Human papillomavirus-related carcinomas of the sinonasal tract

Abstract

High-risk human papillomavirus (HPV) is an established cause of head and neck carcinomas arising in the oropharynx. The presence of HPV has also been reported in some carcinomas arising in the sinonasal tract, but little is known about their overall incidence or their clinicopathologic profile. The surgical pathology archives of The Johns Hopkins Hospital were searched for all carcinomas arising in the sinonasal tract from 1995 to 2011, and tissue microarrays were constructed. p16 immunohistochemical analysis and DNA in situ hybridization for high-risk types of HPV were performed. Demographic and clinical outcome data were extracted from patient medical records. Of 161 sinonasal carcinomas, 34 (21%) were positive for high-risk HPV DNA, including type 16 (82%), type 31/33 (12%), and type 18 (6%). HPV-positive carcinomas consisted of 28 squamous cell carcinomas and variants (15 nonkeratinizing or partially keratinizing, 4 papillary, 5 adenosquamous, 4 basaloid), 1 small cell carcinoma, 1 sinonasal undifferentiated carcinoma, and 4 carcinomas that were difficult to classify but exhibited adenoid cystic carcinoma-like features. Immunohistochemistry for p16 was positive in 59/161 (37%) cases, and p16 expression strongly correlated with the presence of HPV DNA: 33 of 34 (97%) HPV-positive tumors exhibited high p16 expression, whereas only 26 of 127 (20%) HPV-negative tumors were p16 positive (P<0.0001). The HPV-related carcinomas occurred in 19 men and 15 women ranging in age from 33 to 87 years (mean, 54 y). A trend toward improved survival was observed in the HPV-positive group (hazard ratio=0.58, 95% confidence interval [0.26, 1.28]). The presence of high-risk HPV in 21% of sinonasal carcinomas confirms HPV as an important oncologic agent of carcinomas arising in the sinonasal tract. Although nonkeratinizing squamous cell carcinoma is the most common histologic type, there is a wide morphologic spectrum of HPV-related disease that includes a variant that resembles adenoid cystic carcinoma. The distinctiveness of these HPV-related carcinomas of the sinonasal tract with respect to risk factors, clinical behavior, and response to therapy remains to be clarified.

Figure 1

HPV-related sinonasal carcinomas. A–B. Most of the HPV-related sinonasal squamous cell carcinomas were morphologically identical to HPV-related oropharyngeal carcinomas, exhibiting little or no keratinization, tumor infiltration by lymphocytes, and limited desmoplastic stromal reaction (Hematoxylin and eosin, X100 (A) and X200 (B)). C. All but one of the HPV-positive cases was diffusely positive for p16 in a nuclear and cytoplasmic distribution (p16 immunohistochemistry, X200). D. HPV positivity was defined by the presence of dot-like in situ hybridization signals in tumor nuclei (High risk HPV in situ hybridization, X400).

Figure 2

HPV-related sinonasal carcinomas. Histologic variants of HPV-related sinonasal carcinomas included: A. Five papillary squamous cell carcinomas (Hematoxylin and eosin, X100); B. Five adenosquamous carcinomas (Hematoxylin and eosin, and mucicarmine (inset), X200); C. One small cell carcinoma (Hematoxylin and eosin, X200); and D. One sinonasal undifferentiated carcinoma (Hematoxylin and eosin, X200).

Figure 3

HPV-related sinonasal carcinomas. A. Four HPV-associated carcinomas exhibited features of salivary gland carcinomas, particularly adenoid cystic carcinoma. Although these tumors were predominantly solid (right), they also showed cribriform areas with duct formation (left) (Hematoxylin and eosin, X400). B. The tumors were strongly immunoreactive to p16 (p16 immunohistochemistry, X400), and punctate hybridization signals were seen in tumor nuclei on HPV in situ hybridization (inset, high-risk HPV in situ hybridization, X400).

Figure 4

Kaplan-Meier plots showing the 15-year survival curves of all types of HPV positive and HPV negative sinonasal carcinomas (A), and squamous cell carcinomas only (B).