title: Human papillomavirus mutational insertion: specific marker of circulating tumor DNA in cervical cancer patients.
abstract: BACKGROUND
  In most cases of cervical cancers, HPV DNA is integrated into the genome of carcinoma cells. This mutational insertion constitutes a highly specific molecular marker of tumor DNA for every patient. Circulating tumor DNA (ctDNA) is an emerging marker of tumor dynamics which detection requires specific molecular motif. To determine whether the sequence of the cell-viral junction could be used in clinical practice as a specific marker of ctDNA, we analyzed a series of cervical cancer patient serums.
  
  
  RESULTS
  Serum specimens of 16 patients diagnosed with HPV16/18-associated cervical cancer, and for which the viral integration locus had been previously localized, were analyzed. Sequential serum specimens, taken at different times during the course of the disease, were also available for two of these cases. ctDNA was found in 11 out of 13 patients with tumor size greater than 20 mm at diagnosis, and analysis of sequential serum specimens showed that ctDNA concentration in patients serum was related to tumor dynamics.
  
  
  CONCLUSIONS
  We report that HPV mutational insertion constitutes a highly specific molecular marker of ctDNA in HPV-associated tumor patients. Using this original approach, ctDNA was detected in most cervical cancer patients over stage I and ctDNA concentration was found to reflect tumor burden. In addition to its potential prognostic and predictive value, HPV mutation insertion is likely to constitute a new molecular surrogate of minimal residual disease and of subclinical relapse in HPV-associated tumor. This is of major importance in the perspective of specific anti-HPV therapy.
authors.affiliation: Department of Radiation Oncology, Institut Curie, Hospital, Paris, France.
authors.forename: Maura
authors.initials: M
authors.lastname: Campitelli
authors.forename: Emmanuelle
authors.initials: E
authors.lastname: Jeannot
authors.forename: Martine
authors.initials: M
authors.lastname: Peter
authors.forename: Emmanuelle
authors.initials: E
authors.lastname: Lappartient
authors.forename: Stéphanie
authors.initials: S
authors.lastname: Saada
authors.forename: Anne
authors.initials: A
authors.lastname: de la Rochefordière
authors.forename: Virginie
authors.initials: V
authors.lastname: Fourchotte
authors.forename: Séverine
authors.initials: S
authors.lastname: Alran
authors.forename: Peter
authors.initials: P
authors.lastname: Petrow
authors.forename: Paul
authors.initials: P
authors.lastname: Cottu
authors.forename: Jean-Yves
authors.initials: JY
authors.lastname: Pierga
authors.forename: Olivier
authors.initials: O
authors.lastname: Lantz
authors.forename: Jérôme
authors.initials: J
authors.lastname: Couturier
authors.forename: Xavier
authors.initials: X
authors.lastname: Sastre-Garau
mesh_terms: D004279:DNA, Viral / Q000097:blood / Q000235:genetics*; D005260:Female; D006801:Humans; D027383:Papillomaviridae / Q000235:genetics*; D030361:Papillomavirus Infections / Q000097:blood / Q000235:genetics* / Q000821:virology*; D002583:Uterine Cervical Neoplasms / Q000097:blood / Q000235:genetics* / Q000821:virology*
chemical_list: D004279:DNA, Viral