escapes these limited senses. To gain complete insight, embracing easy-to-use advanced tools and techniques is essential.

In addition, the visual and tactile examination is subjective and prone to examiner bias. In fact, this technique is not very sensitive* - the number of wrongly diagnosed positive cases (false negatives) is still high - making it harder to identify precancerous oral lesions. The absence of symptoms in the early stages (I-II) of the disease can also delay the diagnosis. More than 70% of oral cancer diagnoses are not made until the disease is in stage III or IV. At these later stages, the five-year survival rate drops to less than 50%. Unfortunately, only 28% of patients with oral cancer in the U.S. are diagnosed at an early stage, when the malignancy is localized, treatable, and the 5-year survival is high.

stages of cancer

The power of salivary RNA testing for detecting biomarkers

As we have described before (here, here, and here) RNA is more relevant for health than DNA. This is because genetics (DNA) plays a minor role in chronic diseases and cancers. RNA describes the current state of affairs in any part of the body, such as saliva, stool, and blood. Viome’s RNA tests meet all clinical standards and have received CLIA licenses. We have thoroughly validated and characterized these tests, and the results have been published in peer-reviewed journals (here, here, and here). Our RNA tests accurately quantify the abundance of RNA molecules from all cells (bacterial, fungal, human, etc.) and viruses.

Detecting cancer in its early stages increases the chances of successful treatment and survival. It is like spotting a flickering flame in a vast forest and extinguishing it before it becomes a raging inferno. However, if left unchecked, it has the potential to spread and consume the entire forest, making it much harder to control and causing devastating consequences.

In its early stages, cancer cells are localized, confined, and more responsive to treatment options. Medical interventions such as surgery, radiation, and targeted therapies are often more effective when applied to a smaller, localized tumor. Moreover, the body's immune system can better combat the disease when it is not yet overpowering. In contrast, when cancer advances and spreads or metastasizes to other parts of the body, it becomes more challenging to treat, like a wildfire that has engulfed a large portion of the forest. At this stage, treatment becomes more aggressive, often involves complex procedures and stronger medications, and may result in a higher risk of complications.

Regular screenings, awareness of potential symptoms, and proactive healthcare play a crucial role in identifying cancer when it's still manageable, allowing for a higher likelihood of recovery and a better quality of life for patients. However, current screening tools are far from perfect as explained earlier. Luckily, we have an objective, reproducible, highly sensitive, and specific test that overcomes the high variability, lack of reproducibility and poor performance of the current standard of care. 

sensitivity - specificity

Viome’s Oral Health Pro™ with CancerDetect™ test can surpass these limitations and provide better results.  Oral health professionals can register to order the test on our website.

sequence to detected - not detected

This single-use kit provides materials and instructions for collecting and preserving genetic material (RNA) from a saliva sample which will be analyzed to detect molecular features associated with Oral Cancer and/or Throat Cancer. Like a powerful telescope charting the depths of the galaxy, the test embarks on a journey of RNA sequencing analysis, uncovering hundreds of human and microbial RNA features. These features serve as essential markers, guiding the way toward the early detection of oral and throat cancer.

It is an easy-to-use saliva-based detection test, with 95% specificity and sensitivity of 90% for both oral squamous cell carcinoma (the most common type of oral cavity cancer) and oropharyngeal squamous cell carcinoma (the most common type of throat cancer). This test has the potential to save many lives, and was designated Breakthrough Device for accelerated Review by FDA (link to publication in Oral Oncology)

Molecular markers that provide clues to health issues

Even if a biomarker associated with cancer is not detected, Viome's oral health test provides a unique set of scores focusing on activity in the oral microbiome and potentially associated with elements of the biomarker. For example, the biomarker contains a significant number of fungal elements such as Candida, Malassezia, and certain species of Saccharomyces. Unlike other tests that focus on composition, our RNA sequencing technology enables us to measure the molecular activity of the oral microbiome in your mouth to identify early biomarkers that may be associated with the cancer biomarker.

Fungal activity and genotoxic activity scores

The Fungal Activity score quantifies the abundance of cancer-associated fungi (Candida, Malassezia, and certain species of Saccharomyces). The ability of these fungi to chronically settle in the mouth depends on their properties, host defenses, and the composition of the oral microbiome. When one or more species are left unchecked, they may flourish, and oral health may be compromised. Our data show that an increased abundance of the fungi assessed in this score is associated with oral and throat cancer. A significant increase in these fungal species signals an opportunity to address a dysbiotic microbiome and strengthen impaired host defenses. In the figure above, we show the distributions of the Fungal Activity score in 173 individuals across distinct subpopulations: 120 cancer-free individuals and 39 cancerous individuals (20 individuals with oral cavity cancer (OCC) and 19 individuals with oropharyngeal cancer (OPC)). On average, our findings show individuals in the cancerous subpopulations (cases) have significantly higher Fungal Activity scores compared to cancer-free individuals (controls).

Within healthy oral microbiomes, Lactobacillus species are found in small quantities, while many Streptococcus species are detected in moderate quantities. When host defenses are impaired, these species accumulate in large quantities, and this increase is associated with microbial production of reactive oxygen species, formaldehyde, acetaldehyde, and acetoin. These compounds have genotoxic potential, and therefore, large quantities of these microbes may pose a health risk, which we capture as a Genotoxic Activity score.  In the figure above, we show the distributions of this score across the three subpopulations described earlier. Again, our findings show that individuals in the cancerous subpopulations have significantly higher Genotoxic Activity scores when compared to cancer-free individuals.

An easy-to-use protocol for dental professionals

You may be wondering, should I purchase this test? How often should I test? Where can I find it? The answers mainly depend on your medical history and individual circumstances. The test is available on our website; you can also ask your dentist or hygienist during your annual visits or dental cleanings. Here is a picture of how they will think about this test.

Protocol for Clinicians

1. People at risk of oral cancer or those presenting any lesion or symptom should be the ones requesting the test. The American Cancer Society (ACS) defines people at risk as those adults with a history of tobacco use, who drink alcohol, or who have been infected with HPV are at a high risk of developing oral cavity and throat cancers. Age is also a risk factor; the risk increases more rapidly after age 50 and peaks between ages 60 and 70. Other risk factors include family history or previous history of oral or throat cancer, excess body weight, and some genetic syndromes like fanconi anemia or dyskeratosis congenita.


2. Even if you don't belong to any of these groups, you may present any sign or symptom that doesn't go away. For example, canker sores, continuous bleeding or any lumps on your oral cavity or lips. If these symptoms don't disappear after two weeks, the ACS recommends seeing a doctor or dentist. 

The next step should be testing with Oral Health Pro™ with CancerDetect™. There are two possible scenarios. 

3. The test DETECTs markers for oral or throat cancer. Seek a definitive diagnosis by visiting a specialist, like an oncologist, ENT, or head and neck surgeon. They may perform a biopsy and determine a treatment plan. 

4. The test does NOT DETECT markers of oral and throat cancer. A clinician may decide to watch and wait for a period of time depending on the patient’s particular situation, in conjunction with the functional report from Oral Health Pro™ with CancerDetect™. In some cases, the clinician may diagnose a premalignant disorder (such as Dysplasia, Leukoplakia, Erythroplakia, Lichenoid lesions, Keratosis, etc.) and use an appropriate treatment regimen for the specific disorder, if available. All follow-up decisions are at the discretion of the clinician. 

According to the Oral Cancer Foundation, everyone should be screened for oral cancer once per year. A semi-annual follow-up is recommended when a lesion has been resected (i.e. dysplasia). In the context of leukoplakia, the International Agency for Research on Cancer (IARC) states that two to four weeks is a reasonable interval to observe the possible regression or disappearance of a white lesion after elimination of potential causative factors (i.e. frictional keratosis, habitual cheek or lip biting). 

In conclusion

Here are the takeaways from this article:

  • Detecting cancer in its early stages significantly increases the chances of successful treatment and survival.

  • The current standard of care is subjective and prone to examiner bias; its specificity and sensitivity is too low.

  • Oral Health Pro™ with CancerDetect™ specificity is 95%; oral cancer biomarker detection sensitivity is 90%; and throat cancer biomarker detection sensitivity is 90%.

  • This test enables early detection of biomarkers of oral and throat cancer and was designated Breakthrough Device for accelerated Review by FDA.

CancerDetect™ test is not an FDA-approved or cleared test.