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Background  In clinical oncology, only a few applications have been developed using HPV as a personalized tumor marker, a lack most probably related to the limited information obtained by the classical Polymerase Chain Reaction (PCR) approach. To overcome this limitation, we have recently developed the capture-based Next-Generation Sequencing (NGS) “CaptHPV” assay, designed to provide an extensive and comprehensive molecular characterization of HPV DNA sequences associated with neoplasias, ie the sequence of the viral genome (245 genotypes), its physical state, viral load, integration site and genomic alterations at integration locus. These data correspond to highly specific tumor markers that can be used to improve diagnosis and patient’s follow-up.    Case presentation  We report here a case that is a straightforward and practical illustration of the power of the CaptHPV method. A patient developed successively a carcinoma of the anal canal and of the tongue. The two tumors were squamous cell carcinoma, found associated with HPV16 using PCR. In order to document a possible metastasis to the tongue from the anal cancer, we performed CaptHPV analysis on the two tumors. The analysis of the anal carcinoma found 55 viral/human hybrid reads allowing the identification of the HPV16 DNA integration in the 4q25 chromosomal band locus with a 178,808 bp deletion in the cell genome. Molecular analysis of the tongue tumor disclosed 6110 reads of HPV16, with a viral pattern strictly identical to that of the anal tumor. A total of 131 hybrid reads between HPV16 and the cell genome were found, corresponding exactly to the same locus of integration of viral DNA at the 4q25 site. The 178,808 bp genomic deletion was also found in the lingual tumor. The exact identity of HPV insertional signatures in the two tumors, demonstrates unambiguously that the tongue tumor derived from the anal cancer whereas neither histological immunophenotyping nor classical viral analysis using PCR could allow a definitive diagnosis.    Conclusion  Our observation indicates that the establishment of a detailed cartography of HPV DNA sequences in a tumor specimen provides crucial information for the design of specific biomarkers that can be used for diagnostic, prognostic or predictive purposes.

bmc cancer

HPV insertional pattern as a personalized tumor marker for the optimized tumor diagnosis and follow-up of patients with HPV-associated carcinomas: a case report