Circulating HPV DNA as a Marker for Early Detection of Relapse in Patients with Cervical Cancer

Nom de la revue
Clinical Cancer Research
Emmanuelle Jeannot, Aurélien Latouche, Claire Bonneau, Marie-Ange Calméjane, Corine Beaufort, Kirsten Ruigrok-Ritstier, Guillaume Bataillon, Linda Larbi Chérif, Célia Dupain, Charlotte Lecerf, Marina Popovic, Anne de la Rochefordière, Fabrice Lecuru, Virginie Fourchotte, Ekaterina S. Jordanova, Heiko von der Leyen, Carine Tran-Perennou, Marie-Emmanuelle Legrier, Sylvain Dureau, Laurence Raizonville, Diana Bello Roufai, Christophe Le Tourneau, Ivan Bièche, Roman Rouzier, Els M.J.J. Berns, Maud Kamal, Suzy Scholl


Almost all cervical cancers are caused by human papillomavirus (HPV) and patients with advanced stage are at high risk for relapse. Circulating HPV DNA (HPV ctDNA) may serve as a residual tumor marker at the end of chemoradiation or to predict relapse during the follow-up period.

Experimental Design:
We analyzed serum samples from 94 HPV16- or HPV18-related CCs from the BioRAIDs prospective cohort. Samples were collected before and after treatment and during an 18-month follow-up period. Using digital droplet PCR (ddPCR), we assessed the relevance of circulating HPV E7 gene as a marker for residual disease compared to HPV integration site and PIK3CA mutations. Finally, the prognostic impact of circulating HPV E7 gene was assessed with its prediction value of relapse.

HPV E7 gene was the most sensitive tumor marker, superior to both HPV integration sites and PIK3CA mutations in serum. Circulating HPV DNA (HPV ctDNA) was detected in 63% (59/94) of patients, before treatment. HPV ctDNA detection in serum sample was associated with high FIGO stage (P = 0.02) and para-aortic lymph node involvement (P = 0.01). The level of HPV ctDNA was positively correlated with HPV copy number in the tumor (R = 0.39, P < 0.001). Complete clearance of HPV ctDNA by the end of treatment was significantly associated with a longer PFS (P < 0.0001). Patients with persistent HPV ctDNA in serum relapsed with a median time of 10 months (range, 2–15) from HPV ctDNA detection.

HPV ctDNA detection is a useful marker to predict relapse in cervical cancer.
See related commentary by Wentzensen and Clarke, p. 5733