The present study investigated the possible correlation between 18F-2-fluorodeoxyglucose (18F-FDG)-uptake parameters and clinicopathological parameters in hypopharyngeal squamous cell carcinoma (HPSCC). A total of 53 patients, newly diagnosed with HPSCC, received pretreatment 18F-FDG-positron emission tomography/computed tomography (PET/CT). Metabolic tumor volume (MTV), total lesion glycolysis (TLG), and maximum and peak standardized uptake values (SUVmax and SUVpeak) were calculated as 18F‑FDG‑uptake parameters of the primary tumor. Tumor thickness, depth of invasion and pathological tumor volume were pathologically measured. Upon univariate survival analysis, SUVmax ≥28.5, SUVpeak ≥19, MTV ≥12 and TLG ≥42 were significantly associated with a shorter overall survival (OS) time, and MTV ≥12 and TLG ≥42 were significantly associated with a shorter distant metastasis‑free survival (DMFS) time. Upon multivariate analysis with adjustment for clinical T category and treatment group, patients with SUVmax ≥28.5 exhibited a significantly shorter OS time, while TLG ≥42 was significantly correlated with shorter OS and DMFS times. Upon simple regression analysis, TLG was found to be significantly associated with tumor thickness and depth of invasion, while MTV was found to be closely associated with pathological tumor volume. In conclusion, pretreatment 18F‑FDG‑PET/CT is likely to provide valuable prognostic parameters in HPSCC.

Background/Aim: Near-infrared photoimmunotherapy (NIR-PIT) is a recently developed cancer treatment modality that selectively kills cancer cells and may induce a therapeutic host immune response. The aim of this study was to determine the feasibility of combining NIR-PIT with immune checkpoint inhibitor (ICI) therapy for unresectable recurrent head and neck cancer. Patients and Methods: Five patients underwent NIR-PIT at Ryukyu University Hospital between January 2022 and April 2024. These patients had unresectable recurrent head and neck squamous cell carcinoma. Among these five patients, four received a combination NIR-PIT and pembrolizumab administration. Results: A total of seven lesions in the oropharynx and oral cavity were targeted. One patient was treated for three different target lesions. The best observed response (BOR) rate was 100%, with three complete responses and four partial responses. The most common treatment-related adverse event was Grade 1 or 2 local pain lasting one to two days postoperatively, which occurred in all patients. Grade 3 adverse events occurred in three cases (42.9%), including pneumonia, pharynx-cutaneous fistula, and trismus. Three patients received ICI therapy following NIR-PIT, achieving a 60% BOR rate. No immune-related adverse events were noted, and the aforementioned Grade 3 adverse events did not worsen during ICI therapy. At a median follow-up of 376 days (range=157-845 days), four target lesions showed no recurrence, while three had recurred. All five patients were alive, including three with no evidence of disease. Conclusion: The combination of NIR-PIT and ICI therapy for unresectable recurrent head and neck cancer was feasible.

Laryngeal papilloma (LP) associated with human papillomavirus (HPV)-6 or -11 infection shows aggressive growth. However, the detailed molecular mechanism of virus-driven tumorigenesis has not been uncovered fully. HPV-6 viral gene expression and dynamic alterations were investigated with in situ localization of viral DNA and RNA in 13 patients with HPV-6-infected laryngeal papilloma. The average viral load was 4.80 × 10⁵ ± 1.86 × 10⁵ copies/ng DNA. E4, E5a, and E5b mRNAs accounted for 96% of the expression of 9 mRNAs. The alteration of viral DNA load during recurrence paralleled the mRNA expression levels, and the expression of all mRNAs showed a similar curve. E4, E5a, and E5b were expressed in the middle to upper part of the epithelium and were co-expressed in the same cells. E4 immunohistochemistry demonstrated an extensively positive reaction in the upper cell layer in accordance with E4 mRNA expression. These results suggest that individual viral genes are coordinately expressed for viral replication, virus release, and immunosurveillance avoidance. The newly developed E4-specific monoclonal antibody can be applied to further functional studies and clinical applications such as targeted molecular therapies.

Laryngeal papilloma (LP), which is associated with infection by human papillomavirus (HPV)-6 or -11, displays aggressive growth. The precise molecular mechanism underlying the tumorigenesis of LP has yet to be uncovered. Building on our earlier research into HPV-6, in this study, the viral gene expression of HPV-11 was investigated by quantitative PCR and DNA/RNA in situ hybridization. Additionally, newly developed antibodies against the E4 protein of HPV-6 and HPV-11 were evaluated by immunohistochemistry. The average viral load of HPV-11 in LP was 1.95 ± 0.66 × 10⁵ copies/ng DNA, and 88% of HPV mRNA expression was found to be E4, E5a, and E5b mRNAs. According to RNA in situ hybridization, E4 and E5b mRNAs were expressed from the middle to upper part of the epithelium. E4 immunohistochemistry revealed a wide positive reaction in the upper cell layer in line with E4 mRNA expression. Other head and neck lesions with HPV-11 infection also showed a positive reaction in E4 immunohistochemistry. The distribution pattern of HPV DNA, viral mRNA, and E4 protein in LP with HPV-11 infection was quite similar to that of HPV-6. Therefore, it might be possible to apply these E4-specific antibodies in other functional studies as well as clinical applications, including targeted molecular therapies in patients with HPV-6 and HPV-11 infection.

This study aimed to clarify the roles of high-risk human papillomavirus (HR-HPV) infection and epidermal growth factor receptor (EGFR) exon 20 mutations in sinonasal inverted papilloma (IP) and sinonasal squamous cell carcinoma (SNSCC). Samples were collected from 20 cases with IP, 7 with IP and squamous cell carcinoma (IP-SCC), and 20 with SNSCC and examined for HPV infection and EGFR exon 20 mutations. Low- or high-risk HPV DNA was observed in 25% of IP, 57.1% of IP-SCC, and 35% of SNSCC cases. Transcriptionally active HR-HPV infections in IP-SCC and SNSCC, accompanied by p16 overexpression, were observed in 28.5% and 25% of cases, respectively. Heterozygous EGFR exon 20 amino acid insertions (ex20ins), located between amino acids 768–774, were observed in 45% of IP, 28.5% of IP-SCC, and 0% of SNSCC and chronic sinusitis cases. EGFR phosphorylation sites were located at tyrosine (Y) 845, Y1068, Y1086, and Y1197 and induced PI3K/AKT/mTOR activation. The phosphorylation pattern of EGFR with ex20ins resembled that of HPV-related SNSCC and oropharyngeal cancer. The transcriptionally active HR-HPV infection and ex20ins might be responsible for the pathogenesis of IP-SCC cases with different fashions. Since IP-SCC might be a multifactorial disease, further investigation is needed to understand IP-SCC etiology.

In recurrent or metastatic head and neck squamous cell carcinoma (R/M-HNSCC), survival outcomes are significantly better in patients who receive anti-programmed cell death-1 (PD-1) monoclonal antibody therapy than in those who receive standard therapy. However, there is no established biomarker that can predict the anti-PD-1 antibody treatment effect and immune-related adverse events (irAEs) in these patients. This study investigated the inflammatory and nutritional status in 42 patients with R/M-HNSCC and programmed cell death ligand-1 (PD-L1) polymorphisms (rs4143815 and rs2282055) in 35 of the 42 patients. The 1- and 2-year overall survival was 59.5% and 28.6%, respectively; the 1- and 2-year first progression-free survival was 19.0% and 9.5%, respectively, and the respective second progression-free survival was 50% and 27.8%. Performance status and inflammatory and nutritional status (assessed by the geriatric nutritional risk index, modified Glasgow prognostic score, and prognostic nutritional index) were identified as significant indicators of survival outcomes in multivariate analysis. Patients with ancestral alleles in PD-L1 polymorphisms had less frequent irAEs. Performance status and inflammatory and nutritional status before treatment were closely related to survival outcomes after PD-1 therapy. These indicators can be calculated using routine laboratory data. PD-L1 polymorphisms may be biomarkers for predicting irAEs in patients receiving anti-PD-1 therapy.