HPV ctDNA detection of high-risk HPV types during chemoradiotherapy for locally advanced cervical cancer

Cabel, Luc; Bonneau, Claire; Bernard‐Tessier, Alice; Héquet, Delphine; Tran-Perennou, Carine; Bataillon, Guillaume; Rouzier, Roman; Féron, Jean Guillaume; Fourchotte, Virginie; Brun, J; Benoît, C.; Rodrigues, Manuel; Scher, N.; Minsat, Mathieu; Legrier, Marie-Emmanuelle; Bièche, Ivan; Proudhon, Charlotte; Sastre-Garau, X.; Bidard, F-C; Jeannot, Emmanuelle

doi:10.1016/j.esmoop.2021.100154

Cited by 45 publications

(44 citation statements)

References 36 publications

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“…Screening with Pap and/or HPV tests remains the best strategy for cervical cancer screening. Although the value of HPV ctDNA in diagnosing cervical premalignant lesions is limited, we believe that this biomarker might nonetheless have the potential to be applied in disease monitoring following the diagnosis of cancer, as shown elsewhere ( 32 , 35 , 36 ). However, the retrospective design of our study did not include the collection of samples at different time points and, therefore, does not allow the evaluation of this biomarker in disease monitoring.…”

Section: Discussionmentioning

confidence: 68%

Detection of Circulating HPV16 DNA as a Biomarker for Cervical Cancer by a Bead-Based HPV Genotyping Assay

et al. 2022

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Section: Discussionmentioning

confidence: 68%

Detection of Circulating HPV16 DNA as a Biomarker for Cervical Cancer by a Bead-Based HPV Genotyping Assay

et al. 2022

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“…Using HPV-seq, 2 of these 3 samples had no detectable HPV fragments, suggesting that they may have been false positive dPCR results. Single positive dPCR droplets within these samples highlighted their low HPV DNA levels or the possibility of false positives ( 57 ). Conversely, 5 (23%) of the dPCR-negative surveillance samples harbored residual HPV ctDNA fragments detectable by HPV-seq.…”

Section: Discussionmentioning

confidence: 99%

HPV Sequencing Facilitates Ultrasensitive Detection of HPV Circulating Tumor DNA

Leung

Han

Zou

et al. 2021

Clinical Cancer Research

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◥Purpose: Human papillomavirus (HPV) DNA offers a convenient circulating tumor DNA (ctDNA) marker for HPV-associated malignancies, but current methods, such as digital PCR (dPCR), provide insufficient accuracy for clinical applications in patients with low disease burden. We asked whether a next-generation sequencing approach, HPV sequencing (HPV-seq), could provide quantitative and qualitative assessment of HPV ctDNA in low disease burden settings.Experimental Design: We conducted preclinical technical validation studies on HPV-seq and applied it retrospectively to a prospective multicenter cohort of patients with locally advanced cervix cancer (NCT02388698) and a cohort of patients with oropharynx cancer. HPV-seq results were compared with dPCR. The primary outcome was progression-free survival (PFS) according to end-of-treatment HPV ctDNA detectability.Results: HPV-seq achieved reproducible detection of HPV DNA at levels less than 0.6 copies in cell line data. HPV-seq and dPCR results for patients were highly correlated (R 2 ¼ 0.95, P ¼ 1.9 Â 10 -29 ) with HPV-seq detecting ctDNA at levels down to 0.03 copies/mL plasma in dPCR-negative posttreatment samples. Detectable HPV ctDNA at end-of-treatment was associated with inferior PFS with 100% sensitivity and 67% specificity for recurrence. Accurate HPV genotyping was successful from 100% of pretreatment samples. HPV ctDNA fragment sizes were consistently shorter than non-cancer-derived cell-free DNA (cfDNA) fragments, and stereotyped cfDNA fragmentomic patterns were observed across HPV genomes.Conclusions: HPV-seq is a quantitative method for ctDNA detection that outperforms dPCR and reveals qualitative information about ctDNA. Our findings in this proof-of-principle study could have implications for treatment monitoring of disease burden in HPV-related cancers. Future prospective studies are needed to confirm that patients with undetectable HPV ctDNA following chemoradiotherapy have exceptionally high cure rates.

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“…In a recent study, Cabel et al showed that HPV-ctDNA can be detected before chemo-radiotherapy in 69% patients diagnosed with locally advanced cervical cancer [ 32 ]. HPV-ctDNA level was correlated significantly with HPV copy number in the tumour, with lowest levels found among HPV18-positive patients.…”

Section: Hpv-ctdna Detection In Blood Of Cin and Cervical Cancer Pati...mentioning

confidence: 99%

Clinical applications and utility of cell-free DNA-based liquid biopsy analyses in cervical cancer and its precursor lesions

et al. 2022

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Human papilloma virus (HPV) is an infectious carcinogenic agent. Nearly all cervical cancers are positive for one of the high-risk HPV subtypes. Although the introduction of the HPV vaccines in many countries have shown tremendous positive effects on the incidence of both cervical intraepithelial lesions (CIN) and invasive cancer, the large majority of females worldwide are still not vaccinated. Patients with diagnosed high-grade CIN need a lifelong close monitoring of possible relapse or development of invasive cancer. Different blood-based liquid biopsy approaches have shown great promise as an easily obtainable minimally invasive tool for early detection and monitoring of disease. Among the different liquid biopsy approaches the clinical relevance of cell-free DNA (cfDNA) in cervical cancer has been best investigated. In cervical cancer, the DNA fragments can be of both, human as well as viral origin. Thus, the mutation and methylation status of genes related to carcinogenesis as well as the HPV status can be analysed in plasma from cervical cancer patients. This review describes recent advances in different cfDNA approaches for early detection and monitoring of cervical cancer and its precursor lesions.

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HPV ctDNA detection of high-risk HPV types during chemoradiotherapy for locally advanced cervical cancer

Cited by 45 publications

References 36 publications

Detection of Circulating HPV16 DNA as a Biomarker for Cervical Cancer by a Bead-Based HPV Genotyping Assay

Detection of Circulating HPV16 DNA as a Biomarker for Cervical Cancer by a Bead-Based HPV Genotyping Assay

HPV Sequencing Facilitates Ultrasensitive Detection of HPV Circulating Tumor DNA

Clinical applications and utility of cell-free DNA-based liquid biopsy analyses in cervical cancer and its precursor lesions

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