ABSTRACT
The aim of the study was to investigate prevalence of high-risk human papillomavirus (HR-HPV) infection in sinonasal carcinomas by immunohistochemistry, in situ hybridization, and polymerase chain reaction, detecting p16(INK4a) protein (p16) expression and presence of both HPV DNA and HPV E6/E7 messenger RNA (mRNA). The study comprised 47 males and 26 females, aged 23-83 years (median 62 years), mostly (67 %) with a squamous cell carcinoma (SCC). Of the tumors, 53 % arose in the nasal cavity, 42 % in the maxillary sinus, and 5 % in the ethmoid complex. The follow-up period ranged 1-241 months (median 19 months). HPV16, HPV18, or HPV35 were detected in 18/73 (25 %) tumors, 17 SCCs, and 1 small cell neuroendocrine carcinoma. There was a strong correlation between results of HPV detection methods and p16 expression (p < 0.005). HPV-positive SCCs occurred more frequently in smokers (p = 0.04) and were more frequently p16-positive (p < 0.0001) and nonkeratinizing (p = 0.02), the latter occurring more commonly in nasal cavity (p = 0.025). Median survival for HPV-positive SCC patients was 30 months, while for HPV-negative SCC patients was 14 months (p = 0.23). In summary, we confirm that HR-HPV is actively involved in the etiopathogenesis of a significant subset of sinonasal SCCs. p16 may be used as a reliable surrogate marker for determination of HPV status also in sinonasal SCCs. Although we observed a trend toward better overall survival in HPV-positive SCCs, the prognostic impact of HPV status in sinonasal carcinomas needs to be elucidated by further studies.
Subject(s)
Carcinoma, Squamous Cell/virology , Head and Neck Neoplasms/virology , Papillomaviridae/isolation & purification , Paranasal Sinus Neoplasms/virology , RNA, Messenger/analysis , Adult , Aged , Aged, 80 and over , Carcinoma, Squamous Cell/mortality , Carcinoma, Squamous Cell/pathology , Cyclin-Dependent Kinase Inhibitor p16 , DNA, Viral/analysis , Female , Head and Neck Neoplasms/mortality , Head and Neck Neoplasms/pathology , Humans , Immunohistochemistry , Male , Middle Aged , Neoplasm Proteins/analysis , Oncogene Proteins, Viral/genetics , Papillomavirus E7 Proteins/genetics , Paranasal Sinus Neoplasms/mortality , Paranasal Sinus Neoplasms/pathology , Repressor Proteins/genetics , Reverse Transcriptase Polymerase Chain Reaction , Squamous Cell Carcinoma of Head and Neck , Transcription, GeneticABSTRACT
The aim of the study was to test the hypothesis that oral plasma cell granuloma may represent a mucosal manifestation of immunoglobulin (Ig)G4-related disease (IgG4-RD) in the oral cavity. The study sample comprised two males and four females, aged 54-79 years (median 62 years). The lesions were localized on gingival/alveolar mucosa (four cases), hard palate, and floor of the mouth, measuring 17-40 mm (median 31 mm). The duration of the lesions ranged from 3 months to several years. Information on IgG4 serum levels was available for two patients, and these were increased to 1.85 and 1.65 g/L, respectively. The follow-up period ranged 11-30 months (median 13 months). None of the lesions recurred, and none of the patients developed any manifestation of IgG4-RD. Microscopically, all cases presented as nodular lesions composed of numerous polyclonal plasma cells admixed with lymphocytes, histiocytes, mast cells, and eosinophils, set within collagenized stroma in variable proportions. Obliterative phlebitis was observed in two cases. The number of IgG4-positive plasma cells ranged between 51 and 142 per HPF (median 114), while the IgG4/IgG ratio values ranged between 0.16 and 0.72 (median 0.44) and were above 0.40 in three cases. Based on international criteria, two cases were diagnosed as definite and one as probable IgG4-RD. Oral plasma cell granuloma is a heterogeneous group of lesions, and a subset may represent a mucosal manifestation of IgG4-RD in the oral cavity.
