HPV ctDNA testing identifies cervical cancer patients at high risk of relapse after CRT

Detection of human papilloma virus (HPV) circulating tumour DNA (ctDNA) after completion of chemoradiation therapy (CRT) is independently associated with inferior progression-free survival (PFS) in patients with cervical cancer, a prospective multicentre study has shown. According to the researchers, early HPV ctDNA testing after CRT can identify patients at high risk of relapse.

The study was conducted to validate HPV ctDNA as a biomarker and compare it with PET imaging for early detection of molecular residual disease in patients with stage IB–IVA cervical cancer. Participants underwent phlebotomy at baseline, end of CRT, 4– 6 weeks post-CRT, and 3 months post-CRT for measurement of HPV ctDNA levels. Plasma HPV genotype–specific DNA levels were quantified using both digital polymerase chain reaction (dPCR) and HPV next-generation sequencing (HPV-seq) assays. Patients enrolled after April 2019 also underwent PET imaging 3 months after CRT. The primary endpoint was PFS at 2 years.

[J Clin Oncol 2023;doi:10.1200/JCO.23.00954]

Among 70 patients with HPV-positive disease treated with CRT in 2017–2022 who were followed up for a median of 2.2 years, a total of 24 PFS events were reported. PFS rate at 2 years was 66 percent.

“Persistence of HPV ctDNA at all time points after CRT was independently associated with inferior PFS,” the researchers reported.

Two-year PFS rates were significantly lower in patients with detectable vs undetectable HPV ctDNA on dPCR at the end of CRT (51 percent vs 77 percent; p=0.036), 4–6 weeks post-CRT (15 percent vs 82 percent; p<0.001) and 3 months post-CRT (24 percent vs 82 percent; p<0.001). Similar 2-year PFS results were shown for patients with detectable vs undetectable HPV ctDNA on HPV-seq at the end of CRT (53 percent vs 87 percent; p=0.009), 4–6 weeks post-CRT (39 percent vs 79 percent; p<0.001), and 3 months post-CRT (26 percent vs 85 percent; p<0.001).

Median lead time from the first positive HPV ctDNA test to identification of relapse by clinical examination or radiologic imaging was 5.9 months for both dPCR and HPV-seq.

“On multivariable analysis, detectable HPV ctDNA on dPCR and HPV-seq remained significantly associated with inferior PFS,” the researchers noted. “No significant differences in performance [C-indices] were found between HPV-seq and dPCR in predicting PFS [p=0.42 for end of treatment; p=0.22 for 4–6 weeks post-CRT; p=0.34 for 3 months post-CRT].”

“Overall, we found no statistically significant differences in relapse prediction between [HPV ctDNA at] the different time points or compared with 3-month PET imaging,” they continued.