Malnutrition is a frequent comorbidity in head and neck cancer patients and has been shown to impair immunotherapy response in other cancer types. The geriatric nutritional risk index (GNRI) assesses malnutrition using the patient’s ideal weight, actual weight, and serum albumin. The aim of this study was to evaluate the prognostic relevance of malnutrition as determined by the GNRI for the response to immunotherapy in recurrent and/or metastatic head and neck squamous cell carcinoma (R/M HNSCC). A total of 162 patients with R/M HNSCC who received immune checkpoint inhibitors were included. The associations between the GNRI and progression-free survival (PFS), overall survival (OS), and the disease control rate (DCR) were computed. Univariable analysis showed worse PFS for GNRI ≤ 98 (p < 0.001), ECOG performance status (PS) ≥ 2 (p = 0.012), and enteral (p = 0.009) and parenteral (p = 0.015) nutritional supplementation, and worse OS for GNRI < 92 (p < 0.001), ECOG PS ≥ 2 (p < 0.001), and enteral (p = 0.008) and parenteral (p = 0.023) nutritional supplementation. In our multivariable model, GNRI ≤ 98 (p = 0.012) and ECOG PS ≥ 2 (p = 0.025) were independent prognostic factors for PFS. For OS, GNRI < 92 (p < 0.001) and ECOG PS ≥ 2 (p < 0.001) were independent prognostic factors. A GNRI ≤ 98 was significantly associated with a lower DCR compared to a GNRI > 98 (p = 0.001). In conclusion, our findings suggest that the GNRI may be an effective predictor for response to immunotherapy in R/M HNSCC.

Although mostly associated with good survival outcomes, some patients with HPV-positive oropharyngeal squamous cell carcinoma develop distant metastasis and face dire prognosis. The aim of this study was to analyze distant metastatic patients in regards to survival, clinical staging, therapy approach and p16/HPV status. This retrospective single-centre study assessed patients with HPV-associated oropharyngeal cancer with distant metastasis treated in a tertiary referral center from 2005 to 2019. Overall- (OS) and survival after diagnosis of distant metastasis (OMS), clinical staging and different therapy approaches were assessed. Moreover, the overall mortality was assessed, as well as the association of different therapy approaches and p16/HPV status with the survival outcome. Out of 211 patients with HPV-associated oropharyngeal cancer that were treated in the study period, 15 developed distant metastases (7.1%). Median OS and OMS of the total group were 11 months (range 0.1-32 months) and 3 months (range 0.1-21 months), respectively. The overall mortality rate was 53.3% (n = 8). Significantly better outcome was present in patients treated with primary chemoradiotherapy (median OS 17 months vs. not reached, p = .03, median OMS 8 months vs not reached, p = .05). The OMS was significantly better in patients treated with chemotherapy initially after diagnosis (mean OMS 21 months vs 4 months; P = .001). Surgical resection after initial diagnosis was associated with a significantly shorter OMS (median OMS 3 vs. 21 months, p = .005). Interestingly, postoperative adjuvant therapy was delayed in all of these cases due to surgical site complications. Systemic treatment after initial diagnosis may be beneficial in clinical outcome of HPV associated distant metastases. Furthermore, surgical site complications should be treated with immediate care in order to avoid delay of adjuvant therapy. Further studies are warranted for validation of our results.

Wnt/Beta-Catenin signaling is involved in the carcinogenesis of different solid malignant tumors. The interaction of Creb-binding protein (CBP) with Beta-Catenin is a pivotal component of the Wnt/Beta-Catenin signaling pathway. The first aim of this study was to evaluate the association of CBP expression with survival in patients with human papillomavirus (HPV)-positive head and neck squamous cell carcinoma (HNSCC). Second, the in vitro effects of the inhibition of CBP/Beta-Catenin interaction were analyzed. In particular, the effects of ICG-001, an inhibitor of CBP/Beta-Catenin interaction, on proliferation, cell death, modulation of Wnt/Beta-Catenin target expression, and cell migration were examined in vitro. High CBP expression is significantly associated with better survival on mRNA and protein levels. Furthermore, we observed cytotoxic as well as anti-migratory effects of ICG-001. These effects were particularly more potent in the HPV-positive than in the -negative cell line. Mechanistically, ICG-001 treatment induced apoptosis and led to a downregulation of CBP, c-MYC, and Cyclin D1 in HPV-positive cells, indicating inhibition of Wnt/Beta-Catenin signaling. In conclusion, high CBP expression is observed in HPV-positive HNSCC patients with a good prognosis, and ICG-001 showed a promising antineoplastic potential, particularly in HPV-positive HNSCC cells. Therefore, ICG-001 may potentially become an essential component of treatment de-escalation regimens for HPV-positive HNSCC. Further studies are warranted for additional assessment of the mechanistic background of our in vitro findings.

Purpose: Human papilloma virus (HPV)-positive head and neck squamous cell carcinoma (HNSCC) displays distinct epidemiological, clinical, and molecular characteristics compared to the negative counterpart. Alterations in autophagy play an important role in cancer, and emerging evidence indicates an interplay of autophagy in HNSCC carcinogenesis and tumor promotion. However, the influence of HPV infection on autophagy in HNSCC has received less attention and has not been previously reviewed. Therefore, we here aimed to systematically review the role of autophagy explicitly in HPV⁺ HNSCC. Methods: Studies accessible in PubMed, Embase, Scopus, and Web of Science investigating HNSCC, highlighting the molecular biological differences between HPV⁻ and HPV⁺ HNSCC and its influences on autophagy in HNSCC were analyzed according to the PRISMA statement. A total of 10 articles were identified, included, and summarized. Results: The HPV16 E7 oncoprotein was reported to be involved in the degradation of AMBRA1 and STING, and to enhance chemotherapy-induced cell death via lethal mitophagy in HNSCC cells. Autophagy-associated gene signatures correlated with HPV-subtype and overall survival. Additionally, immunohistochemical (IHC) analyses indicate that high LC3B expression correlates with poor overall survival in oropharyngeal HNSCC patients. Conclusion: HPV may dampen general bulk autophagic flux via degradation of AMBRA1 but may promote selective autophagic degradation of STING and mitochondria. Interpretations of correlations between autophagy-associated gene expressions or IHC analyses of autophagy-related (ATG) proteins in paraffin embedded tissue with clinicopathological features without biological validation need to be taken with caution.

Many patients with adenoid-cystic carcinoma (ACC) experience an indolent course of disease over many years but face late recurrence, and long-term survivors are rare. Due to its infrequent occurrence, it is hard to predict outcome in these patients. The fibrinogen-to-lymphocyte ratio (FLR) was recently proposed as an outcome prognosticator in different cancer entities. We aimed to investigate its prognostic relevance in patients with head and neck ACC. This retrospective analysis was performed including all patients treated for ACC between 1998 and 2020. The FLR ratio was calculated based on pretreatment values (0–7 days). The study cohort was dichotomized based on optimized threshold value and compared for differences in outcome (overall survival (OS) and disease-free survival (DFS)). In the cohort of 39 included patients, the OS was significantly longer in the low (n = 28) compared to the high pretreatment FLR group (n = 11) (median OS 150.5 months, 95% confidence intervals (CI) 85.3–215.7 months vs. 29.4 months, 95% CI not reached; p = 0.0093). Similarly, the DFS was significantly longer in the low FLR group (median DFS 74.5 months, 95% CI 30.6–118.4 months vs. 11.0 months, 95% CI 5.1–16.9 months; p = 0.019). The FLR is an easily obtainable and simple marker and may be a valuable outcome prognosticator in patients with ACC. Further studies are needed for validation of our results.

Background: Young patients with tongue squamous cell carcinoma (TSCC) mostly lack typical prognostic markers and face a dire prognosis. The aim of this study was to analyze the prognostic relevance of lymphocyte-to-monocyte ratio (LMR) in TSCC patients, with a special emphasis on patients under 45 years. Methods: This retrospective study included all patients primarily treated for TSCC. The prognostic relevance of LMR was investigated in terms of predicting the overallsurvival (OS) and disease-free survival (DFS). Results: A total of 74 patients were included and the young cohort (<45 years) comprised 27 individuals. The mortality and recurrence rates were 39.2% (n = 29) and 37.8% (n = 28), respectively. OS and DFS were significantly shorter in the low LMR group within the whole cohort. Furthermore, low LMR was associated with worse prognosis, particularly inferior OS (median OS 1.7 vs. 14.6 years, p = 0.0156) and worse DFS (median DFS 0.8 years vs. not reached, p = 0.0405) in the young patient cohort. Conclusions: Our results reveal that pretreatment LMR might become a prognostic tool for young TSCC patients, especially due to its availability. However, further studies on larger cohorts are necessary to validate our results.