Classical epidermoid carcinoma is the most frequent head and neck malignant neoplasm. Some particular variants are nevertheless of interest as they harbor a different prognosis, require specific care management and may arise from an alternate oncogenesis path. Best examples are verrucous carcinoma, basal-like or spindle cell carcinoma. Recent studies pointed out the critical role of infection with oncogenic HPV strains in the development of these carcinomas, especially in the oropharynx. In addition, HPV infection is changing the epidemiological profile of these cancers seems to have a prognostic value. New targeted therapies and prognostic markers will be discussed as they may dramatically improve the outcome of these tumors.