Trends and epidemiology of human papillomavirus‐related oropharyngeal cancer in Chinese populations from 2010 to 2024

China's economic and societal transformations may influence cancer incidence, particularly as regional disparities shape lifestyles and sexual behaviors. This cohort study included 1002 patients, comprising 821 males (81.9%) and 181 females (18.1%), with oropharyngeal squamous cell carcinoma (OPSCC), at two medical centers in Beijing and Shanghai from 2010 to 2024. Human papillomavirus (HPV) status was assessed using p16 immunohistochemistry. The p16-positivity rate increased from 43.8% to 68.4%, reaching 57.5% overall. The proportion of p16-positive cases was significantly higher in southern China (65% vs. 51.4%) and females (83.4% vs. 51.8%) compared to northern China and males, respectively (p < 0.001). Although p16-positive cases were more frequently observed in urban areas (61% vs. 44.7%, p < 0.001), rural areas saw a significant increase from 8.3% to 62.2%. Regardless of p16 status, southern patients were generally older, had more tonsil lesions, and were at earlier stages than northern patients. p16-positive OPSCCs were more prevalent in younger individuals, with early-stage disease occurring more frequently in the tonsil compared to p16-negative ones (73.1% vs. 41.1%, p < 0.001). Recently, the burden has shifted to older men. p16-negative OPSCCs were more common in non-tonsillar regions among male smokers or drinkers. From 2010 to 2024, the p16-positive rate in tonsillar cancers increased from 48.4% to 79%, while the proportion among non-tonsil OPSCCs remained stable in males but increased significantly in females (33.3% to 80%). A substantial proportion of OPSCC cases is caused by HPV, with an increasing trend, especially in the south, underscoring the importance of vaccination programs in China.