Monitoring circulating cell-free HPV DNA in metastatic or recurrent cervical cancer: clinical significance and treatment implications.

Background: Monitoring circulating HPV cell-free DNA (cfDNA) offers a minimally invasive method for surveillance in HPV-associated cancers, particularly cervical cancer. However, the role of dynamic HPV cfDNA monitoring in guiding clinical treatment decisions for recurrent or metastatic cervical cancer remains underexplored. Methods: In this prospective pilot observational study, levels of HPV cfDNA in serum samples from 28 patients with recurrent or metastatic HPV-positive cervical cancer were measured via digital droplet polymerase chain reaction. Results for HPV cfDNA levels were matched to clinical outcomes and to serum levels of squamous cell carcinoma antigen (SCC-Ag) to assess the clinical potential of HPV cfDNA as a tumor marker. Results: HPV cfDNA was detected in all 28 patients. Notably, median baseline HPV cfDNA levels varied according to the metastatic pattern observed in individual patients (p=0.019). All participants exhibited changes in HPV cfDNA levels over a median monitoring period of 2 months (range 0.3-16.9 months) prior to evaluations for treatment response or disease progression. Among 26 patients initially diagnosed with squamous cell cervical cancer, the positivity rate was 100% for HPV cfDNA and 69.2% for SCC-Ag (p=0.004, 95% confidence interval (CI), 0-0.391). Among 20 patients longitudinally monitored for squamous cell cervical cancer, the concordance with changes in disease status was 90% for HPV cfDNA and 50% for SCC-Ag (p=0.014, 95% CI, 0.022-0.621). Conclusions: Our study demonstrates that HPV cfDNA is a promising tumor marker for monitoring of recurrent or metastatic HPV-positive cervical cancer. Funding: This work was supported by the Key R&D Program of Zhejiang (2022C04001), the Zhejiang Province Medicine and Health Science and Technology Program (2020KY454), the Zhejiang Science and Technology Department Public Welfare Project (LGF22H160075).