Oropharyngeal squamous cell carcinomas (OPSCC) represent a major public health challenge. In 2020, the international agency for research on cancer (IARC) recorded 98,421 cases of OPSCC worldwide. Over the past decade, the epidemiological profile of patients with OPSCC has shifted, mainly due to a change in etiological factors. Previously, alcohol and tobacco were considered the primary contributors, but the human papillomavirus (HPV) is now recognized as the leading cause of these tumors. This study aimed to conduct a literature review on the relationship between OPSCC and HPV for the general practitioner. The review examined the primary clinical differences between HPV+and HPV−OPSCC, their prognosis and treatment. In addition, the various HPV diagnostic methods were analyzed. Although there is a vast amount of literature on HPV, this review is unique in its ability to present the key information in an organized and accessible way and enables healthcare professionals to gain a better understanding of the relationship between HPV and oropharyngeal cancer. This, in turn, can contribute to the prevention of various cancers caused by the HPV virus, including oropharyngeal cancer.