Diverging trends in head and neck cancer incidence: SEER 17 analysis of HPV-related and non–HPV-related sites, 2000–2019.

e22584 Background: Population-based evidence suggests divergent incidence patterns for head and neck squamous cell carcinoma (HNSCC) at HPV-related versus non–HPV-related sites, but contemporary estimates spanning both groups are limited. Methods: We analyzed SEER Research Plus 17 registries (November 2024 submission), diagnosis years 2000–2019. HNSCC was restricted to squamous histology (ICD-O-3 8050–8084). HPV-related HNC was defined by oropharyngeal subsites (base of tongue, tonsil, soft palate, oropharynx, Waldeyer’s ring) as a site-based proxy; non–HPV-related HNC comprised oral cavity, hypopharyngeal, and laryngeal subsites. Age-adjusted incidence rates (per 100,000; 2000 U.S. standard) were calculated overall and by sex and age group. Average annual percent change (AAPC) with 95% CIs summarized 2000–2019 trends. Results: Overall HNC incidence declined modestly from 11.5 (8,011 cases) in 2000 to 10.5 (11,074 cases) in 2019 (AAPC −0.6; 95% CI −0.7 to −0.4). HPV-related HNC increased from 3.3 (2,323 cases) to 4.4 (4,694 cases) (AAPC 1.5; 95% CI 1.1 to 1.8), while non–HPV-related HNC decreased from 9.3 to 7.7 (AAPC −1.1; 95% CI −1.2 to −0.9). Among men, HPV-related HNC rose from 5.4 (1,766 cases) to 7.7 (3,933 cases) (AAPC 1.7; 95% CI 1.1 to 2.2), with the steepest increases at ages 60–69 (AAPC 2.6) and ≥70 (AAPC 3.0). The proportion of all HNCs that were HPV-related increased from ~29% (2000) to 42% (2019). Conclusions: From 2000–2019, overall HNC incidence decreased slightly in SEER 17, but HPV-related (oropharyngeal-proxy) HNC increased, most notably among older men, while non–HPV-related sites declined. Because HPV-related disease was defined by anatomic proxy rather than tumor HPV status, findings should be interpreted as site-based trend divergence. Results support sustaining tobacco/alcohol control while maintaining high HPV vaccination coverage and monitoring HPV-related HNC burden over time. Overall incidence trends in head and neck cancer, HPV-related (oropharyngeal-proxy), and non–HPV-related sites in SEER 17, 2000–2019. Outcome group Incidence rate, 2000 (cases) Incidence rate, 2019 (cases) AAPC, 2000–2019 (95% CI) All HNC 11.5 (8,011) 10.5 (11,074) −0.6 (−0.7 to −0.4) HPV-related HNC (oropharyngeal proxy) 3.3 (2,323) 4.4 (4,694) 1.5 (1.1 to 1.8) Non–HPV-related HNC 9.3 7.7 −1.1 (−1.2 to −0.9) Incidence rates are per 100,000 persons and age-adjusted to the 2000 U.S. standard population. HPV-related HNC was defined using anatomic oropharyngeal subsites as a site-based proxy (not tumor HPV status). AAPC indicates average annual percent change; CI, confidence interval; HNC, head and neck cancer.