No abstract

High-risk human papillomavirus (HPV) infection in conjunctival and lacrimal sac squamous cell carcinomas (SCCs) has been sporadically reported; however, its prevalence, clinicopathologic significance and surrogate markers have not been fully elucidated. Here, we attempted to clarify these questions in Japanese patients with conjunctiva and lacrimal sac SCCs. We retrospectively collected 51 conjunctival SCC and 7 lacrimal sac SCC samples and analyzed them for (1) transcriptionally active high-risk HPV infection using messenger RNA in situ hybridization and (2) protein expressions of p16 and Rb using immunohistochemistry (IHC). Among a total of 58 cases, 25 (43.1%) and 16 (27.6%) tumors were positive for p16-IHC and HPV in situ hybridization, respectively. Ten (19.6%) of the 51 conjunctival SCCs, especially in the palpebral conjunctiva, and 6 (85.7%) of the 7 lacrimal sac SCCs were positive for high-risk HPV. High-risk HPV infection was significantly associated with younger patients, nonkeratinizing SCC histology, p16-positivity and partial loss of Rb expression, but not with recurrence risk. Notably, p16-IHC was not a perfect surrogate marker for highrisk HPV infection; only 64% (16/25) of p16-positive tumors were positive for high-risk HPV. In contrast, the p16+/Rb partial loss pattern was exclusively correlated with high-risk HPV-positivity.The results suggest that the combination of p16 and Rb expression patterns by IHC could be a useful method to predict high-risk HPV infection in conjunctival and lacrimal sac SCCs. HPV infection may be of less prognostic value in this field of cancers.

Background/Aim: Surgery remains the standard treatment for salivary gland carcinoma (SGC). Our study investigated the association between epidermal growth factor receptor (EGFR) status in recurrent/metastatic SGC and the effectiveness of treatment with cisplatin/carboplatin and 5fluorouracil plus cetuximab (EXTREME). Patients and Methods: We retrospectively collected 19 SGCs from patients treated with the EXTREME regimen. After analyzing EGFR expression and gene copy number gain, we evaluated the correlation between EGFR status and clinicopathological factors and prognosis. Results: EGFR overexpression was detected in 77.8% cases, but not statistically associated with clinicopathological factors or prognosis. EGFR gene copy number gain was detected in 16.7% cases, and statistically positively correlated with lymph node metastasis (p=0.0291). The best overall response was partial response in two cases, stable disease in 15, and progressive disease in one case. The EXTREME regimen was discontinued in all cases. Conclusion: Our results suggest that SGCs are positive for EGFR protein expression but the response rate to the EXTREME regimen was unremarkable.Recurrent, locally advanced or distant metastatic salivary gland cancer (SGC) has no established systemic therapy. Surgical resection followed by radiation therapy is sometimes performed for SGC of advanced stage or with poor prognostic factors (1). SGC has different kinds of histopathological subtypes and three grading systems (2, 3), so it is frequently difficult to choose an optimum treatment.Epidermal growth factor receptor (EGFR) is a receptor tyrosine kinase that has an important role in tumor growth and progression in various kinds of cancer and serves as a therapeutic target of molecular targeted therapy (e.g., cetuximab) (4, 5). In fact, the EXTREME regimen (cisplatin/carboplatin, 5-fluorouracil plus cetuximab) is 979 This article is freely accessible online.

No abstract

Objectives/Hypothesis: The tumor immune microenvironment in temporal bone squamous cell carcinoma (TBSCC), including the programmed death-ligand 1 (PD-L1) expression and tumor-infiltrating lymphocytes (TILs), has not been established.Study Design: Retrospective cohort study. Methods: We performed immunohistochemistry analyses to retrospectively analyze 123 TBSCC cases for PD-L1 expression and TILs and their prognostic significance. We also evaluated the prognostic correlations between these immunomarkers and the therapeutic responses to chemoradiotherapy (CRT).Results: PD-L1 expression (≥1%) was detected in 62 (50.4%) TBSCC cases and was significantly associated with worse prognosis: progression-free survival (PFS), P < .0001; overall survival (OS), P = .0009. A high density of CD8 + TILs was significantly associated with better prognosis (PFS, P = .0012; OS, P = .0120). In contrast, a high density of Foxp3 + TILs tended to be associated with an unfavorable prognosis (PFS, P = .0148; OS, P = .0850). With regard to the tumor microenvironment subtypes defined by CD8 + TILs and PD-L1 expression, the CD8 low /PD-L1 + group showed significantly worse prognosis. Among the 36 neoadjuvant CRT-treated cases, PD-L1 expression was significantly associated with worse OS (P = .0132). Among the 32 CRT-treated cases without surgery, a high density of CD8 + TILs tended to be more highly associated with complete response to CRT compared to a low density of CD8 + TILs (P = .0702).Conclusions: These results indicate that the evaluation of the tumor immune microenvironment may contribute to the prediction of prognoses and the selection of an individualized therapeutic strategy for patients with TBSCC.