# Diagnostic Accuracy of HPV Circulating Tumor DNA Following Non‐Diagnostic FNA of a Cystic Lateral Neck Mass

**Authors:** Michael R. Papazian, Melanie D. Hicks, Kyle Mannion, Meghan Turner, Michael C. Topf

PMC · DOI: 10.1002/hed.70060 · 2025-10-07

## TL;DR

This study shows that HPV circulating tumor DNA testing can help diagnose cancer in neck masses when traditional methods fail.

## Contribution

The study evaluates the diagnostic accuracy of HPV ct-DNA in non-diagnostic FNA cases of cystic neck masses.

## Key findings

- HPV ct-DNA was positive in 62.5% of cases and all were HPV-associated OPSCC.
- The test had 83% sensitivity, 100% specificity, and 100% positive predictive value.
- Negative results had a 67% negative predictive value, suggesting caution in interpretation.

## Abstract

Cystic lateral neck masses in adults commonly represent nodal metastases from HPV‐associated oropharyngeal squamous cell carcinoma (OPSCC) or benign lesions. Because cystic lesions are relatively acellular, fine‐needle aspiration (FNA) is often non‐diagnostic. HPV circulating tumor DNA (ct‐DNA) may aid diagnosis in these cases.

We conducted a two‐institution retrospective review of patients with cystic neck masses and non‐diagnostic FNA who underwent pre‐treatment HPV ct‐DNA testing. Sensitivity, specificity, and predictive values were calculated based on final pathology.

Thirty‐two patients were included. HPV ct‐DNA was positive in 20/32 (62.5%) cases, all of which were HPV‐associated OPSCC. Four patients with negative HPV ct‐DNA were ultimately diagnosed with HPV‐associated OPSCC (sensitivity: 83%, specificity: 100%, PPV: 100%, NPV: 67%).

HPV ct‐DNA demonstrated high specificity and may complement standard workup in adult cystic neck masses with non‐diagnostic FNA. Positive HPV ct‐DNA results should prompt further evaluation for HPV‐associated OPSCC.

## Full-text entities

- **Diseases:** Cystic Lateral Neck Mass. (MESH:D018297), benign lesions (MESH:D001932), OPSCC (MESH:D000077195), Tumor (MESH:D009369), nodal metastases (MESH:D009362)
- **Species:** Homo sapiens (human, species) [taxon 9606]

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Source: https://tomesphere.com/paper/PMC12796992