Prevalence of high-risk human papillomavirus DNA in nonkeratinizing (cylindrical cell) carcinoma of the sinonasal tract: a distinct clinicopathologic and molecular disease entity

Carcinomas of the nose and paranasal sinuses are a heterogeneous group of neoplasms that differ histologically, biologically, and clinically. Some of these tumors are known to harbor high-risk human papillomavirus (HPV) DNA. In an attempt to identify specific phenotypes associated with HPV infection, 39 cases of sinonasal carcinomas were evaluated by PCR for the presence of HPV DNA. The tumors were also studied with a panel of immunohistochemical stains, including p16, p53, and Ki-67 antibodies. Twenty-one cases were identified as keratinizing squamous cell carcinoma (KSCC) with a male-to-female ratio of 3:1. Eight cases were nonkeratinizing (cylindrical cell) carcinoma (NKCa) with a male-to-female ratio of 1:1. Ten cases were sinonasal undifferentiated carcinoma (SNUC), and 9 of these patients were men. HPV DNA, particularly type 16, was detected in 9 cases: 4 of 21 (19%) of KSCC, 4 of 8 (50%) of NKCa, and 1 of 10 (10%) of SNUC. In addition to a higher prevalence of HPV DNA in NKCa, the tumors also showed a distinct immunophenotype characterized by strong and diffuse staining for p16, high labeling scores for Ki-67, and negative or low reactivity to p53. On the other hand, KSCC and SNUC were either negative or weakly reactive to p16 antibodies. KSCC cases were more likely to be positive and more strongly reactive to p53 stain. Unlike KSCC, SNUC had high Ki-67 labeling scores. These observations suggest that NKCa of the sinonasal tract is a distinct histopathologic and molecular disease entity, which should be added to the list of upper aerodigestive tract tumors with strong etiologic relationship to high risk HPV.