Expanded subtype testing for circulating tumor HPV DNA reliably detects the presence of advanced-stage cervical cancer.

OBJECTIVES

To demonstrate the detection of circulating human papillomavirus (HPV) DNA fragments can serve as a biomarker for presence of tumor and provide a universal, non-invasive tool for monitoring treatment response in HPV-related cervical cancers (CC).

METHODS

A multi-site prospective study of HPV-positive high-grade cervical dysplasia (CIN2/3) and CC was conducted. Serum samples were collected pre-, during, and post-treatment. NavDx® (Naveris,Inc) digital droplet polymerase chain reaction testing was used to detect tumor tissue modified viral (TTMV)-HPV DNA. The expanded panel included 14 HPV subtypes. Sensitivity and specificity were calculated for the pre-treatment Score only. Scores were quantified for on-treatment timepoints and trends were compared against treatment response.

RESULTS

80 patients were included in the analysis: 46 (57.5%) CC, 26 (32.5%) CIN2/3, 8 (10.0%) benign. TTMV-HPV DNA was undetectable in all CIN 2/3 and benign cases. For CC, 38 (82.6%) had primary disease and 8 (17.4%) recurrent. For primary CC, 28 (73.7%) had stage I/II and 10 (26.3%) stage III/IV. Specificity for TTMV-HPV DNA for CC detection was 100% (95% CI: 89.7%-100.0%) for all stages. Sensitivity was 39.2% (95% CI: 21.5-59.4%) for stage I/II, 90% (95% CI: 55.5-99.7%) for stage III/IV, and 62.5% (95% CI: 24.4-91.48%) at recurrence. Disease progression/persistence occurred in 7 patients with corresponding increased Scores.

CONCLUSIONS

TTMV-HPV DNA is a sensitive and specific biomarker for advanced CC, with Scores dynamically corresponding to treatment response, and has the potential to serve an unmet need as a universal biomarker for patients with HPV-related CC.