Surveillance of ctDNA in HPV-Positive Head and Neck Cancers May Predict Recurrence

Bhisham Chera, MD

Bhisham Chera, MD

The detection of circulating tumor DNA (ctDNA) in human papillomavirus (HPV) with an experimental blood test has been associated with high positive predictive value (PPV) and negative predictive value (NPV) for identifying disease recurrence in HPV-positive oropharyngeal cancer, according to a press release from the University of North Carolina (UNC) Lineberger Comprehensive Cancer Center.¹

“The major utility of this test is it’s going to improve our ability to monitor patients after they complete treatment,” said Bhisham Chera, MD, associate professor in the UNC School of Medicine Department of Radiation Oncology. “Currently, our methods to assess whether the cancer has recurred are invasive, expensive and not always accurate.”

In a prospective biomarker clinical trial published in theJournalof Clinical Oncology, investigators obtained 1006 blood samples for their analysis, 999 of which were evaluable for plasma circulating tumor human papillomavirus DNA (ctHPVDNA). The goal was to determine if surveillance of ctHPVDNA can facilitate earlier detection of recurrence compared with normal clinical follow-up.²

Patients were followed for a median of 23.7 months (range, 6.1-54.7 months), and out of 115 patients, 13% developed disease recurrence (n = 15). Of these recurrences, 1 was local only, 1 was regional only, 10 were distant only, 1 was local and distant, and the remaining 2 were regional and distant. Following treatment, 87 patients had undetectable ctHPVDNA, and none developed recurrence (95% CI, 96%-100%). The development of a positive ctHPVDNA occurred in 28 patients during post-treatment surveillance.

The median time to abnormal ctHPVDNA signal was 12.3 months after complete chemoradiotherapy (CRT; range, 2.6-29.1 months). Sixteen patients had 2 consecutive positive ctHPVDNA results, and 15 of those patients developed biopsy-proven recurrence. The 2 ctHPVDNA blood tests that were consecutively positive had a PPV of 54% (95% CI, 0.339-0.725). A 3.9-month median lead time between ctHPVDNA positivity and biopsy-proven recurrence was observed (range, 0.37-12.9). the actuarial 2-year response-free survival (RFS) rate was 30% in patients who had an abnormal blood test during post-treatment surveillance compared with 100% among the remaining participants (P<.001).&nbsp;

In the study, CRT included cetuximab 250 mg/m², carboplatin AUC 1.5, and paclitaxel 45 mg/m². Patients received intravenous chemotherapy during intensity-modulated radiotherapy treatment, which was given weekly. There were 6 doses of chemotherapy in total.

The secondary end points of the study were local control rate, regional control rate, local-regional control rate, distant metastasis-free survival, OS, head and neck quality of life assessments, and speech and swallowing function.

Patients aged 18 years and older were eligible to enroll if they had T0-3, N0 to N2c, M0 squamous head and neck cancer, HPV and p16 positivity, radiologically confirmed hematogenous metastasis within 12 weeks before treatment, and ECOG performance status of 0 to 1, and adequate bone marrow, renal, and hepatic function. Individuals with prior history of radiation to the head and neck, head and neck cancer, those with unresectable disease, severe comorbidity, or known human immunodeficiency virus, or those taking disease-modifying rheumatoid drugs were excluded from the study.

Based on this research the investigators reported a 99% accuracy in confirming whether or not patients remained recurrence-free with their screening method, compared with other methods. For patients who had 2 HPV-positive blood tests, the accuracy was said to be 94%.¹

&ldquo;With this new technology, it offers a noninvasive way to accurately monitor patients for cancer recurrence,&rdquo; Chera said. &ldquo;In the long run, blood-based surveillance could be more effective, and possibly help us to detect cancer sooner.&rdquo;

References

1. Study finds blood test accurately tracks HPV-linked head and neck cancer [news release]. Chapel Hill, North Carolina: University of North Carolina Lineberger Comprehensive Cancer Center; February 4, 2020. https://bit.ly/2tzlw7x. Accessed February 6, 2020.
2. Chera BS, Kumar S, Shen C, et al. Plasma circulating tumor HPV DNA for the surveillance of cancer recurrence in HPV-associated oropharyngeal cancer.J Clin Oncol. doi: 10.1200/JCO.19.01598.