The insight into the biological nature of head and neck squamous cell carcinoma has evolved significantly in the last few years. Tobacco use and alcohol consumption are proven risk factors of head and neck squamous cell carcinoma. Cancer patients possessing such a tumor are generally elderly, mostly in fifth or sixth decade of life. In addition, significant association of head and neck squamous cell carcinoma with infection by human papillomavirus (HPV) was proven. HPV is now considered to be one of the most important risk factors, particularly for oropharyngeal carcinoma. HPV positive tumors of oropharynx are associated with significantly better prognosis. Experimental and clinical data indicate that HPV positive and HPV negative tumors can be considered as two different entities and it has not been clarified which factors are crucial for better prognosis of HPV positive tumors. The character of immune reaction, which contributes to distinct prognosis, may be one of the important factors. This review summarizes current knowledge concerning various aspects of antitumor immune responses in HPV positive and HPV negative tumors. Recent studies have shown that a broad repertoire of tumor infiltrating HPV specific T-cells is detectable in almost all patients with HPV positive tumors. Despite this, there is a development of tumor, which may be facilitated by abnormalities in antigen processing, T-cell dysfunction or prevalence of immunosuppressive cells. Nonetheless, the immunologic profile of HPV positive vs. HPV negative head and neck squamous cell carcinoma is associated with better outcome, and HPV specific immune response is suggested to play an essential role in the better response to conventional therapy of HPV positive patients. We also discuss HPV specific antitumor immunotherapy approaches, which are now tested in clinical trials.

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