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. 2024 Sep 19;150(12):1089-1096.
doi: 10.1001/jamaoto.2024.2702. Online ahead of print.

Diagnostic Accuracy of Circulating Tumor HPV DNA Testing in Patients With a Lateral Neck Mass

Rocco M Ferrandino  1 , Joshua Barlow  1 , Brandon Gold  1 , Daniel Kraft  1 , Scott A Roof  1 , Marita S Teng  1 , Mohemmed N Khan  1 , Michael H Berger  1 , Krzysztof J Misiukiewicz  2 , Kunal K Sindhu  3 , Richard L Bakst  3 , Marshall R Posner  2 , William H Westra  4 , Eric M Genden  1 , Raymond L Chai  1
Affiliations

Diagnostic Accuracy of Circulating Tumor HPV DNA Testing in Patients With a Lateral Neck Mass

Rocco M Ferrandino et al. JAMA Otolaryngol Head Neck Surg. .

Abstract

Importance: The most frequent presenting symptom for patients with human papillomavirus (HPV)-associated oropharyngeal squamous cell carcinoma (OPSCC) is a lateral neck mass. Circulating tumor tissue-modified viral (TTMV)-HPV DNA is a unique biomarker produced by the fragmentation of HPV DNA during the degradation of HPV-associated tumors, and its detection and quantitation are currently being used as an adjunct to imaging in monitoring for disease recurrence and may have utility for diagnosis.

Objective: To measure the diagnostic characteristics of TTMV-HPV DNA compared with gold standard tissue biopsy for diagnosing HPV-OPSCC in patients presenting with an indeterminate lateral neck mass.

Design, setting, and participants: This prospective diagnostic test study enrolled patients 18 years or older who presented with a lateral neck mass to a large urban tertiary health care system from December 2021 to June 2023. Participants underwent standard-of-care testing to obtain a tissue diagnosis and a single TTMV-HPV DNA measurement.

Main outcomes and measures: The primary outcome of interest was sensitivity, while specificity, positive predictive value, and negative predictive value were secondary end points. A subset analysis was performed comparing test performance metrics between TTMV-HPV DNA testing and fine-needle aspiration.

Results: A total of 138 patients were included, of whom 80 (58.0%) were men, with median age of 57.5 years (IQR, 43.3-67.0 years). Of 138 patients, 87 (63.0%) had neck masses in level 2 and 47 (34.1%) had HPV-OPSCC. TTMV-HPV DNA testing exhibited a sensitivity of 95.7% (95% CI, 85.5%-99.5% [45 of 47 patients]), specificity of 97.8% (95% CI, 92.3%-99.7% [89 of 91 patients]), positive predictive value of 95.7% (95% CI, 85.5%-99.5% [45 of 47 patients]), and negative predictive value of 97.8% (95% CI, 92.3%-99.7% [89 of 91 patients]).

Conclusions and relevance: In this diagnostic study of patients presenting with a lateral neck mass, circulating TTMV-HPV DNA demonstrated excellent diagnostic test characteristics for the detection of HPV-OPSCC. Such testing may have particular utility for patients in whom obtaining adequate tissue is problematic, as is often the case with cystic neck masses and unknown primary tumors.

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Conflict of interest statement

Conflict of Interest Disclosures: Dr Posner reported receiving a speaker’s fee for a symposium from Naveris outside the submitted work. Dr Chai reported receiving research assay support without personal remuneration from Naveris during the conduct of the study. No other disclosures were reported.

Figures

Figure.
Figure.. Enrollment Schematic
ctDNA indicates circulating tumor DNA; FNA, fine-needle aspiration; and HPV, human papillomavirus.
See this image and copyright information in PMC

References

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