A novel saliva test has been shown to detect HPV-associated oropharyngeal squamous cell carcinoma (OPSSC) with high accuracy in a small study.
If the results are validated in subsequent studies, the test has the potential to be used as a screening tool in the general population, say the investigators.
In the small study, the NavDx (Naveris) detected tumor-tissue-modified virus DNA (TTMV) in 43 of 46 plasma samples and in 44 of 46 saliva samples. One plasma sample failed quality control measures, one of each sample type had undetectable TTMV, and one of each type was indeterminate.
The results were presented recently at at the American Society of Clinical Oncology (ASCO) 2021 annual meeting by Charlotte Kuperwasser, PhD, professor of developmental, molecular, and chemical biology at Tufts University School of Medicine, Medford, Massachusetts. She is also employed by Naveris, the manufacturer of the test.
“Head and neck cancer is rapidly growing and has surpassed cervical cancer as far as its prevalence,” she said. “It is predicted to keep growing, and by 2035, it is predicted to be the third highest cancer in white males. So if there is no screening paradigm put into place, it’s going to be very problematic, much the way cervical cancer was before screening programs.”
Screening guidelines recommend Pap smears for all women, she noted. “We see this type of test to be somewhat analogous to the Pap smear, except it would be for all males over the age of 18.”
She emphasized that head and neck cancer isn’t limited to men. “It’s just enriched in men, and this might become screening that is recommended for everyone over 18,” she said.
Promising, but More Work Needed
“This test looks very promising, but there is a lot more work to be done,” commented Marshall Posner, MD, director of head and neck medical oncology at the Tisch Cancer Institute at Mount Sinai, New York City.
He told Medscape Medical News that he thinks it’s a great idea and noted that the National Institutes of Health is conducting trials related to screening using antibody tests. “But that’s more invasive than the saliva test,” he said.
“But the difficulty here is that about 3% of men and about 1% of women will have a positive test for HPV-16 in their saliva. We don’t know what that means — if its an incidental infection, if its transient, or if it reflects the development of cancer,” Posner told Medscape Medical News.
A small proportion of those individuals may have cancer, but “it will require you to also demonstrate that they don’t have cancer, or that the percentage of positives that turn out to be false positives is very low, since it’s a screening test,” he continued.
“Its not surprising that its positive in patients who are positive, but the real test is if it is positive in patients who aren’t, and that requires a lot of work,” he said. “But false positives — if they are far in excess of true positives — leads to excessive testing and anxiety in patients. So the true positive rate has to be determined.”
Overall, this is a great preliminary study, he added. “We are anxious to have a test like this, something that can be easily done in a dentist’s office, and inexpensively.”
Details of the Test
The NavDx test detects circulating tumor HPV DNA, which has emerged as a reliable biomarker for surveillance of patients with HPV-positive OPSSC. “Tumor-tissue modified HPV DNA distinguishes between standard infectious HPV and HPV that is associated with cancer,” said Kuperwasser. “This analyte can cover multiple strains of HPV, but we were just looking at five strains — the most common ones.”
This technology has been previously used in plasma tests, but this study used a saliva test.
In a cohort of 46 patients with HPV-positive OPSCC, pretreatment frozen plasma and saliva samples were paired.
All samples were assessed for DNA integrity and TTMV using the NavDx assay to measure TTMV for HPV-16. In addition, HPV-18, -31, -33, and -35 were measured for negative or indeterminate samples that were previously tested for HPV-16.
Of 41 evaluable patients with paired samples, the majority were male (n = 38, 93%); 36 (88%) had stage I-II, five (12%) had stage III-IV, and 25 (61%) had a history of smoking (median, 37.5 pack-years).
The researchers found that in comparison with plasma, TTMV was significantly enriched in saliva (P < .0001); the median copy number waws 14,139 copies/mL for saliva and 774.7 copies/mL for plasma. There was a significant positive correlation between plasma and saliva TTMV levels (r = 0.344; P = .028).
No differences were observed for overall disease stage in either specimen type, but there was a trend in both sample types toward higher TTMV in patients with a history of smoking. When grouped by pack-years, plasma TTMV approached significance (P = .058), but high saliva TTMV was significantly associated with >10 pack-year history (P = .011).
“As with all clinical studies, we want to increase the sample size and get a larger base,” she said. “There are about 20 studies currently ongoing in this area — not just with the saliva test. So that’s what our next steps are, to provide further validation and then ideally roll this out as a clinical test.”
The study was funded by Naveris. Kuperwasser is an employee of Naveris. Posner has disclosed no relevant financial relationships.
American Society of Clinical Oncology (ASCO) 2021: Abstract 6063. Presented June 5, 2021