Circulating Tumor Tissue-Modified-Viral HPV DNA and Correlations With Disease Burden in Oropharyngeal Cancer

Tumor-tissue modified viral (TTMV)-human papillomavirus (HPV) DNA is an increasingly utilized biomarker for patients with HPV-mediated oropharyngeal squamous cell carcinoma (OPSCC). However, much remains to be studied regarding the quantitative importance of a positive pre-treatment result and correlations with disease burden.

Retrospective cohort study.

Single tertiary care center; January 2022 to July 2024.

Patients with HPV-associated OPSCC and baseline pre-treatment TTMV-HPV DNA levels were evaluated for primary tumor and lymph node disease extent on clinical imaging, exam, and surgical pathology results when applicable. Associations with log(pre-treatment TTMV-HPV DNA levels) were evaluated via multivariable linear regression. A commercially available TTMV-HPV DNA test was used.

In total, 94 patients were included, who were 93% male, with median age of 63 years (interquartile range [IQR] 55-70). Most patients were clinical tumor class cT1 (40%) or cT2 (38%) and clinical nodal class cN1 (77%). Surgical resection was performed in 37% of patients. Median pretreatment TTMV-HPV level was 225 (IQR 46-1132) fragments/mL. Independent associations were found between pretreatment TTMV-HPV levels and clinical nodal staging (P < .001), largest lymph node dimension on pretreatment CT (r = 0.63 [95% confidence interval [CI]: 0.46-1.2]; P < .001) and surgical pathology (r = 0.63 [0.18-1.08; P = .01), number of metastatic nodes on CT (r = 0.52 [0.2-0.84]; P < .001), clinical signs of extranodal extension (r = 1.66 [0.12-3.2]; P = 0.04), and SUV-max of lymph nodes (r = 0.16 [0.05-0.27]; P < 0.001).

Pre-treatment TTMV-HPV DNA was significantly associated with lymph node disease burden in HPV-associated OPSCC, on pre-treatment CT, PET, and surgical pathology.