Biology of human papillomavirus infection and immune therapy for HPV-related head and neck cancers.

This article outlines the biology of human papillomavirus (HPV) infection of human mucosa and the cellular pathways that are altered through viral infection. The article provides a conceptual framework with which to understand the 2 major immunologic strategies to address HPV-related diseases: (1) prevention of primary HPV infection through the use of prophylactic vaccines and (2) treatment of established infection and diseases through therapeutic vaccines. Nonimmunologic therapy that targets cellular dysregulation induced by HPV infection is also discussed. The challenges in actualizing these conceptually attractive therapies on both a societal and biological level are examined.

Prognostic significance of human papillomavirus in oropharyngeal squamous cell carcinomas.

OBJECTIVES/HYPOTHESIS: The human papillomavirus (HPV) has been identified as a causative factor in 20% to 25% of all head and neck squamous cell carcinomas (HNSCC). Ongoing research suggests that the presence of HPV DNA in HNSCC predicts a positive prognosis with respect to disease-free and overall survival. However, most studies have been limited by the heterogeneity in treatment regimens and/or anatomic subsites of tumor origin. In this study, we correlate clinical outcomes with HPV status for patients with oropharyngeal carcinomas who were uniformly treated with a concurrent chemoradiation treatment protocol. STUDY DESIGN: Retrospective study. METHODS: Demographic and clinicopathologic parameters, including age at diagnosis, gender, race, smoking and alcohol history, tumor stage and grade, locoregional recurrence, metastatic spread, recurrence-free survival, overall survival and disease-specific death, were obtained from medical charts and established databases. These parameters were correlated with HPV status of the tumors established by in situ hybridization analysis. RESULTS: HPV positivity correlated with improved clinical outcomes regarding locoregional control (P = .042), recurrence-free survival (P = .009), overall survival (P = .017), and disease-specific death (P = .09). Advanced T stage was a significant risk factor for recurrence and death independent of HPV status. CONCLUSIONS: In patients with oropharyngeal carcinoma uniformly treated with chemoradiation, the presence of HPV is a favorable prognostic indicator with respect to recurrence and overall survival. However, advanced T stage was an independent risk factor for recurrence and death that can to some degree offset this benefit.

Immunotherapy for head and neck cancer.

Head and neck cancer represents a challenging disease. Despite recent treatment advances, which have improved functional outcomes, the long-term survival of head and neck cancer patients has remained unchanged for the past 25 years. One of the goals of adjuvant cancer therapy is to eradicate local regional microscopic and micrometastatic disease with minimal toxicity to surrounding normal cells. In this respect, antigen-specific immunotherapy is an attractive therapeutic approach. With the advances in molecular genetics and fundamental immunology, antigen-specific immunotherapy is being actively explored using DNA, bacterial vector, viral vector, peptide, protein, dendritic cell, and tumor-cell based vaccines. Early phase clinical trials have demonstrated the safety and feasibility of these novel therapies and the emphasis is now shifting towards the development of strategies, which can increase the potency of these vaccines. As the field of immunotherapy matures and as our understanding of the complex interaction between tumor and host develops, we get closer to realizing the potential of immunotherapy as an adjunctive method to control head and neck cancer and improve long-term survival in this patient population.