Faculty Collaboration Database

Sensitive MRD Detection from Lymphatic Fluid after Surgery in HPV-Associated Oropharyngeal Cancer. Clin Cancer Res 2024 Apr 01;30(7):1409-1421

Date

11/08/2023

Pubmed ID

37939112

Pubmed Central ID

PMC10982646

DOI

10.1158/1078-0432.CCR-23-1789

Scopus ID

2-s2.0-85189772434 (requires institutional sign-in at Scopus site)   1 Citation

Abstract

PURPOSE: Our goal was to demonstrate that lymphatic drainage fluid (lymph) has improved sensitivity in quantifying postoperative minimal residual disease (MRD) in locally advanced human papillomavirus (HPV)-associated oropharyngeal squamous cell carcinoma (OPSCC) compared with plasma, and leverage this novel biofluid for patient risk stratification.

EXPERIMENTAL DESIGN: We prospectively collected lymph samples from neck drains of 106 patients with HPV (+) OPSCC, along with 67 matched plasma samples, 24 hours after surgery. PCR and next-generation sequencing were used to quantify cancer-associated cell-free HPV (cf-HPV) and tumor-informed variants in lymph and plasma. Next, lymph cf-HPV and variants were compared with TNM stage, extranodal extension (ENE), and composite definitions of high-risk pathology. We then created a machine learning model, informed by lymph MRD and clinicopathologic features, to compare with progression-free survival (PFS).

RESULTS: Postoperative lymph was enriched with cf-HPV compared with plasma (P < 0.0001) and correlated with pN2 stage (P = 0.003), ENE (P < 0.0001), and trial-defined pathologic risk criteria (mean AUC = 0.78). In addition, the lymph mutation number and variant allele frequency were higher in pN2 ENE (+) necks than in pN1 ENE (+) (P = 0.03, P = 0.02) or pN0-N1 ENE (-) (P = 0.04, P = 0.03, respectively). The lymph MRD-informed risk model demonstrated inferior PFS in high-risk patients (AUC = 0.96, P < 0.0001).

CONCLUSIONS: Variant and cf-HPV quantification, performed in 24-hour postoperative lymph samples, reflects single- and multifeature high-risk pathologic criteria. Incorporating lymphatic MRD and clinicopathologic feature analysis can stratify PFS early after surgery in patients with HPV (+) head and neck cancer. See related commentary by Shannon and Iyer, p. 1223.

Author List

Earland N, Semenkovich NP, Ramirez RJ, Gerndt SP, Harris PK, Gu Z, Hearn AI, Inkman M, Szymanski JJ, Whitfield D, Wahle BM, Xu Z, Chen K, Alahi I, Ni G, Chen A, Winckler W, Zhang J, Chaudhuri AA, Zevallos JP

Author

Nicholas Semenkovich MD Assistant Professor in the Medicine department at Medical College of Wisconsin

MESH terms used to index this publication - Major topics in bold

Head and Neck Neoplasms
Humans
Neoplasm Staging
Neoplasm, Residual
Oropharyngeal Neoplasms
Papillomavirus Infections
Prognosis
Retrospective Studies