Blood Test Predicts Recurrence of HPV-Driven Oropharyngeal Cancer After Treatment

Get Permission

A blood-basedliquid biopsy may accurately predict recurrence of human papillomavirus (HPV)-driven oropharyngeal squamous cell carcinoma following treatment, according to data presented at the 2022 Multidisciplinary Head and Neck Cancers Symposium.1

Results of the large, multi-institutional study suggest that the biomarker test of tumor tissue–modified viral HPV DNA may also detect recurrent disease earlier than imaging or other standard methods of posttreatment surveillance. Among the 80 patients (approximately 7% of the total sample) who tested positive for the biomarker during surveillance, 95% were confirmed through imaging, biopsy, and/or endoscopy to have recurrent HPV-positive disease.

Glenn J. Hanna, MD

Glenn J. Hanna, MD

“This is the first study to demonstrate broad clinical utility and validity of a circulating tumor biomarker in HPV-driven disease as part of routine, posttreatment surveillance in clinical practice,” said presenting author Glenn J. Hanna, MD, Director of the Center for Salivary and Rare Head and Neck Cancers at the Dana-Farber Cancer Institute. “Given these data, updated surveillance guidelines should incorporate this biomarker or at least consider it.” He added: “I would argue that these results are also generalizable to the broader head and neck community.”

As Dr. Hanna reported, approximately 20% to 25% of patients with HPV-driven cancers will relapse with potentially distant disease or locoregional recurrence. These recurrences tend to occur late in the natural history of disease and can include atypical patterns of spread at distant sites. Although current posttreatment surveillance practices rely on physical exams and imaging, Dr. Hanna noted wide variability in how physicians monitor patients in imaging follow-up. The detection of tumor-specific DNA has shown potential as a powerful yet minimally invasive diagnostic tool for several cancers, he said.

Naveris has developed an ultrasensitive digital droplet polymerase chain reaction test to quantify circulating tumor tissue–modified viral HPV DNA for five high-risk HPV subtypes known to cause cancer: HPV-16, -18, -31, -33, and -35. These biomarkers are shed during tumor degradation, said Dr. Hanna.


The primary aim of the study was to determine the positive predictive value of circulating cell-free tumor tissue–modified viral HPV DNA to identify patients with recurrent disease during surveillance as part of routine clinical practice. Dr. Hanna and colleagues reported on 1,076 patients with primary HPV-driven oropharyngeal cancers without distant disease at least 3 months after completion of standard therapy of any modality across 118 U.S. sites.

All biomarker test results were subsequently compared with provider-reported clinical disease status, which was established based on endoscopy, exam, or imaging, with biopsy confirmation when appropriate.

Key Findings

Among the 1,076 patients included in the analysis, 996 results were negative, and 80 (approximately 7%) were positive for the test. Of these 80 patients, 21 tested positive for the biomarker with known clinically active disease as indicated by their provider, and 59 patients had clinically indeterminate or no evidence of disease (NED) status. Among those who tested positive for the biomarker with NED status, 55 patients later developed biopsy-proven recurrent metastatic disease. The four remaining patients are still being followed.

The presence of the biomarker was the first indicator of recurrence for 72% of the patients whose cancer returned, said Dr. -Hanna, and nearly half of recurrences (48%) occurred in patients more than 1 year after completion of therapy. The investigators have not yet established a numeric cutoff of HPV DNA fragments needed to determine the likelihood of clinically detectable disease. However, Dr. Hanna emphasized that a newly positive test result obtained during surveillance should prompt an exam and reimaging to identify recurrence early.

“Most patients had no other evidence of disease or clinically indeterminate disease status at the time of their first positive biomarker test,” he said. “Incorporating a test for [tumor tissue–modified viral] HPV DNA into routine posttreatment follow-up can enable physicians to detect recurrent cancers earlier and allow us to start recommended interventions more quickly to improve outcomes.” 

DISCLOSURE: This study was supported by Naveris. Dr. Hanna has received research support from ACCRF, Actuate Therapeutics, ASCO Conquer Cancer Foundation, Bicara, Bristol Myers Squibb, Elevar, Exicure, Gateway for Cancer Research, Genentech, GlaxoSmithKline, Kartos Therapeutics, Kite Pharma, KSQ Therapeutics, Kura Oncology, NantKwest/Altor Bioscience, Regeneron, Repertoire, Sanofi Genzyme, Secura Bio, and V Foundation; and has served as a consultant or advisor and received honoraria from Bicara, Bio-Rad, Boxer Capital, Bristol Myers Squibb, Exicure, General Catalyst, Kura Oncology, Maverick Therapeutics, Merck, Naveris, Prelude, Rain Therapeutics, Regeneron, Remix, Sanofi Genzyme, and SIRPant.


1. Berger B*, Hanna GJ*, Posner M, et al: Detection of occult recurrence using circulating HPV tumor DNA among patients treated for HPV-driven oropharyngeal squamous cell carcinoma. 2022 Multidisciplinary Head and Neck Cancers Symposium. Abstract 3. Presented February 24, 2022. *First two authors contributed equally.

Related Articles

Expert Point of View: Quynh-Thu Le, MD, FACR, FASTRO

According to Quynh-Thu Le, MD, FACR, FASTRO, Professor and Chair of Radiation Oncology at Stanford, these results suggest that monitoring circulating human papillomavirus (HPV) DNA may lead to the detection of relapse prior to imaging. In an interview with The ASCO Post, Dr. Le also noted that...