Introduction/Background Almost all cervical cancers (CC) are caused by human papillomavirus (HPV) and patients with advanced stage are at high risk for relapse. Studies has shown that most patients with HPV-associated tumors have detectable circulating HPV DNA (HPV ctDNA) in the blood at time of diagnosis, before treatment. Development in sensitive technologies led to the use of cell-free DNA for monitoring patients. In the present study, we investigated if HPV ctDNA may serve as a residual tumor marker at the end of chemo-radiation or to predict relapse during the follow-up period.

Methodology We analyzed serum samples from 94 HPV16- or HPV18-related CCs from the BioRAIDs (NCT02428842) prospective cohort. Samples were collected before and after treatment and during an 18-month follow-up period. Using digital droplet PCR (ddPCR), we assessed the relevance of circulating HPV E7 gene as a marker for residual disease. Finally, the prognostic impact of circulating HPV E7 gene was assessed with its prediction value of relapse.

Results Circulating HPV DNA (HPV ctDNA) was detected in 63% (59/94) of patients, before treatment. HPV ctDNA detection in serum sample was associated with high FIGO stage (p=0.02) and para-aortic lymph node involvement (p=0.01). The level of HPV ctDNA was positively correlated with HPV copy number in the tumor (R=0.39, p<0.001). Complete clearance of HPV ctDNA by the end of treatment was significantly associated with a longer PFS (p<0.0001). Patients with persistent HPV ctDNA in serum relapsed with a median time of 10 months (range, 2–15) from HPV ctDNA detection.

Conclusion HPV ctDNA detection is a useful marker to predict relapse in cervical cancer.