TTMV-HPV DNA Biomarker Predicts Recurrence of Oropharynx Cancer

A large, multi-institutional study demonstrates that a blood test to detect circulating tumor DNA can accurately predict recurrence of HPV-driven oropharyngeal cancer following treatment. Results also indicate that the biomarker test may detect recurrent disease earlier than imaging or other standard methods of post-treatment surveillance, allowing physicians to personalize treatment more quickly for patients whose cancer returns.

Despite generally favorable outcomes, up to 20% of patients with human papillomavirus (HPV)-driven oropharyngeal squamous cell carcinoma (OPSCC) will experience recurrence within five years of curative-intent therapy; approximately half of recurrences present with distant disease.

Currently, recurrence is detected primarily through imaging and physical exams, but there is wide variability in the use and frequency of these surveillance methods. There are indications that a biomarker test may detect recurrent disease earlier than imaging or other standard methods of post-treatment surveillance, allowing physicians to personalize treatment more quickly for patients whose cancer returns.

Oncologists at the Dana-Farber Cancer Institute (Boston, MA, USA) and their colleagues demonstrated in large, multi-institutional study that a blood test to detect circulating tumor DNA can accurately predict recurrence of HPV-driven oropharyngeal cancer following treatment. In a retrospective clinical case series included 1,076 consecutive patients across 124 USA sites who were > 3 months post therapy for HPV-driven OPSCC and who had one or more circulating cell-free tumor tissue modified HPV DNA (TTMV-HPV DNA) test (NavDx, Naveris Laboratories, Natick, MA, USA) between 2/6/2020 and 6/11/2021. TTMV-HPV DNA for HPV subtypes 16, 18, 31, 33, and 35 was analyzed with ultrasensitive digital droplet PCR. Test results were compared to the results of subsequent clinical evidence of OPSCC, using nasopharyngolaryngoscopy and/or radiologic (CT, MRI, or PET-CT) evaluations and/or tissue biopsy.

The investigators reported that circulating TTMV-HPV DNA was positive in 80/1,076 patients (7.4%, TTMV range: 7 - 123,148 fragments (frgs)/mL) tested after definitive therapy. At the first positive surveillance test, 21/80 (26.2%) patients had known recurrence while 59/80 (73.8%) had no other evidence of disease (NED) or indeterminate disease status. Clinical follow-up was available on all patients. Among the 59 positive tests without clinically known recurrence, 55 (93.2%, TTMV range: 8 - 23,296 frgs/mL) had confirmed recurrence identified with 52 HPV 16-driven, and 1 and 2 with HPV 31 or 35-driven OPSCC respectively. Two patients have clinically suspicious lesions with negative biopsies, one with a base of tongue ulcer and one with a pulmonary nodule (TTMV range: 9-67 frgs/mL) and two are currently clinically NED (TTMV range: 16-79 frgs/mL) with scheduled repeat TTMV and radiologic surveillance.

Glenn J. Hanna, MD, an Assistant Professor of Medicine and lead author of the study, said, “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.”

The authors concluded that their findings demonstrated the clinical validity and utility of circulating TTMV-HPV DNA testing in daily clinical practice as an effective surveillance tool for identifying patients with active and occult recurrent HPV-driven OPSCC. To date the positive predictive value for recurrence or persistence of HPV-driven OPSCC is 95.0% (76/80), which may increase with additional follow-up of cases remaining in active surveillance. Notably, the presence of circulating TTMV-HPV DNA was the first indication of recurrence for 72.4% of cases. These data will help inform clinical and guideline-endorsed strategies concerning the inclusion of circulating TTMV HPV-DNA as a biomarker of molecularly detectable HPV-driven OPSCC in the setting of recurrence surveillance. The study was presented at the on February 24, 2022, at the 2022 Multidisciplinary Head and Neck Cancers Symposium held in Phoenix, AZ, USA.

Related Links:
Dana-Farber Cancer Institute 
Naveris Laboratories