JAMA otolaryngology-- head & neck surgery · 2025
Pretreatment Liquid Biopsy and Clinicopathologic Features in HPV-Associated Oropharyngeal Squamous Cell Carcinoma.
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Cooke Peter V, Chennareddy Susmita, Kraft Daniel O, Kappauf Catharine, Lam Austin S, Chen Sida, Sindhu Kunal K, Berger Michael H, Ferrandino Rocco M, Kulkarni Raksha, Tang Megan, Ghesani Nasrin, Misiukiewicz Krzysztof, Bakst Richard L, Posner Marshall R, Genden Eric M, Chai Raymond L, Roof Scott A
Аннотация
IMPORTANCE: Despite the favorable prognosis for HPV-positive oropharyngeal squamous cell carcinoma (HPV+ OPSCC), efforts to de-escalate treatment intensity, while maintaining low recurrence and mortality rates, have proven challenging. Identifying appropriate prognostic factors remains elusive; however, the association of pretreatment circulating tumor tissue viral-modified HPV (TTMV-HPV) DNA level with known characteristics of disease burden-clinical staging, characteristics of pretreatment imaging, and aggressive histopathologic features of surgical specimen-may offer insights that could shift treatment paradigms for HPV+ OPSCC.
OBJECTIVE: To investigate the association of pretreatment TTMV-HPV DNA levels with clinical, radiologic, histopathologic, and outcome metrics in patients with HPV+ OPSCC.
DESIGN, SETTING, AND PARTICIPANTS: This cohort study of patients with HPV+ OPSCC and positive test results for pretreatment TTMV-HPV DNA fragment levels used data from a single tertiary center from April 2020 to September 2023. TTMV-HPV DNA fragments levels were categorized into 3 cohorts: low (≤99 fragments/mL), moderate (100-999/mL), and high (≥1000/mL).
MAIN OUTCOMES AND MEASURES: Association of clinical tumor (cT) and nodal (cN) staging with TTMV-HPV DNA fragment level. Secondary outcomes included the association between TTMV-HPV DNA fragment level and positive emission tomography-computed tomography (PET-CT) characteristics as well as histopathologic features of surgical specimen. The association of pretreatment fragment level with receiving adjuvant therapy for surgical patients was also analyzed. Recurrence-free survival and disease-specific survival were also assessed.
RESULTS: The study population included 203 patients (mean [SD] age, 62 [10] years; 24 [12%] females and 179 males [88%]), 58 (29%) of whom were in the low, 73 (36%) in the moderate, and 72 (35%) in the high TTMV-HPV DNA fragment-level cohort. Compared to patients with cT0/1 stage, those with cT2 stage and cT3/4 stage had increased odds of higher TTMV-HPV DNA levels, with adjusted odds ratios (aORs) of 2.33 (95% CI, 1.24-4.46) and 2.51 (95% CI, 1.17-5.46), respectively. Compared to patients with cN0 stage, those with cN1 stage and cN2/3 stage also had increased odds of higher TTMV-HPV DNA levels, with aORs of 4.26 (95% CI, 1.82-10.34) and 3.64 (95% CI, 1.46-9.36), respectively. In adjusted analysis of pretreatment PET-CT characteristics, total primary tumor plus nodal volume was associated with higher TTMV-HPV DNA levels, with an aOR of 1.04 (95% CI, 1.02-1.07). Among 94 surgical patients, no significant association was found between pretreatment fragment level and lymphovascular invasion, perineural invasion, pathologic T stage, number of positive nodes, or extranodal extension on pathological analysis of surgical specimen. No significant differences in recurrence-free survival or disease-specific survival were found.
CONCLUSION AND RELEVANCE: This cohort study found that higher pretreatment TTMV-HPV DNA fragment levels were associated with more advanced clinical staging and higher aggregate primary and cervical nodal volume on PET-CT results. Future studies are needed to explore how pretreatment fragment level may influence treatment decisions.
OBJECTIVE: To investigate the association of pretreatment TTMV-HPV DNA levels with clinical, radiologic, histopathologic, and outcome metrics in patients with HPV+ OPSCC.
DESIGN, SETTING, AND PARTICIPANTS: This cohort study of patients with HPV+ OPSCC and positive test results for pretreatment TTMV-HPV DNA fragment levels used data from a single tertiary center from April 2020 to September 2023. TTMV-HPV DNA fragments levels were categorized into 3 cohorts: low (≤99 fragments/mL), moderate (100-999/mL), and high (≥1000/mL).
MAIN OUTCOMES AND MEASURES: Association of clinical tumor (cT) and nodal (cN) staging with TTMV-HPV DNA fragment level. Secondary outcomes included the association between TTMV-HPV DNA fragment level and positive emission tomography-computed tomography (PET-CT) characteristics as well as histopathologic features of surgical specimen. The association of pretreatment fragment level with receiving adjuvant therapy for surgical patients was also analyzed. Recurrence-free survival and disease-specific survival were also assessed.
RESULTS: The study population included 203 patients (mean [SD] age, 62 [10] years; 24 [12%] females and 179 males [88%]), 58 (29%) of whom were in the low, 73 (36%) in the moderate, and 72 (35%) in the high TTMV-HPV DNA fragment-level cohort. Compared to patients with cT0/1 stage, those with cT2 stage and cT3/4 stage had increased odds of higher TTMV-HPV DNA levels, with adjusted odds ratios (aORs) of 2.33 (95% CI, 1.24-4.46) and 2.51 (95% CI, 1.17-5.46), respectively. Compared to patients with cN0 stage, those with cN1 stage and cN2/3 stage also had increased odds of higher TTMV-HPV DNA levels, with aORs of 4.26 (95% CI, 1.82-10.34) and 3.64 (95% CI, 1.46-9.36), respectively. In adjusted analysis of pretreatment PET-CT characteristics, total primary tumor plus nodal volume was associated with higher TTMV-HPV DNA levels, with an aOR of 1.04 (95% CI, 1.02-1.07). Among 94 surgical patients, no significant association was found between pretreatment fragment level and lymphovascular invasion, perineural invasion, pathologic T stage, number of positive nodes, or extranodal extension on pathological analysis of surgical specimen. No significant differences in recurrence-free survival or disease-specific survival were found.
CONCLUSION AND RELEVANCE: This cohort study found that higher pretreatment TTMV-HPV DNA fragment levels were associated with more advanced clinical staging and higher aggregate primary and cervical nodal volume on PET-CT results. Future studies are needed to explore how pretreatment fragment level may influence treatment decisions.