Potential Transcript-Based Biomarkers Predicting Clinical Outcomes of HPV-Positive Head and Neck Squamous Cell Carcinoma Patients

Abstract

Human papillomavirus (HPV)-positive Head and Neck Squamous Cell Carcinomas (HNSCC) comprise a particular cancer entity traditionally associated with better clinical outcomes. Around 25% of HNSCC are HPV positive, HPV16 being the most prevalent type. Nevertheless, close to 30% of the HPV-positive patients have an unfavorable prognosis, revealing that this type of tumor exhibits great heterogeneity leading to different clinical behaviors. Efforts have been made to identify RNA molecules with prognostic value associated with the clinical outcome of patients with HPV-positive HNSCC, with the aim of identifying patients at high risk of metastasis, disease recurrence, and poor survival, who would require closer clinical follow-up and timely intervention. Moreover, the molecular identification of those HPV-positive HNSCC patients with good prognosis will allow the implementation of de-escalating therapeutic strategies, aiming to reduce side effects, resulting in a better quality of life. This review compiles a series of recent studies addressing different methodological and conceptual approaches aimed at searching for potential gene expression-based biomarkers associated with the prognosis of patients with HPV-positive HNSCC.

Keywords: biomarkers; gene expression; head and neck squamous cell carcinoma; human papillomavirus; transcripts.

Figure 1

The heterogeneity of HPV-positive HNSCC requires an understanding of the molecular biology underlying the abundance in the expression of viral proteins (HPV-on or HPV-off) or events generated by the integration of the viral genome into the cellular genome. Moreover, accurate stratification of patients based on transcriptional biomarkers such as NF-κB and APOBEC genes, dependent on non-canonical HPV drivers, would allow better selection of treatment strategies. Recently, liquid biopsy has been represented as a promising methodological tool for the identification of biomolecules such as circulating miRNAs associated with the clinical outcome of patients with HPV-positive HNSCC.