Circulating TTMV HPV Tumor DNA May Detect Recurrence of HPV-Driven Oropharyngeal Cancers


Research presented at the 2022 Multidisciplinary Head and Neck Cancers Symposium highlighted the potential to detect oropharyngeal cancer recurrence using circulating tumor tissue modified viral–human papillomavirus DNA.

A blood test was able to accurately predict disease recurrence using circulating tumor tissue modified viral (TTMV)–human papillomavirus (HPV) DNA among patients treated for HPV-driven oropharyngeal squamous cell carcinoma, according to research presented at the 2022 Multidisciplinary Head and Neck Cancers Symposium.

The test produced a high positive predictive value (PPV) of 95% for patients who received treatment for HPV-driven oropharyngeal cancer and may detect recurrence earlier than imaging or other standard methods of recurrence monitoring.

“While detection of tumor-specific DNA circulating in a patient's bloodstream has shown potential as a powerful yet minimally invasive diagnostic tool for several cancers, this is the first study to demonstrate broad clinical utility and validity of the biomarker in HPV-driven oropharyngeal cancer,” Glenn J. Hanna, MD, director of the Center for Salivary and Rare Head and Neck Cancers at Dana-Farber Cancer Institute, and assistant professor of medicine, Harvard Medical School, Boston, Massachusetts, said in his presentation of the data.

The primary aim of the multi-institutional study is to determine the PPV of circulating TTMV-HPV DNA to determine recurrent HPV-driven oropharyngeal cancer during the surveillance period for patients.

The population of patients consisted of those treated for HPV-driven oropharyngeal cancer without distant disease and were at least 3 months after completion of standard definitive therapy. HPV status was provided by the clinician and patients also needed at least 1 TTMV-HPV DNA result found during surveillance.

The investigators compared all positive results from the study to clinical disease status reported by the provider for confirmation.

A total of 1076 test results were included in the research across 118 clinical sites. Investigators reported a median of 2 cases per site. The median age for the population was 63 years, and most patients were male (88%), had positive p16 status (99%), and had at least 1 TTMV-HPV DNA test result (78%). Twenty-two percent of the population had more than 1 test result. The median follow up was 9 months (range, 6-22).

A total of 996 tests (92.6%) were negative, with the remaining 80 (7.4%) being positive. When evaluating those who were positive, 26% had known or confirmed disease and 74% had clinically indeterminate/no evidence of disease (NED) status.

HPV16 disease was eventually identified in 55 (93%) of 59 patients with a positive TTMV-HPV DNA test result. Of the 4 remaining patients, 2 have clinically suspicious lesions and 2 remain clinical NED. All 4 patients have TTMV-HPV DNA values between 16 and 79 frg/mL. Moreover, 48% of patients with positive results and 46% with indeterminate/NED status were tested over 12 months after treatment completion.

The values between patients with active disease and those with indeterminate/NED status were relatively similar and not statistically significant, although a trend exists towards higher values in patients with active disease (P = .27).

Hanna noted that establishing a cutoff value for determining clinical detectable disease is not feasible at this moment, although he argues that newly positive test results found during surveillance should prompt further examination 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. Incorporating a test for TTMV-HPV DNA into routine post-treatment follow-up can enable physicians to detect recurrent cancers earlier and allow us to start recommended interventions more quickly to improve outcomes,” Hanna explained.


Berger BM, Hanna GJ, Genden E, et al. Detection of occult recurrence using circulating HPV tumor DNA among patients treated for HPV-driven oropharyngeal squamous cell carcinoma. Presented at: 2022 Multidisciplinary Head and Neck Symposium; February 24-26, 2022; Phoenix, AZ. Abstract 3. Accessed February 24, 2022.

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