Boakye EA, et al. - Among patients who develop second primary malignancies (SPMs), researchers investigated their features when they develop from an index human papillomavirus (HPV)-related head and neck squamous cell carcinoma (HNSCC) and HPV-unrelated HNSCC and compared overall survival between those with HPV-related and HPV-unrelated index HNSCC. The study sample for this retrospective cohort analysis consisted of 113,259 subjects diagnosed with HNSCC between 2000 and 2014. Data reported that nearly 13,900 patients (12.3%) developed SPM. According to findings, HPV-unrelated HNSCC patients have a greater risk of developing SPM vs HNSCC-related HPV patients. To improve the long-term outcomes of patients, effective secondary disease prevention strategies should be developed. A higher risk of death was seen in patients with SPM whose index HNSCC was HPV-unrelated vs those whose index HNSCC was potentially HPV-related.