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Objectives The prognostic significance of human papillomavirus (HPV) genotypes in oropharyngeal squamous cell carcinoma (OPSCC) has garnered considerable attention due to the increasing reliance on HPV status for clinical decision‐making. This study aimed to compare the survival outcomes associated with different HPV genotypes in patients with OPSCC relative to HPV‐negative tumors, providing insights into the potential implications for treatment de‐intensification strategies. Methods Patients diagnosed with invasive OPSCC were included from the National Cancer Database (NCDB). Patients were stratified based on HPV status and genotype, with HPV‐negative tumors serving as the reference group. Multivariable Cox regression analysis was performed to assess the independent prognostic value of different HPV genotypes. Results Th majority of patient were classified as HPV‐positive ( N = 17,358, 70.0%), with HPV 16 being the most common genotype ( N = 15410/17358, 88.8%) compared with other high‐risk ( N = 1217/17,358, 7.0%) and low‐risk ( N = 731/17,358, 4.2%) HPV genotypes. A significantly lower risk of death was measured for all HPV‐positive compared with HPV‐negative tumors (HPV 16: adjusted HR 0.51; 95% CI: 0.49–0.54; other high‐risk HPV: adjusted HR 0.56; 95% CI: 0.49–0.63; low‐risk HPV: adjusted HR 0.59; 95% CI: 0.50–0.68; p < 0.001). Conclusion This study highlights the significant prognostic value of HPV genotypes in OPSCC, underscoring the superior survival outcomes of HPV‐positive tumors across all genotypes compared with HPV‐negative tumors. Detailed HPV subtype analysis can inform better treatment decisions and support de‐intensification strategies for patients with low‐risk genotypes. Level of Evidence 3 Laryngoscope , 135:695–704, 2025
Costantino et al. (Wed,) studied this question.