Oncogenic human papillomavirus (HPV) has been strongly implicated in the etiology of cervical cancer and its prevalence in patients with head and neck cancers, particularly oropharyngeal cancers (OPCs), is increasing at an alarming rate. In developed Western nations, HPV is responsible for approximately 90% of all OPC cases, while the proportion of HPV-related OPCs is progressively rising in developing countries. The 8th edition of the American Joint Committee on Cancer (AJCC) now incorporates HPV status as part of the staging system for oropharyngeal cancers. Moreover, due to distinct molecular pathways, the clinical presentation of HPV-positive tumors differs from that of HPV-negative tumors, a phenomenon supported by numerous studies. Despite these differences, the treatment regimens for HPV-associated cancers generally remain analogous to those for their HPV-negative counterparts. This review aims to elucidate the unique tumor characteristics and underlying molecular aberrations associated with HPV-induced malignancies.