Human papillomavirus (HPV) is a small, non-enveloped deoxyribonucleic acid (DNA) virus that infects skin or mucosal cells. HPV genomic DNA in plasma and saliva has been widely studied. More recently, circulating tumor human papillomavirus DNA (ctHPVDNA) has emerged as a reliable biomarker for surveillance in HPV+ oropharyngeal squamous cell carcinoma (OPSCC).

ASCOOropharyngeal cancer, which can develop at the base of the tongue, tonsils, and the middle part of the throat, used to be closely associated with smoking and heavy drinking. However, Today, oropharyngeal cancer is primarily caused by human papillomavirus (HPV) infection, the most common sexually transmitted virus and infection in the United States. More than one in five U.S. adults are infected with a high-risk strain of HPV that can potentially develop into cancer.[1][2]

Over the last two decades, cases of HPV-positive oropharyngeal cancer have been increasing at an exponential rate among men in the United States. [3][4]. And, according to the American Cancer Society, approximately 54,000 cases of oropharyngeal and oral cavity cancer are diagnosed in the nation this year, and more than 10,000 patients will die of the disease. [5]

Oropharyngeal cancers usually are not identified early because they grow slowly in locations that are not easy to see. By the time the cancers are recognized they frequently have spread to the lymph nodes and are difficult to treat. Early detection, however, enables highly effective treatment.

Clinically validated test
Researchers at Washington University School of Medicine in St. Louis, MO, used a clinically validated ddPCR-based assay (NavDx™; Naveris Inc, Natick, MA) to analyze saliva for sequences of the human papillomavirus (HPV) genome that are specific for HPV DNA released from malignant tumors.

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The new test has been shown to detect HPV-associated head and neck cancer with high accuracy, a first-of-its-kind study result. The study results show that the test successfully distinguishes tumor-tissue modified-virus from non-cancerous sources of HPV DNA and precisely measures the number of tumor-tissue modified viral HPV (TTMV-HPV) DNA strands present in a saliva sample.

Significant improvement
The study results point to the potential for a significant improvement in early detection of the most common type of head and neck cancer, HPV-associated oropharyngeal squamous cell carcinoma.

“[Our] patient-friendly saliva test has the potential to radically advance early detection of HPV-positive head and neck cancer, which has been growing rapidly among men in the United States. Early detection of these cancers would make a dramatic difference in patient outcomes,” said Piyush Gupta, Ph.D., Chief Executive Officer of Naveris.

Naveris’ lead product, NavDx®, is a liquid biopsy that uses proprietary technology to enable ultrasensitive surveillance of HPV-related cancer. NavDx® identifies tumor-tissue-modified HPV DNA (TTMV) which is far more prevalent (50-1,000 times more concentrated) in blood than circulating tumor DNA. NavDx® has been clinically validated through a 3-year longitudinal study, demonstrating 100% negative predictive value and 94% positive predictive value in detecting recurrence of HPV-related head and neck cancer. Image Courtesy: © 2021 Naveris, Inc. Used with permission.

The study quantified participants’ tumor-tissue modified viral HPV DNA in saliva samples and compared it to the levels found in their blood by utilizing Naveris’ NavDx® test. The results showed that TTMV-HPV DNA was commonly found in the saliva of HPV-associated head and neck cancer patients (44/46 cases), and at 18 times higher levels in the saliva samples than in the blood samples. One sample had undetectable TTMV-HPV and one was indeterminate for HPV DNA.

Researchers from Washington University presented an abstract of the study during the annual meeting of the American Society of Clinical Oncology (ASCO), held June 4 – 8, 2021. [6]

Although the researchers believe that more research is needed to elucidate the effects of smoking on TTMV levels, they di agree that this study is the first study to demonstrate successful quantification of tumor-tissue modified HPV DNA in saliva. They observed that, compared to plasma, pre-treatment saliva samples demonstrated significantly higher levels of TTMV, which distinguishes ctHPVDNA from other sources of HPV.

“The results of our study highlight the potential of accurately analyzing saliva to improve the early detection of HPV-associated oropharyngeal squamous cell carcinoma. If validated in larger studies, this test could lead to earlier diagnosis and treatment,” said the study’s principal investigator Jose P. Zevallos, MD, chief of the division of Head and Neck Surgery in the Department of Otolaryngology at Washington University School of Medicine.

Naveris’ new saliva test, a liquid biopsy test that detects HPV-associated head and neck cancer earlier than is possible with imaging, is based upon the proprietary technology employed by the NavDx® blood test that is in use at centers of excellence treating HPV-associated oropharyngeal cancer across the United States.


[1] Prevalence of HPV in Adults Aged 18–69: United States, 2011–2014. National Center for Health Statistics Online. Last accessed on June 2, 2021.
[2] Viens LJ, Henley SJ, Watson M, et al. Human papillomavirus-associated cancers—United States, 2008–2012. MMWR Morb Mortal Wkly Rep 65(26):661–6. 2016.
[3] Johnson D.E., Burtness B., Leemans C.R. et al. Head and neck squamous cell carcinoma. Nat Rev Dis Primers 6, 92 (2020).
[4] Gillison ML, Chaturvedi AK, Anderson WF, Fakhry C. Epidemiology of Human Papillomavirus-Positive Head and Neck Squamous Cell Carcinoma. J Clin Oncol. 2015 Oct 10;33(29):3235-42. doi: 10.1200/JCO.2015.61.6995. Epub 2015 Sep 8. PMID: 26351338; PMCID: PMC4979086.
[5] Key Statistics for Oral Cavity and Oropharyngeal Cancers. American Cancer Society. Online. Last accessed on June 2, 2021
[6] Gerndt SP, Ramirez RJ, Wahle BM, Kuperwasser C, Gunning A, Chaudhuri AA, Zevallos JP. Evaluating a clinically validated circulating tumor HPV DNA assay in saliva as a proximal biomarker in HPV+ oropharyngeal squamous cell carcinoma. Abstract: 6063; Presented at: American Society of Clinical Oncology (ASCO), held June 4 – 8, 2021. J Clin Oncol 39, 2021 (suppl 15; abstr 6063).

Featured image: Blood test. Photo courtesy: © 2018 – 2021 Fotolia/Adobe. used with permission.

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