Evaluation of Fine Needle Aspiration Cytopathology in Salivary Gland Tumors under Milan System: Challenges, Misdiagnosis Rates, and Clinical Recommendations.

(1) Background: Salivary gland tumors are rare in the head and neck. To determine the need and extent of surgical intervention, fine needle aspiration (FNA) is a widely accepted tool to approach salivary gland lesions. However, the FNA cytology varies between entities, while the lack of uniform terminology makes diagnosis more challenging. Since establishing the Milan system for reporting salivary gland cytopathology (MSRSGC) has become an increasingly accepted reporting standard, further examination and detailed recommendations were needed. (2) Methods: Between April 2013 and October 2021, 375 cases with FNA and salivary gland resection were retrospectively collected. All FNA specimens were reclassified according to the criteria of MSRSGC. After surgical excision, the FNA data were compared with the histological diagnosis to estimate the risk of malignancy (ROM), the risk of neoplasm (RON), and the diagnostic accuracy for each diagnostic category. (3) Results: Our cohort's distribution of ROM and RON was similar to the MSRSGC's recommendation. Carcinoma ex pleomorphic adenoma (CXPA) has the highest rate (66.7%) of misdiagnosed as a nonneoplastic lesion or benign salivary gland tumor. Pleomorphic adenoma (PA) and Warthin's tumor were the most common benign salivary gland tumors, while the cytology diagnosis of Warthin's tumor seems more challenging than PAs. (4) Conclusions: Despite the convenience and effectiveness of MSRSGC, we suggest close follow-up, re-biopsy, or surgical removal for salivary lesions even in Milan IVA-Benign for possibly missing FNA of malignancy, mixed lesions, or prevention of malignant transformation.

Distinct Failure Patterns in Hypopharyngeal Cancer Patients Receiving Surgery-Based Versus Radiation-Based Treatment.

BACKGROUND: To cure advanced hypopharyngeal squamous cell carcinoma (HPSCC), primary operation followed by adjuvant (chemo-)radiotherapy (OP-CRT) or definitive chemoradiation (CCRT) are the two primary options. This study aimed to compare the failure patterns and long-term survival outcomes of HPSCC patients treated with these two strategies. PATIENTS AND METHODS: From 2007 to 2015, 198 pathologically confirmed HPSCC patients receiving either OP-CRT or CCRT were retrospectively reviewed. Failure patterns and survival outcomes stratified by the 7th American Joint Committee on Cancer staging system and treatment modalities were compared. RESULTS: One hundred and eighty-nine patients (95.4%) were stage III/IV and 62 patients (31.3%) received OP-CRT. Median follow-up duration was 4.9 years. Compared with CCRT, OP-CRT provided better 3-year local relapse-free survival for T3 (93 vs 48%, p < 0.0001), T4a (88 vs 37%, p = 0.0005) and better 3-year regional relapse-free survival for N2b+2c (93 vs 60%, p < 0.0001). Of note, for stage IVA subjects, OP-CRT provided better 3-year loco-regional relapse-free survival (85 vs 37%, p < 0.0001), marginal poor 3-year distant metastasis-free survival (62 vs 79%, p = 0.06), but comparable 3-year OS (52 vs 44%, p = 0.37) and 5-year OS (44 vs 31%, p = 0.15) compared with CCRT. CONCLUSIONS: For patients with advanced HPSCC, although OP-CRT and CCRT provided similar overall survival, failure patterns were distinct. OP-CRT provided better loco-regional control but was more likely to encounter distant metastases than CCRT. The detailed analysis of failure patterns will pave the way to improve this devastating disease.

Relationship Between Pharyngeal Residues Assessed by Bolus Residue Scale or Normalized Residue Ratio SCALE and Risk of Aspiration in Head and Neck Cancer Who Underwent Videofluoroscopy.

Dysphagia affects 60-75% of patients treated for head and neck cancer (HNC). We aimed to evaluate the association between residue severity and airway invasion severity using a videofluoroscopic swallowing study and identify risk factors for poor penetration-aspiration outcomes in patients with dysphagia treated for HNC. Penetration-Aspiration Scale (PAS) was used to assess airway invasion severity, while residue severity was assessed using both the Bolus Residue Scale (BRS) for residue location and the Normalized Residue Ratio Scale (NRRS) for residue amount. Relevant covariates were adjusted in the logistic regression models to account for potential confounding. Significantly higher abnormal PAS was reported for increased piriform sinus NRRS (NRRSp) [odds ratio (OR), 4.81; p = 0.042] with liquid swallowing and increased BRS value (OR, 1.52; p = 0.014) for semi-liquid swallowing in multivariate analysis. Tumor location, older age, and poorer Functional Oral Intake Scale (FOIS) were significant factors for abnormal PAS in both texture swallowings. After adjusting for confounding factors (sex, age, and FOIS score), NRRS model in liquid swallowing (area under the curve [AUC], 0.83; standard error = 0.04, 95% confidence interval [CI]: 0.75, 0.91) and BRS in semi-liquid swallowing (AUC, 0.83; SE = 0.04; 95% CI: 0.76, 0.91) predicted abnormal PAS. The results indicate that while assessing residue and swallowing aspiration in patients with HNC, it is important to consider age, tumor location, and functional swallowing status. The good predictability of abnormal PAS with BRS and NRRS indicated that residue location and amount were both related to the aspiration event in patients with HNC.

The Additive Effectiveness of Inspiratory Muscle Training on Glottic Closure and Subjective Voice Outcomes of Patients With Benign Lesion After Hyaluronic Acid Laryngoplasty.

OBJECTIVES: For patients with glottic insufficiency disease, injection laryngoplasty is a rapid and efficient management option that complements voice therapy. Some studies have indicated that respiratory muscle training may also show promise in patients with voice disorders. However, the effect of respiratory muscle training in patients with glottic insufficiency was reported to be limited, and whether it provides additional benefit after standard management requires further evaluation. We aimed to investigate the effectiveness of inspiratory muscle training on glottis closure and patient-reported voice quality in glottic insufficiency patients who had been treated with hyaluronic acid injection. STUDY DESIGN: Retrospective observational study. METHODS: We included 46 patients with glottic insufficiency who had undergone hyaluronic acid injection. Twenty of them had undergone inspiratory muscle training during three months. We measured patients' changes in glottic status according to the normalized glottal gap area and bowing index, as well as voice quality of life according to the voice handicap index 10 and the voice outcome survey, before and after training. RESULTS: Patients who underwent inspiratory muscle training had higher odds of experiencing better improvement in all scores. The range of odds ratios ranged from 2.5 to 6.3 for changes in scores, and from 3.8 to 22.2 for changes in score percentages. Of note, the effect of training on percentage changes in the normalized glottal gap area score was significant (P= 0.0127) after adjustment for the duration of vocal disease, body mass index and BMI, and history of gastroesophageal reflux disease. CONCLUSIONS: Inspiratory muscle training can improve the glottal gap after injection laryngoplasty, and may be applied in clinical practice.

Improved overall survival is associated with adjuvant chemotherapy after definitive concurrent chemoradiotherapy for N3 nasopharyngeal cancer.

Concurrent chemoradiotherapy is the established treatment for locally advanced nasopharyngeal carcinoma (NPC). However, there is no evidence supporting routine adjuvant chemotherapy. We aimed to demonstrate the effect of adjuvant chemotherapy on survival and distant metastasis in high-risk N3 NPC patients. We linked the Taiwan Cancer Registry and Cause of Death database to obtain data. Clinical N3 NPC patients were divided as those receiving definitive concurrent chemoradiotherapy (CCRT) with adjuvant 5-fluorouracil and platinum (PF) chemotherapy and those receiving no chemotherapy after CCRT. Patients receiving neoadjuvant chemotherapy were excluded. We compared overall survival, disease-free survival, local control, and distant metastasis in both groups using Cox proportional hazards regression analysis. Propensity-score matching was also performed to evaluate the independent effect of adjuvant PF in a matched cohort with similar baseline characteristics. We included 431 patients (152 and 279 patients in the adjuvant PF and observation groups, respectively). Median follow-up was 4.3 years. The 5-year overall survival were 69.1% and 57.4% in the adjuvant PF chemotherapy and observation groups, respectively (p = 0.02). Adjuvant PF chemotherapy was associated with a lower risk of death (hazard ratio [HR] 0.61, 95% confidence interval [CI] 0.43-0.84; p = 0.003), even after adjusting for baseline prognostic factors (HR 0.61, 95% CI 0.43-0.86; p = 0.005). Distant metastasis-free survival at 12 months was higher in the adjuvant PF chemotherapy group than in the observation group (98% vs 84.8%; p < 0.001). After adjusting for baseline prognostic factors, adjuvant PF chemotherapy was associated with freedom from distant metastasis (HR 0.11, 95% CI 0.02-0.46; p = 0.003). Adjuvant chemotherapy was also associated with a decreased risk of death (HR 0.59, 95% CI 0.41-0.85, p = 0.004) in a propensity score-matched cohort. Prospective evaluation of adjuvant PF chemotherapy in N3 NPC patients treated with definitive CCRT is warranted because adjuvant PF chemotherapy was associated with improved overall survival and decreased risk of distant metastasis.

YAP1 acts as a negative regulator of pro-tumor TAZ expression in esophageal squamous cell carcinoma.

PURPOSE: Although YAP1 and TAZ are believed to be equivalent downstream effectors of the Hippo pathway, differential expression of YAP1 or TAZ suggests distinct functions during cancer progression. The exact role of YAP1 and TAZ in esophageal cancer, the 6th leading cancer-related mortality in the world, remains elusive. METHODS: Following single or double manipulation of YAP1 or TAZ expression, we subjected these manipulated cells to proliferation, migration, invasion, and xenograft tumorigenesis assays. We used RT-qPCR and Western blotting to examine their expression in the manipulated cells with or without inhibition of transcription or translation. We also examined the impact of YAP1 or TAZ deregulation on clinical outcome of esophageal cancer patients from the TCGA database. RESULTS: We found that YAP1 functions as a tumor suppressor whereas TAZ exerts pro-tumor functions in esophageal cancer cells. We also found a significant increase in TAZ mRNA expression upon YAP1 depletion, but not vice versa, despite the downregulation of CTGF and CYR61, shared targets of YAP1 and TAZ, in xenografted tissue cells. In addition to transcriptional regulation, YAP1-mediated TAZ expression was found to occur via protein synthesis. Restored TAZ expression mitigated YAP1-mediated suppression of cellular behavior. By contrast, TAZ silencing reduced the promoting effect exerted by YAP1 depletion on cellular behaviors. The observed anti-tumor function of YAP1 was further supported by a better overall survival among esophageal cancer patients with a high YAP1 expression. CONCLUSION: From our data we conclude that YAP1 functions as a suppressor and negatively regulates pro-tumor TAZ expression via transcriptional and translational control in esophageal cancer.

Evaluation of Objective and Subjective Swallowing Outcomes in Patients with Dysphagia Treated for Head and Neck Cancer.

We evaluated objective and subjective swallowing function outcomes in patients with dysphagia treated for head and neck cancer (HNC) and identified risk factors for poor swallowing outcomes. Patients undergoing videofluoroscopic swallowing studies (VFSS) between January 2016 and March 2021 were divided into four groups according to primary tumor sites; post-treatment dysphagia was assessed. The penetration-aspiration scale (PAS) and bolus residue scale (BRS) were used to objectively assess swallowing function through VFSS. The Functional Oral Intake Scale (FOIS) was used for subjective analyses of swallowing statuses. To account for potential confounding, important covariates were adjusted for in logistic regression models. Oropharyngeal tumors were significantly more likely to have poor PAS and BRS scores than oral cavity tumors, and the patients with nasopharyngeal tumors were significantly less likely to have poor FOIS scores. Old age, having multiple HNCs, and a history of radiotherapy were associated with an increased odds of poor PAS scores (for all types of swallows), poor BRS scores (for semiliquid and solid swallows), and poor FOIS scores, respectively. This indicates using only subjective assessments may not allow for accurate evaluations of swallowing function in patients treated for HNC. Using both objective and subjective assessments may allow for comprehensive evaluations.

Clinical Outcomes of Taiwanese Patients with Resected Oral Cavity Squamous Cell Carcinoma Who Underwent Reconstruction with Free Versus Local Flaps.

BACKGROUND: We sought to compare the clinical outcomes of Taiwanese patients with resected oral cavity squamous cell carcinoma (OCSCC) who underwent reconstruction with free versus local flaps. METHODS: From 2011 to 2017, we examined 8646 patients with first primary OCSCC who received surgery either with or without adjuvant therapy. Of these patients, 7297 and 1349 received free and local flap reconstruction, respectively. Two propensity score-matched groups of patients who underwent free versus local flap (n = 1268 each) reconstructions were examined. Margin status was not included as a propensity score-matched variable. RESULTS: Compared with local flaps, patients who received free flaps had a higher prevalence of the following variables: male sex, age < 65 years, pT3-4, pN1-3, p-Stage III-IV, depth ≥ 10 mm, margin > 4 mm, extranodal extension (ENE), and adjuvant therapy (all p < 0.0001). Multivariable analysis identified the reconstruction method (local vs. free flaps, only overall survival [OS]), age ≥ 65 years, pT3-4, pN1-3, p-Stage III-IV, depth ≥ 10 mm (only OS), margins ≤ 4 mm, and ENE as independent adverse prognosticators for disease-specific survival (DSS) and OS. The results of propensity score-matched analyses revealed that, compared with free flaps, patients who underwent local flap reconstruction showed less favorable 5-year DSS (hazard ratio [HR] 1.26, 82%/77%; p = 0.0100) and OS (HR 1.21, 73%/68%; p = 0.0079). CONCLUSIONS: After adjusting for covariates using multivariate models, and also by propensity score modeling, OCSCC patients who underwent free flap reconstruction showed a higher frequency of clear margins and a significant survival advantage compared with those who received local flaps.

Investigating the association between serum human papillomavirus type 16 E7 antibodies and risk of head and neck cancer.

Human papillomavirus (HPV) is recognized as a major cause of oropharyngeal cancer (OPC) in Western countries. Less is known regarding its contribution to the OPC occurring in Asia. The current study aimed to investigate the association between antibody responses to HPV16 E7 and head and neck cancer (HNC) risk in a hospital-based case-control study conducted in Taiwan with 693 HNC cases and 1,035 controls. A positive association was observed between seropositivity to HPV16 E7 and OPC risk, whereas no significant association was found in the non-OPC cases. The increased OPC risk associated with seropositivity to HPV16 E7 was more significant among nonbetel quid or noncigarette users. Seropositivity to HPV16 E7 showed moderate agreement with P16 expression in OPC. OPC patients that were seropositive to HPV16 E7 or p16 positive were more highly educated and less likely to use alcohol, betel quids, and cigarettes compared to HPV16 E7 seronegative or p16 negative OPC patients. Furthermore, patients with p16 positive OPC were more likely to be women compared to patients with p16 negative OPC, likely owing to the low prevalence of alcohol, betel quid, and cigarette users among women. Overall, this study suggested that similar to Western countries, HPV may also be an important risk factor of OPC in Taiwan. With the declining consumption of betel quids and cigarettes in Taiwan, a higher percentage of OPC cases in Taiwan will be attributed to HPV in the future. Public health measures, including HPV vaccination, need to be implemented to prevent the occurrence of HPV-positive OPC.

Adequate surgical margins for oral cancer: A Taiwan cancer registry national database analysis.

BACKGROUND: Margin status and lymph node metastasis are the most important prognostic factors for oral cancers. However, while adequate surgical resection is crucial for local control and prognosis, the definition of clear margins has long been a subject of debate. In this study, we analyzed data from a nationwide population-based cancer registry database and evaluated the impact of surgical margins on cancer-specific survival (CSS) and overall survival (OS) as well as the optimal cutoff of adequate surgical margins. METHODS: This analysis included all cases of oral cancer diagnosed from 2011 to 2017 that were reported to the Taiwan Cancer Registry database. The staging system was converted from American Joint Committee on Cancer (AJCC) version 7 to AJCC version 8. Kaplan-Meier analysis and Cox proportional-hazards regression were performed to identify covariates that were significantly associated with CSS and OS. RESULTS: Between 2011 and 2017, 15,654 of a total of 36,091 cases diagnosed with oral cancers were included in the final analyses. Advanced N stage, positive margins, and advanced T stage are the leading risk factors for poor CSS and OS. When surgical margins were subdivided into 1-mm intervals from 5 mm to positive margin, we found that surgical margins <4 mm and <5 mm predict poor CSS and OS, respectively. CONCLUSIONS: This is the first nationwide, population-based cohort to revisit the question of the adequate surgical margins for oral cancers. We conclude that surgical margins ≥4 mm and ≥5 mm are adequate for good CSS and OS, respectively.

Investigating the health disparities in the association between lifestyle behaviors and the risk of head and neck cancer.

Many studies have reported a positive association between lower socioeconomic status (SES) and higher head and neck cancer (HNC) risk. Fewer studies have examined the impact of SES on the association between alcohol or cigarette use and HNC risk. The current case-control study (1104 HNC cases and 1363 controls) investigated the influence of education, a SES indicator, on the association between HNC and the use of alcohol, cigarettes, or betel quids in Taiwan, a country with universal health care. Our results showed a larger increase in HNC risk associated with alcohol among those with lower educational level (odds ratio [OR] = 2.07; 95% confidence interval [CI], 1.53-2.80) than those with higher educational level (OR = 1.38; 95% CI, 1.04-1.85) (heterogeneity-P = .03). Educational level had an influence on the association between alcohol use and HNC risk among those with genetic susceptibility (ALDH2-deficient) to the carcinogenic effect of alcohol. The association between cigarette or betel quid use and HNC risk was similar between the high and low educational groups. National policies and social interventions have led to the decline in the prevalence of cigarette and betel quid users in Taiwan. In contrast, due to the lack of adequate alcohol control policies, alcohol consumption in Taiwan has continued to rise. A higher impact of alcohol on HNC risk among lower SES individuals even with universal health care could be the result of insufficient alcohol control policies in Taiwan.

The Tumor Suppressor TGFBR3 Blocks Lymph Node Metastasis in Head and Neck Cancer.

The TGF-ß type III receptor (TGFBR3) is an essential constituent of the TGF-ß signaling. In this study, we observed a down-regulation of TGFBR3 in oral cancer, a subtype of head and neck cancer (HNC), and patients with low TGFBR3 had poor clinical outcomes. Ectopic expression of TGFBR3 decreased migration and invasion of oral cancer cells and lymph node metastasis of tumors, whereas depletion of TGFBR3 had the opposite effect. In SMAD4-positive OC-2 oral cancer cells, TGFBR3-mediated suppression requires both of its cytoplasmic interacting partners ARRB2 and GIPC1. We demonstrated that TGFBR3 induces the abundance of secreted angiogenin (ANG), a known pro-angiogenic factor, and ANG is essential and sufficient to mediate TGFBR3-dependent inhibition of migration and invasion of oral cancer cells. Notably, in SMAD4-deficient CAL-27 oral cancer cells, only GIPC1 is essential for TGFBR3-induced suppressive activity. Accordingly, HNC patients with low expressions of both TGFBR3 and GIPC1 had the poorest overall survival. In summary, we conclude that TGFBR3 is as a tumor suppressor via SMAD4-dependent and -independent manner in both tumor and stromal cells during oral carcinogenesis. Our study should facilitate the possibility of using TGFBR3-mediated tumor suppression for HNC treatment.

Cancer-associated fibroblast-derived interleukin-1ß activates protumor C-C motif chemokine ligand 22 signaling in head and neck cancer.

Oral cancer, a subtype of head and neck cancer, is characterized by increased infiltrating regulatory T cells (Treg); however, the pathological significance of the increase in Tregs in disease prognosis and progression and their underlying mechanism remain unestablished. C-C motif chemokine ligand 22 (CCL22) has been implicated in the recruitment of Tregs. We used RT-qPCR to determine CCL22 mRNA expression in clinical specimens and cultured cells. Loss-of-function and gain-of-function studies were carried out to analyze the effects of CCL22 modulations on cell proliferation, migration, invasion, and tumorigenesis and the mechanism involved in the deregulation of CCL22. In oral cancer specimens, CCL22 mRNA was upregulated. The increase was not only associated with reduced disease-free survival but also strongly correlated with an increase in FOXP3 mRNA, a master regulator of Treg development and functions. Silencing CCL22 expression reduced cell proliferation, migration, and invasion, whereas ectopic overexpression showed opposite effects. Manipulation of CCL22 expression in cancer cells altered tumorigenesis in both immune-compromised and -competent mice, supporting both autonomous and non-autonomous actions of CCL22. Release of interleukin 1ß (IL-1ß) from cancer-associated fibroblasts (CAF) induces CCL22 mRNA expression in oral cancer cells by activating transcription factor nuclear factor kappa B (NF-κB). Our data support a model in which CAF-derived IL-1ß, CCL22, and its receptor CCR4 foster a protumor environment by promoting cell transformation and Treg infiltration. Intervention of the IL-1ß-CCL22-CCR4 signaling axis may offer a novel therapeutic strategy for oral cancer treatment.

Validation of Alcohol Flushing Questionnaire to Identify ALDH2 Status in a Case-Control Study of Head and Neck Cancer.

BACKGROUND: Carriers of the ALDH2*2 allele have impaired alcohol metabolism and are more susceptible to the development of alcohol-related cancers, including head and neck cancer (HNC). Screening for ALDH2*2 allele may identify high-risk individuals for alcohol health education. Although genotyping of ALDH2 is the most accurate way to identify ALDH2 deficiency, it may not be practical due to the cost and requirement for genotyping service. METHODS: This study evaluated the accuracy of the alcohol flushing questionnaire to identify ALDH2 deficiency in a case-control study of HNC conducted in Taiwan using data collected from 904 patients with HNC and 1,078 controls. RESULTS: Overall, alcohol flushing questionnaire had a high sensitivity (89%) of identifying ALDH2*2 carriers among the control subjects and a good sensitivity (79%) among the patients with HNC. The sensitivity of the alcohol flushing questionnaire in identifying ALDH2*2 carriers was affected by alcohol use, with a lower sensitivity among individuals who consumed alcohol, particularly among current regular (drinking alcohol once per week or more) alcohol drinkers. CONCLUSIONS: The current validation study showed that the alcohol flushing questionnaire may be a reasonable method to identify ALDH2-deficient individuals. However, current regular users of alcohol who reported no alcohol flushing may need to undergo genotyping of ALDH2 for a more accurate assessment of the ALDH2 status.

Oral hygiene and the overall survival of head and neck cancer patients.

Poor oral hygiene is an established risk factor of head and neck cancer (HNC); however, its role in the survival of HNC patients is unclear. This study evaluated the association between oral hygiene habits, including regular dental visits, frequency of tooth brushing, and use of dental floss, and the overall survival (OS) of HNC patients using interview data collected from 740 HNC patients. In addition, the interactions between oral hygiene and the polymorphisms of TLR2 and TLR4 on the OS of HNC patients were assessed. The analysis indicated that poor oral hygiene was significantly associated with poorer OS of HNC patients (hazard ratio (HR) = 1.38, 95% confidence interval (CI): 1.03-1.86). This association was modified by a single nucleotide polymorphism, rs11536889, of TLR4. A significant association between poor oral hygiene and worse survival of HNC was observed among those with the CG or CC genotype (HR = 2.32, 95% CI: 1.41-3.82) but not among those with the GG genotype (HR = 0.95, 95% CI: 0.65-1.40). Our results suggested that poor oral hygiene is not only a risk factor but may also be a prognostic factor of HNC.

Resected specimen size: A reliable predictor of severe Frey syndrome after parotidectomy.

BACKGROUND: Frey syndrome is a common complication after parotidectomy. This study aimed to investigate the potential predictors for developing severe Frey syndrome after parotidectomy and to identify patients who may benefit from additional preventive maneuvers. METHODS: A total of 485 patients received parotidectomy because of parotid tumors at the Otolaryngology Department of the National Cheng Kung University Hospital, from July 2009 to November 2015. Only 115 of 485 patients were included in this study and to fill in a questionnaire to determine the occurrence and severity of Frey syndrome. RESULTS: A total of 115 parotidectomies were identified. 84 (73%, 84/115) patients were aware of the discomfort and were thus considered symptomatic. 39 (34%, 39/115) patients considered the symptoms apparently affected their quality of life. MSI tests showed that 56 (49%, 56/115) patients had a positive MSI test. By combining the results from symptom questionnaire and MSI test, 23 patients (20%, 23/115) had a severe form of Frey syndrome. Among all clinicopathological variables, the resected specimen size was the only significant predictor of the severe Frey syndrome group (P = 0.04). Disease pathology, tumor size, and adjuvant radiotherapy did not correlate with the severe Frey syndrome. Using receiver operating curve analysis, the best cutoff value of the resected specimen size (in largest dimension) for predicting severe Frey syndrome was 40 mm(sensitivity: 71.7%, specificity: 42.0%; area under the curve = 0.6483). The odds ratio of severe Frey syndrome with every 10 mm increase in the largest diameter of resected specimen was 1.30 (95% confidence interval, 1.01-1.68; P = 0.04). CONCLUSIONS: Resected specimen size is the only significant predictor of developing severe Frey syndrome after parotidectomy. Preventive interventions may have to be considered in high-risk patients whose resected specimen size (in largest dimension) is greater than 40 mm.

Cost-effectiveness analysis of the oral cancer screening program in Taiwan.

OBJECTIVES: We assess the incremental cost-effectiveness ratio (ICER) of the oral cancer (OC) screening program in Taiwan. MATERIALS AND METHODS: We interlinked the Cancer Registry, Mortality Registry, National Vital Statistics, reimbursement database of National Health Insurance, and the National Oral Cancer Screening database of Taiwan. A total of 40,092 pathologically verified OC patients were identified and followed during 2002-2014. After stratification by stages, lifetime survival curves were estimated by a rolling extrapolation algorithm to obtain life expectancy (LE), expected years of life lost (EYLL), and lifetime medical costs (LMC). RESULTS: The LE for stages I-IV were 19.5, 14.0, 11.9, and 7.7 life-years, respectively, while those of EYLL were 7.3, 12.2, 15.4, and 18.7 life-years, respectively. The LMC for stages I-IV were US$ 65,752, 60,086, 53,675, and 47,570, respectively. We assumed no life loss for stage 0 with LMC of US$ 5380 spent for the first year after diagnosis. During 2010-2013, 967 out of the 28,018 cases detected with abnormal oral pathology by screening were found to develop OC. The ICER of the screening program was US$ 28,516 per life-year saved, which could be improved to US$ 5579 per life-year saved if all cancers transformed from abnormal oral pathology were detected before stage I. CONCLUSION: The ICER of the current OC screening program in Taiwan slightly exceeds 1 GDP (gross domestic product) per capita per life-year saved. Intensive follow-up and treatment for all patients with abnormal oral pathology would improve screening efficiency and effectiveness of prevention.

Sequential therapy of neoadjuvant biochemotherapy with cetuximab, paclitaxel, and cisplatin followed by cetuximab-based concurrent bioradiotherapy in high-risk locally advanced oral squamous cell carcinoma: Final analysis of a phase 2 clinical trial.

BACKGROUND: The prognosis of advanced oral squamous cell carcinoma is poor. We investigated the effect of cetuximab-based sequential therapy as a primary treatment. METHODS: Forty-seven treatment-naive patients with advanced tumors originating from the oral cavity or oropharynx were enrolled. Neoadjuvant cetuximab, paclitaxel, and cisplatin were administered, followed by cetuximab-based radiotherapy. Immunohistochemical staining was applied to study the tissues. RESULTS: The best overall response rate was 70.2%, including 4 patients with a complete response and 29 with a partial response. The median progression-free and overall survival rates were 10.3 and 15.2 months, respectively. Patients with more than 50% tumor reduction with neoadjuvant therapy had better survival outcomes. Twenty-two patients had severe adverse events with mostly dermatological complications. Of the 16 patients who received operations, 9 had increased PD-L1 staining compared to pretreatment biopsy in the post hoc study. CONCLUSION: The regimen was effective in selected patients. Increased PD-L1 suggested altered tumor features.