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 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 immunohistochemistry and DNA in situ hybridization for high-risk types of HPV were performed. Demographic and clinical outcomes 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 non- 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 < .0001). The HPV-related carcinomas occurred in 19 men and 15 women ranging in age from 33 to 87 years (mean 54). 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. While non-keratinizing 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.

Sinonasal Squamous Cell Carcinoma: A Review with Emphasis on Emerging Histologic Subtypes and the Role of Human Papillomavirus

“…The relative fraction of KSCC versus NKSCC in the literature has varied somewhat, probably depending on subtle variations in definitions of the two. Summarizing results of the three largest studies to define them (Table 1), there were 99 KSCC (60 %) and 66 NKSCC (40 %) [6][7][8][9][10]. KSCC is morphologically identical to such tumors arising elsewhere ( Fig.…”

Genetic and molecular alterations in olfactory neuroblastoma: implications for pathogenesis, prognosis and treatment

“…Additionally, HPV is almost always positive in oropharyngeal NEC, which may help in finding the right diagnosis in tumors involving the oropharynx [95]. Also sinonasal undifferentiated carcinoma (SNUC) can exhibit HPV positivity in between 6% to 47% of patients [96, 97]. …”

Among Sinonasal Tumors, CDX-2 Immunoexpression is not Restricted to Intestinal-Type Adenocarcinomas

“…The cases included 6 cases of sinonasal ITAC on whole slides and 176 non-intestinal sinonasal tumors present on previously constructed tissue microarrays [21]. Two to three cores 1 mm in diameter were taken from each donor block to address tumor heterogeneity.…”

“…The non-intestinal sinonasal neoplasms included 81 squamous cell carcinomas and variants, 48 esthesioneuroblastomas, 20 salivary-type adenocarcinomas, 16 sinonasal undifferentiated carcinomas, 6 non-intestinal surface-type adenocarcinomas, 3 NUT midline carcinomas, and 2 small cell carcinomas. The human papillomavirus status for each sinonasal carcinoma was previously determined as previously described [21].…”