A Potential New Detection Tool for Invasive Cervical Cancer
Circulating human papilloma virus DNA shows promise as a universal biomarker.

The lack of a sensitive and specific tumor marker for invasive cervical cancer makes detection of the disease difficult. But there may be hope in the form of circulating human papilloma virus (HPV) DNA fragments.
In the abstract presentation, “Tumor tissue-modified HPV DNA reliably detects the presence of advanced-stage invasive cervical carcinoma with levels corresponding to treatment response,” which was presented earlier today, lead investigator Kersten Rothnie, MBBS, gynecologic oncology fellow at Northwell Health in New York City, said research in this area could be a game changer for diagnosis and treatment of cervical cancer.
“Circulating tumor HPV DNA can serve as a universal tumor marker for these HPV-driven cancers and will meet this unmet need (for new methods of detection),” she said. “This has the potential to be a practice-changer.”
The multisite, prospective study included patients with biopsy-proven high-grade cervical dysplasia (CIN2/3) or invasive cervical carcinoma (CC), with positive HPV 16/18 subtypes included. NavDx digital droplet chain reaction testing was used to detect circulating fragments of tumor tissue-modified viral (TTMV)-HPV DNA released by the HPV-associated cancer cells in the serum. Samples were collected pre-treatment, during treatment, and post treatment.
At the time of analysis, results were available for 34 patients (12 with CIN2/3 and 22 with CC). Of the patients with CC, 15 (68.2%) presented with primary disease and seven (31.8%) presented with recurrence. In that same group, eight of those with primary CC were at stage I/II, while seven were at stage III/IV. Researchers found TTMV-HPV DNA was not detected in patients with CIN2/3, but was detected for those with CC.
All CC patients with positive TTMV-HPV DNA at baseline had a decrease in scores following the start of treatment. Disease progression or persistence was diagnosed in five patients, and corresponding increased scores were observed in those patients.
The researchers found that the presence of tumor-tissue modified viral HPV DNA is predictive of the presence of advance-stage disease in patients with newly diagnosed cervical cancer, with scores dynamically corresponding to treatment response.
According to Dr. Rothnie, the pilot study is ongoing, and more patients and subtypes are being added. The available data will only continue to grow from here.
“As our pilot study continues, additional patients are enrolling and an expanded panel including the 16 most prevalent high-risk HPV subtypes has been developed, and analysis of specimens is under way,” she said. “The availability of these additional subtypes will allow TTMV-HPV DNA to truly serve as a universal biomarker for these HPV-driven cancers.”
Although the potential biomarker has shown promise, Dr. Rothnie cautions that the results are preliminary, and there is still more work to be done.
“While our study has demonstrated the monitoring of TTMV-HPV DNA dynamically corresponds with treatment response for cervical cancer, as well as persistence or progression of the disease, we are unable to comment on TTMV-HPV DNA as a prognostic biomarker until there is sufficient mutation of survival data,” she said. “From these promising preliminary results, the use of TTMV-HPV DNA presents a potential non-invasive tool for the detection and monitoring of cervical cancer.”
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