biostudies-literatureJeannot EFondation ARC pour la Recherche sur le CancerEuropean Commission5869-5877https://www.ebi.ac.uk/biostudies/studies/S-EPMC9401545biostudies-literatureUnknown27(21)<h4>Purpose</h4>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.<h4>Experimental design</h4>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 <i>E7</i> gene as a marker for residual disease compared to HPV integration site and <i>PIK3CA</i> mutations. Finally, the prognostic impact of circulating HPV <i>E7</i> gene was assessed with its prediction value of relapse.<h4>Results</h4>HPV <i>E7</i> gene was the most sensitive tumor marker, superior to both HPV integration sites and <i>PIK3CA</i> 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 (<i>P</i> = 0.02) and para-aortic lymph node involvement (<i>P</i> = 0.01). The level of HPV ctDNA was positively correlated with HPV copy number in the tumor (<i>R</i> = 0.39, <i>P</i> < 0.001). Complete clearance of HPV ctDNA by the end of treatment was significantly associated with a longer PFS (<i>P</i> < 0.0001). Patients with persistent HPV ctDNA in serum relapsed with a median time of 10 months (range, 2-15) from HPV ctDNA detection.<h4>Conclusions</h4>HPV ctDNA detection is a useful marker to predict relapse in cervical cancer.<i>See related commentary by Wentzensen and Clarke, p. 5733</i>.Clinical cancer research : an official journal of the American Association for Cancer ResearchCirculating HPV DNA as a Marker for Early Detection of Relapse in Patients with Cervical Cancer.PMC9401545304810de la Rochefordiere ADureau SPopovic MBonneau CRaizonville LLarbi Cherif LFourchotte VBieche ILe Tourneau CBerns EMJJDupain CLatouche ABataillon GBeaufort CJeannot ETran-Perennou CKamal MRouzier RLecuru FLecerf CCalmejane MARuigrok-Ritstier KBello Roufai DLegrier MEScholl Svon der Leyen HJordanova ESfalseCirculating HPV DNA as a Marker for Early Detection of Relapse in Patients with Cervical Cancer.<h4>Purpose</h4>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.<h4>Experimental design</h4>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 <i>E7</i> gene as a marker for residual disease compared to HPV integration site and <i>PIK3CA</i> mutations. Finally, the prognostic impact of circulating HPV <i>E7</i> gene was assessed with its prediction value of relapse.<h4>Results</h4>HPV <i>E7</i> gene was the most sensitive tumor marker, superior to both HPV integration sites and <i>PIK3CA</i> 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 (<i>P</i> = 0.02) and para-aortic lymph node involvement (<i>P</i> = 0.01). The level of HPV ctDNA was positively correlated with HPV copy number in the tumor (<i>R</i> = 0.39, <i>P</i> < 0.001). Complete clearance of HPV ctDNA by the end of treatment was significantly associated with a longer PFS (<i>P</i> < 0.0001). Patients with persistent HPV ctDNA in serum relapsed with a median time of 10 months (range, 2-15) from HPV ctDNA detection.<h4>Conclusions</h4>HPV ctDNA detection is a useful marker to predict relapse in cervical cancer.<i>See related commentary by Wentzensen and Clarke, p. 5733</i>.2021-01-01T00:00:00Z2021 Nov2026-06-24T03:19:02.766Z2025-04-04T13:08:56.247ZS-EPMC94015453421068610.1158/1078-0432.CCR-21-0625