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Background The incidence of human papillomavirus (HPV) positive oropharyngeal cancer (OPC) is rising but HPV negative OPC is decreasing in Western countries. In Taiwan, the incidence of HPV negative OPC is common but the incidence of HPV positive OPC remains unknown. The objective of this study is to estimate the incidence trend and the survival of HPV positive OPC in Taiwan. Methods Between 1999 and 2014, primary tumor tissues from 425 incident OPCs were obtained from 5 medical centers in Taiwan. 408 OPCs were evaluated by the EasyChip HPV genotyping (King-Car, I-Lan, Taiwan) and 369 OPCs by p16 staining. The clinical data were retrospectively obtained from the medical records. Results In our study, 29% of OPCs were HPV positive. The percentage of HPV positive OPC was stable from 1999 to 2014 (25% (1999–2002), 30% (2003–2006), 30% (2007–2010), 29% (2011–2014)). The estimated crude incidence rate of HPV positive OPC increased significantly from 0.62 (1999–2002), 1.06 (2003–2006), 1.52 (2007–2010) to 1.74 (2011–2014) per 100,000 person-year. The sensitivity and specificity of p16 staining for positive HPV infection were 92% and 91%, respectively. The 5-year overall survival rates for patients with HPV positive OPC and with HPV negative OPC were 67.8% and 49.0%, respectively (HR = 0.52 (0.35–0.76), p  = 0.0005). Patients with HPV positive OPC but no betel nut/cigarette exposure had the best overall survival (5-year: 88.2%, p  < 0.0001). Patients with HPV negative OPC and betel nut/cigarette exposure had the worst overall survival (5-year: 46.6%, p  < 0.0001). Patients with HPV positive OPC but also with betel nut/cigarette exposure had poorer 5-year overall survival (48.3%, p  < 0.01). Conclusion The incidence of HPV positive OPC is increasing along with HPV negative OPC, which leads to stably low percentage of HPV positive OPC in Taiwan. HPV positive OPC may become an important head and neck cancer when the incidence of HPV negative OPC declines in the near future. P16 is a useful surrogate marker for HPV infection in OPC and a good prognostic indicator for treatment outcome of OPC. Patients with HPV positive OPC but no betel nut/cigarette exposure has an excellent prognosis. Betel nut/cigarette exposure significantly worsens the prognosis of HPV positive OPC.

Genetic susceptibility is likely involved in nasopharyngeal carcinoma (NPC), a cancer caused by Epstein-Barr virus (EBV) infection. Understanding of genetic factors involved in NPC and how they contribute to EBV-induced carcinogenesis is limited. We conducted whole-exome capture/sequencing among 251 individuals from 97 multiplex families from Taiwan (205 affected, 21 obligate carriers, and 25 unaffected) using SeqCap EZ Human Exome Library v3.0 and Illumina HiSeq. Aligned sequences were filtered to identify likely-to-be-functional deleterious variants that co-segregated with disease. Ingenuity Pathway analysis was performed. Circulating magnesium levels were measured in 13 individuals in 2 families with NIPAL1 mutations and in 197 sporadic NPC cases and 237 controls. We identified variants in 12 genes likely involved in cancer pathogenesis, viral infection or immune responses to infection. These included genes postulated to be involved in magnesium transport (NIPAL1), EBV cell entry (ITGB6), modulation of EBV infection (BCL2L12, NEDD4L), telomere biology (CLPTM1L, BRD2, HNRNPU), modulation of cAMP signaling (RAPGEF3), DNA repair (PRKDC, MLH1), and Notch signaling (NOTCH1, DLL3). Pathway based analysis demonstrated enrichment for Notch signaling genes (p-value = 0.0006). Evaluation of individuals within NIPAL1 families suggested lower serum magnesium in NPC compared to unaffected members. A significant reduction in serum magnesium levels was observed among sporadic NPC cases compared to controls (7.1% NPC/1.7% controls below normal range; OR = 4.5; 95% CI = 1.4,14) and is consistent with findings demonstrating a role for magnesium channeling in T-cell responses to EBV. We identified novel genes associated with NPC that point to new areas of inquiry to better understand genetic factors that determine the fate of viral infections and/or otherwise predisposes to NPC.

Background Oropharyngeal squamous cell carcinoma (OPSCC) is increasing worldwide, with a well-established link to human papillomavirus (HPV). However, evidence on how lifestyle risk factors—particularly smoking, alcohol consumption, and betel-quid chewing—modify the prognostic impact of HPV-associated disease remains limited, especially in regions with high exposure burden such as Taiwan. Understanding the interplay between viral and lifestyle determinants is essential for accurate prognostication and treatment planning. Methods We conducted a retrospective cohort study of 5,671 OPSCC patients using data from the Taiwan Cancer Registry between 2018 and 2021. p16 status was used as a surrogate marker for HPV infection. Overall survival and cancer-specific survival were compared across p16 status, age, sex, tumor location, cancer stage, lifestyle risk factors and treatment pattern using Kaplan–Meier method and multiple Cox models. Treatment-stratified analyses were additionally performed to evaluate whether lifestyle risk factors modified prognosis within p16-positive disease. Results Overall, 23.2% of OPSCC cases were p16-positive, with substantially higher p16 positivity among females (52.5%) and in tonsillar subsites. p16-positive patients had significantly better 5-year overall survival (69.0%; 95% CI, 66.0%-71.8%) than p16-negative patients (37.9%; 36.1%-39.6%). However, among p16-positive individuals, the presence of multiple lifestyle risk factors markedly attenuated the survival advantage, reducing 5-year overall survival from 78.6% (74.0%-82.5%) in those without lifestyle exposures to 57.6% (52.6%-62.4%) in those with smoking plus other risks. These gradients persisted after multivariable adjustment and across treatment modalities. In contrast, lifestyle risk factors were not independently associated with survival in p16-negative OPSCC, where prognosis was primarily driven by tumor stage, subsite, and treatment. Conclusions This nationwide study provides novel evidence that the prognostic benefit associated with p16 positivity is substantially attenuated by multiple lifestyle risk factors. These findings highlight the importance of integrating viral and behavioral determinants into prognostic assessment and treatment planning. They also underscore the need to pair HPV-associated prevention strategies with efforts to reduce tobacco, alcohol, and betel-quid use in regions with high burdens of these exposures.

The clinical characteristics of oropharyngeal squamous cell carcinoma (OPSCC) may be different between endemic and non-endemic regions of betel nut chewing. The impact of combined alcohol drinking/betel quid chewing/cigarette smoking (ABC) exposure on the survival of OPSCC remains unclear. We reviewed the medical records of OPSCC patients between 1999 and 2013. Immunohistochemical staining of p16 and HPV genotype detection by DNA Polymerase chain reaction were both performed for each tumor. A total of 300 eligible patients including 74 HPV+ OPSCC patients and 226 HPV− OPSCC patients were enrolled. The 5-year disease-free survival rates for the HPV−, HPV+ OPSCC with and without ABC patients were 49.8%, 58.4% and 94%, respectively. The 5-year overall survival rates for the patients with HPV−, HPV+ OPSCC with and without ABC patients were 46%, 57.4% and 86%, respectively. Advanced locoregionally disease (T3/T4, N2/N3), HPV- OPSCC, combined 2 or all ABC exposure were the independent adverse prognostic factors for disease-free and overall survival. Therefore, our data suggest that in an endemic region of betel quid chewing, HPV− OPSCC comprises the majority of OPSCC and has a worse survival. Combined 2 or all ABC exposure had a significant negative impact on disease-free and overall survival.

This study investigated the diagnostic accuracy and affecting factors of ultrasound (US)-guided core-needle biopsy (CNB) in patients with treated head and neck squamous cell carcinoma (HNSCC). We retrospectively reviewed patients with treated HNSCC who received US-guided CNB from January 2011 to December 2018 with corresponding imaging. Pathological necrosis and fibrosis of targeted lymph nodes (LNs) were evaluated. We analyzed the correlation between CNB accuracy and clinical and pathological characteristics. In total, 260 patients were included. The overall sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV), and accuracy of CNB for nodal recurrence were 84.47%, 100%, 100%, 54.67%, and 86.92%, respectively. CNB of fibrotic LNs had significantly worse sensitivity, NPV, and accuracy than that of non-fibrotic LNs. Similarly, CNB of necrotic LNs had significantly worse sensitivity, NPV, and accuracy than non-necrotic LNs. Multivariate regression revealed that fibrotic LN was the only independent factor for a true positive rate, whereas both necrotic LN and fibrotic LN were independent factors for a false negative rate. The diagnostic accuracy of CNB in treated HNSCC patients is affected by LN necrosis and fibrosis. Therefore, CNB results, particularly for necrotic or fibrotic LNs, should be interpreted carefully.

PurposeThe purposes of the study were (1) to assess the physical activity (PA) status, muscle strength (MS), and flexibility of survivors of head and neck cancer (HNC) and compare these findings with normative data from national labor fitness measures; (2) to examine the differences among PA subgroups, as categorized using Godin’s scores; and (3) to examine the association between stretching exercises and cervical range of motion (CROM).MethodsA cross-sectional study with consecutive sampling was used to recruit HNC survivors from a medical center in Northern Taiwan who had completed either radiation therapy (RT) or multimodality treatments including RT within the current 5 years. The level of PA, daily function, fatigue, quality of life (QOL), MS (handgrip and hip flexor), BMI, and flexibility (CROM and fingertip-to-floor tests) of the participants were assessed.ResultsA total of 108 participants completed the assessments from 135 eligible patients (80% response rate). Although 60.2% reported engaging in PA, only 16.7% met WHO guidelines. Compared to subjects in the normative data, the survivors of HNC in this study had poorer handgrip strength, BMI, and CROM, but better forward flexion. The participants who were consistent with WHO PA guidelines reported less fatigue, better right hip flexor MS, and better QOL than those who did not engage in any PA.ConclusionLack of sufficient PA and generally poorer fitness were found in study subjects. Longitudinal research to explore changes in fitness and barriers to PA compliance is strongly suggested to better enhance HNC patients’ PA and fitness.

Fluorescence lifetime imaging microscopy of a fluorescence probe, 3,6-bis(1-methyl-2-vinylpyridinium) carbazole diiodide ( o -BMVC), provides an objective method for preoperative diagnosis of fine-needle aspiration (FNA) of thyroid nodules. The key of this o -BMVC test of FNA smears is the measurement of the digital number of o -BMVC foci in the nucleus. Thus, there are three categories classified in the o -BMVC test, which are nondiagnostic for unsatisfactory samples, benign for less numbers of o -BMVC foci, and malignant for more numbers of o -BMVC foci. The discrimination of indeterminate (including atypia, follicular neoplasm, suspicious) cytology into benign or malignant cases can reduce diagnostic uncertainty and benefit clinical decision making. This pilot study strongly suggests that the o -BMVC test is an invaluable method for diagnosing FNA samples. Particularly, the combination of FNA cytology and the o -BMVC test holds great promise to improve the efficacy of diagnosis and reduce the healthcare costs.

Background For early-stage oral squamous cell carcinoma (OSCC) patients, the impact of perineural invasion (PNI) and lymphovascular invasion (LVI) on disease control and survival has not been clarified. Methods The medical records of all early-stage OSCC patients who underwent curative surgery between 2004 and 2009 were reviewed. Results A total of 442 early stage patients were included in this study. There were 360 patients in group A (without PNI or LVI) and 82 patients in group B (with PNI and/or LVI). Between groups A and B patients, there were no significant differences in the 5-year disease-free survival (73.8 vs 68.7 %, p  = 0.48) and overall survival (90.9 vs 86.1 %, p  = 0.25). Between groups A and B patients without postoperative radiotherapy (PORT), there were no significant differences in the 5-year disease-free survival (73.8 vs 70.2 %, p  = 0.51) and overall survival (90.9 vs 85.2 %, p  = 0.18). Between group B patients with and without PORT, there was no significant difference in either the disease-free survival (61.1 vs 70.2 %, p  = 0.98) and overall survival (88.9 vs 85.2 %, p  = 0.64). Multivariate analyses revealed that PNI, LVI, and PORT could not provide significant effect on treatment outcome. Conclusions PNI and LVI were not significant risk factors for the disease control and overall survival for early stage OSCC patients. Furthermore, PORT could not provide an additional benefit for the disease control and overall survival for stages I and II OSCC patients with PNI and/or LVI.

Given salvage treatment for recurrent nasopharyngeal carcinoma (NPC) remains a clinical dilemma, immunotherapy targeting NPC-specific immunosuppression may bring new hope. We analyzed the expression of CD8, CD4, Foxp3 and Tim-3 in lymphocytes, and of Galectin-9 in tumour cells between paired primary and recurrent NPC from 95 patients and we noted that there was significant increase in the expression of Galectin-9+ tumour cells (p < 0.001) and Foxp3+ lymphocytes (p < 0.001) but a significant decrease in the expression of CD8+ lymphocytes (p = 0.01) between paired primary and recurrent NPC. Of all patients, 53 patients (55.79%) and 57 patients (60%) had increased percentages of Galectin-9+ tumour cells and of Foxp3+ lymphocytes, respectively. Conversely, 42 patients (44.21%) had decreased percentages of CD8+ lymphocytes. The patients with high Galectin-9 expression in recurrent NPC frequently also had high Tim-3 (p = 0.04) and Foxp3 (p = 0.01), and low CD8 (p = 0.04) expression in lymphocytes. After multivariate analyses, low CD8 expression in lymphocytes was an independent risk factor for relapse-free survival (p = 0.002) and overall survival (p = 0.02). Our data suggests that recurrent NPC may had more immunologic advantage than primary NPC, especially the Galectin-9/Tim-3 pathway. The immunotherapies targeting Galectin-9/Tim-3/Foxp3 interaction may serve as a potential salvage treatment for recurrent NPC.

Background Cancers of unknown primary origin (CUPs) are reported to be the 3-4th most common causes of cancer death. Recent years have seen advances in mutational analysis and genomics profiling. These advances could improve accuracy of diagnosis of CUPs and might improve the prognosis of patients with CUPs. Case presentation A 76-year old male with an adenocarcinoma of unknown primary origin in the lung presented with another tumor of the palate mucosa. The tumor cells in the pleural effusion were all negative for immunohistochemical markers (TTF-1 and Napsin A) and lung-specific oncogenic driver alterations ( EGFR mutation and ALK translocation). The tumor of the palate mucosa was likewise identified as an adenocarcinoma, and the cells showed cytological similarities with the tumor cells in the pleural effusion; TTF-1, Napsin A, EGFR mutation and ALK translocation were all negative. This result suggested that origins of the tumors of the palate mucosa and in the lung were the same, even though the origin had not yet been determined. Next, we addressed whether the tumor of the palate mucosa was a primary tumor or not. Secretory carcinoma (SC), which is a common type of minor salivary gland tumor (MSGT), was suspected; however, mammaglobin was negative and ETV6-NTRK3 (EN) fusion was not observed. Other MSGTs were excluded based on histological and immunohistochemical findings. Furthermore, an additional examination demonstrated an oncogenic KRAS mutation at codon 12 (p.G12D) in both palate tumor and in pleural effusion. KRAS mutation is known to exist in one-third of lung adenocarcinomas (LUADs), but quite rare in MSGTs. The possibility of metastasis from other organs was considered unlikely from the results of endoscopic and imaging studies. This result indicated that the primary site of the CUP was indeed the lung, and that the tumor of the palate mucosa was a metastasis of the LUAD. Conclusions A tumor of the palate mucosa that showed diagnostic difficulties was determined to be a metastatic LUAD by genomic alterations and histopathological findings.