Circulating HPV DNA as a Marker for Early Detection of Relapse in Patients with Cervical Cancer.

Abstract

Almost all cervical cancers are caused by human papillomavirus (HPV) and patients with advanced stage are at high risk for relapse. Circulating HPV DNA (HPV ctDNA) may serve as a residual tumor marker at the end of chemoradiation or to predict relapse during the follow-up period. We analyzed serum samples from 94 HPV16- or HPV18-related CCs from the BioRAIDs 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 <i>E7</i> gene as a marker for residual disease compared to HPV integration site and <i>PIK3CA</i> mutations. Finally, the prognostic impact of circulating HPV <i>E7</i> gene was assessed with its prediction value of relapse. HPV <i>E7</i> gene was the most sensitive tumor marker, superior to both HPV integration sites and <i>PIK3CA</i> mutations in serum. 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 (<i>P</i> = 0.02) and para-aortic lymph node involvement (<i>P</i> = 0.01). The level of HPV ctDNA was positively correlated with HPV copy number in the tumor (<i>R</i> = 0.39, <i>P</i> < 0.001). Complete clearance of HPV ctDNA by the end of treatment was significantly associated with a longer PFS (<i>P</i> < 0.0001). Patients with persistent HPV ctDNA in serum relapsed with a median time of 10 months (range, 2-15) from HPV ctDNA detection. HPV ctDNA detection is a useful marker to predict relapse in cervical cancer.<i>See related commentary by Wentzensen and Clarke, p. 5733</i>.