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

Abstract : 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. See related commentary by Wentzensen and Clarke, p. 5733
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Submitted on : Thursday, July 21, 2022 - 11:16:20 AM
Last modification on : Saturday, October 22, 2022 - 5:02:05 AM
Long-term archiving on: : Saturday, October 22, 2022 - 9:54:36 PM


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Emmanuelle Jeannot, Aurélien Latouche, Claire Bonneau, Marie-Ange Calméjane, Corine Beaufort, et al.. Circulating HPV DNA as a Marker for Early Detection of Relapse in Patients with Cervical Cancer. Clinical Cancer Research, 2021, 27 (21), pp.5869 - 5877. ⟨10.1158/1078-0432.ccr-21-0625⟩. ⟨hal-03733979⟩



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