TY - JOUR
T1 - Circulating HPV DNA as a marker for early detection of relapse in patients with cervical cancer
AU - Jeannot, Emmanuelle
AU - Latouche, Aurelien
AU - Bonneau, Claire
AU - Calmejane, Marie Ange
AU - Beaufort, Corine
AU - Ruigrok-Ritstier, Kirsten
AU - Bataillon, Guillaume
AU - Cherif, Linda Larbi
AU - Dupain, Celia
AU - Lecerf, Charlotte
AU - Popovic, Marina
AU - de la Rochefordiere, Anne
AU - Lecuru, Fabrice
AU - Fourchotte, Virginie
AU - Jordanova, Ekaterina S.
AU - von der Leyen, Heiko
AU - Tran-Perennou, Carine
AU - Legrier, Marie Emmanuelle
AU - Dureau, Sylvain
AU - Raizonville, Laurence
AU - Roufai, Diana Bello
AU - Le Tourneau, Christophe
AU - Bieche, Ivan
AU - Rouzier, Roman
AU - Berns, Els M.J.J.
AU - Kamal, Maud
AU - Scholl, Suzy
N1 - Funding Information:
M. Popovic reports grants from FP7 project Rational molecular Assessment and Innovative Drug Selection - RAIDs during the conduct of the study. H. von der Leyen reports grants from EU FP7 program: "PRIORITY" during the conduct of the study. C. Le Tourneau reports personal fees from MSD, BMS, Merck Serono, Nanobiotix, Rakuten, Seattle Genetics, AstraZeneca, Roche, GSK, and Celgene outside the submitted work. M. Kamal reports grants from European commission and Agence de la Recherche Contre le Cancer during the conduct of the study; personal fees from F. Hoffmann-La Roche Ltd outside the submitted work. No disclosures were reported by the other authors.
Publisher Copyright:
© 2021 The Authors; Published by the American Association for Cancer Research
PY - 2021/11/21
Y1 - 2021/11/21
N2 - Purpose: 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. Results: 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 ¼ 0.02) and para-aortic lymph node involvement (P ¼ 0.01). The level of HPV ctDNA was positively correlated with HPV copy number in the tumor (R ¼ 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. Conclusions: HPV ctDNA detection is a useful marker to predict relapse in cervical cancer.
AB - Purpose: 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. Results: 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 ¼ 0.02) and para-aortic lymph node involvement (P ¼ 0.01). The level of HPV ctDNA was positively correlated with HPV copy number in the tumor (R ¼ 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. Conclusions: HPV ctDNA detection is a useful marker to predict relapse in cervical cancer.
UR - http://www.scopus.com/inward/record.url?scp=85118980300&partnerID=8YFLogxK
U2 - 10.1158/1078-0432.CCR-21-0625
DO - 10.1158/1078-0432.CCR-21-0625
M3 - Article
C2 - 34210686
AN - SCOPUS:85118980300
VL - 27
SP - 5869
EP - 5877
JO - Clinical Cancer Research
JF - Clinical Cancer Research
SN - 1078-0432
IS - 21
ER -
