TY - JOUR
T1 - Diagnostic Accuracy of Circulating Tumor HPV DNA Testing in Patients with a Lateral Neck Mass
AU - Ferrandino, Rocco M.
AU - Barlow, Joshua
AU - Gold, Brandon
AU - Kraft, Daniel
AU - Roof, Scott A.
AU - Teng, Marita S.
AU - Khan, Mohemmed N.
AU - Berger, Michael H.
AU - Misiukiewicz, Krzysztof J.
AU - Sindhu, Kunal K.
AU - Bakst, Richard L.
AU - Posner, Marshall R.
AU - Westra, William H.
AU - Genden, Eric M.
AU - Chai, Raymond L.
N1 - Publisher Copyright:
© 2024 American Medical Association. All rights reserved.
PY - 2024/12/12
Y1 - 2024/12/12
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=85209954902&partnerID=8YFLogxK
U2 - 10.1001/jamaoto.2024.2702
DO - 10.1001/jamaoto.2024.2702
M3 - Article
C2 - 39298177
AN - SCOPUS:85209954902
SN - 2168-6181
VL - 150
JO - JAMA Otolaryngology - Head and Neck Surgery
JF - JAMA Otolaryngology - Head and Neck Surgery
IS - 12
ER -