Predictive value of TTMV HPV DNA kinetics in induction chemotherapy in HPV-positive head and neck squamous cell carcinoma.

Abstract

e18057 Background: Tumor tissue-modified viral (TTMV) HPV DNA is a sensitive, highly specific biomarker for human papillomavirus-positive (HPV+) head and neck squamous cell carcinoma (HNSCC). However, TTMV clearance patterns during induction chemotherapy (IC) or chemoimmunotherapy (ICI) have not been well described.We monitored the kinetics of TTMV responses to IC(I) and analyzed the results for predictive implications for treatment outcomes. Methods: This is a retrospective cohort study of patients treated at a single institution between June 2020 and December 2024. Adult patients with previously untreated, locally advanced, unresectable molecularly identified HPV+ HNSCC with high-risk features (e.g. extracapsular extension, T4, or >N2c) treated with IC(I) were identified. Patientswere treated with 3 cycles of IC (docetaxel-cisplatin-fluorouracil) or anti-PD1 ICI (docetaxel-cisplatin-Cemiplimab or docetaxel-cisplatin-Pembrolizumab). Depending on clinical trial enrollment, patients were followed by standard- or reduced-dose CRT alone or with adjuvant therapy. TTMV testing was done pre-treatment, after each cycle and CRT, and throughout surveillance and analyzed retrospectively. Patients were required to have a positive pretreatment TTMV test. TTMV clearance kinetics throughout IC and CRT with post cycle TTMV testing were correlated with clinical outcomes during post-treatment surveillance and TTMV testing during surveillance was monitored and is reported. Results: Twenty-eight subjects (26 male, 13 smokers) had a median pre-treatment TTMV of 1321 (range 27-90770, IQR 200-3217). Patients had a mean 33.7 months of follow-up and a mean 10.1 TTMV tests over the study period. 10/28 patients reached full TTMV clearance after one IC cycle (IC1), 8/28 after two cycles (IC2), 3/28 after three cycles (IC3), and 1/28 remained TTMV+ throughout IC and cleared after CRT. 6/28 had unknown kinetics due to missing data. All patients were TTMV-negative following completion of CRT. During surveillance, 6/28 patients developed recurrences and all were both TTMV+ and eventually PET+ (1 locoregional, 5 metastatic); of these, 2/6 had reached TTMV clearance after IC2, 2/6 after IC3, 1/6 after CRT, and 1/6 unknown. Rapid clearance after IC1 was associated with having no evidence of disease (p=0.046) and lower baseline TTMV (p=0.049). TTMV detection of recurrence had a mean lead-time of 115 days (range 0-340) over PET detection. Conclusions: Recurrences occurred in patients who failed to clear plasma TTMV after one IC(I) cycle. Delayed TTMV clearance strongly predicted systemic failure and may help identify patients requiring more systemic therapy. Future studies should validate these findings in larger cohorts.