Figures and data
CONSORT flow diagram showing the enrollment of an observational cohort of patients diagnosed with recurrent or metastatic HPV-cervical cancer undergoing serum human papillomavirus (HPV) cell-free DNA surveillance.
Characteristics of patients with metastatic or recurrent cervical cancer
(A) Serum HPV cfDNA copy number for six HPV subtypes at baseline. (B) Baseline HPV cfDNA copy numbers for five recurrence/metastasis pattern subgroups. Statistical significance was determined using a two-sided Kruskal-Wallis test. (C) Relationship between HPV cfDNA viral copy number and metastatic pattern. Statistical significance was determined using a two-sided Mann-Whitney U test. All plots show the median and interquartile range on a log10 scale.
Paired plots for serum HPV cfDNA (copies/mL) and squamous cell carcinoma antigen (SCC-Ag) (ng/mL) levels were measured longitudinally in patients with metastatic or recurrent HPV+ cervical cancer (lines of the same color for each patient). HPV cfDNA levels in serum were scaled using log10. (A1, A2) Patients whose disease progressed during treatment. (B1,B2) Selected patients who showed a response to cytotoxic chemotherapy. (C1,C2) Response to immune therapy in a patient with stage IVB cervical cancer positive for HPV subtypes 33 and 16, treated with paclitaxel + cisplatin, concurrent chemoradiotherapy, brachytherapy, and bevacizumab. (D1, D2) Selected patients with a response to radiotherapy.(E1, E2) HPV cfDNA levels were significantly higher than normal at some of the longitudinal time points in five patients, but SCC-Ag levels were within the normal range (<1.5 ng/mL) at all time points. (F1, F2) HPV cfDNA levels for all patients with longitudinal samples (n=21) and matched SCC-Ag levels for the patients with squamous cell cancer (n=20). Each colored line corresponds to one patient, except in C. Horizontal dashed lines indicate the days between plasma HPV cfDNA levels suggestive of a response or progression (rise or fall in levels) and imaging-confirmed changes in disease status. The associated number of days (D) is listed adjacent to the horizontal dashed line for comparison. It should be noted that not all HPV cfDNA data points are plotted for each patient.
(A) Overall survival for patients stratified by HPV subtype (HPV 16+ versus non-HPV16+). (B) Overall survival for patients stratified by baseline serum HPV cfDNA copy number using a cutoff of 3.9×104 copies/mL. P-values were calculated using a two-sided log-rank test.
