A highly sensitive assay was able to detect a large percentage of high-risk human papillomavirus (HPV) subtypes in men with head and neck cancer, though still not to the degree of conventional tumor testing, a prospective single-center study found.
In the sample of over 200 men with oropharyngeal squamous cell carcinoma (OPSCC), the assay was able to detect HPV genotypes in 82.8% of patients using saliva compared with 93.0% with p16 immunostaining of tumor tissue, Christine H. Chung, MD, of Moffitt Cancer Center in Tampa, Florida, and colleagues reported.
“Our study showed that oral gargle samples can be used to detect the majority of the clinically relevant HPV genotypes found in men with OPSCC,” they wrote in JAMA Otolaryngology–Head & Neck Surgery. “The interpretation of HPV detected in oral gargle samples should be assessed with caution in cancer risk assessment of a cancer-free population given that sensitive assays can concomitantly detect low-risk genotypes.”
Overall, the saliva test was able to confirm HPV infection status in all but one patient, with 17.2% testing negative and 82.8% testing positive. Multiple HPV subtypes were detected in 9.9% of the men. Seventeen low-risk HPV genotypes were detected with the oral gargle sample, though in all cases patients had coinfection with a high-risk HPV, the authors noted.
For tumor specimen analysis by p16 immunostaining, 85.8% were p16 positive, 9.3% were p16 negative, and 4.9% were not evaluable due to an insufficient amount of available tissue. Multiple HPV subtypes were detected in 7.6% of patients with this method. There were three low-risk HPV subtypes detected in the tissue specimens, but again, each patient had coinfection with a high-risk genotype.
The authors noted that therapeutic HPV vaccines are currently being assessed in clinical trials for patients with HPV-related cancers, both alone or combined with other treatment methods, and that “based on our study, HPV genotyping could be easily obtained using HPV DNA from readily accessible oral gargle samples.”
But in a commentary that accompanied the study, Ricardo Ramirez, MD, and Jose Zevallos, MD, MPH, both of Washington University School of Medicine in St. Louis, Missouri, sounded a note of caution. “Although this may be true, the data from their study showed that HPV DNA from oral gargle samples is an imperfect surrogate,” they wrote. “The detection of HPV 16 between saliva samples and tumor specimens was discordant in over a quarter of patients.”
The saliva test detected HPV 16 in 128 of 203 patients (63.1%) compared with 143 of 172 (83.1%) with p16 immunostaining, with an agreement of 73.7% between the two tests. For HPV 18, the tests detected the genotype in eight samples each, for a between-test agreement of 94.2%.
Ramirez and Zevallos continued to say that it would be difficult to imagine that trials of therapeutic vaccines would rely on anything other than tumor tissue sampling for “critical” treatment decisions.
“As long as patients are undergoing tissue biopsies or surgical resection, tumor tissue would be available for genotyping,” they said. “Why then would saliva ever be used for this indication?”
Ultimately, they wrote, the study “does not bring us any closer to defining practical, clinically relevant applications for this technology.”
A study presented last year at the American Society for Radiation Oncology (ASTRO) meeting found that an HPV DNA blood test could potentially rule out relapse in patients treated for their head and neck cancers, but the practicality of such a test was again called into question.
For the current study, Chung’s group screened adult men (median age 61) with newly diagnosed OPSCC who were treated at the head and neck and radiation oncology clinics at Moffitt from 2014 to 2017. Patients with stage I-IV cancer were eligible, and nearly half had stage I disease (49.0%). Most patients were white (93.1%) and a majority had a history of smoking (55.9%). The in vitro reverse hybridization assay RHA Kit HPV SPF10-LiPA25 was used for HPV DNA assessment in saliva. Tumor specimen analysis used p16 immunohistochemical staining.
Aside from those limitations previously mentioned (only men, single institution), the authors noted several other important limitations to their findings: there were a low number of HPV-negative cases in the cohort, Moffitt is a specialized cancer center so the sample may have included more harder-to-treat cases than would be typical, and there was a short follow-up period (12.7 months).
Chung reported no disclosures. One study co-author is an employee of GlaxoSmithKline and another serves on a Merck advisory board.
Ramirez and Zevallos reported no conflicts of interest.