Oropharyngeal cancer, which can develop at the base of the tongue, tonsils, and the middle part of the throat, is primarily caused by human papillomavirus (HPV) infection, the most common sexually transmitted virus and infection in the United States.1 Over the past 2 decades, cases of HPV-positive oropharyngeal squamous-cell carcinoma (OPSCC) have been increasing at an alarming rate among men in the United States.2,3 According to the American Cancer Society, approximately 54,000 cases of oropharyngeal and oral cavity cancer will be diagnosed in the United States in 2021, and more than 10,000 individuals will die from the disease.4 OPSCC is often diagnosed at an advanced stage, resulting in increased mortality and morbidity.
During the American Society of Clinical Oncology 2021 virtual annual meeting, researchers from the Washington University School of Medicine, St. Louis, MO, discussed results from a study using a clinically validated saliva test to accurately detect HPV-associated head and neck cancer. The assay used in the study (NavDx) analyzes saliva for sequences of the HPV genome that are specific for HPV DNA released from malignant tumors. It distinguishes tumor-tissue modified viral HPV (TTMV-HPV) from noncancerous sources of HPV DNA and measures the number of TTMV-HPV DNA strands present in a saliva sample.
Among 46 patients identified with HPV-positive OPSCC, TTMV-HPV DNA in saliva samples was detected in 44 patients. The levels of TTMV-HPV in saliva were 18 times higher than in blood samples from the same patients, reported the study’s principal investigator, Jose P. Zevallos, MD, MPH, FACS, Chief, Head & Neck Oncologic Surgery, Washington University School of Medicine, St. Louis, MO, during a poster presentation at the meeting.
“The results of our study highlight the potential of accurately analyzing saliva to improve the early detection of HPV-associated OPSCC. If validated in larger studies, this test could lead to earlier diagnosis and treatment,” Dr Zevallos said.
Study Details
In the study, 46 patients with HPV-positive OPSCC with paired pretreatment plasma and saliva samples were identified from a banked biospecimen repository. Using the NavDx assay, TTMV was detectable for HPV-16 from 44 evaluable saliva samples and 43 evaluable plasma samples. There were 41 evaluable paired saliva and plasma samples, and HPV-16 status was positive in all. Of the 41 patients, 8 (19.5%) were current smokers and 18 (43.9%) were former smokers, with a median pack-years of 37.5. Of 41 evaluable patients, 38 (92.7%) were men, 36 (87.8%) had stage I-II cancer, and 5 (12.2%) had stage III-IV cancer.
HPV-18, -31, -33, and -35 were measured in the negative or indeterminate samples that were previously tested for HPV-16.
Compared with plasma, TTMV was significantly enriched in saliva (P <.0001), with median copy numbers of 14,139 copies/mL for saliva and 774.7 copies/mL for plasma. Plasma and saliva TTMV levels showed a significant positive correlation (r = .344; P = .028).
There was no difference in overall disease stage between sample types. In both sample types, there was a trend toward higher TTMV in patients with a history of smoking. When grouped by pack-years, plasma TTMV approached significance (P = .058) whereas high saliva TTMV was significantly associated with >10 pack-year history (P = .011).
References
- McQuillan G, Kruszon-Moran D, Markowitz LE, et al. Prevalence of HPV in adults aged 18-69: United States, 2011–2014. NCHS Data Brief. 2017;(280):1-8.
- Johnson DE, Burtness B, Leemans CR, et al. Head and neck squamous cell carcinoma. Nat Rev Dis Primers. 2020;6:92.
- Gillison ML, Chaturvedi AK, Anderson WF, Fakhry C. Epidemiology of human papillomavirus-positive head and neck squamous cell carcinoma. J Clin Oncol. 2015;33:3235-3242.
- American Cancer Society. Key statistics for oral cavity and oropharyngeal cancers. Updated March 23, 2021. www.cancer.org/cancer/oral-cavity-and-oropharyngeal-cancer/about/key-statistics.html. Accessed June 23, 2021.
