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Persistent human papillomavirus (HPV) infection is associated with the development of oropharyngeal squamous cell carcinoma (OPSCC), and increasing incidences of OPSCC are reported. The generally favorable treatment outcome in patients with HPV-driven OPSCC has brought de-escalation of treatment into discussion. Nevertheless, 13% to 25% develop a relapse within two years after current standard treatment. New biomarkers are urgently required to monitor therapy response, tumor burden, and minimal residual disease during follow-up. This observational study examined 50 patients with OPSCC to investigate plasma cell-free (cf) HPV-DNA derived from tumor cells before therapy and during follow-up. Real-time quantitative PCR was applied to quantify the DNA concentration of HPV oncogenes E6 and E7. A total of 85.7% of pretreatment samples from patients with HPV-driven OPSCC (n = 28) were positive for at least one marker, and cfHPV-DNA concentration increased with tumor size. Virtually no signals were detected in HPV-negative OPSCC patients (n = 20; P ≤ 0.001). Patients without clinical evidence of recurrence had significantly reduced cfHPV-DNA concentrations after therapy (P ≤ 0.001). Conversely, cfHPV-DNA levels increased or remained above threshold in five patients who had residual disease or developed recurrence. In conclusion, plasma cfHPV-DNA detection correlates with the clinical course of disease in patients with HPV-driven OPSCC. Consequently, extensive clinical investigation should be considered if cfHPV-DNA is detected during follow-up of patients with HPV-driven OPSCC.

Objectives Despite improved survival rates of patients with HPV-associated OPSCC, a subset has distant metastasis or develops local recurrence during follow-up. To investigate potential underlying genetic alterations, we analyzed patients with HPV-driven OPSCC who suffered from recurrence in comparison to matching pairs with successful tumor control. Materials and methods We performed chromosomal copy number analyses and targeted next generation sequencing using a custom panel comprising genes that are frequently mutated in HPV-associated OPSCC. Results Specific differences regarding chromosomal aberrations were not observed between both groups. In HPV-driven OPSCC from patients with recurrence we found higher mutation rates compared to patients with successful tumor control. Especially mutation rates of HRAS (p ≤ 0.05) PIK3R1, STK11 and TP63 (p ≤ 0.1 each) were statistically significant or trending towards significance. The respective genes can be linked to transcription factors and signaling pathways involved in cell cycle regulation, proliferation and survival. Additionally, combinations of alterations were observed on chromosomes 16 and 19, which might also influence outcome. Conclusion Patients with HPV-driven OPSCC who develop recurrence or have metastasis may be defined by genetic alterations that might be responsible for poor outcome after standard therapy. This might be of importance for stratification in future de-escalation and targeted therapy.

Objectives 18 F-FDG PET/CT is widely used in clinical oncology. Human papillomavirus (HPV)-related oropharyngeal squamous cell carcinoma (OPSCC) represents an emerging disease that differs from HPV-negative OPSCC in clinical behavior and tumour biology. In these tumours, HPV-oncogenes might lead to distinct alterations in metabolic pathways. Therefore, we compared metabolic parameters using 18 F-FDG PET/CT in HPV-positive and HPV-negative OPSCC in relation to histopathological findings. Materials Eighty-six patients with OPSCC received pre-therapeutic 18 F-FDG PET/CT. Standardised uptake volume (SUV), total lesion glycolysis (TLG) and metabolic tumour volume (MTV) were analysed for the primary tumour. SUVmax was determined for neck lymph nodes. HPV-status was determined; overall survival rates (OS) were estimated. Results 32/86 patients (37.2%) had HPV-related OPSCC. Overall, PET-parameters in primary tumours of both groups did not differ significantly. Comparing early with locally advanced primary tumours, there was a significant increase in 18 F-FDG uptake in HPV-negative patients (p 18 F-FDG uptake between primary and respective positive nodes in HPV-related primary OPSCC (p = 0.001). SUV-max and –mean values did not correlate with OS in HPV-related OPSCC. Conclusion The intraindividual homogeneity of 18 F-FDG uptake in HPV-related OPSCC could reflect the more homogenously, HPV-triggered carcinogenesis compared to the mutation-driven carcinogenesis in the HPV-negative OPSCC with heterogenic 18 F-FDG uptake.