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OBJECTIVES: Laryngeal transplantation can restore the voice in patients who have undergone laryngectomy. However, the prospect of lifelong immunosuppression is a drawback to this procedure. We present data from a study aimed at minimizing the need for immunosuppression while maintaining graft viability through a novel pulsed-dosing protocol. METHODS: Larynges were transplanted from Lewis-brown Norway (RT1(l+n, F1) rats to Lewis (RT1(l)) recipients. All recipients received 7 days of treatment with everolimus and mouse anti-rat alphabeta T-cell receptor (anti-TCR) monoclonal antibodies beginning the day before transplantation. At 90 days after transplantation, all recipients received a pulse of the same treatment combination for 5 days. From 90 to 180 days after transplantation, the rats received no treatment (group 1, n = 5), 2.5 mg/kg everolimus per day (group 2, n = 5), or 1.0 mg/kg everolimus per day (group 3, n = 5). RESULTS: Histologic analysis of rats that received everolimus as pulse therapy evidenced no signs of rejection, whereas animals that were untreated after 90 days had normal to mild chronic rejection. T-cell reconstitution occurred 65 days after perioperative immunosuppressive treatment, but less rapidly after pulse therapy. Also, peripheral chimerism was generated in all 3 groups. CONCLUSIONS: In the rat laryngeal transplantation model, short-term perioperative therapy with everolimus and anti-TCR followed by pulsing is a viable alternative to the concerns associated with continuous, lifelong immunosuppression. [ABSTRACT FROM AUTHOR]

Introduction: Cervical spine defects result in spinal instability, putting the spinal cord and vertebral arteries at risk of damage and possibly devastating neurological injuries. The fibula free flap can span the spinal defects for stability. There is a paucity of literature on this technique., Method: Multi-institutional retrospective case series reviewing patients who underwent cervical spine reconstruction with a fibula free flap. Patient demographic information, comorbidities, characteristics of cervical spine defects, and free flap complications were collected., Results: A total of 1187 fibula free flaps across 10 different institutions were reviewed. Thirteen patients (1.09%) underwent cervical spine reconstruction with a fibula free flap. Average age was 52.3 years old with an age range of 12-79 years. There were six males (46.1%) and seven females (53.8%). The most common defect etiology was infection (n = 6, 46.1%). Most commonly involved cervical spine level of the defect was C5 (n = 10) followed by C6 (n = 9) and C4 (n = 8). The majority of reconstructed defects spanned three or more cervical levels, (n = 9, 69.2%). Facial artery was the most common arterial anastomosis (n = 8). Eight patients (61.5%) required a tracheostomy during their postoperative course. None of the patients had symptomatic or radiographic nonunion., Conclusion: This case series demonstrates that a vascularized fibula flap is a potential reconstructive option for cervical spine defects, especially in defects greater than three cervical levels, in the setting of infection, and previously radiated patients., Level of Evidence: 4 Laryngoscope, 134:4923-4928, 2024., (© 2024 The American Laryngological, Rhinological and Otological Society, Inc.)

Background: India has the highest incidence worldwide of smokeless tobacco (SLT)-associated oral cancer, accounting for nearly 70% of all SLT users globally. Nicotine and tobacco-specific N -nitrosamines (TSNA) play critical roles in the addictive and carcinogenic potential, respectively, of SLT products. Our group has previously reported substantial variability in nicotine and TSNA levels across a small SLT product sample in India, calling for systematic surveillance. However, there is no information available on the current levels of these constituents in Indian SLT., Methods: We analysed 321 samples representing 57 brands of eight popular types of manufactured SLT products purchased from five local markets in Mumbai, India between August, and September 2019. The sampling locations were Mumbai Central, Kurla, Thane, Vashi, and Airoli. Product pH, moisture content, total and unprotonated (biologically available) nicotine, and TSNA levels were measured at the Advanced Centre for Treatment, Research, and Education in Cancer (ACTREC) in Mumbai., Findings: Total nicotine content ranged from 0.45 to 35.1 mg/g across products. The unprotonated nicotine fraction contributed 0.1-100% of the total nicotine content. The carcinogenic TSNA levels ranged 0.06-76 ug/g for N' -nitrosonornicotine (NNN), 0.02-19.2 ug/g for 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK), and 0.01-6.51 ug/g for 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanol (NNAL). Consistent with our previous study, we observed substantial variations across different brands of the same product type., Interpretation: This is the most extensive and the first within-country study to report brand-specific nicotine and TSNA levels in SLT products marketed in Mumbai, India. Our results show that levels of these constituents remain extremely variable across Indian SLT and are strikingly high in many products. Enhanced public education and continued efforts to reduce SLT use prevalence in India are critical for reducing the global burden of SLT-associated morbidity and mortality. Regulation of nicotine and TSNA levels in SLT products should be considered., Funding: This work was supported by the National Institutes of Health (USA) grant R01-TW010651 and, in part, by grants R01-CA180880 and R50-CA211256. The LC-MS/MS analysis was supported in part by XII Plan project funding from the Department of Atomic Energy, Government of India., Competing Interests: S.K. provided an expert testimony, with the payment received institutionally by the University of Minnesota. J.S.A. received travel compensation for the 2021 and 2022 Annual Global Tobacco and Nicotine Forum and is a consultant and has equity in Qnovia, a start-up company developing a nicotine replacement product for U.S. Food and Drug Administration prescription product approval. We declare no other competing interests., (© 2024 The Author(s).)

Human papillomavirus (HPV)-related oropharyngeal cancers associated with sexual contact are increasing, with high rates in men who have sex with men. HPV-related cancers have the advantage of being frequently detectable through oropharyngeal visual examination and having much higher survival rates than classic oropharyngeal cancers. It has been demonstrated that gay and bisexual men can take smartphone oropharyngeal "selfies" of sufficient quality for screening. However, there is an issue with the inability to move the tongue to allow a clear view of the palatine tonsils, where a majority of oropharyngeal cancer cases occur. We attempted to investigate the feasibility of using commercially available videoscopes to visualize the oropharynx. Fourteen healthy volunteers used a provided low-cost commercial endoscope to video their oropharynx. Participants used the videoscope connected to a laptop and could visualize the oropharynx on the screen. Attempts were observed, and the process was noted. A focus group of participants was carried out immediately afterwards to ascertain barriers and facilitators to using the videoscopes. All participants were able to use the videoscope and obtain videos of sufficient clarity to note major oropharyngeal landmarks. The palatine tonsils were initially difficult to visualize because the tongue could not be sufficiently controlled. Participants were given time to practice using visual cues to control the position of the tongue, which helped in obtaining good videos. Videoscopes can be used effectively with minimal instruction and provide a better view than still images, as they illuminate and magnify the site. Low-cost commercially available videoscopes may be an improvement over smartphone "selfies"., Competing Interests: Conflict of interest No conflicts of interest are reported for any author.

Background: Men who have sex with men (MSM) are at increased risk for human papillomavirus-associated oropharyngeal cancer (HPV-OPC). The objective of this analysis was to create a psychometrically validated scale to measure perception of risk for HPV-OPC., Methods: We conducted an exploratory and a confirmatory factor analysis to determine and confirm the latent factor structure. We used a path diagram to evaluate the relationship between the validated scale and perceived risk for HPV-OPC. The model was determined to be a good fit if it met all criteria: root mean square error of approximation ≤0.06, standardized root mean residual ≤0.08, Comparative Fit Index ≥0.90, and Tucker-Lewis Index ≥0.90. We report standardized estimates and 95% confidence intervals., Results: This cross-sectional study recruited 1315 MSM. A majority (73.33%) of MSM had performed fellatio on ≥20 partners, 36.98% had rimmed ≥20 partners, and 5.31% had performed cunnilingus on ≥10 partners in their lifetime.Six sexual history survey items loaded onto 2 latent factors: sexual risk behaviors: class 1 and sexual risk behaviors: class 2. The final model statistics indicated good fit: root mean square error of approximation = 0.064, standardized root mean residual = 0.059, Comparative Fit Index = 0.996, and Tucker-Lewis Index = 0.993. Sexual risk behaviors: class 1 was associated with greater perceived risk for HPV-OPC (0.217; 95% confidence interval, 0.138-0.295). Age, HIV status, HPV vaccination status, and sexual risk behaviors: class 2 were not associated with perceived risk for HPV-OPC., Conclusion: Men who have sex with men assessed risk for HPV-OPC based on their lifetime number of cisgender male sexual partners, rimming partners, and fellatio partners but not other sexual behaviors. Men who have sex with men may be responsive to future HPV-OPC educational interventions and opportunities for screening., Competing Interests: Conflict of Interest and Sources of Funding: The authors declare no potential conflicts of interest., (Copyright © 2024 The Author(s). Published by Wolters Kluwer Health, Inc. on behalf of the American Sexually Transmitted Diseases Association.)

Objective: To report our updated experience in the management of esophageal perforation resulting from anterior cervical spine surgery, and to compare two wound management approaches., Methods: This is a retrospective review of patients managed for esophageal perforations resulting from anterior cervical spine surgery (2007-2020). We examine outcomes based on 2 wound management approaches: closed (closed incision over a drain) versus open (left open to heal by secondary intention). We collected data on demographics, operative management, resolution (resumption of oral intake), time to resolution, number of procedures needed for resolution, microbiology, length of stay, and neck morbidity., Results: A total of 13 patients were included (10 men). Median age was 52 years (range, 24-74 years). All patients underwent surgical drainage, repair, or attempted repair of perforation, hardware removal, and establishment of enteral access. Wounds were managed closed versus open (6 closed, 7 open). There were 2 early postoperative deaths due to acute respiratory distress syndrome and aspiration (open group), and 1 patient was lost to follow-up (closed group). Among the remaining 10 patients: resolution rate was 80% versus 100%, resolution in 30 days was 20% versus 100%, median number of procedures needed for resolution was 3 versus 1, and median hospital stay was 23 versus 14 days, for the closed and open groups, respectively., Conclusions: Esophageal perforation following anterior cervical spine surgery should be managed in a multidisciplinary fashion with surgical neck drainage, primary repair when feasible, hardware removal, and establishment of enteral access. We advocate open neck wound management to decrease the time-to-resolution, number of procedures, and length of stay., Competing Interests: The authors reported no conflicts of interest. The Journal policy requires editors and reviewers to disclose conflicts of interest and to decline handling manuscripts for which they may have a conflict of interest. The editors and reviewers of this article have no conflicts of interest., (© 2024 The Author(s).)

Both targeted therapies and immunotherapies provide benefit in resected Stage III melanoma. We hypothesized that the combination of targeted and immunotherapy given prior to therapeutic lymph node dissection (TLND) would be tolerable and drive robust pathologic responses. In NeoACTIVATE (NCT03554083), a Phase II trial, patients with clinically evident resectable Stage III melanoma received either 12 weeks of neoadjuvant vemurafenib, cobimetinib, and atezolizumab (BRAF-mutated, Cohort A, n = 15), or cobimetinib and atezolizumab (BRAF-wild-type, Cohort B, n = 15) followed by TLND and 24 weeks of adjuvant atezolizumab. Here, we report outcomes from the neoadjuvant portion of the trial. Based on intent to treat analysis, pathologic response (≤50% viable tumor) and major pathologic response (complete or near-complete, ≤10% viable tumor) were observed in 86.7% and 66.7% of BRAF-mutated and 53.3% and 33.3% of BRAF-wild-type patients, respectively (primary outcome); these exceeded pre-specified benchmarks of 50% and 30% for major pathologic response. Grade 3 and higher toxicities, primarily dermatologic, occurred in 63% during neoadjuvant treatment (secondary outcome). No surgical delays nor progression to regional unresectability occurred (secondary outcome). Peripheral blood CD8 + T CM cell expansion associated with favorable pathologic responses (exploratory outcome)., (© 2024. The Author(s).)

Importance: Lymph node metastases from oral cavity cancers are seen frequently, and there is still inconsistency, and occasional controversies, regarding the surgical management of the neck in patients with oral cancer. This review is intended to offer a surgically focused discussion of the current recommendations regarding management of the neck, focusing on the indications and extent of dissection required in patients with oral cavity squamous cell carcinoma while balancing surgical risk and oncologic outcome., Observations: The surgical management of the neck for oral cavity cancer has been robustly studied, as evidenced by substantial existing literature surrounding the topic. Prior published investigations have provided a sound foundation on which data-driven treatment algorithms can generally be recommended., Conclusions: Existing literature suggests that patients with oral cavity cancer should be fully staged preoperatively, and most patients should receive a neck dissection even when clinically N0. Quality standards supported by the literature include separation of each level during specimen handling and lymph node yield of 18 or more nodes. Sentinel lymph node biopsy can be considered in select tumors and within a well-trained multidisciplinary team.

Background: Gay and bisexual men (GBM) are at increased risk of developing human papillomavirus (HPV)-associated oropharyngeal cancer (OPC). Vaccination may prevent OPC in GBM; however, vaccination rates are low. The authors explored the correlates associated with HPV vaccination intent for OPC prevention among GBM., Methods: The authors conducted a cross-sectional study in which they surveyed 1,700 adult GBM with a profile on 2 online dating sites. Eligibility criteria included self-identified GBM living in the United States, aged 18 through 45 years who had sex with a man in the past 5 years. Factors associated with participants' HPV vaccination status and intent to vaccinate were assessed via the online questionnaire using the Health Belief Model., Results: Most of the 1,108 eligible GBM had not received 1 dose or more of the HPV vaccine (54.2%), were aged 27 through 37 years (52.3%), were White (58.3%), identified as cisgender men (93.4%), were gay (79.3%), were in a monogamous relationship (99.4%), and had a bachelor's degree (29.4%) or higher college education (26.1%). Among unvaccinated GBM, 25.3% reported intent to receive the vaccine. In the multivariable model, independent associations (P < .05) were found for the Health Belief Model constructs (perceived benefits and perceived barriers) with HPV vaccine intent, after adjusting for all other predictor variables in the model., Conclusions: The benefits of HPV vaccination for the prevention of OPC is associated with intent to vaccinate among GBM. Dental care providers can use this information to educate patients in this high-risk population on prevention of HPV-associated OPC., Practical Implications: Dentists can advocate for HPV vaccination uptake among GBM patients by means of discussing the benefits of vaccination in the prevention of HPV-associated OPC., Competing Interests: Disclosure None of the authors reported any disclosures., (Copyright © 2024 American Dental Association. Published by Elsevier Inc. All rights reserved.)

Oropharyngeal cancers (OPCa) caused by HPV have emerged as one of the leading causes of malignancies caused by HPV infection. They are also significantly more likely to occur in males and in people with a history of oral sex with multiple partners. Gay and bisexual men are disproportionately affected by HPV-positive oropharyngeal cancers. We studied 1699 gay and bisexual men on 2 major dating sites in the US to assess their knowledge about HPV-related OPCa, attitudes toward screening for it, beliefs about oropharyngeal cancer screening based on the Health Belief Model, and attitudes toward possible screening approaches for OPCa. Knowledge on a 12-item scale was low, with a median of 5 items correct: 72% knew of the benefits of HPV vaccination. Significant predictors of needing OPCa screening included perception of risk for OPCa, seeing it as severe, having lower barriers, fewer reasons to avoid screening, higher knowledge, and being HPV vaccinated were significant predictors, explaining half the total variance. Most participants would accept routine, virtual/online doctor or dental appointments, and over half would accept an in-person screening. Nearly two-thirds stated that they would accept getting checked for OPCa if they could do self-screening at home, and half were prepared to use an online screening tool or app, where they could take an "oral selfie" and send it to a healthcare provider for examination. One-third stated that they would trust the results of a home screening completed by themselves and posted to a website equally as cancer screening completed online by a healthcare provider. Data indicate that despite low OPCA knowledge levels, the risk of HPV-associated OPCa was known. Being at personal risk and having knowledge of disease severity had 70% of the sample thinking about, or preparing to get, screening. Self-screening by a smartphone "oral selfie" transmitted to a screening website was acceptable to many gay and bisexual men, and online screening by a doctor or dentist was acceptable to most. OPCa screening in this population using electronic technology, together with the increasing incidence of HPV-associated OPCa in gay and bisexual men, brings together an opportunity to detect OPCa early., Competing Interests: Conflicts of Interest: The authors declare no conflict of interest.

Objectives: This study aims to determine the potential uptake and quality of oropharyngeal "selfies" taken by gay/bisexual men as a screening approach for HPV-associated oropharyngeal cancer., Methods: From 1,699 gay/bisexual men in the US, surveyed about knowledge and attitudes to HPV-associated oropharyngeal cancer, a random sample of 320 men were invited to take an oropharyngeal "selfie" by smartphone and send it to the study website: 113 (35.5%) did so. Images were rated for quality by three healthcare professional raters blinded to each other's rating, with an otolaryngologist as the gold standard. In the second wave, those whose images were rated as unacceptable were sent a short instructional video and asked to send another image. Of the 65 invited, 46 did so. An additional 15.2% sent acceptable images, and a total of 28.3% of the sample was acceptable., Results: A total of 1,121 men willing to participate in the future study who believed they could take a quality "oral selfie" were potentially eligible for this activity. A random sample of 320 participated: 153 participants started (47.8%) and 113 participants (35.3%) submitted an image. Responders were more likely to be younger, have higher knowledge scores on oropharyngeal HPV-related cancer, and have had HPV vaccination. There was high agreement between the three raters. Images of good/acceptable quality were 22.1%; oropharynx partially occluded images were 29.2%; oropharynx not visible images were 18.6%; images too dark were 21.2%; and images too small were 8.8%. From the second wave of requests with instructional videos, an additional 15.2% sent in quality images, with the remaining issues being partial occlusion of the tonsils by the tongue., Conclusion: One-third of the invited gay and bisexual men sent oropharyngeal selfie images to the study website and a total of 28.3% were of clinically acceptable quality. Following an instructional video on poorer-quality images, additional quality images were received. One barrier, i.e., partial occlusion of the oropharynx by the tongue remained. Quality oropharyngeal "selfies" are obtainable online., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Ross, Bennis, Nichols, Zoschke, Wilkerson, Rosser, Stull, Nyitray, Flash and Khariwala.)

Introduction: Among US men, oropharyngeal cancer (cancer of the back of the mouth and throat) is the 8th most common cancer. If detected early, human papillomavirus (HPV)-16-associated oropharyngeal cancer has a high 5-year survival rate. Risk factors such as high numbers of oral sex partners, disparities in smoking and drinking, and low rates of HPV vaccination may put gay and bisexual men at even higher risk for oropharyngeal cancer., Methods: We recruited 21 healthcare providers in Minneapolis-St. Paul, Minnesota and Houston, Texas to participate in semi-structured interviews. Nurses, physician assistants, dental hygienists, and dentists were asked about their clinical experiences serving gay and bisexual men and opinions on potential interventions for the early detection of oropharyngeal cancer., Results: Providers typically did not tailor health screenings and examinations for gay and bisexual men. Participants lacked confidence in their ability to effectively implement routine screening for oropharyngeal cancer. The extent to which oropharyngeal cancer screening was incorporated into clinical practice varied by specialty, and practices necessary to detect it were scattered across clinical environments. HIV- and LGBTQ-focused healthcare providers were more aware of HPV-associated oropharyngeal cancer in gay and bisexual men, and appeared readier to act and lead on this issue., Discussion: Further studies should (1) evaluate protocols for oropharyngeal cancer detection; (2) identify and assess the acceptability of screening in the community; and (3) study how to best close gaps in health services for gay and bisexual men which might contribute to low early detection rates of oropharyngeal cancer., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Zoschke, Bennis, Wilkerson, Stull, Nyitray, Khariwala, Nichols, Rosser, Flash and Ross.)

Importance: Smoking during and after treatment has been linked to increased morbidity and mortality in patients with head and neck squamous cell carcinoma (HNSCC). Posttreatment tobacco use patterns and the appropriate timing for cessation interventions are understudied., Objective: To determine the frequency and patterns of posttreatment smoking cessation in smokers with HNSCC., Design, Setting, and Participants: This prospective cohort study assessed smoking status after a new diagnosis of HNSCC among daily smokers who were treated at a tertiary care center at an academic institution between January 1, 2009, and December 31, 2017., Exposures: Being current daily cigarette smoker at the time of diagnosis of HNSCC and having smoked at least 5 cigarettes per day for at least 5 years., Main Outcomes and Measures: Patients provided data indicating smoking intensity, duration of tobacco use, number of cessation attempts, number of successful cessation days, and symptoms during cessation attempts, as well as demographic and clinical information at the time of diagnosis, as well as smoking and disease status at 6 months, 12 months, 18 months, and 24 months after treatment., Results: Eighty-nine smokers with HNSCC (mean [SD] age at enrollment, 60.1 [9.2] years; 74 [83.1%] male and 15 [16.9%] female; 2 [2.2%] American Indian or Alaska Native, 1 [1.1%] Asian, 3 [3.4%] Black, 71 [79.8%] White, and 12 [13.5%] of unknown race and ethnicity or whose race and ethnicity were not reported) completed 24 months of posttreatment follow-up and were included in the study. Fifty-two patients (58.4%) continued to smoke at 6 months after treatment, 47 patients (52.8%) smoked at 12 months after treatment, 41 patients (46.1%) smoked at 18 months after treatment, and 40 patients (44.9%) smoked at 24 months after treatment. The probability of smoking cessation was highest during the first 6 months after treatment, at 0.36. Mean (SD) number of cigarettes per day (17.8 [9.6] vs 12.4 [10.0], mean difference, 5.1 [95% CI, 0.2 to 10.6]), duration of tobacco use (28.2 [18.1] vs 16.4 [17.4] years, mean difference, 11.8 [1.9 to 21.7] years), and lower number of prior quit attempts (5.3 [5.9] vs 10.4 [22.9], mean difference, -5.2 [95% CI, -15.7 to 5.4]) were all associated with persistent tobacco use at 24 months after treatment vs those who successfully quit., Conclusions and Relevance: The results of this cohort study suggest that a significant proportion of patients with HNSCC who are daily smokers at the time of diagnosis continue to smoke after treatment. Smokers with HNSCC who successfully quit smoking were most likely to do so in the first 6 months after treatment, which could potentially serve as a preferred window for smoking cessation interventions. These data highlight the need for inclusion of aggressive smoking cessation intervention in head and neck cancer care pathways.

Biomarkers of exposure to harmful tobacco constituents are key tools for identifying individuals at risk and developing interventions and tobacco control measures. However, tobacco biomarker studies are scarce in many parts of the world with high prevalence of tobacco use. Our goal was to establish a robust method for simultaneous analysis of urinary total 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanol (NNAL), N'-nitrosonornicotine (NNN), and cotinine at the Advanced Centre for Treatment, Research and Education in Cancer (ACTREC) in Mumbai, India. These biomarkers are validated measures of exposure to the carcinogenic tobacco nitrosamines 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK) and NNN and the addictive alkaloid nicotine, respectively. The established method is characterized by excellent accuracy, linearity, and precision, and was successfully applied to the analysis of 15 smokeless tobacco (SLT) users and 15 non-users of tobacco recruited in Mumbai. This is the first report of establishment of such procedure in a laboratory in India, which offers the first in-country capacity for research on tobacco carcinogenesis in Indian SLT users., (© 2021. The Author(s).)

Background: To assess variations in adherence to guideline-recommended processes of care for oral cavity cancer patients., Methods: Retrospective study using a U.S. healthcare research database (MarketScan). Index diagnoses were considered from 2010 to 2012 with follow-up from 2013 to 2014. Diagnostic and procedure codes were utilized to identify oral cavity patients with a defined treatment modality. Compliance with guideline-recommended processes of care, which included pre-treatment imaging, thyroid-function testing (TFTs), multidisciplinary consultation and gastrostomy-tube insertion rates, were assessed., Results: A total of 2752 patients were identified. Surgery alone was the most common treatment (60.8%), followed by surgery with adjuvant chemoradiotherapy (20.4%) and surgery with adjuvant radiotherapy (18.8%). Head/neck and chest imaging were obtained in 60% and 62.5% of patients respectively. Significant geographical differences in head and neck imaging were observed between North-central (64%), South (58.4%) and West (56.1%) regions (p = 0.026). Differences in chest imaging were also present between North-east (65%) and West (56.8%; p = 0.007). TFTs were obtained in 54.4% of the patients after radiation treatment, and 18.6% of patients had multidisciplinary consultation during the 6 months before and 3 months after initiation of treatment. During the year after treatment initiation, 21.2% of patients underwent G-tube placement, with significantly higher rates in patients receiving triple modality treatment (58%) when compared to surgery plus radiation (27%) and surgery alone (15%; p < 0.01)., Conclusion: Adherence to evidence-based practices was low based on the database coding. These data suggest a potential to improve adherence and increase the routine use of practices delineated in national clinical practice guidelines., Clinical Relevance: This study reflects a suboptimal adherence to guidelines based on the database employed. This study should be considered by healthcare providers and efforts should be maximized to follow the processes of care which have proven to impact on patient's outcomes.

Objective: Parotid neoplasms are a rare heterogeneous group of tumors with varied clinical presentation and behavior. Here we provide an evidence-based review of the contemporary approach to evaluation and surgical management of parotid tumors., Data Source: PubMed and Web of Science Databases., Review Methods: Searches of the PubMed and Web of Science databases were performed on subjects related to the diagnosis and surgical management of parotid neoplasms. Particular emphasis was placed on the following areas: evaluation of parotid tumors, including imaging workup and the utility of fine-needle aspiration; extent of surgery of the primary lesion, including the extent of parotidectomy as well as oncologic management of the facial nerve; the extent of surgery of involved and at-risk cervical lymphatics; and parotid bed reconstruction. Articles published from 2014 to the present were prioritized, supplementing with information from prior studies in areas where data are lacking., Conclusion: A summary of the literature in these areas is outlined to provide an evidence-based approach to evaluation and management of parotid neoplasms., Implications for Practice: While data are available to help guide many aspects of workup and management of parotid neoplasms, further research is needed to refine protocols for this heterogeneous group of diseases.

Importance: While regression is a commonly reported microscopic feature of melanoma, its prognostic significance is unclear., Objective: To examine the impact of regression on sentinel node status and the likelihood of recurrence in primary cutaneous melanoma of the head and neck., Design: Retrospective analysis of 191 adults who underwent surgical management for primary cutaneous melanoma of the head and neck between May 2002 and March 2019., Setting: Tertiary academic center., Participants: Patients appropriate for the study were identified by the Academic Health Center Information Exchange using a list of current procedural terminology codes. One hundred and ninety-one cases of invasive melanoma of the head and neck were included from 830 patients identified. Clinical features assessed for each patient included age, sex, location of primary lesion, date of diagnosis, and current disease status (alive with or without disease). Histologic features assessed were histological melanoma subtype (nodular vs non-nodular), Breslow thickness, Clark level, presence/absence of ulceration, mitotic rate per square millimeter, and regression. If applicable, sentinel lymph node biopsy (SLNB) status, date of recurrence, interval treatments, and date of death related to melanoma were recorded. Exclusion criteria included melanoma outside the anatomic parameters of head and neck, ocular or choroidal melanoma, mucosal melanoma, metastatic melanoma to the head or neck with no known primary tumor, melanoma of the head or neck with no surgical intervention, and non-melanoma skin cancers of the head and neck., Intervention/exposure: Surgery for cutaneous melanoma of the head and neck., Main Outcomes and Measures: The association between presence of regression and Breslow thickness, sentinel node status, and recurrence., Results: Of the 191 patients identified, 30.9% were female and 69.1% were male with a mean age at diagnosis of 62.6 (range 20-97) years. Mean Breslow thickness was 1.2 mm in those with regression and 2.0 mm in those without regression. In patients with regression, 17.6% had a positive sentinel node, and 13.0% experienced a recurrence. In patients without regression, 26.5% had a positive sentinel node, and 31.4% experienced a recurrence. When adjusted for other factors above, regression was not associated with positive sentinel node (odds ratio [OR] = 0.59, 95% confidence interval [CI] = 0.13-2.00) or recurrence (OR = 0.33, CI = 0.07-1.01). Mitotic rate >2 was associated with recurrence (OR = 2.71, CI = 1.11-6.75, P = .03)., Conclusions and Relevance: Patients with presence of regression had thinner melanomas and trended toward decreased rates of sentinel node positivity and recurrence, suggesting regression may not be a negative prognostic indicator in patients with cutaneous melanoma of the head and neck., Competing Interests: The authors declare no potential conflict of interest., (© 2020 The Authors. Laryngoscope Investigative Otolaryngology published by Wiley Periodicals LLC. on behalf of The Triological Society.)

Objectives: Gutka is industrially manufactured in India and some Indian states have instituted bans on the sale of manufactured gutka as a public health initiative. We explored whether gutka was still available for purchase after the ban and also sought to observe methods of ban circumvention., Methods: We visited 5 different markets at different locations separated by at least 15-20 km around the Mumbai Metropolitan Region (MMR) area, consisting of Mumbai and its satellite towns in Maharashtra, India during August- September, 2019. In each location, purveyors were queried as to the availability of gutka., Results: Tobacco purchases were made in 5 locations/sections of MMR. At all markets, banned gutka was not displayed , and could only be purchased after requesting from the shopkeeper. Three methods of ban circumvention were observed: (1) packages marked 'export only'; (2) use of twin packaging in which pan masala and tobacco are sold together for immediate mixing to create gutka; and, (3) non-descript packaging without mention of 'gutka'., Conclusions: Although not readily displayed in shops, gutka is readily available in MMR, despite a statewide ban in Maharashtra. Marketers have used multiple methods to circumvent the statewide gutka ban., Competing Interests: Conflict of Interest Disclosure Statement The authors have no conflicts of interest to disclose.

While smoking is inextricably linked to oral/head and neck cancer (HNSCC), only a small fraction of smokers develop HNSCC. Thus, we have sought to identify other factors, which may influence the development of HNSCC in smokers including microbiology. To determine microbial associations with HNSCC among tobacco users, we characterized oral microbiome composition in smokers with and without HNSCC. 16S rRNA MiSeq sequencing was used to examine the oral mucosa microbiome of 27 smokers with (cases) and 24 without HNSCC (controls). In addition, we correlated previously reported levels of DNA damage with the microbiome data. Smokers with HNSCC showed lower microbiome richness compared with controls (q = 0.012). Beta-diversity analyses, assessed as UniFrac (weighted and unweighted) and Bray-Curtis distances, showed significant differences in oral mucosal microbiome signatures between cases and controls ( r 2 = 0.03; P = 0.03) and higher interindividual microbiome heterogeneity in the former (q ≤ 0.01). Higher relative abundance of Stenotrophomonas and Comamonadaceae and predicted bacterial pathways mainly involved in xenobiotic and amine degradation were found in cases compared with controls. The latter, in contrast, exhibited higher abundance of common oral commensals and predicted sugar degradation pathways. Finally, levels of DNA damage in the oral cavity were correlated with the microbiome profiles above. Oral microbiome traits differ in smokers with and without HNSCC, potentially informing the risk of eventual HNSCC and shedding light into possible microbially mediated mechanisms of disease. These findings present data that may be useful in screening efforts for HNSCC among smokers who are unable to quit., (©2020 American Association for Cancer Research.)

Background: Tobacco cessation methods employed by patients with head and neck cancer (HNSCC) are previously unstudied and have the potential to inform choice of cessation method and necessary abstinence support., Methods: A total of 130 current smokers with HNSCC were queried regarding prior unsuccessful tobacco cessation techniques, product used (cold turkey, varenicline, and nicotine patch/gum), and maximum time abstained from smoking., Results: One hundred six smokers retrospectively reported using one of the four main quit methods. Unassisted cessation ("cold turkey") was the most commonly used method (P < .001). A multiple ordinal logistic general estimating equation analysis revealed that cold turkey had increased odds [5.2 (95% confidence interval [CI]: 2.2, 11.8) and 4.3 (95% CI: 1.5, 12.9)] of achieving a longer quit duration than the nicotine patch or varenicline, respectively., Conclusions: Among smokers developing HNSCC, previous cessation attempts were most commonly unassisted. This method was associated with longest abstinence periods. These data suggest insufficient support and education regarding behavioral and pharmacologic cessation therapies., (© 2019 Wiley Periodicals, Inc.)

Education regarding the health effects associated with tobacco use has made important progress worldwide over the last few decades. Still, tobacco remains a significant cause of cancer and other diseases. As a result, significant worldwide morbidity and mortality is still attributable to tobacco use in modern times. Research into tobacco products, the carcinogens they contain, and how users metabolize them is an important benefit to the advancement of research aimed at reducing harm associated with tobacco use. This review summarizes the use of this type of research to study tobacco users' risk of developing cancer, especially head and neck cancer. In addition, we discuss the use of tobacco research to provide support for increasing levels of federal regulation of tobacco products., Level of Evidence: 4.

Importance: Among smokers with head and neck squamous cell carcinoma (HNSCC), there is ample evidence regarding the benefits of smoking cessation prior to treatment. Prior data indicates that increased attempts at cessation result in higher likelihood of cessation after diagnosis but the prediagnostic patterns of smoking cessation attempts among those smokers developing HNSCC has not been characterized. Data of this kind may direct cessation efforts toward increased efficacy., Objective: To determine the frequency and character of tobacco cessation attempts and symptoms experienced prior to development of HNSCC, as well as to determine the correlation of these symptoms with number of cessation attempts and maximum quit days., Design, Setting, and Participants: Cross-sectional study including 123 active smokers with HNSCC recruited from a tertiary medical center at an academic institution from February 2014 to May 2017., Exposures: All included patients were active cigarette smokers prior to developing HNSCC., Main Outcomes and Measures: Patients provided data indicating intensity of smoking, duration, number of cessation attempts, maximum number of days during which they successfully ceased smoking, and symptoms during cessation attempts. Principal component analysis was used to identify clustering of symptoms., Results: In total, 123 patients were identified (97 men, 23 women, and 3 unspecified) from February 2014 to May 2017 as active smokers (mean [SD] age, 59.4 [9.0] years; median [interquartile range] age, 58.5 [54.8-66.0] years); patients had oral (n = 39 [32%]), oropharyngeal (n = 44 [36%]), laryngeal (n = 32 [26%]) or hypopharyngeal (n = 7 [6%]) tumors. Overall, 108 patients (88%) had made at least 1 prior attempt at cessation, and the mean number of lifetime cessation attempts was 6.6. Symptoms of cravings, restlessness, irritability, and anxiety were reported most frequently. Symptoms were clustered into 2 component groups: component group 1 (C1; increased appetite, cravings, depression) and component group 2 (C2; restlessness, irritability, insomnia, anxiety, and difficulty concentrating). Component group 2 correlated with quit attempts (Spearman correlation, 0.268 [95% CI, 0.07 to 0.45]), and C1 and C2 were not correlated with maximum quit days. Cessation attempts and maximum quit days positively correlated with each other., Conclusions and Relevance: Our analysis shows that symptoms during cessation attempts tend to cluster and that most patients made 1 or more cessation attempts. Many patients successfully ceased before restarting. Our data suggest that patients experiencing C2 symptoms make more quit attempts; C1 symptoms may be more difficult to overcome because they are associated with fewer quit attempts. Future work will address whether amelioration of these symptoms may help smoking cessation among smokers with HNSCC.

Purpose of Review: The purpose of this study is to describe the supraclavicular flap and its utility in head and neck reconstruction in the context of recent studies., Recent Findings: Current literature regarding the supraclavicular flap has described its expanded uses in a variety of head and neck reconstructive settings. Its reliability and limited morbidity have been well demonstrated, and it has been cited as a reasonable alternative to other reconstructive options including, in some situations, free tissue transfer., Summary: The supraclavicular flap has shown dependability in reconstruction of defects in the head and neck, and it warrants consideration among reconstructive surgeons, especially for circumstances in which free tissue or other pedicled flaps are less than ideal.

Background: Non-cigarette other tobacco products (OTP; e.g., cigarillos, little cigars) are typically used in combination with cigarettes, but limited data exists on the tobacco toxicant exposure profiles of dual cigarette-OTP (Cig-OTP) users. This study examined biomarkers of nicotine and carcinogen exposure in cigarette smokers who used or did not use OTP., Methods: 111 Cig-OTP and 111 cigarette only (Cig Only) users who smoked equivalent cigarettes per day were matched on age (< 40, >=40), race (African American, White), and gender. Participants reported past 7-day daily use of cigarettes and OTP and provided urine for nicotine, cotinine, total nicotine equivalents (TNE) and total NNAL concentrations., Results: Cig-OTP users reported greater past 7-day tobacco use (15.9 versus 13.0 products/day, p<0.01) but had significantly lower creatinine-normalized nicotine (606 versus 1301ng/mg), cotinine (1063 versus 2125ng/mg), TNE (28 versus 57 nmol/mg) and NNAL (251 versus 343pg/mg) than Cig Only users (p<0.001)., Conclusions: Cig-OTP users had lower levels of nicotine and metabolites of a lung carcinogen relative to Cig-Only users, but concentrations of toxicants among Cig-OTP users were still at levels that place smokers at great risk from the detrimental health effects of smoking., Impact: Our study finds that nicotine and carcinogen exposure in Cig-OTP users are lower compared to cigarette only users, but still likely to be associated with substantial harm. A better understanding of why toxicant levels may be lower in Cig-OTP is an important area for future study., (Copyright © 2017 Elsevier B.V. All rights reserved.)

Head and neck cancer (head and neck squamous cell carcinoma (HNSCC)) is a devastating disease. Patients require intensive treatment that is often disfiguring and debilitating. Those who survive are often left with poor speech articulation, difficulties in chewing and swallowing, and cosmetic disfigurement, as well as loss of taste. Furthermore, given that HNSCC survivors are frequently disabled and unable to return to work, the economic and societal costs associated with HNSCC are massive. HNSCC is one of many cancers that are strongly associated with tobacco use. The risk for HNSCC in smokers is approximately ten times higher than that of never smokers, and 70-80% of new HNSCC diagnoses are associated with tobacco and alcohol use. Tobacco products have been used for centuries; however, it is just within the last 60-70 years that we have developed an understanding of their damaging effects. This relatively recent understanding has created a pathway towards educational and regulatory efforts aimed at reducing tobacco use. Understanding the carcinogenic components of tobacco products and how they lead to HNSCC is critical to regulatory and harm reduction measures. To date, nitrosamines and other carcinogenic agents present in tobacco products have been associated with cancer development. The disruption of DNA structure through DNA adduct formation is felt to be a common mutagenic pathway of many carcinogens. Intense work pertaining to tobacco product constituents, tobacco use, and tobacco regulation has resulted in decreased use in some parts of the world. Still, much work remains as tobacco continues to impart significant harm and contribute to HNSCC development worldwide.

Exposure to tobacco-specific nitrosamines (TSNA) and polycyclic aromatic hydrocarbons (PAH) is recognized to play an important role in the development of oral/head and neck squamous cell cancer (HNSCC). We recently reported higher levels of TSNA-associated DNA adducts in the oral cells of smokers with HNSCC as compared with cancer-free smokers. In this study, we further investigated the tobacco constituent exposures in the same smokers to better understand the potential causes for the elevated oral DNA damage in smokers with HNSCC. Subjects included cigarette smokers with HNSCC (cases, n = 30) and cancer-free smokers (controls, n = 35). At recruitment, tobacco/alcohol use questionnaires were completed, and urine and oral cell samples were obtained. Analysis of urinary 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanol (NNAL) and N '-Nitrosonornicotine (NNN; TSNA biomarkers), 1-hydroxypyrene (1-HOP, a PAH), cotinine, 3'-hydroxycotinine, and the nicotine metabolite ratio (NMR) were performed. Cases and controls differed in mean age, male preponderance, and frequency of alcohol consumption (but not total alcoholic drinks). Univariate analysis revealed similar levels of NNN, 1-HOP, and cotinine between groups but, as reported previously, significantly higher DNA adduct formation in the cases. Multiple regression adjusting for potential confounders showed persistent significant difference in DNA adduct levels between cases and controls [ratio of geometric means, 20.0; 95% CI, 2.7-148.6). Our cohort of smokers with HNSCC demonstrates higher levels of TSNA-derived oral DNA damage in the setting of similar exposure to nicotine and tobacco carcinogens. Among smokers, DNA adduct formation may act as a predictor of eventual development of HNSCC that is independent of carcinogen exposure indicators. Cancer Prev Res; 10(9); 507-13. ©2017 AACR See related editorial by Johnson and Bauman, p. 489 ., (©2017 American Association for Cancer Research.)

Chewing of areca nut in different forms such as betel quid or commercially produced pan masala and gutkha is common practice in the Indian subcontinent and many parts of Asia and is associated with a variety of negative health outcomes, particularly oral and esophageal cancers. Areca nut-specific alkaloids arecoline, arecaidine, guvacoline, and guvacine have been implicated in both the abuse liability and the carcinogenicity of the areca nut. Therefore, variations in the levels of areca alkaloids could potentially contribute to variations in addictive and carcinogenic potential across areca nut-containing products. Here, we developed an accurate and robust liquid chromatography-tandem mass-spectrometry (LC-MS/MS) method for simultaneous quantitation of all four areca alkaloids and applied this method to the analysis of a range of products obtained from India, China, and the United States. The results of the analyses revealed substantial variations in the levels of alkaloids across the tested products, with guvacine being the most abundant (1.39-8.16 mg/g), followed by arecoline (0.64-2.22 mg/g), arecaidine (0.14-1.70 mg/g), and guvacoline (0.17-0.99 mg/g). Substantial differences in the relative contribution of individual alkaloids to the total alkaloid content were also observed among the different products. Our results highlight the need for systematic surveillance of constituent levels in areca nut-containing products and a better understanding of the relationship between the chemical profile and the harmful potential of these products.

Metabolic activation of the carcinogenic tobacco-specific N-nitrosamines leads to the formation of 4-hydroxy-1-(3-pyridyl)-1-butanone (HPB)-releasing DNA adducts. We recently developed a liquid chromatography (LC)-tandem mass spectrometry (MS/MS) method for the analysis of HPB-releasing DNA adducts in human oral cells. However, given the limited amounts of DNA that can be extracted from oral cells, higher sensitivity and selectivity are required for the reliable analysis of these adducts in future studies. We have developed a new sensitive LC-nanoelectrospray ionization-high-resolution MS/MS method for the analysis of HPB-releasing DNA adducts in oral cells. A new procedure was also developed for guanine analysis by LC-MS/MS. The detection limit of the developed assay is 5 amol, and the limit of quantitation is 0.35 fmol HPB on-column, starting with 50 pg of DNA. The method was tested by analyzing oral samples from 65 smokers, including 30 head and neck squamous cell carcinoma (HNSCC) patients and 35 cancer-free controls. In all smokers, the levels of HPB-releasing DNA adducts averaged 6.22 ± 16.18 pmol/mg DNA, with significant interindividual variation being consistent with previous reports. The median HPB-releasing DNA adduct level was 6.6 times greater for those with HNSCC than for smokers without HNSCC (p = 0.002). The developed highly sensitive and selective method is a valuable tool for future measurement of HPB-releasing DNA adducts in tobacco users, which can potentially provide critical insights for the identification of individuals at risk for cancer.