THURSDAY, May 29, 2025 (HealthDay News) — Human papillomavirus (HPV) whole-genome sequencing (WGS)-based circulating tumor DNA (ctDNA) detection has the highest sensitivity, specificity, and diagnostic accuracy for head and neck squamous cell carcinoma (HNSCC), according to a study published online May 20 in Clinical Cancer Research.

Michael E. Bryan, from Harvard Medical School in Boston, and colleagues developed a multifeature HPV WGS liquid biopsy for improved low-level ctHPVDNA detection. Blood samples were tested from 304 participants: 152 with untreated incident HPV + HNSCC and 152 general population controls. WGS-based ctHPVDNA detection was compared to single-plex Droplet Digital polymerase chain reaction (ddPCR)-based ctHPVDNA detection, multiplex ddPCR-based ctHPVDNA detection, multiplex HPV antibody (Ab) detection, and clinical standard-of-care tissue biopsy.

The researchers found that the sensitivity and specificity of HPV WGS were 98.7 and 98.7 percent, respectively, compared with 94.2 and 98.6 percent for single-plex ddPCR; 90.6 and 96.3 percent for multiplex ddPCR; and 86.4 and 96.3 percent for HPV Ab, respectively. Sensitivity and specificity were 87.4 and 98.8 percent for a combinatorial approach using both HPV WGS and HPV Ab. In a head-to-head comparison, significantly improved diagnostic accuracy was seen for HPV WGS compared with ddPCR, HPV Ab, and clinical workup (Youden index, 0.99 versus 0.90, 0.83, and 0.82, respectively); this was maintained in an analysis of early-stage disease cases only. HPV WGS yielded the lowest number needed to screen (2,903 men) and the highest positive predictive value (2.6) for men aged 55 to 74 years.

“Taken together, these results highlight the potential utility of an HPV WGS liquid biopsy approach for screening, early detection, and diagnosis of HPV + HNSCC,” the authors write.

Several authors disclosed ties to the biopharmaceutical industry; one author has a study-related patent pending.

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