Circulating HPV DNA as a marker for early detection of relapse in patients with cervical cancer

Emmanuelle Jeannot*, Aurelien Latouche, Claire Bonneau, Marie Ange Calmejane, Corine Beaufort, Kirsten Ruigrok-Ritstier, Guillaume Bataillon, Linda Larbi Cherif, Celia Dupain, Charlotte Lecerf, Marina Popovic, Anne de la Rochefordiere, Fabrice Lecuru, Virginie Fourchotte, Ekaterina S. Jordanova, Heiko von der Leyen, Carine Tran-Perennou, Marie Emmanuelle Legrier, Sylvain Dureau, Laurence RaizonvilleDiana Bello Roufai, Christophe Le Tourneau, Ivan Bieche, Roman Rouzier, Els M.J.J. Berns, Maud Kamal, Suzy Scholl

*Corresponding author for this work

Research output: Contribution to journalArticleAcademicpeer-review

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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.

Original languageEnglish
Pages (from-to)5869-5877
Number of pages9
JournalClinical Cancer Research
Volume27
Issue number21
DOIs
Publication statusPublished - 21 Nov 2021

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