Plant Bioactive Constituents and Their Therapeutic Potential in HPV-Positive Oropharyngeal Squamous Cell Carcinoma

Human papillomavirus (HPV) has become a leading cause of oropharyngeal cancers, alongside well-known risk factors such as tobacco and alcohol use. Currently, HPV-positive oropharyngeal squamous cell carcinoma (HPV-OPSCC) has increased significantly in developed countries, with HPV-16 being the most common high-risk subtype. Clinically, HPV-OPSCC shows clear differences in prognosis compared to HPV-negative tumors, especially regarding survival rates and treatment responses. Patients with HPV-OPSCC tend to have notably better survival outcomes and a more favorable outlook. Strong evidence indicates that HPV-related oropharyngeal cancers form a distinct epidemiological, clinical, and molecular group, setting them apart from non-HPV-related cancers. As a result, treatment strategies for these subtypes should follow specific clinical protocols to achieve the best outcomes. Additionally, the viral oncoproteins E6 and E7, which systematically disrupt host tumor-suppressor networks, provide compelling reasons for targeted phytotherapeutic interventions. Therefore, there is growing interest in exploring plant bioactive compounds with promising anti-HPV and anticancer effects that target key oncogenic pathways. This review aims to compile the latest data on bioactive phytochemicals—such as polyphenols, flavonoids, carotenoids, glucosinolate derivatives, terpenoids, and alkaloids—with mechanistic evidence in HPV-OPSCC and to highlight their molecular interactions across oncogenic signaling pathways, focusing on research published from 2015 to 2025.