Basaloid squamous cell carcinoma of the head and neck is a mixed variant that can be further resolved by HPV status.

Basaloid squamous cell carcinoma (BSCC) of the head and neck is set apart as a distinct subtype of squamous cell carcinoma on the basis of its basaloid appearance and aggressive behavior. The purpose of this study was to determine whether BSCC could be further subdivided on the basis of human papillomavirus 16 (HPV16) status. HPV16 in situ hybridization was performed on 53 BSCCs of the head and neck. Of the 53 BSCCs, 21 (40%) arose in the oropharynx and 32 (60%) arose in nonoropharyngeal sites. HPV16 was detected in 34% of BSCCs overall, but the frequency varied by site. HPV16 was detected in 16 of 21 (76%) BSCCs of the oropharynx, but in only 2 of 32 (6%) BSCCs from nonoropharyngeal sites (P<0.0001, Fisher exact). The absence of HPV16 was significantly associated with decreased overall survival (Hazard ratio=17.1; 95% confidence interval=7.2-40.3, log-rank P=0.0001), even though patients with HPV16-positive carcinomas were more likely to present with lymph nodes metastases (P=0.01, Fisher exact). Morphologic similarities aside, BSCCs are composed of a mixed group of tumors that can be separated on the basis of HPV16 status. The distinction is important. HPV16-positivity in squamous cell carcinomas of the head and neck is now recognized as a powerful indicator of improved patient survival. HPV16 detection thus permits resolution of a less aggressive component within a high-grade subtype of head and neck carcinoma.