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. 2025 Mar;97(3):e70278.
doi: 10.1002/jmv.70278.

HPV Biomarkers in Oral and Blood-Derived Body Fluids in Head and Neck Cancer Patients

Luisa Galati  1 , Marta Tagliabue  2   3 , Tarik Gheit  4 , Rita De Berardinis  2 , Fausto Maffini  5 , Sandrine McKay-Chopin  4 , Giuseppe De Palma  6 , Stefania Vecchio  7 , Angelo Virgilio Paradiso  6 , Laura Sichero  8   9 , Luisa Lina Villa  8   10 , Francesco Chu  2 , Francesco Bandi  2 , Chiara Mossinelli  2 , Jacopo Zocchi  2 , Giacomo Pietrobon  2 , Stefano Filippo Zorzi  2 , Enrica Grosso  2 , Stefano Riccio  2 , Roberto Bruschini  2 , Gioacchino Giugliano  2 , Giovanni Blandino  11 , Maria Lina Tornesello  12 , Mohssen Ansarin  2 , Massimo Tommasino  4 , Susanna Chiocca  1
Affiliations

HPV Biomarkers in Oral and Blood-Derived Body Fluids in Head and Neck Cancer Patients

Luisa Galati et al. J Med Virol. 2025 Mar.

Abstract

Oral HPV DNA and circulating tumor (ct) HPV DNA in plasma were evaluated as potential biomarkers for HPV-associated head and neck cancer (HNC). Samples from HNC patients (n = 132), including 23 oropharyngeal cancers (OPC), and non-HNC controls (n = 10) were analyzed. HPV status was determined using a multiplex bead-based test (E7-MPG) applied to formalin-fixed paraffin-embedded (FFPE) tissues (n = 90), plasma (n = 141), gargle samples (n = 141), and oral swabs (n = 142). HPV DNA was detected in 25.8% of HNC tissues, 12% of plasma samples, 20.6% of gargles and 7% of oral swabs with HPV16 as the most prevalent genotype. Among OPC cases, HPV16 DNA was found in 71.4% of FFPE samples. High concordance was observed between paired OPC tissues and plasma (91.3%) or gargles (95.2%), with moderate concordance for oral swabs (59.1%). Gargle samples alone demonstrated a 100% detection rate for HPV16-positive OPC, regardless of the cT stage, outperforming plasma (86.7%). Combined oral gargle and plasma analyses detected all HPV-positive OPC cases (7/7) at the early cT1 stage. These findings highlight the limited involvement of HPV in non-oropharyngeal HNC compared to OPC, and support gargle and plasma samples as minimally invasive diagnostic tools for detecting HPV-associated OPC.

Keywords: HPV; HPV DNA; HPV16; Head and neck squamous cell carcinoma; biomarkers; body fluids; head neck cancer; oropharyngeal cancer; plasma; saliva.

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Conflict of interest statement

The authors declare no conflicts of interest.

Figures

Figure 1
Figure 1
Workflow of applied methodology. Left panel: Description of patients’ sample collection and assays used for analysis. Right panel: Description of sample preparation, processing and analysis. Created with Biorender.
Figure 2
Figure 2
Patient cohort and stratification of HNC cases by cancer sites and clinical tumor (cT) stages. Abbreviations are specified within the figure. Created with Biorender.
Figure 3
Figure 3
Distribution of HPV genotypes detected by beads‐based Luminex assay (E7‐MPG) stratified by specimen types. (A) HPV genotypes in FFPE tissues. (B) HPV genotypes detected in plasma samples. (C) HPV types detected in gargles and (D) HPV genotypes detected in oral swabs.
See this image and copyright information in PMC

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