Plasma ctHPVDNA Predicts Recurrence of HPV-Associated Oropharyngeal Cancer

Post-treatment surveillance via plasma circulating tumor human papillomavirus DNA (ctHPVDNA) monitoring can help detect the risk for recurrence in patients with HPV-associated oropharyngeal squamous cell carcinoma (OPSCC), according to findings from a prospective study by Bhishamjit S. Chera, MD, Department of Radiation Oncology, University of North Carolina School of Medicine, Chapel Hill, and colleagues (J Clin Oncol. 2020 Feb 4. Epub ahead of print).

Plasma ctHPVDNA is a sensitive and specific biomarker of HPV-associated OPSCC, explained Dr Chera et al explained, who sought to evaluate whether longitudinal monitoring of ctHPVDNA during post-therapy surveillance could accurately detect recurrence.

A total of 115 patients with nonmetastatic HPV-associated (p16-positive) OPSCC were enrolled in the biomarker clinical trial, yielding 1006 blood samples for analysis.

All patients were given curative-intent chemoradiotherapy and underwent a 3-month post-chemoradiotherapy PET/CT scan before being clinically evaluated every 2 to 4 months (years 1-2), then every 6 months (years 3-5).

The investigators carried out chest imaging every 6 months and collected blood specimens every 6 to 9 months for analysis of plasma ctHPVDNA using a multianalyte digital polymerase chain reaction assay.

The primary end point of the study was the estimated negative predictive value (NPV) and positive predictive value (PPV) of ctHPVDNA surveillance.

Overall, 15 (13%) patients had disease recurrence after a median follow-up of 23 months. There were 87 patients with undetectable ctHPVDNA at all time points post-treatment, none of whom had disease recurrence (NPV, 100%; 95% CI, 96%-100%).

Among 28 patients who had a positive ctHPVDNA during post-treatment surveillance, 15 had a biopsy-proven disease recurrence. In addition, of 16 patients who had 2 consecutively positive ctHPVDNA blood tests, 15 had biopsy-proven disease recurrence.

There were 2 consecutively positive ctHPVDNA blood tests yielding a PPV of 94% (95% CI, 70%-99%), and the median lead time between ctHPVDNA positivity and biopsy-proven recurrence was 3.9 months.

“Detection of ctHPVDNA in two consecutive plasma samples during post-treatment surveillance has high PPV and NPV for identifying disease recurrence in patients with HPV-associated oropharyngeal cancer and may facilitate earlier initiation of salvage therapy,” Dr Chera and colleagues concluded.—Hina M. Porcelli