Human papillomavirus-positive basaloid squamous cell carcinomas of the upper aerodigestive tract: a distinct clinicopathologic and molecular subtype of basaloid squamous cell carcinoma

Abstract

Basaloid squamous cell carcinoma of the upper aerodigestive tract is a rare, morphologically distinct variant of squamous cell carcinoma that is thought to be clinically aggressive. The histologic features are distinct from, but often confused with, those of human papillomavirus-related oropharyngeal nonkeratinizing squamous cell carcinoma. The role of human papillomavirus as an etiologic agent in true basaloid squamous cell carcinoma is controversial. The purpose of this study was to determine human papillomavirus prevalence and its clinicopathologic significance in upper aerodigestive tract tumors with true basaloid squamous cell carcinoma histology. Twenty-eight cases were identified, 12 in the oropharynx and 16 in the larynx and/or hypopharynx. High-risk human papillomavirus in situ hybridization and immunohistochemistry for p16 and p53 were performed. Nine (75%) of the oropharyngeal and none of the larynx/hypopharynx tumors were human papillomavirus positive. Human papillomavirus-positive tumors affected younger patients. No significant statistical differences in patients' sex, tumor stage, treatment modality, or length of follow-up were observed between the 2 groups. Viral status showed a strong, positive correlation with p16 (P < .001) and a strong, negative correlation with p53 (P < .0001) immunoreactivity. Overall survival was better for human papillomavirus-positive basaloid squamous cell carcinomas (P < .05), with 86% of patients alive at 3 years compared with 35.3% of patients with human papillomavirus-negative tumors. These findings suggest that a subset of basaloid squamous cell carcinomas is virally driven. These tumors occur almost exclusively in the oropharynx, are molecularly distinct from their human papillomavirus-negative counterparts, and have a more favorable clinical outcome.

Fig. 1

Basaloid squamous cell carcinoma has a lobular architecture (‘jigsaw puzzle’ growth pattern) with frequent overlying squamous dysplasia (A, 100×); focal, abrupt squamous differentiation with keratin pearl formation and areas of central necrosis (B, 200×); stromal hyalinosis (C, 200×); and crowded, round, hyperchromatic cells with scant cytoplasm and cystic spaces containing mucin-like material (D, 400×).

Fig. 2

Nonkeratinizing squamous cell carcinoma composed of nests of tumor cells with central necrosis (A, 100×). The tumor cells have indistinct cell borders and spindled, hyperchromatic nuclei with indistinct nucleoli (B, 600×).

Fig. 3

HPV-positive tumor (A, 600×) and HPV-negative tumor (B, 600×).

Fig. 4

p16-positive tumor (A, 400×) and p16-negative tumor (B, 400×). p53-positive tumor (C, 400×). p53-negative tumor with less than or equal to 5% p53-positive cells (D, 400×).

Fig. 5

Kaplan-Meier curves of overall survival (A) and disease-specific survival (B) by HPV status.