Human papillomavirus (HPV) infection is one of the most important etiologic causes of oropharyngeal head and neck squamous cell carcinoma (HNSCC). Patients with HPV-positive HNSCC were reported to have a better clinical outcome than patients with HPV-negative cancers. However, little is known about the possible causes of different clinical outcomes. In this study, we analyzed a detailed immune profile of tumor samples from HNSCC patients with respect to their HPV status. We analyzed the characteristics of immune cell infiltrates, including the frequency and distribution of antigen-presenting cells and naïve, regulatory and effector T cells and the cytokine and chemokine levels in tumor tissue. There was a profound difference in the extent and characteristics of intratumoral immune cell infiltrates in HNSCC patients based on their HPV status. In contrast to HPV-negative tumor tissues, HPV-positive tumor samples showed significantly higher numbers of infiltrating IFNγ CD8 T lymphocytes, IL-17 CD8 T lymphocytes, myeloid dendritic cells and proinflammatory chemokines. Furthermore, HPV-positive tumors had significantly lower expression of mRNA and higher expression of PD1 mRNA compared to HPV-negative tumors. The presence of a high level of intratumoral immune cell infiltrates might play a crucial role in the significantly better response of HPV-positive patients to standard therapy and their favorable clinical outcome. Furthermore, characterization of the HNSCC immune profile might be a valuable prognostic tool in addition to HPV status and might help identify novel targets for therapeutic strategies, including cancer immunotherapy.

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.

Narrow band imaging is considered a significant improvement in the possibility of detecting early mucosal lesion of the upper aerodigestive tract. Early detection of mucosal neoplastic lesions is of utmost importance for patients survival. There is evidence that, especially in patients previously treated by means of curative radiotherapy or chemoradiotherapy, the early detection rate of recurrent disease is quite low. The aim of this study was to prove whether the videoendoscopy coupled with NBI might help detect recurrent or secondary tumors of the upper aerodigestive tract. 66 patients previously treated by means of RT or CRT with curative intent were enrolled in the study. All patients underwent transnasal flexible videoendoscopy with NBI mode under local anesthesia. When a suspicious lesion was identified in an ambulatory setting, its nature was proved histologically. Many of these changes were not identifiable by means of conventional white light (WL) endoscopy. The accuracy, sensitivity, specificity, and positive and negative predictive value of the method are very high (88%, 92%, 76%, 96%, and 91%, resp.). Results demonstrate that outpatient transnasal endoscopy with NBI is an excellent method for the follow-up of patients with carcinomas of the larynx and the hypopharynx primarily treated with radiotherapy.

Narrow band imaging (NBI) HDTV (high definition television) magnifying endoscopy is considered to be superior for the accurate display of the microvascular patterns of superficial mucosal lesions. Observation of changes in intraepithelial papillary capillary loops (IPCL) can help distinguish benign from malignant lesions as part of an “optical biopsy.” However, IPCL changes in papillomas may be mistaken for spinocellular cancer (SCC). The aim of the study was to determine whether observing microvascular changes alone is sufficient for discriminating between laryngeal SCC and papillomatosis. An additional aim was to identify associated characteristics that could clarify the diagnosis. The study included 109 patients with a suspected laryngeal tumor or papilloma. HDTV NBI magnifying endoscopy was performed during direct laryngoscopy. It was possible to visualize IPCL changes in 82 out of 109 patients (75.2%). In 71 (86.6%) patients, the diagnosis was correctly determined. In 4 (4.9%) cases, the diagnosis of SCC was expressed on the basis of finding pathologic IPCL, but histology did not demonstrate malignancy. To achieve a correct diagnosis using HDTV NBI magnifying endoscopy, it is important not only to observe changes in the shape of IPCL but also to note possible papillary structures with central-axis capillaries typical of papillomatosis.

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Biopsy/stripping are best abandoned for persistent glottic lesions. A single laser endoscopic procedure provides reliable staging and definitive treatment in most cases using fewer resources. Biopsied patients presenting for treatment should be offered laser surgery as an alternative to radiotherapy.

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