808P - Cell-free human papillomavirus (HPV) DNA is a sensitive biomarker for monitoring treatment response and for detecting relapse in locally advanced cervical cancer

Background

Human papillomavirus (HPV) is the cause of the majority of cervical cancer cases and has been suggested to be released as cell-free DNA (ctHPV DNA) into the circulation. We here analyse if ctHPV DNA could be detected in plasma from patients with locally advanced cervical cancer (LACC) and if ctHPV DNA could be used as a prognostic biomarker and/or to detect relapses earlier than by traditional methods.

Methods

74 patients with LACC were included, 66/74 had biopsies positive for one of 13 high-risk HPV-types using a bead-based assay. Droplet digital PCR (ddPCR) assays were developed for the HPV-types found. 418 longitudinal plasma samples from these 66 patients were then analysed using ddPCR assays for the corresponding HPV-type found in the biopsies. Results were correlated to tumor- and clinical characteristics.

Results

92.4% of pre-treatment plasmas were positive for ctHPV DNA. ctHPV DNA levels were correlated to tumor stage. Persistent ctHPV DNA in end-of-treatment or early follow-up (1-4 months after finished treatment) plasma were correlated with worse progression-free survival (log rank test, p < 0.001) compared to if ctHPV DNA was not found. The positive predictive value (PPV) of ctHPV-status at early follow-up for predicting disease progression was 87.5% and the negative predictive value (NPV) was 89.3%. ctHPV DNA was found in plasma before relapse was diagnosed on radiology (median 315 days, mean 280 days) in all patients (n=10) who experienced relapsed after complete clinical response to treatment.

Conclusions

ctHPV DNA in follow-up plasma is a promising prognostic biomarker in patients with locally advanced cervical cancer, useful for analysis of response to therapy and for early detection of relapses. Drs. E. Tham and K. Hellman have equally contributed to the study.

Clinical trial identification

Editorial acknowledgement

Legal entity responsible for the study

The authors.

Funding

Karolinska Institutet, Magnus Bergvalls Foundation.

Disclosure

All authors have declared no conflicts of interest.