Plasma HPV DNA as a Biomarker of Response in Patients with Locally Advanced Cervical Cancer Treated With Definitive Chemoradiation Therapy

PURPOSE: To evaluate the feasibility of detecting human papillomavirus E6 (HPVE6) gene mRNA in the peripheral blood of patients with locally advanced cervical cancer, and the relationship of the circulating HPV viral–specific mRNA with clinicopathologic factors and prognosis of locally advanced cervical cancer.PATIENTS AND METHODS: The presence of types 16 and 18 HPVE6 gene mRNA was determined by reverse transcription followed by nested polymerase chain reaction. Thirty-five patients with locally advanced cervical cancer who were positive for HPV type 16 or 18 DNA were included in the study. All patients received external-beam radiation therapy followed by intracavitary brachytherapy.RESULTS: Eighteen (51.4%) of 35 HPV DNA–positive cervical cancer patients had HPV-specific mRNA in their peripheral blood cells, compared with none of 17 HPV DNA–negative cervical cancer patients and none of 12 control volunteers. The presence of HPVE6 gene mRNA in peripheral blood was associated with bulky tumor volume (> 4 cm) and pelvic lymph node metastasis (tumor volume, P = .03; lymph node status, P = .03). After a median follow-up of 22 months, patients who were positive for peripheral-blood HPVE6 gene mRNA had a significantly higher risk of recurrence than those who were negative (10 of 18 v three of 17, P = .02; mean recurrent time, 20.7 months v 12.6 months, P = .02). There was also a statistically significant association of peripheral-blood HPVE6 gene mRNA positivity with distant metastasis (eight of 18 v one of 17; P = .01).CONCLUSION: Results of this study seem to suggest that the presence of HPVE6 gene mRNA in peripheral blood may provide an early marker that identifies patients who are at risk for metastasis.

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Circulating Human Papillomavirus DNA as a Biomarker of Response in Patients With Locally Advanced Cervical Cancer Treated With Definitive Chemoradiation

JCO Precision Oncology ◽

10.1200/po.18.00152 ◽

2018 ◽

pp. 1-8 ◽

Cited By ~ 3

Author(s):

Kathy Han ◽

Eric Leung ◽

Lisa Barbera ◽

Elizabeth Barnes ◽

Jennifer Croke ◽

...

Keyword(s):

Cervical Cancer ◽

Fdg Pet ◽

Residual Disease ◽

Locally Advanced ◽

Progression Free Survival ◽

Advanced Cervical Cancer ◽

Free Survival ◽

Hpv Dna ◽

Locally Advanced Cervical Cancer ◽

Undetectable Plasma

Purpose To determine whether plasma human papillomavirus (HPV) DNA predates clinical recurrence and compare its accuracy with 3-month fluorodeoxyglucose positron emission tomography (FDG-PET) in locally advanced cervical cancer. Methods This prospective multicenter study accrued 23 women with stage IB to IVA cervical cancer planned for definitive chemoradiation therapy (CRT). Plasma HPV DNA was measured serially by digital polymerase chain reaction, and FDG-PET was performed at 3 months post-CRT. Results Of the 19 women with HPV+ cervical cancer included in this analysis, 32% were stage IB, 58% IIB, and 10% IIIB/IVA. Median follow-up was 24 months (range, 18 to 30 months). All patients had detectable plasma HPV DNA before treatment. Six patients had detectable plasma HPV DNA at the end of CRT, and three of them developed metastases at 3 months. Of the 13 patients with undetectable plasma HPV DNA at end of CRT, to date, only one has developed recurrence. Six of those 13 patients had a positive 3-month FDG-PET with no definite residual disease on subsequent imaging or clinical examination to date, and four of these six had undetectable plasma HPV DNA at 3 months. Patients with undetectable plasma HPV DNA at end of CRT had significantly higher 18-month progression-free survival than those with detectable plasma HPV DNA (92% v 50%; P = .02). The area under the receiver operating characteristic curve (accuracy) of 3-month plasma HPV DNA and 3-month FDG-PET imaging for predicting recurrence at 18 months were 77% and 60%, respectively ( P = .008). Conclusion Detectable plasma HPV DNA at end of CRT predates the clinical diagnosis of metastases and is associated with inferior progression-free survival. Moreover, 3-month plasma HPV DNA level is more accurate than 3-month FDG-PET imaging in detecting residual disease. The clinical utility of plasma HPV DNA detection for guiding adjuvant/salvage therapy should be evaluated in future studies.

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