Liquid biopsy okay for diagnosis of HPV-associated oropharyngeal cancer: JAMA

The cohort study of 399 patients in a contemporary clinical setting revealed that TTMV-HPV DNA testing at the time of the diagnosis of OPSCC demonstrated excellent specificity and sensitivity of 100% and 91.5%, respectively. The TTMV-HPV DNA test concerning surveillance had a specificity of 100% and a sensitivity of 88.4% for recurrence detection.

There has been a growing interest in using circulating plasma tumor HPV DNA for surveillance and diagnosis of patients with HPV-associated OPSCC. Recent advances in the assays, combining the identification of circulating HPV tumor DNA and tumor DNA fragment analysis (tumor tissue–modified viral [TTMV]-HPV DNA), are highly accurate. However, using these techniques got limited to small clinical trials and cohort studies.

Therefore, Rocco M. Ferrandino, Icahn School of Medicine at Mount Sinai, New York, New York, and colleagues aimed to establish the clinical effectiveness of plasma TTMV-HPV DNA testing in the surveillance and diagnosis of HPV-associated OPSCC in a retrospective observational cohort study.

The study included 399 patients with oropharyngeal squamous cell carcinoma who underwent TTMV-HPV DNA testing between 2020 and 2022 during routine clinical care. Patients with at least 1 TTMV-HPV DNA measurement before initiation of primary therapy were included in the diagnosis cohort (n-=163). In the surveillance cohort (n=290), those patients were included who had at least 1 TTMV-HPV DNA test performed after the completion of salvage or definitive therapy.

The authors revealed the following findings:

• Of the 163 patients in the diagnostic cohort, 93.3% had HPV-associated OPSCC, while 6.7% had HPV-negative OPSCC.
• The TTMV-HPV DNA sensitivity in pretreatment diagnosis was 91.5%, and the specificity was 100%.
• In the surveillance cohort, 591 tests conducted on 290 patients were evaluated.
• A total of 23 patients had molecularly confirmed pathologic recurrences.
• The TTMV-HPV DNA test demonstrated a sensitivity of 88.4% and specificity of 100% in detecting recurrences.
• The positive predictive value was 100%, and the negative predictive value was 99.1%.
• The median lead time from a positive TTMV-HPV DNA test to pathologic confirmation was 47 days.

The TTMV-HPV DNA assay, when evaluated in a clinical setting, demonstrated 100% specificity in both diagnosis and surveillance. However for the diagnosis cohort, the sensitivity was 91.5% and for the surveillance cohort it was 88.4%, implying that about 1 in 10 negative tests among patients with HPV-associated OPSCC was a false negative.

"Additional research is needed to validate the assay’s performance and, if validated, then further research will be required into the implementation of this assay into standard clinical practice guidelines," the researchers concluded.

Reference:

Ferrandino RM, Chen S, Kappauf C, et al. Performance of Liquid Biopsy for Diagnosis and Surveillance of Human Papillomavirus–Associated Oropharyngeal Cancer. JAMA Otolaryngol Head Neck Surg. Published online July 09, 2023. doi:10.1001/jamaoto.2023.1937