Abstract Background Clinical evidence for the rapidity and effectiveness of fentanyl buccal soluble film (FBSF) in reducing pain intensity of breakthrough cancer pain (BTcP) remains inadequate. This study aimed to evaluate the efficacy of FBSF proportional to the around-the‐clock (ATC) opioid regimens in rapidly relieving the intensity of BTcP episodes by determining the percentage of patients requiring further dose titration. Methods The study procedure included a dose-finding period followed by a 14-day observation period. Pain intensity was recorded with a Numeric Rating Scale (NRS) at onset and 5, 10, 15, and 30 min after FBSF self-administration. Meaningful pain relief was defined as the final NRS score ≤ 3. Satisfaction survey was conducted for each patient after treatment using the Global Satisfaction Scale. Results A total of 63 BTcP episodes occurred in 30 cancer patients. Only one patient required rescue medication at first BTcP episode and then achieved meaningful pain relief after titrating FBSF by 200 µg. Most BTcP episodes relieved within 10 min. Of 63 BTcP episodes, 30 (47.6%), 46 (73.0%), and 53 (84.1%) relieved within 5, 10, and 15 min after FBSF administration. Only grade 1/2 adverse events were reported, including somnolence, malaise, and dizziness. Of the 63 BTcP episodes, 82.6% were rated as excellent/good satisfaction with FBSF. Conclusion FBSF can be administrated “on demand” by cancer patients at the onset of BTcP, providing rapid analgesia by achieving meaningful pain relief within 10 min. Trial registration This study was retrospectively registered 24 December, 2021 at Clinicaltrial.gov (NCT05209906): https://clinicaltrials.gov/study/NCT05209906 .

While an increasing number of patients now undergo lobectomy for low-risk differentiated thyroid cancer, a subset of patients require completion thyroidectomy to facilitate radioactive iodine therapy. Completion thyroidectomy is generally as safe as the initial operation, but a previous study showed that a longer hospitalization is required for completion thyroidectomy. In this study, we reviewed 61 consecutive patients who had been treated with an initial lobectomy and subsequent completion thyroidectomy at our institution from 2012 to 2021. We detected a changepoint in 2016 for the proportion of patients who were treated with a thyroid lobectomy (Pettitt’s test P = 0.049). The rate of completion thyroidectomy remained stable throughout the study period. There was no difference in operating time, intraoperative blood loss, perioperative drop in calcium levels, and postoperative hospital stay between surgeries. The patients reported higher pain scores on the day of operation ( P = 0.007) and the postoperative day 1 ( P = 0.022). Occult papillary microcarcinomas were identified in the contralateral thyroid lobe in 13 (21%) patients. Multifocality was the only predictor for residual malignancy in multivariate regression. In conclusion, patients with differentiated thyroid cancer experienced more pain in the immediate postoperative period following completion thyroidectomy. Hospital stays do not change with appropriate opioid-free pain control.

Radiotherapy (RT) is an important modality for laryngeal cancer treatment to preserve laryngeal function. During beam delivery, laryngeal motion remains uncontrollable and may compromise tumor-targeting efficacy. We aimed to examine real-time laryngeal motion by developing a surface depth-sensing technique with preliminary testing during RT-based treatment of patients with laryngeal cancer. A surface depth-sensing (SDS) camera was set up and integrated into RT simulation procedures. By recording the natural swallowing of patients, SDS calculation was performed using the Pose Estimation Model and deep neural network technique. Seven male patients with laryngeal cancer were enrolled in this prospective study. The calculated motion distances of the laryngeal prominence (mean ± standard deviation) were 1.6 ± 0.8 mm, 21.4 ± 5.1 mm, 6.4 ± 3.3 mm, and 22.7 ± 4.9 mm in the left–right, cranio–caudal, and anterior–posterior directions and for the spatial displacement, respectively. The calculated differences in the 3D margins for generating the planning tumor volume by senior physicians with and without SDS data were −0.7 ± 1.0 mm (−18%), 11.3 ± 6.8 mm (235%), and 1.8 ± 2.6 mm (45%) in the left–right, cranio–caudal, and anterior–posterior directions, respectively. The SDS technique developed for detecting laryngeal motion during swallowing may be a practical guide for individualized RT design in the treatment of laryngeal cancer.

PURPOSETwo Epstein-Barr virus (EBV)-based testing approaches have shown promise for early detection of nasopharyngeal carcinoma (NPC). Neither has been independently validated nor their performance compared. We compared their diagnostic performance in an independent population.METHODSWe tested blood samples from 819 incident Taiwanese NPC cases (213 early-stage, American Joint Committee on Cancer version 7 stages I and II) diagnosed from 2010 to 2014 and from 1,768 controls from the same region, frequency matched to cases on age and sex. We compared an EBV antibody score using immunoglobulin A antibodies measured by enzyme-linked immunosorbent assay (EBV antibody score) and plasma EBV DNA load measured by real-time PCR followed by next-generation sequencing (NGS) among EBV DNA-positive individuals (EBV DNA algorithm).RESULTSEBV antibodies and DNA load were measured for 2,522 (802 cases; 1,720 controls) and 2,542 (797 cases; 1,745 controls) individuals, respectively. Of the 898 individuals positive for plasma EBV DNA and therefore eligible for NGS, we selected 442 (49%) for NGS testing. The EBV antibody score had a sensitivity of 88.4% (95% CI, 86.1 to 90.6) and a specificity of 94.9% (95% CI, 93.8 to 96.0) for NPC. The EBV DNA algorithm yielded significantly higher sensitivity (93.2%; 95% CI, 91.3 to 94.9; P = 1.33 x 10-4) and specificity (98.1%; 95% CI, 97.3 to 98.8; P = 3.53 x 10-7). For early-stage NPC, the sensitivities were 87.1% (95% CI, 82.7 to 92.4) for the EBV antibody score and 87.0% (95% CI, 81.9 to 91.5) for the EBV DNA algorithm (P = .514). For regions with a NPC incidence of 20-100/100,000 person-years (eg, residents in southern China and Hong Kong), these two approaches yielded similar numbers needed to screen (EBV antibody score: 5,656-1,131; EBV DNA algorithm: 5,365-1,073); positive predictive values ranged from 0.4% to 1.7% and 1.0% to 4.7%, respectively.CONCLUSIONWe demonstrated high sensitivity and specificity of EBV antibody and plasma EBV DNA for NPC detection, with slightly inferior performance of the EBV antibody score. Cost-effectiveness studies are needed to guide screening implementation.

Neuroendocrine carcinomas (NECs) are poorly differentiated neuroendocrine tumors of the upper respiratory tract. We present an extremely rare case of nasopharyngeal large cell neuroendocrine carcinoma (LCNEC) synchronized with nasopharyngeal squamous cell carcinoma (SCC). Both SCC and LCNEC are associated with Epstein-Barr virus (EBV) infection, supported by the positive result of Epstein-Barr encoding region in-situ hybridization. Strong correlation is found between EBV infection and nasopharyngeal malignancies. Furthermore, the EBV status might be a crucial prognostic factor in nasopharyngeal LCNEC. EBV-positive LCNEC is effective to chemoradiotherapy, and may have preferable outcome than EBV-negative LCNEC arising in the nasopharynx or other sites. The recognition of the EBV status is important for patients to receive appropriate treatment.

Trigeminal schwannomas are rare tumours comprising 0.2% of all intracranial tumours and 0.5% of all head and neck tumours. Patients with trigeminal schwannomas presented with facial hypoesthesia and pain. We presented a case with left bulging oropharynx. The CT scan showed a 3.8x2.6x4.9cm left parapharyngeal tumour compressed to the oropharynx and middle cranial fossa. We performed 3 ways in two times of operation to excise the whole tumour. We chose the transoral approach for parapharyngeal space, trans-parotid approach for deep parotid part and the endoscopic endonasal trans-pterygoid approach and trans-maxillary with Canine fossa trephination for intracranial lesions. The pathology showed schwannoma. A huge schwannoma extended from intracranial to several spaces is difficult to resect just by one approach. We should separate the tumour to several parts by clinical image before the operation and design a plan to remove the whole tumour in different approach. The different space of tumour involvement had several ways to access. We needed to choose the less harm but with better surgical field.

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. 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. 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). 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.

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.

OBJECTIVES/HYPOTHESIS:Evaluation of the clinical outcomes after 6 months of treatment with a novel adjustable implant, the APrevent® Vocal-Implant-System (VOIS), in conjunction with medialization thyroplasty (MT) in patients with unilateral vocal fold paralysis. STUDY DESIGN:Prospective case series study at single tertiary referral center. METHODS:Preoperative and 1 week, 7 weeks, and 6 months postoperative glottal efficiency (maximum phonation time [MPT]), voice quality (including GRBAS-scores and acoustic parameters) and self-perceived voice-related handicap (voice handicap index [VHI-30]) were measured and analyzed, whereas type of vocal fold closure was evaluated and determined by flexible videolaryngoscopy based on Södersten and Lindestad classification (Wilcoxon signed-rank test). RESULTS:Thirteen patients underwent MT with VOIS under local anesthesia. Six months after surgery, the VHI-30 and MPT had improved from a preoperative mean of 75.0 ± 22.9 and 2.7 ± 2.1 s to a postoperative mean of 20.6 ± 19.7 and 6.3 ± 4.0 s, respectively. The mean GRBAS score improved from preoperative scores of Gpreop = 2.7, Rpreop = 2.6, Bpreop = 2.6, Apreop = 2.2, and Spreop = 2.0 to Gpostop = 0.3, Rpostop = 0.3, Bpostop = 0.2, Apostop = 0.2, and Spostop = 0.3 at 6 months postoperatively. Improved glottal closure was achieved in all patients (n = 13). Five patients received postoperative adjustment for the optimization of voice quality and glottal closure. No intra- or postoperative complications were observed. Significant improvements in acoustic parameters, including percentage jitter, percentage shimmer, and signal-to-noise ratio, were also observed after MT. All results were statistically significant (P < .05, Cohen's d > .8). CONCLUSIONS:APrevent® VOIS-Implantation is a safe procedure with good voice outcomes. Postoperative adjustments can be performed smoothly to optimize voice quality and glottal closure. LEVEL OF EVIDENCE:3 Laryngoscope, 132:1622-1629, 2022.

Thyroglossal duct cysts are typically benign and usually asymptomatic. Malignant transformation is uncommon. Intralaryngeal extension is rare and results in dysphonia or dyspnea. There is no literature nowadays reporting the thyroglossal duct cyst carcinoma combining the clinical features of intralaryngeal extension. The authors present a case of progressive hoarseness and midline neck mass for 2 years. The laryngoscope and computed tomography revealed a 6-cm thyroglossal duct cyst containing ectopic thyroid tissue with intralaryngeal extension and causing airway obstruction. Complete excision with Sistrunk operation revealed papillary thyroid carcinoma. The patient resumed normal phonation after the surgery. There was no evidence of tumor recurrence and no hoarseness or dyspnea at 6 months follow up. This is the first reported case of a huge thyroglossal duct cyst carcinoma with intralaryngeal extension causing airway compromise. Complete excision of tumor is essential and vital to the symptom relief. A thyroglossal duct cyst carcinoma with endolaryngeal involvement should be considered in the differential diagnosis when the case has a massive midline neck mass with ectopic thyroid tissue and develops dyspnea or hoarseness concurrently.

INTRODUCTION:Induction chemotherapy (IC) followed by concurrent chemoradiotherapy (CCRT) is recommended for larynx-preserving treatment of locally advanced hypopharyngeal cancer (LAHC). However, the conventional evaluation of response is not robust enough to predict the outcome of subsequent treatments. This study aimed to develop an imaging biomarker using changes in radiomic features in invasive tumor front (ITF) by IC to predict treatment outcome of subsequent CCRT in LAHC. METHODS:From 2006 to 2018, 59 computed tomography (CT) scan images before and after IC in patients with LAHC were used to contour the gross tumor volumes (GTVs). A total of 48 delta-volume radiomics features were acquired from the absolute spatial difference of GTVs (delta-GTV) before and after IC, conceptually representing a consistent portion of ITF. Least absolute shrinkage and selection operator regression (LASSO) was used to select features for establishing the model generating radiomic score (R score). RESULTS:A model including 5 radiomic features from delta-GTV to predict better progression-free survival (PFS) of patients receiving subsequent CCRT was established. The R score was validated with all datasets (area under the curve 0.77). Low R score (<-0.16) was associated with improved PFS (p < 0.05). CONCLUSIONS:The established radiomic model for ITF from radiomic features of delta-GTV after IC might be a potential imaging biomarker for predicting clinical outcome of subsequent CCRT in LAHC.

Background and purpose: To investigate the association between progressive muscle loss and survival outcomes of patients with advanced-stage oral squamous cell carcinoma (OSCC) undergoing surgery and adjuvant (chemo)radiotherapy. Methods: We analyzed the computed tomography (CT) scans of 155 patients with stage III-IVB OSCC at baseline, at simulation CT for radiotherapy, and at 3- and 9-months post-treatment. Skeletal muscle index (SMI) was measured using CT at the C3 vertebral level. The predictors of overall survival (OS) and recurrence-free survival (RFS) were evaluated using Cox regression models. Results: The median follow-up period was 75.0 months. Fifty-one patients (32.9%) developed recurrence, with the median time from the fourth CT to recurrence being 9.1 months. The SMI progressively decreased from baseline to simulation CT by 1.1% (p = 0.006), to 3 months post-treatment by 5.1% (p < 0.001), and to 9 months post-treatment by 15.6% (p < 0.001) in patients developing recurrence. Patients without recurrence lost SMI at the simulation CT by 0.7% (p = 0.001) and at 3 months post-treatment by 2.1% (p < 0.001); their SMI returned to the baseline level at 9 months post-treatment. SMI changes were weakly correlated with changes in body mass index (BMI) (Spearman q, 0.13; p = 0.11). In multivariate analysis, SMI changes (per 5% decrease) were independently associated with significantly worse OS (hazard ratio: 1.88, 95% confidence interval: 1.58-2.23; p < 0.001) and RFS (hazard ratio: 1.89, 95% confidence interval: 1.61-2.20; p < 0.001). Conclusion: Progressive muscle loss was independently associated with worse survival outcomes in patients with stage III-IVB OSCC. Muscle loss might not be detected by changes in BMI. (C) 2021 Elsevier B.V. All rights reserved.

Background: Cisplatin is the drug of choice for the treatment of head and neck cancer (HNC) worldwide; however, the efficacy of this chemotherapeutic agent is counterbalanced with the risk of severe toxicities in certain patient populations. Definitive clinical criteria that identify patients susceptible to cisplatin toxicity across various demographic groups remain unavailable. The genetic and sociodemographic characteristics of HNC patients in Taiwan differ from global patient populations and therefore warrant Taiwan-specific guidelines. Methods: To address this unmet medical need, a panel of 20 senior physicians and experts from the Taiwan Head and Neck Society drafted clinical recommendations for defining patients who are unsuitable for treatment with cisplatin. Results: This clinical review describes the resulting consensus document, including the definition of cisplatin ineligibility criteria in HNC patients and supporting literature, which will support clinicians in defining platinum-unsuitable HNC patients in Taiwan. Conclusions: This recommendation will help to minimize toxicity-related morbidity from platinum-unsuitable HNC patients and improve patients' quality of life.

Objectives Sarcopenia and systemic inflammation can affect survival of advanced-stage oral squamous cell carcinoma (OSCC) patients; however, their reciprocal associations with survival outcomes are yet to be investigated. Study Design Retrospective review at a tertiary cancer center. Methods Patients with stage III-IVB OSCC that underwent surgery and (chemo)radiotherapy at our institution between 2010 and 2015 were reviewed. Skeletal muscle index (SMI) was assessed using computed tomography scans at the C3 vertebra. Sarcopenia was defined at the lowest sex-specific tertile for SMI. Systemic inflammation was estimated using the modified Glasgow prognostic score (mGPS), which ranges from 0 to 2 based on serum C-reactive protein and albumin levels. The predictors of overall survival (OS) were evaluated using Cox regression models. Results A total of 174 patients were included in the study. The cut-off values for sarcopenia were set at SMI <52.4 cm(2)/m(2) (men) and < 36.2 cm(2)/m(2) (women) corresponding to the lowest sex-specific tertile. An mGPS 1-2 was independently associated with sarcopenia (odds ratio: 2.05; 95% confidence interval: 1.06-3.97; P = .03). On multivariate analysis for OS, sarcopenia and mGPS 1-2 independently predicted OS (hazard ratio: 2.12; 95% confidence interval: 1.17-3.85; P = .01 and hazard ratio: 7.85; 95% confidence interval: 3.7-16.65; P < .001, respectively). Patients with both sarcopenia and mGPS 1-2 (vs. neither) had worse OS (hazard ratio: 16.80; 95% confidence interval: 6.01-46.99; P < .001). Conclusions Sarcopenia and systemic inflammation may exert a negative synergistic prognostic impact in advanced-stage OSCC patients. Level of Evidence 4 Laryngoscope, 2020

Background: Concurrent chemoradiotherapy (CCRT) is an important therapeutic strategy in locally advanced squamous cell carcinoma of the head and neck (LA-SCCHN). We evaluated the efficacy and toxicity of two CCRT regimens in treating LA-SCCHN. Materials and Methods: LA-SCCHN patients receiving CCRT with either a modified 3-weekly cisplatin 75 mg/m2 (Group A, n = 86) or 5-day continuous infusion of cisplatin 12 mg/m2 plus 5-fluorouracil (5-FU) 600 mg/m2 (Group B, n = 87) were enrolled. The Kaplan−Meier method was used to estimate overall survival (OS), progression-free survival (PFS), and locoregional recurrence-free survival (LRFS). Univariate and multivariate analyses were performed using Cox proportional hazard models to assess correlations between clinical parameters and survival. Results: With a median of 35.8 months' follow-up, the median OS and PFS in Group A and Group B were 65.9 versus 55.0 months (P = 0.546) and 34.6 versus 33.3 months (P = 0.948), respectively. LRFS was not reached in either group. Group B patients had more Grade 3−4 mucositis (53.7% vs. 32.28%, P= 0.001) and dermatitis (49.8% vs. 21.5%, P= 0.0001). Trends of higher incidence rates of Grade 3−4 hematologic and renal toxicity were observed in Group A. After statistical adjustment, higher disease stage (Stage IVb) (hazard ratio [HR] = 6.657, 95% confidence interval [CI] 1.786−24.81, P= 0.005) and pretreatment anemia (hemoglobin <13 g/dL) (HR = 1.896, 95% CI 1.063−3.391, P= 0.030) were associated with poor OS. Conclusion: A 5-day cisplatin-5-FU regimen was associated with more frequent Grade 3−4 mucositis and dermatitis than a 3-weekly cisplatin regimen. A multiagent CCRT regimen did not provide survival benefits but increased adverse events.

Neoadjuvant concurrent chemoradiotherapy (CCRT) followed by surgery is widely used for treating locally advanced esophageal cancer in the thorax. This study evaluated the feasibility of neoadjuvant CCRT as a larynx preservation strategy for treating cervical esophageal squamous cell carcinoma (SCC) by a multidisciplinary team. Fifteen patients with cervical esophageal SCC who received neoadjuvant CCRT and radical surgery at our institution were reviewed. All patients received CCRT using the intensity-modulated radiation therapy with 48 Gy to gross tumor and 43.2 Gy to regional lymphatic basin in 24 fractions. Side effects, clinical tumor responses, pathological responses, and surgical margin status were analyzed. Pathological T down-staging was noted in seven patients (46.7%); pathological complete response was achieved in three patients (20%). Fourteen patients (93.3%) had larynx preservation; eight patients (53.3%) achieved negative surgical margins. The 2-year overall survival, local relapse-free survival, and regional relapse-free survival were 50.6%, 62.2%, and 47.5%, respectively. Neoadjuvant CCRT and larynx-sparing surgery are feasible and tolerable in patients with cervical esophageal SCC. Prospectively designed studies for large patient groups and long-term follow-up results are needed for validating this multimodality therapy.

The nasal structure is closely related to nasal diseases. If an individual presents a discomfort in the nose for an extended period of time, the nasal tissue might have abnormal phenomena. Chronic sinusitis can cause nasal sinus shrinkage, especially the maxillary sinus, while allergic rhinitis can cause inferior turbinate pachynsis. Therefore, the volumes of the inferior turbinate and maxillary sinus are important indexes for otolaryngologists to judge nasal diseases. At present, the volumes of the inferior turbinate and maxillary sinus are estimated by radiologists manually contouring computed tomography (CT) images of the head and neck. The process consumes time and the results are not objective. This study aimed to propose an automatic recognition and volume calculation for the inferior turbinate and maxillary sinus by using image processing techniques. The back propagation neural network (BPNN) was used for automatic recognition of the inferior turbinate and maxillary sinus. Parametric template matching (PTM) and the sub-region similarity were used as feature inputs. The level set method (LSM) was applied to circle the contour of the inferior turbinate and maxillary sinus. The marching cubes algorithm was employed for 3D reconstruction and visualization. The volume information was obtained from the nonlinear regression curve. The accuracy and sensitivity of the automatic recognition results for inferior turbinate and maxillary sinus was 96.3 % and 95.1 %, respectively. The relationship between volume and nasal lesion has been analyzed as well. (C) 2019 Elsevier Ltd. All rights reserved.

Abstract Background The study aims are to evaluate the associations between nasopharyngeal carcinoma (NPC) risk and cigarette smoking and to explore the effects of cigarette smoking on Epstein‐Barr virus (EBV) infection for NPC risk. Methods 1235 male NPC cases and 1262 hospital‐based male controls matched to cases were recruited across six collaborative hospitals between 2010 and 2014. Using a standardized questionnaire, information on cigarette smoking and other potential risk factors for NPC was obtained. Blood was collected and used for anti‐EBV VCA IgA and anti‐EBV EA‐EBNA1 IgA testing using standard methods. Unconditional logistic regression analysis was used to estimate odds ratio (OR) with 95% confidence interval (CI) for each risk factor after adjusting for confounders. Results 63.6% of cases and 44.0% of controls reported ever smoking cigarettes. After full adjustment, current smokers had a significant 1.60‐fold (95% CI = 1.30‐1.97) and former smokers a borderline significant 1.27‐fold (95% CI = 1.00‐1.60) increased NPC risk compared to never smokers. NPC risk increased with increasing duration, intensity, and pack‐years of cigarette smoking but not with age at smoking initiation. Among controls, anti‐EBV VCA IgA seropositivity rate was higher in current smokers than never smokers (14.0% vs 8.4%; OR = 1.82; 95% CI = 1.19‐2.79). Mediation analyses showed that more than 90% of the cigarette smoking effect on NPC risk is mediated through anti‐EBV VCA IgA. Conclusion This study confirms the association between long‐term cigarette smoking and NPC and demonstrates that current smoking is associated with seropositivity of anti‐EBV VCA IgA antibodies.

A 44-year-old man was previously healthy. He developed right cheek paresthesia and swelling for months without obvious progression in size. On palpation, the nontender mass seemed to be multifocal with extension to right parotid, submandibular, and buccal area. The buccal mucosa was grossly smooth and there’s no palpable lymph node along the neck. Posterior anterior mandible view demonstrated an osteolytic lesion involving right posterior body of the mandible (Figure 1). Computer tomography (CT scan) of oropharynx (Figure 2), with and without contrast, revealed a 7-cm, cystic, and expansile lesion in right mandible with loculated margin with faint peripheral enhancement and compression of right submandibular gland. It is suspicious for a benign or malignant odontogenic tumor. There is also a cystic lesion, measuring 5.5 cm in greatest dimension, at right parapharyngeal space, with tight connection to the right mandibular lesion. The evidence of compression of the right carotid space by the cystic lesion is also noted. Technetium-99m-diphosphonates whole-body bone scan showed moderately increased uptake in the right mandible, reflecting the existing lesion as noticed in CT scan. Incisional biopsy of the mandibular mass reported chronic inflammation with an increased spindle cell in focal area. En bloc excision of the right mandibular and right parapharyngeal mass, as well as dissection of surrounding submandibular lymph nodes, were performed. Mandibular reconstruction with fibular free flap was then carried out by oral surgeon and plastic surgeon (Figure 3). Microscopically, it shows the presence of streaming fascicles of spindle-shaped cells arranged in a well-organized pattern in focal areas, consistent with Antoni A tissue with adjacent myxoid, and less-organized Antoni B tissue. The spindle cells are further highlighted by immunostaining with S-100 protein. The evidence of cystic change, hemosiderin deposition, and an infiltrate of foamy histiocytes is also noted (Figure 4). The above pictures support the diagnosis of an ancient schwannoma. The dissected lymph nodes showed lymphoid hyperplasia. On 6-month follow-up after surgery, the patient still felt right mandibular pain occasionally. Oral intake was fair on soft diet then. We arranged swallowing rehabilitation for the patient. Schwannomas are indolent, benign neoplasms derived from Schwann cells. The clinical presentations are mainly affected by tumor size, surrounding structures, and the nerve of origin