Zhu G, Amin N, Herberg ME, et al. - In human papillomavirus (HPV)-positive oropharyngeal but not non-oropharyngeal tumors, findings revealed an association of tumor site with the immune landscape as well as with improved survival, providing a rationale for stratifying HPV-associated tumors by site.

• Participants were 768 patients, including 514 (66.9%) with head and neck squamous cell carcinoma (HNSCC) (380 male [73.9%]; mean [SD] age, 59.5 [10.8] years) and 254 (33.1%) with CESC (cervical squamous cell carcinoma and/or endocervical adenocarcinoma) (mean [SD] age, 48.7 [14.1] years).

• A statistically significant improvement in overall survival was observed in relation to HPV positivity in patients with oropharyngeal squamous cell carcinoma (OPSCC) (adjusted hazard ratio [aHR], 0.06) but not in those with non-OP (nonoropharyngeal) HNSCC (aHR, 0.64) or CESC (aHR, 0.50).

• Increased tumor immune infiltration and immunomodulatory receptor expression was noted in HPV-positive OPSCCs vs HPV-negative OPSCCs.

• There was a greater expression of immune-linked metrics including B cells, T cells, CD8+ T cells, T-cell receptor diversity, B-cell receptor diversity, and cytolytic activity scores, independent of tumor variant burden, in HPV-positive OPSCCs vs HPV-positive non-OP HNSCCs.

• On comparing HPV-positive non-OP HNSCCs and HPV-positive CESCs to their HPV-negative counterparts, findings revealed similar immune-related metrics.

• Patients with HPV-positive OPSCC had significantly higher 2-year overall survival rate vs those with HPV-negative OPSCC (92.0% vs 45.8%; HR, 0.10).