Search

Background: Human papillomavirus (HPV) is an increasing risk factor for cancer. HPV‐associated oropharyngeal squamous cell carcinoma (OPSCC) is associated with a favorable outcome. Blockstaining for p16 is a surrogate marker for HPV+ OPSCC. In oral and laryngeal squamous cell carcinoma (OSCC/LSCC), the relevance of p16 immunohistochemistry, alone or in combination with other cell cycle‐related proteins, to identify HPV‐driven non‐OPSCC is less well understood. Methods: We stained for p16, pRb, cyclin D1, and p53 in 327 HNSCC. In 310 OPSCC, HPV‐status was assessed by HPV DNA PCR. In 119 non‐OPSCC, RNA in situ hybridization was additionally performed. HPV‐status was correlated with staining patterns, p53 and clinical data. Results: The OPSCC showed blockstaining for p16 in 36%, 8% were equivocal. Of these, HPV‐testing was performed in 57%, and 53% were positive for HPV DNA. HPV‐association correlated with absence of pRb and cyclin D1 and favorable outcome. In non‐OPSCC, 18% showed p16‐blockstaining, and 13% showed E6/E7 RNA. Six of seven HPV+ OSCC and 8/8 LSCC lost pRb and cyclin D1. Compared to HPV‐negative counterparts, patients with HPV+ cancers had lower rates of alcohol consumption and keratinizing morphology. HPV‐positive OSCC had a longer overall survival (p < 0.05). HPV subtype 16 was the most common. Conclusions: We conclude that HPV‐positive non‐OPSCC are associated with p16 overexpression and low levels of pRb and cyclin D1. High expression of pRb and cyclin D1 indicates HPV‐negativity. [ABSTRACT FROM AUTHOR]

Objectives: The World Health Organization's definition of oral epithelial dysplasia includes differentiated dysplasia, which is defined by purely architectural abnormalities of oral mucosa without cytological changes. We analysed differentiated dysplasia's frequency, progression risk and correlation with oral brush cytology. Materials and Methods: Cytoarchitectural criteria and expression patterns of keratin 13/17 and ki67 were studied in oral biopsies clinically diagnosed with leukoplakia. Biopsies were assessed for dysplasia and its grade. Available brush cytology findings were obtained from clinical records. Results: We included 159 biopsies from 112 patients (33% differentiated dysplasia; 27% keratosis without dysplasia; oral epithelial dysplasia with atypia of mild, moderate and severe degree including invasive cancers in 9%, 8% and 7%, respectively). Keratin 13 loss and keratin 17 gain were higher in differentiated‐dysplasia cases (p < 0.0001), which had the highest hypergranulosis frequency. Keratin 17 expression was associated with higher malignant‐transformation rates (p = 0.0028). The transformation rate and time were comparable between dysplasia with atypia and differentiated‐dysplasia cases, which had higher progression rates and shorter time periods than keratosis cases without dysplasia (p = 0.08). Cytology prior to differentiated dysplasia all indicated normal oral mucosa. Conclusions: Keratin 17 but not oral brush cytology can help identify patients with differentiated dysplasia with higher risk for malignant transformation. [ABSTRACT FROM AUTHOR]

Upper tract urothelial carcinoma (UTUC) accounts for 5–10% of all UCs. Immune checkpoint inhibitors (ICIs) have been established for UCs. The prognostic and predictive potential of programmed cell death ligand 1 (PD-L1) expression to stratify patients benefiting from ICIs is not fully understood, and additional markers influencing the impact of PD-L1-mediated ICI response are needed. Previously, the chemokine-like MARVEL transmembrane domain-containing protein 6 (CMTM6) was identified as a positive regulator of PD-L1. Our aim was to investigate the expression profiles and impact of PD-L1 and CMTM6 protein status on the prognostic parameters and survival of UTUC patients. In this retrospective study, the combined positive score (CPS), tumor proportion score (TPS), and immune cell score (ICS) for PD-L1 and CMTM6 were determined. High PD-L1 CPS, ICS, and TPS were found in 77.4%, 58.3%, and 45.2% of cases, and high CMTM6 CPS, ICS, and TPS were seen in 52.5%, 51.5%, and 55.5% of cases, respectively. The scores of both markers had a significant positive correlation. High PD-L1 and CMTM6 expression was coupled with higher pT status, WHO grade, necrosis, and metastasis (p < 0.05, respectively). In the univariate survival analysis, patients with a PD-L1 ICS high and higher degree of intratumoral inflammation showed significantly longer overall survival. Compared to other studies on UC, our study shows a substantially higher rate of PD-L1-positive tumors. CMTM6 was associated with more aggressive tumors. [ABSTRACT FROM AUTHOR]