Catherine Haring, MD & Paul Swiecicki, MD from University of Michigan Medical School discuss an ASCO 2020 abstract entitled HPV ctDNA analysis in unresectable recurrent/metastatic oropharyngeal cancer
The incidence of related human papillomavirus (HPV+) oropharyngeal cancer (OPC) is growing. While HPV + portents enhanced prognosis, survival remains low for patients with unresectable recurrent / metastatic (R / M) OPC. Extant data indicate that HPV ctDNA levels correlate in the primary setting with disease burden and treatment outcomes in patients with HPV + OPC, although there is little data in the metastatic setting. Objective: To establish a highly precise digital droplet (ddPCR) assay for ctDNA plasma HPV quantification and to determine whether ctDNA HPV predicts treatment response in HPV+ R / M OPC patients.
HPV + R / M OPC patients beginning systemic therapy were enrolled in a biorepository in which blood was obtained prior to each therapy period. The most popular high-risk HPV subtypes, 16 and 18, were produced with PCR probes. HPV ctDNA was removed from plasma, and ddPCR quantified. After 1 and 2 treatment cycles a percent improvement in HPV ctDNA was measured. After 2-3 cycles of patient, treatment response was evaluated according to the standard of care or study protocol. Analyzes of the ROC curves were conducted.
A precise ddPCR assay was designed to classify plasma HPV ctDNA in 10 patients who received 16 distinct courses of treatment. The percent change in HPV ctDNA after 2 cycles of treatment was predictive of radiographic response in the ROC curve study (AUC 0.82, p = 0.03). A 30 percent improvement in HPV ctDNA (Table) was defined as the optimal cutoff point for optimizing sensitivity and specificity. Changes in HPV ctDNA were also predictive for the radiographic response after 1 treatment cycle (AUC 0.82, p = 0.05).
Changes in HPV ctDNA in patients with R / M HPV + OPC can be predictive for the treatment response. In addition, earlier than traditional imaging, HPV ctDNA predicts response. Although confirmation is required, this assay shows promise to recognize weak respondents who may be targeted at clinical trials or alternative therapies early on.