Tak Hong Cheung1, So Fan Yim1, Mei Yun Yu2, Michael J Worley3, Stephen J Fiascone3, Rossa W K Chiu4, Keith W K Lo1, Nelson S S Siu1, Martin C S Wong5, Apple C M Yeung6, Raymond R Y Wong1, Zi Gui Chen6, Kevin M Elias3, Tony K H Chung1, Ross S Berkowitz7, Yick Fu Wong8, Paul K S Chan9. 1. Department of Obstetrics & Gynaecology, The Chinese University of Hong Kong, Hong Kong. 2. Department of Anatomical and Cellular Pathology, The Chinese University of Hong Kong, Hong Kong. 3. Division of Gynecologic Oncology, Department of Obstetrics, Gynecology and Reproductive Biology, Brigham and Women's Hospital, Dana Farber Cancer Institute, Harvard Medical School, Boston, MA, USA. 4. Department of Chemical Pathology, The Chinese University of Hong Kong, Hong Kong. 5. Division of Family Medicine and Primary Care, The Chinese University of Hong Kong, Hong Kong. 6. Department of Microbiology, The Chinese University of Hong Kong, Hong Kong. 7. Division of Gynecologic Oncology, Department of Obstetrics, Gynecology and Reproductive Biology, Brigham and Women's Hospital, Dana Farber Cancer Institute, Harvard Medical School, Boston, MA, USA. Electronic address: Ross_Berkowitz@dfci.harvard.edu. 8. Department of Obstetrics & Gynaecology, The Chinese University of Hong Kong, Hong Kong; Division of Gynecologic Oncology, Department of Obstetrics, Gynecology and Reproductive Biology, Brigham and Women's Hospital, Dana Farber Cancer Institute, Harvard Medical School, Boston, MA, USA. Electronic address: yickfuwong@cuhk.edu.hk. 9. Department of Microbiology, The Chinese University of Hong Kong, Hong Kong. Electronic address: paulkschan@cuhk.edu.hk.
Abstract
BACKGROUND: A blood test to serve as a tumor marker for cervical cancer would be useful to clinicians to guide treatment and provide an early signal for recurrence. The development of droplet digital PCR has enabled the detection of HPV DNA in patient serum, providing a potential marker for cervical cancer. OBJECTIVES: To report on a blood-based test for HPV-specific E7 and L1 genes, which may serve as a tumor marker to guide treatment and detect early recurrence in cervical cancer. STUDY DESIGN: Pre-treatment plasma samples were investigated from 138 Hong Kong Chinese women with primary invasive squamous cell carcinoma and adenocarcinoma of the cervix with tumor samples expressing HPV16 or HPV18. Two genes specific to the human papillomavirus, E7 and L1, were measured in cell free DNA (cfDNA) extracted from plasma using droplet digital PCR. Analysis of detectable E7 and L1 levels was performed to investigate the potential of liquid biopsy of E7 and L1 as a clinically useful molecular biomarker. RESULTS: The majority of patients had HPV16 (71.7%), squamous cell carcinoma (78.3%) and stage IB-II disease (82.6%). HPV E7 and L1 sequences were detected in plasma cfDNA from 61.6% (85/138) of patients. Patients with high viral load (defined as ≥20 E7 or L1 copies per 20 μL reaction volume) had increased risk of recurrence and death at 5 years on univariate analysis but not multivariate analysis. CONCLUSIONS: HPV DNA can be quantitatively detected with the use of cfDNA. This has the potential to provide a clinically useful tumor marker for patients with cervical cancer that can aid in post-treatment surveillance and estimating the risk of disease relapse.
BACKGROUND: A blood test to serve as a tumor marker for cervical cancer would be useful to clinicians to guide treatment and provide an early signal for recurrence. The development of droplet digital PCR has enabled the detection of HPV DNA in patient serum, providing a potential marker for cervical cancer. OBJECTIVES: To report on a blood-based test for HPV-specific E7 and L1 genes, which may serve as a tumor marker to guide treatment and detect early recurrence in cervical cancer. STUDY DESIGN: Pre-treatment plasma samples were investigated from 138 Hong Kong Chinese women with primary invasive squamous cell carcinoma and adenocarcinoma of the cervix with tumor samples expressing HPV16 or HPV18. Two genes specific to the human papillomavirus, E7 and L1, were measured in cell free DNA (cfDNA) extracted from plasma using droplet digital PCR. Analysis of detectable E7 and L1 levels was performed to investigate the potential of liquid biopsy of E7 and L1 as a clinically useful molecular biomarker. RESULTS: The majority of patients had HPV16 (71.7%), squamous cell carcinoma (78.3%) and stage IB-II disease (82.6%). HPV E7 and L1 sequences were detected in plasma cfDNA from 61.6% (85/138) of patients. Patients with high viral load (defined as ≥20 E7 or L1 copies per 20 μL reaction volume) had increased risk of recurrence and death at 5 years on univariate analysis but not multivariate analysis. CONCLUSIONS: HPV DNA can be quantitatively detected with the use of cfDNA. This has the potential to provide a clinically useful tumor marker for patients with cervical cancer that can aid in post-treatment surveillance and estimating the risk of disease relapse.
Authors: L Cabel; C Bonneau; A Bernard-Tessier; D Héquet; C Tran-Perennou; G Bataillon; R Rouzier; J-G Féron; V Fourchotte; J-F Le Brun; C Benoît; M Rodrigues; N Scher; M Minsat; M-E Legrier; I Bièche; C Proudhon; X Sastre-Garau; F-C Bidard; E Jeannot Journal: ESMO Open Date: 2021-05-19