Clinical validity of HPV circulating tumor DNA in advanced anal carcinoma: an ancillary study to the Epitopes-HPV02 trial

Purpose: Human papillomavirus (HPV) is found in 90% of squamous cell carcinomas of the anal canal (SCCA). We investigated the clinical validity of HPV circulating tumor DNA (ctDNA) detection in patients enrolled in the Epitopes-HPV02 trial which demonstrated the efficacy of docetaxel, cisplatin and 5FU as first-line chemotherapy (CT) in advanced SCCA. Experimental Design: According to the protocol, serum samples were collected before CT and on completion of CT. HPV16 ctDNA was quantified by ddPCR and correlated with prospectively registered patient characteristics and outcomes. A landmark was set at the time of CT completion for post-CT progression-free survival (PFS) analyses. Results: Among 57 patients with HPV16-related advanced SCCA, HPV ctDNA was detected in 91.1% (95% CI 81.1 to 96.2) of baseline samples. Baseline HPV ctDNA levels were not associated with any patient characteristics; baseline ctDNA level below the cut-off obtained by AUC (area under the curve) was associated with a longer PFS (HR=2.1, p=0.04). Among the 36 patients who completed 5 months of CT, residual HPV ctDNA was detected after CT in 38.9% of patients. Residual HPV ctDNA detected at CT completion was associated with shorter post-CT PFS (median PFS 3.4 months vs not reached; HR=5.5, p<0.001) and a reduction of one-year overall survival rate (OR=7.0, p=0.02). Conclusions: This prospective study in advanced SCCA demonstrated a significant prognostic impact of HPV ctDNA level before first-line CT and HPV ctDNA negativity after CT completion. With a limited cost and short turnaround, this assay is a promising tool to optimize the therapeutic management of SCCA.

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