High-risk genotypes of the human papillomavirus (HPV), particularly HPV type 16, are found in a distinct subset of head and neck squamous cell carcinomas (HNSCC). Thus, these HPV-associated HNSCC may be prevented or treated by vaccines designed to induce appropriate HPV virus-specific immune responses. Infection by HPV may be prevented by neutralizing antibodies specific for the viral capsid proteins. In clinical trials, vaccines comprised of HPV virus-like particles (VLPs) have shown great promise as prophylactic HPV vaccines. However, given that capsid proteins are not expressed at detectable levels by infected basal keratinocytes, vaccines with therapeutic potential must target other non-structural viral antigens. Two HPV oncogenic proteins, E6 and E7, are important in the induction and maintenance of cellular transformation and are co-expressed in the majority of HPV-containing carcinomas. Therefore, therapeutic vaccines targeting these proteins may have potential to control HPV-associated malignancies. Various candidate therapeutic HPV vaccines are currently being tested whereby E6 and/or E7 is administered in live vectors, in peptides or protein, in nucleic acid form, as components of chimeric VLPs, or in cell-based vaccines. Encouraging results from experimental vaccination systems in animal models have led to several prophylactic and therapeutic vaccine clinical trials. Should they fulfill their promise, these vaccines may prevent HPV infection or control its potentially life-threatening consequences in humans.