Smoking, Tumor Subsite, and Stage as Predictors of Second Primary Tumors in Oropharyngeal Squamous Cell Carcinoma ( <scp>OPSCC</scp> ): A Retrospective Cohort Study

BACKGROUND: Late detection of second primary tumors (SPTs) in survivors of oropharyngeal squamous cell carcinoma (OPSCC) remains a major clinical challenge, even during routine follow-up. This study aimed to develop a predictive risk model and a nomogram to estimate the likelihood of SPT development in patients with OPSCC. METHODS: The authors conducted a retrospective cohort study of 514 consecutive patients diagnosed with OPSCC between 2008 and 2018. Sociodemographic and clinical data were obtained from medical records. Bidirectional cause-specific Cox regression analysis was used to identify independent risk factors for SPT development. A predictive nomogram was subsequently constructed based on the final model. RESULTS: Among the 514 patients, 51 (9.9%) developed SPTs, most commonly in the head and neck region, esophagus, or lungs. The cohort was predominantly male (88.7%) with a median age of 58 years. Most tumors were p16-negative (76.7%) and presented at advanced stages (III-IV) in 74.9% of cases. The median time to SPT diagnosis was 34.6 months. Independent risk factors for SPT included a history of smoking (HR = 4.5, p = 0.14), primary tumors located in the soft palate, uvula, vallecula, posterior oropharyngeal wall, or unspecified oropharyngeal sites (HR = 2.17, p = 0.01), and advanced stage at diagnosis (HR = 2.19, p = 0.04). CONCLUSIONS: Non-HPV-related OPSCC subsites, smoking history, and advanced tumor stage were independently associated with a higher risk of SPT. These variables were incorporated into a nomogram designed to support individualized surveillance and facilitate earlier SPT detection in high-risk patients.