Clinical Validity of HPV Circulating Tumor DNA in Advanced Anal Carcinoma: An Ancillary Study to the Epitopes-HPV02 Trial

Abstract

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 that demonstrated the efficacy of docetaxel, cisplatin, and 5-FU as first-line chemotherapy in advanced SCCA.Experimental Design: According to the protocol, serum samples were collected before chemotherapy and on completion of chemotherapy. HPV16 ctDNA was quantified by droplet digital PCR (ddPCR) and correlated with prospectively registered patient characteristics and outcomes. A landmark was set at the time of chemotherapy completion for postchemotherapy progression-free survival (PFS) analyses.Results: Among 57 patients with HPV16-related advanced SCCA, HPV ctDNA was detected in 91.1% (95% confidence interval, 81.1-96.2) of baseline samples. Baseline HPV ctDNA levels were not associated with any patient characteristics; baseline ctDNA level below the cutoff obtained by AUC (area under the curve) was associated with a longer PFS (HR ¼ 2.1; P ¼ 0.04). Among the 36 patients who completed 5 months of chemotherapy, residual HPV ctDNA was detected after chemotherapy in 38.9% of patients. Residual HPV ctDNA detected at chemotherapy completion was associated with shorter postchemotherapy PFS (median PFS 3.4 months vs. not reached; HR ¼ 5.5; P < 0.001) and a reduction of 1-year overall survival rate (OR ¼ 7.0; P ¼ 0.02).Conclusions: This prospective study in advanced SCCA demonstrated a significant prognostic impact of HPV ctDNA level before first-line chemotherapy and HPV ctDNA negativity after chemotherapy completion. With a limited cost and short turnaround, this assay is a promising tool to optimize the therapeutic management of SCCA.See related commentary by Morris, p. 2030

Circulating Tumor DNA Predicts the Response and Prognosis in Patients With Early Breast Cancer Receiving Neoadjuvant Chemotherapy

“…Circulating tumor DNAs (ctDNAs) are mutated gene fragments that are exclusively shed by cancer cells into blood, 7 which can be detected by digital polymerase chain reaction (dPCR) 8 or sequencing. In patients with metastatic breast cancer, ctDNA by dPCR was reported to outperform classic tumor biomarker (CA15-3/CEA) and circulating tumor cells in monitoring disease progression 9 as well as identifying resistant clonal evolution during therapy.…”

Atezolizumab plus modified docetaxel-cisplatin-5-fluorouracil (mDCF) regimen versus mDCF in patients with metastatic or unresectable locally advanced recurrent anal squamous cell carcinoma: a randomized, non-comparative phase II SCARCE GERCOR trial

“…In the Epitopes-HPV02 trial, HPV ctDNA was detected at baseline in 91% of patients. After treatment with DCF, residual HPV ctDNA was present in 39% of patients and was highly predictive of disease progression (HR = 5.5; p < 0.001) and OS (HR = 7.0; p = 0.02) [11], validating the interest of HPV ctDNA in routine clinical practice in advanced SCCA patients [12].…”

“…10 Centre Antoine-Lacassagne, Nice, France. 11 Hôpital Européen Georges-Pompidou, Paris, France. 12 Centre Hospitalier Universitaire de Bordeaux, Bordeaux, France.…”

A comparative study of extracellular vesicle-associated and cell-free DNA and RNA for HPV detection in oropharyngeal squamous cell carcinoma

“…The use of cf-DNA for the detection of circulating HPV-DNA has been investigated in a number of other studies and cancer types, with reported detection sensitivities that are similar to our findings (91%). In different HPV-induced malignancies, detection sensitivities of cf-DNA analyses have been reported to range from 86%-100% in anal SCC (n = 19 and n = 57), cervical SCC (n = 33), and head and neck SCC (n = 93, including oral cavity, oropharynx, hypopharynx and larynx subsites) [22][23][24][25] . For HPV-OPCSCC specifically, three studies have demonstrated detection sensitivities of 95.6% (n = 97), 89% (n = 103), and 88.5% (n = 114) [26][27][28] .…”