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BackgroundStandard treatment of oropharyngeal squamous cell carcinoma (OPSCC) is associated with high morbidity, whereas immunotherapeutic approaches using PD-1:PD-L1 checkpoint blockade only show moderate response rates in OPSCC patients. Therefore, a better stratification of patients and the development of novel therapeutic protocols are crucially needed. The importance of tumor-infiltrating B cells (TIL-Bs) in shaping antitumor immunity remains unclear; therefore, we analyzed frequency, phenotype, prognostic value and possible roles of TIL-Bs in OPSCC.MethodsWe utilized transcriptomic analysis of immune response-related genes in 18 OPSCC samples with respect to human papillomavirus (HPV) status. The density and localization of CD20+, CD8+ and DC-LAMP+ cells were subsequently analyzed in 72 tissue sections of primary OPSCC samples in relation to patients’ prognosis. The immunohistochemical approach was supplemented by flow cytometry-based analysis of phenotype and functionality of TIL-Bs in freshly resected primary OPSCC tissues.ResultsWe observed significantly higher expression of B cell-related genes and higher densities of CD20+ B cells in HPV-associated OPSCC samples. Interestingly, CD20+ TIL-Bs and CD8+ T cells formed non-organized aggregates with interacting cells within the tumor tissue. The densities of both intraepithelial CD20+ B cells and B cell/CD8+ T cell interactions showed prognostic significance, which surpassed HPV positivity and CD8+ TIL density in stratification of OPSCC patients. High density of TIL-Bs was associated with an activated B cell phenotype, high CXCL9 production and high levels of tumor-infiltrating CD8+ T cells. Importantly, the abundance of direct B cell/CD8+ T cell interactions positively correlated with the frequency of HPV16-specific CD8+ T cells, whereas the absence of B cells in tumor-derived cell cultures markedly reduced CD8+ T cell survival.ConclusionsOur results indicate that high abundance of TIL-Bs and high density of direct B cell/CD8+ T cell interactions can predict patients with excellent prognosis, who would benefit from less invasive treatment. We propose that in extensively infiltrated tumors, TIL-Bs might recruit CD8+ T cells via CXCL9 and due to a highly activated phenotype contribute by secondary costimulation to the maintenance of CD8+ T cells in the tumor microenvironment.Electronic supplementary materialThe online version of this article (10.1186/s40425-019-0726-6) contains supplementary material, which is available to authorized users.

The average personnel figures in Europe are now consistent with, or even more favourable than the QUARTS recommendations, probably reflecting a combination of better availability as such, in parallel with the current use of more complex treatments than a decade ago. A considerable variation in available personnel and delivered courses per year however persists among the highest and lowest staffing levels. This not only reflects the variation in cancer incidence and socio-economic determinants, but also the stage in technology adoption along with treatment complexity and the different professional roles and responsibilities within each country. Our data underpin the need for accurate prediction models and long-term education and training programmes.

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.

The aim of the study was to investigate the role of high-risk human papillomavirus (HR-HPV) infection in the etiopathogenesis of oral (OSCC) and oropharyngeal (OPSCC) squamous cell carcinoma in non-smoking and non-drinking patients (NSNDP). Twenty-four OSCCs and 22 OPSCCs were analyzed by immunohistochemistry for p16(INK4a) protein (p16) expression and by chromogene in situ hybridization (CISH) and polymerase chain reaction (PCR) for HR-HPV DNA presence. The series included 23 males and 23 females aged 35-93 years. p16 expression was seen in 7 out of 24 (29%) OSCCs and in 22 out of 22 (100%) OPSCCs. Using CISH, HR-HPV DNA was observed in 6 out of 24 (25%) OSCCs and in 21 out of 22 (95%) OPSCCs. HPV DNA was found in 3 out of 24 (13%) OSCCs and in 18 out of 22 (82%) OPSCCs using PCR. HPV 16 and 33 were detected in 16 and in two cases, respectively. Compared with OSCCs, OPSCCs more frequently showed basaloid morphology (p < 0.0001), lymph node involvement (p = 0.0063), diffuse p16 expression (p < 0.0001), HR-HPV DNA presence using both CISH and PCR (p < 0.0001; p < 0.0001), and better outcome. The sensitivity and specificity of p16 expression for HR-HPV DNA presence detected by CISH were 0.89 and 0.95, respectively, and 0.95 and 0.85 for PCR detected HPV DNA. The sensitivity and specificity of CISH for PCR detected presence of HPV DNA were 1.00 and 0.73, respectively. Our study is the first larger study analyzing OSCC and OPSCC in NSNDP. Our results indicate that unlike OSCC, a vast majority of OPSCCs may be associated with HR-HPV infection.