A NGS-based blood test for the diagnosis of invasive HPV-associated carcinomas with extensive viral genomic characterization

Xavier Sastre-Garau (1, 2) , Mamadou Diop (3) , Fernando Martin (4) , Gilles Dolivet (5, 6) , Frédéric Marchal (6, 5) , Claire Charra-Brunaud (5) , Didier Peiffert (5) , Léa Leufflen (5) , Birama Dembélé (7) , Jessica Demange (5) , Priscillia Tosti (5) , Jacques Thomas (5) , Agnès Leroux (5, 6) , Jean-Louis Merlin (6) , Halimatou Diop-Ndiaye (7) , Jean-Marc Costa (4) , Julia Salleron (5) , Alexandre Harlé (6, 5)

1 Département de Biologie des Tumeurs
2 CHI Créteil
3 Hôpital Aristide-Le-Dantec
4 Laboratoire CERBA [Saint Ouen l'Aumône]
5 UNICANCER/ICL - Institut de Cancérologie de Lorraine - Alexis Vautrin [Nancy]
6 CRAN - Centre de Recherche en Automatique de Nancy
7 CHU Aristide Le Dantec

Purpose: Use of circulating tumor DNA (ctDNA) for diagnosis is limited regarding the low number of target molecules in early-stage tumors. Human papillomavirus (HPV)–associated carcinomas represent a privileged model using circulating viral DNA (ctHPV DNA) as a tumor marker. However, the plurality of HPV genotypes represents a challenge. The next-generation sequencing (NGS)-based CaptHPV approach is able to characterize any HPV DNA sequence. To assess the ability of this method to establish the diagnosis of HPV-associated cancer via a blood sample, we analyzed ctHPV DNA in HPV-positive or HPV-negative carcinomas. Experimental Design: Patients (135) from France and Senegal with carcinoma developed in the uterine cervix (74), oropharynx (25), oral cavity (19), anus (12), and vulva (5) were prospectively registered. Matched tumor tissue and blood samples (10 mL) were taken before treatment and independently analyzed using the CaptHPV method. Results: HPV prevalence in tumors was 60.0% (81/135; 15 different genotypes). Viral analysis of plasmas compared with tumors was available for 134 patients. In the group of 80 patients with HPV-positive tumors, 77 were also positive in plasma (sensitivity 95.0%); in the group of 54 patients with HPV-negative tumors, one was positive in plasma (specificity 98.1%). In most cases, the complete HPV pattern observed in tumors could be established from the analysis of ctHPV DNA. Conclusions: In patients with carcinoma associated with any HPV genotype, a complete viral genome characterization can be obtained via the analysis of a standard blood sample. This should favor the development of noninvasive diagnostic tests providing the identification of personalized tumor markers. See related commentary by Rostami et al., p. 5158

Domaines: Médecine humaine et pathologie

Xavier Sastre-Garau, Mamadou Diop, Fernando Martin, Gilles Dolivet, Frédéric Marchal, et al.. A NGS-based blood test for the diagnosis of invasive HPV-associated carcinomas with extensive viral genomic characterization. Clinical Cancer Research, 2021, 27 (19), pp.5307-5316. ⟨10.1158/1078-0432.ccr-21-0293⟩. ⟨hal-04543989⟩