Insights into expression and localization of HPV16 LCR-associated transcription factors and association with LCR activity in HNSCC

Human papillomavirus (HPV)-positive head and neck squamous cell carcinoma (HNSCC) encompasses a heterogeneous group of malignancies characterized by diverse clinical manifestations. Notably, HPV-positive HNSCC exhibits a more favorable prognosis, particularly when the virus is transcriptionally active. This study aimed to elucidate the role of key transcription factors in activating the HPV long control region (LCR), responsible for its oncogenic potential. Utilizing immunoblotting and immunofluorescence techniques, we analyzed the expression and nuclear localization of LCR-associated transcription factors in HPV-negative and HPV-positive HNSCC cell lines. High expression of JunB and low expression of Fra-1, pSTAT3(S727), SP1, and SOX2 were observed in HPV-positive HNSCC cells. Transcriptomic analysis corroborated these findings, revealing differential expression of transcription factors in HPV-positive lesions. Moreover, the study identified strong correlation of LCR-specific transcription factors with HNSCC patient survival. Evaluation of HPV16 LCR reporter activity further underscored the heterogeneous nature of HNSCC, with some HPV-negative cell lines exhibiting comparable LCR activity to HPV-positive counterparts. These findings elucidate the intricate regulatory mechanisms underlying HPV-associated HNSCC and provide insights into potential prognostic markers and therapeutic targets.