HPV-specific treatment trends in oropharyngeal squamous cell carcinoma: a population-based analysis with...

To characterise population-level treatment trends in oropharyngeal squamous cell carcinoma (OPSCC) over 14 years and determine whether trends differ between p16-positive and p16-negative disease.

We analysed 66,394 OPSCC patients from SEER (2010-2023) for secular trend analysis, and 27,069 treated patients with confirmed squamous cell histology and documented p16/HPV status (2018-2023) for HPV-stratified and stage-stratified analyses. Cochran-Armitage trend tests, multivariable logistic regression, and formal HPV × year and stage × year interaction tests (likelihood ratio test), with Holm-Bonferroni correction for multiplicity, were employed.

CRT increased from 52.6% to 59.9% and surgery declined from 39.0% to 29.5% over 2010-2023 (both p < 0.001). In HPV-stratified analysis, CRT increased significantly in both p16-positive (52.6% to 60.8%) and p16-negative patients (52.9% to 60.2%; both p < 0.001). Surgery declined in p16-positive patients (35.3% to 29.1%; p < 0.001) with a non-significant decline in p16-negative patients (31.0% to 27.7%; p = 0.051). After Holm-Bonferroni correction, only the surgery HPV × year interaction remained significant (adjusted p = 0.040); the CRT interaction did not (adjusted p = 0.185). Treatment shifts persisted across Stage I-II and Stage III-IV disease.

Treatment trends in OPSCC shifted substantially over the AJCC 8th Edition era. The decline in surgical treatment is HPV-specific and stage-independent; the rise in CRT is a broader trend affecting both HPV groups, though more pronounced in p16-positive disease. These findings underscore the importance of formal interaction testing and multiplicity correction when characterising subgroup-specific population trends.