Evaluating human papillomavirus testing, prevalence, and association with prognosis in head and neck squamous cell carcinoma by subsite: A national cancer database study.

PURPOSE: To compare human papillomavirus (HPV) testing, prevalence, and association with prognosis between head and neck squamous cell carcinoma (HNSCC) subsites. MATERIALS AND METHODS: This study utilized the National Cancer Database (NCDB) to identify patients diagnosed with HNSCC between 2010 and 2017. Rates of HPV testing, HPV-positivity, and changes in these rates over time were measured by subsite. The impact of HPV-positivity on overall survival across six head and neck subsites was assessed using multivariable-adjusted Cox proportional hazards analysis. RESULTS: A total of 121,550 patients were included. Of this cohort, 87,575 (72.1%) were tested for HPV, with the oropharynx (55,049/64,158; 85.8%) displaying the highest rates of testing and the sinonasal tract (1519/2853; 53.2%) displaying the lowest testing rates. Of the 86,136 with a definitive result, 46,878 (54.4%) were HPV-positive, with the oropharynx (40,313/54,205; 74.4%) displaying the highest rates of HPV-positivity and the oral cavity (1818/11,505; 15.8%) displaying the lowest. HPV-positive malignancy was associated with significantly improved adjusted overall survival in the oropharynx (HR = 0.42 [95% CI: 0.43-0.47]), oral cavity (HR = 0.86 [95% CI: 0.79-0.95]), sinonasal tract (HR = 0.63 [95% CI: 0.48-0.83]), larynx (HR = 0.78 [95% CI: 0.71-0.87]), and hypopharynx (HR = 0.56 [95% CI: 0.48-0.66]), but not the nasopharynx (HR = 0.93 [95% CI: 0.77-1.14]). CONCLUSION: HPV testing rates were significantly lower in non-oropharyngeal subsites. This is relevant as HPV-associated disease displayed significantly improved overall survival in both the oropharynx and four of five non-oropharyngeal subsites. While validation with prospective studies is necessary, these findings may warrant HPV testing in all HNSCC subsites.

Transoral robotic surgery in HPV+ oropharyngeal cancer of unknown primary.

PURPOSE: This study was designed to assess trends in and outcomes associated with TORS-treated HNCUP using a large national database. MATERIALS AND METHODS: HPV+ oropharyngeal HNCUPs were isolated from the 2004-2017 National Cancer Database. Overall survival (OS) was assessed, with patients stratified by 1) use of TORS and 2) whether the occult tumor was ultimately located. Demographic and oncologic predictors of survival were evaluated on regression. RESULTS: The cohort contained 284,734 cases, of which 8336 were HNCUPs. HNCUPs represented 2.49 % of all HNSCC in 2010 versus 3.13 % in 2017. 3897 (46.7 %) of these unknown primaries were ultimately identified. The proportion of cases treated with TORS increased from 6.9 % in 2010 to 18.1 % in 2017 (p < 0.001). Kaplan-Meier analysis of 2991 HPV+ oropharyngeal HNCUPs demonstrated higher 5-year overall survival (OS) for patients treated with robotic surgery versus no robotic surgery (95.4 % ± 1.7 % standard error [SE] versus 84.0 % ± 0.9 % SE; p < 0.001). Patients with primary tumors identified during treatment had improved OS compared to those whose tumors were not located (5-year OS was 90.5 % ± 0.9 % SE and 77.3 % ± 1.5 % SE, respectively; p < 0.001). For patients in which the primary tumor was found, those who received robotic surgery survived longer than those who did not (96.5 % ± 1.4 % SE versus 89.1 % ± 1.0 % SE 5-year OS; p < 0.001). The relationship between TORS and OS remained significant on Cox regression controlling for confounders. CONCLUSIONS: Use of TORS in the workup for HPV+ HNCUP is associated with higher rates of tumor identification and improved OS.

Evaluating depth of invasion across oral cavity subsites as part of the AJCC 8th edition T staging criteria for oral cavity squamous cell carcinoma.

BACKGROUND: The prognostic impact of depth of invasion (DOI) in American Joint Committee on Cancer 8th edition TNM staging for oral cavity squamous cell carcinoma (OCSCCa) across oral cavity subsites is unknown. METHODS: Overall survival of patients with pT1-4a OCSCCa in the National Cancer Database (2010-2017), stratified by tumor size and DOI across eight oral cavity subsites, was evaluated using multivariable-adjusted Cox proportional hazards modeling. RESULTS: When stratified by tumor size ≤2 cm and >2 cm, DOI >5 mm and DOI >10 mm were only associated with worse overall survival, respectively, for tumors of the oral tongue (Tumor size ≤2 cm, DOI >5 mm v DOI ≤5 mm: HR: 1.31, 95% CI: 1.12-1.53, p < 0.001; Tumor size >2 cm, DOI >10 mm v DOI ≤10 mm: HR: 1.15, 95% CI: 1.01-1.30, p = 0.03). DOI >5 mm and DOI >10 mm was not prognostic for any other tumor location. CONCLUSIONS: These findings suggest that the current staging schema for DOI in OCSCCa may not be prognostic across all oral cavity subsites.

Performance of Liquid Biopsy for Diagnosis and Surveillance of Human Papillomavirus-Associated Oropharyngeal Cancer.

Importance: There is growing interest in the use of circulating plasma tumor human papillomavirus (HPV) DNA for diagnosis and surveillance of patients with HPV-associated oropharyngeal squamous cell carcinoma (OPSCC). Recent advances in the assays, combining the identification of circulating HPV tumor DNA and tumor DNA fragment analysis (tumor tissue-modified viral [TTMV]-HPV DNA), have been shown to be highly accurate. However, use of these newer techniques has been limited to small cohort studies and clinical trials. Objective: To establish the clinical efficacy of plasma TTMV-HPV DNA testing in the diagnosis and surveillance of HPV-associated OPSCC in a contemporary clinical setting. Design, Setting, and Participants: This retrospective observational cohort study included patients with OPSCC who underwent TTMV-HPV DNA testing between April 2020 and September 2022 during the course of routine clinical care. For the diagnosis cohort, patients with at least 1 TTMV-HPV DNA measurement prior to initiation of primary therapy were included. Patients were included in the surveillance cohort if they had at least 1 TTMV-HPV DNA test performed after completion of definitive or salvage therapy. Main Outcomes and Measures: Per-test performance metrics, including sensitivity, specificity, positive predictive value, and negative predictive value, for TTMV-HPV DNA testing. Results: Of 399 patients included in the analysis, 163 were in the diagnostic cohort (median [IQR] age, 63 [56-68.5] years; 142 [87.1%] male), and 290 were in the surveillance cohort (median [IQR] age, 63 [57-70] years; 237 [81.7%] male). Of the 163 patients in the diagnostic cohort, 152 (93.3%) had HPV-associated OPSCC while 11 (6.7%) had HPV-negative OPSCC. The TTMV-HPV DNA sensitivity in pretreatment diagnosis was 91.5% (95% CI, 85.8%-95.4% [139 of 152 tests]), and the specificity was 100% (95% CI, 71.5%-100% [11 of 11 tests]). In the surveillance cohort, 591 tests conducted in 290 patients were evaluated. A total of 23 patients had molecularly confirmed pathologic recurrences. The TTMV-HPV DNA test demonstrated sensitivity of 88.4% (95% CI, 74.9%-96.1% [38 of 43 tests]) and specificity of 100% (95% CI, 99.3%-100% [548 of 548 tests]) in detecting the recurrences. Positive predictive value was 100% (95% CI, 90.7%-100% [38 of 38 tests]), and negative predictive value was 99.1% (95% CI, 97.9%-99.7% [548 of 553 tests]). The median (range) lead time from positive TTMV-HPV DNA test to pathologic confirmation was 47 (0-507) days. Conclusions and Relevance: This cohort study demonstrated that when evaluated in a clinical setting, the TTMV-HPV DNA assay demonstrated 100% specificity in both diagnosis and surveillance. However, the sensitivity was 91.5% for the diagnosis cohort and 88.4% for the surveillance cohort, signifying that nearly 1 in 10 negative tests among patients with HPV-associated OPSCC was a false negative. Additional research is required to validate the assay's performance and, if validated, then further research into the implementation of this assay into standard clinical practice guidelines will be required.

Outcomes of perioperative vasopressor use for hemodynamic management of patients undergoing free flap surgery: A systematic review and meta-analysis.

This systematic review and meta-analysis investigates the objective evidence regarding outcomes in head and neck free flap surgeries using vasoactive agents in the perioperative period. A search was performed in PubMed, Cochrane, Web of Science, and Scopus databases. Inclusion criteria were clinical studies in which vasopressors were used in head and neck free flap surgery during the intraoperative and perioperative period. Eighteen studies (n = 5397) were included in the qualitative analysis and nine (n = 4381) in the meta-analysis. There was no difference in flap failure outcomes with perioperative vasopressor use in head and neck free flap surgery (n = 4015, OR = 0.93, 95% CI [0.60, 1.44]). When patients received vasopressors perioperatively, there was an associated decrease in flap-specific complications (n = 3881, OR = 0.69, 95% CI [0.55, 0.87]). Intraoperative vasopressor use does not negatively impact free tissue transfer outcomes in head and neck surgery and may reduce overall free flap complications.

Selective Facial Muscle Activation with Acute and Chronic Multichannel Cuff Electrode Implantation in a Feline Model.

OBJECTIVES: Facial paralysis is a debilitating condition with substantial functional and psychological consequences. This feline-model study evaluates whether facial muscles can be selectively activated in acute and chronic implantation of 16-channel multichannel cuff electrodes (MCE). METHODS: Two cats underwent acute terminal MCE implantation experiments, 2 underwent chronic MCE implantation in uninjured facial nerves (FN) and tested for 6 months, and 2 underwent chronic MCE implantation experiments after FN transection injury and tested for 3 months. The MCE were wrapped around the main trunk of the skeletonized FN, and data collection consisted of EMG thresholds, amplitudes, and selectivity of muscle activation. RESULTS: In acute experimentation, activation of specific channels (ie, channels 1-3 and 6-8) resulted in selective activation of orbicularis oculi, whereas activation of other channels (ie, channels 4, 5, or 8) led to selective activation of levator auris longus with higher EMG amplitudes. MCE implantation yielded stable and selective facial muscle activation EMG thresholds and amplitudes up to a 5-month period. Modest selective muscle activation was furthermore obtained after a complete transection-reapproximating nerve injury after a 3-month recovery period and implantation reoperation. Chronic implantation of MCE did not lead to fibrosis on histology. Field steering was achieved to activate distinct facial muscles by sending simultaneous subthreshold currents to multiple channels, thus theoretically protecting against nerve damage from chronic electrical stimulation. CONCLUSION: Our proof-of-concept results show the ability of an MCE, supplemented with field steering, to provide a degree of selective facial muscle stimulation in a feline model, even following nerve regeneration after FN injury. LEVEL OF EVIDENCE: N/A.

Characteristics and overall survival in pediatric versus adult esthesioneuroblastoma: A population-based study.

BACKGROUND: Esthesioneuroblastoma (ENB) is an uncommon sinonasal malignancy and is even less common in the pediatric population. OBJECTIVE: The purpose of this study is to compare characteristics and outcomes of ENB between adult and pediatric patients. METHODS: The National Cancer Database was queried for patients with histologically proven ENB of the nasal cavity and paranasal sinuses, and then baseline characteristics, treatment, and survival data compared between the pediatric (age < 18 years) and adult (age ≥ 18 years) populations. RESULTS: 1411 patients were identified, with 45 in the pediatric cohort and 1366 in the adult cohort. Ten-year overall survival (OS) in the pediatric cohort was improved compared to the adult cohort, 87% and 66%, respectively (p < 0.05). Adjuvant chemotherapy was more commonly utilized in the pediatric cohort (p < 0.001). Race was associated with decreased OS in the pediatric cohort (p = 0.013). Pediatric patients had shorter length of stay (p = 0.009) and lived closer to their provider (p = 0.044) than adult ENB patients. CONCLUSION: Treatment of ENB in pediatric patients more commonly includes chemotherapy and more commonly occurs at academic medical centers. OS is improved in pediatric ENB compared to adults as well, but larger studies are necessary.

A National Evaluation of Food Insecurity in a Head and Neck Cancer Population.

OBJECTIVES/HYPOTHESIS: To determine the food security status of patients with a history of head and neck cancer and compare to other types of cancer. STUDY DEIGN: A retrospective analysis using the National Health Interview Series. METHODS: The National Health Interview Series (NHIS) for the calendar years 2014 to 18 was used to elicit food security status (secure, marginally secure/not secure) among adult patients with a history of throat/pharynx head and neck cancer (pHNC), thyroid cancer, and colon cancer. The relationship between food security and the primary site was compared and subanalyses were performed according to sex, race, and ethnicity. RESULTS: The study population included 199.0 thousand patients with pHNC, with 17.7% (95% confidence interval, 10.5%-28.1%) of pHNC patients reporting their food security status as marginally secure or not secure. Food insecurity was significantly higher among pHNC patients when compared to thyroid cancer (insecurity 10.7%, [7.7%-14.7%]) and colon cancer patients (10.1%, [7.8%-13.2%]). Among pHNC patients, there was no significant difference in rates of food insecurity when stratified by gender, race, or ethnicity. However, black individuals were more likely to have food insecurity with a history of thyroid or colon cancer (P < .042) and Hispanics were more likely to have food insecurity with a history of thyroid cancer (P = .005). CONCLUSIONS: Food insecurity disproportionally affects patients with a history of pHNC, though there is less demographic variability when compared to other cancer primary sites. Food security assessments should be part of the tailored approach to survivorship management in head and neck cancer. LEVEL OF EVIDENCE: 4 Laryngoscope, 131:E1539-E1542, 2021.

Surgical management of recurrent Zenker's diverticulum: A multi-institutional cohort study.

OBJECTIVE: This study identifies how recurrent Zenker's diverticula are treated. METHODS: A retrospective chart review was performed from four tertiary referral academic voice and swallowing centers to identify individuals who underwent surgery for recurrent Zenker's diverticulum. Demographic data, surgical modalities for primary and revision surgery, symptoms pre and post revision and complications were recorded. RESULTS: 56 individuals met inclusion criteria. Primary surgery was open in 30.3% (n = 17) and endoscopic in 69.6% (n = 39). Revision surgery was performed via an open approach in 37.5% of cases (N = 21) and via an endoscopic approach in 62.5% of cases (N = 35). Revision surgical technique was based on pouch size, patient age and comorbidities, as well as patient and surgeon preference. There were no major complications and few minor complications. CONCLUSION: Zenker's diverticulum symptoms can recur regardless of primary treatment modality. Both endoscopic and open approaches can safely treat recurrent Zenker's diverticula.

Insurance Status as a Predictor of Treatment in Human Papillomavirus Positive Oropharyngeal Cancer.

OBJECTIVES: The link between human papillomavirus (HPV) and oropharyngeal cancer (OPC) is well known. Locally advanced, HPV-positive OPC (HPV OPC) can be treated with either chemoradiation or primary surgery with or without adjuvant therapy. Head and neck cancer patients with government insurance or uninsured have been shown to have worse prognosis than similar patients with private insurance. In this study, we aimed to determine if insurance status would predict treatment modality in patients with HPV OPC. STUDY DESIGN: A retrospective analysis using the National Cancer Database (NCDB). METHODS: The National Cancer Database was used to identify patients with HPV OPC who underwent primary surgery or primary chemoradiation from 2010-2015. Insurance status was categorized as government, private, or no insurance. The relationship between insurance status and treatment was investigated using Chi square and multivariate regression models. Kaplan-Meier analyses were performed comparing overall survival (OS) by insurance status. RESULTS: There were 10,606 patients were included. There was a statistically significant correlation between insurance status and primary treatment modality for HPV OPC (P < .001). Patients with government insurance were 19.3% less likely to undergo surgery and uninsured patients were 36.9% less likely to undergo primary surgery when compared to those with private insurance (P < .001), even after correcting for TNM stage in multivariate analysis. There was an improved 5-year OS for patients with private insurance (86.6%) versus both government insurance (68.4%) and no insurance (69.9%) (P < .001). CONCLUSIONS: Patients with private insurance are more likely to undergo primary surgery in HPV OPC and have improved overall survival. LEVEL OF EVIDENCE: 4 Laryngoscope, 131:776-781, 2021.

Practice patterns and knowledge among California pediatricians regarding human papillomavirus and its relation to head and neck cancer.

OBJECTIVE: To identify practice patterns regarding human papillomavirus (HPV) vaccination efforts and vaccination rates in context of head and neck cancer prevention, identify barriers to vaccination, and identify gaps in knowledge regarding the link between HPV and head and neck cancer in the pediatrician population. STUDY DESIGN/METHODS: A 27-question cross-sectional survey was distributed to members of the four California chapters of the American Academy of Pediatrics. RESULTS: Of the completed responses, 89.4% identified as "always" recommending the HPV vaccine to patients, but only 19.5% of pediatricians estimated that >75% of their eligible patients had completed the HPV vaccination series. 71.5% of respondents felt that further education about HPV's link to head and neck cancer them more comfortable discussing vaccination. Physicians who were in practice longer were less likely to respond that additional education about HPV and its link to head and neck cancer would make them more comfortable discussing vaccination with patients (p = 0.043). Physicians who were in practice longer were more likely to correctly respond that HPV type 16 is the most common strain linked to head and neck cancer (p = 0.021). CONCLUSION: There is need to improve both the knowledge base and comfort level of pediatricians in counseling their patients during vaccine recommendations. Otolaryngologists have a critical role in providing education to physicians, trainees, and the general public in the effort to combat the epidemic of HPV-associated head and neck cancer.

Assessment of human papillomavirus awareness in association with head and neck cancer at a screening event.

OBJECTIVES/HYPOTHESIS: To assess the baseline awareness of human papillomavirus (HPV) infection as a cause of head and neck cancer (HNC) to design improved targeted screening and education efforts. STUDY DESIGN: Retrospective review of collected survey at a cancer screening event. METHODS: This was a screening event at three hospitals and one community center in Miami, Florida. Participants were recruited throughout the Greater Miami area. Descriptive statistics were used to summarize the demographic characteristics of those who were aware of HPV and those who were not. Adjusted odds ratios, odds ratios, and χ2 tests were used in statistical analysis. RESULTS: A total of 196 women and 112 men were screened across four sites, with 187 participants at hospital-based events and 124 participants at the community-based event. Forty percent of respondents had heard of HPV, and 28.0% identified HPV as a risk factor for HNC. Non-Hispanic and Hispanic respondents were 3.309 and 2.445 times, respectively, more likely than Haitian respondents to have heard of HPV. Women were 2.488 times more likely than men to be aware of HPV. College graduates were 2.268 times more likely than those with less than a college degree to be aware of HPV. Younger respondents were more likely to be aware of HPV. Of those who identified HPV as a risk factor for HNC, 95.4% also correctly identified smoking and 75.9% also correctly identified alcohol as risk factors. CONCLUSIONS: Disparities in HPV and HNC awareness were noted between gender, age, education level, and ethnicity. LEVEL OF EVIDENCE: NA. Laryngoscope, 128:386-392, 2018.

Case of parotid mucoepidermoid carcinoma: Expanding the spectrum of von Hippel-Lindau-related neoplasms.

BACKGROUND: von Hippel-Lindau (VHL)-related tumors occurring outside the spectrum of VHL-defining tumors are rare, and mucoepidermoid carcinoma (MEC) in the setting of VHL disease has not been described. METHODS AND RESULTS: We describe a patient with confirmed VHL mutation who presented with a parotid mass and a history of 2 central nervous system (CNS) hemangioblastomas and 1 pheochromocytoma. Fine-needle aspiration (FNA) of the mass suggested a benign Warthin tumor. The mass was resected and final pathology revealed a low-grade MEC. Fluorescence in situ hybridization for the MECT1/MAML2 fusion gene frequently associated with MEC was performed and was negative. Molecular testing of tumor cells displayed a likely "second hit" VHL gene mutation. CONCLUSION: There is a possible broader role of VHL mutations in tumorigenesis beyond the development of classically described VHL-defining neoplasms. Our case also demonstrates the importance of always considering the possibility of a parotid malignancy in patients with VHL despite a benign FNA. © 2016 Wiley Periodicals, Inc. Head Neck 39: E51-E54, 2017.

Magnetic Resonance-Guided Laser Ablation for the Treatment of Recurrent Dural-Based Lesions: A Series of Five Cases.

BACKGROUND AND OBJECTIVE: Magnetic resonance-guided laser-induced thermotherapy (MR-LITT) is a minimally invasive technique that shows promise in neuro-oncology because of its superiority in delivering precise minimally invasive thermal energy with minimal collateral damage. In this analysis, we investigate initial data on the effect of MR-LITT on dural-based lesions. METHODS: Five patients were identified with dural-based lesions (4 meningiomas, 1 solitary fibrous tumor) with clear evidence of radiologic progression. In all 5 cases, the tumors were localized to the lateral convexity or paramedian locations in the supratentorial space. All patients received MR-LITT and then a follow-up magnetic resonance imaging scan at 24 hours after treatment, at 1 month, and at each subsequent follow-up visit. Local control of the ablated tumor was evaluated with radiographic follow-up and symptomatic progression-free survival was recorded. RESULTS: Five LITT treatments were performed on 5 patients with an average age of 65.2 years. The average tumor volume was 29.7 cm3 and ablation dosage was 12.4 W. On average, 80% of the pretreatment lesion volume was ablated. The mean follow-up time was 59.3 weeks. In total, 2 patients (1 with an anaplastic meningioma and 1 with a solitary fibrous tumor) had radiographic evidence of disease progression. In the observed time of the 3 patients with no progression, there was a 52% reduction in tumor volume. There were no major perioperative complications. CONCLUSIONS: MR-LITT is a promising technology for dural-based lesion treatment. This initial study demonstrates that MR-LITT is safe and offers several advantages over open surgical treatment. Randomized studies are needed to evaluate its role as a treatment adjunct.

Association Between Infertility and Sexual Dysfunction in Men and Women.

INTRODUCTION: The relation between infertility and sexual dysfunction can be reciprocal. Causes of sexual dysfunction that affect fertility include erectile dysfunction, Peyronie's disease (abnormal penile curvature), low libido, ejaculatory disorders in men, and genito-pelvic pain/penetration disorder (GPPPD) and low sexual desire in women. AIM: To review the association between infertility and sexual dysfunction and discuss current management strategies to address sexual disorders in couples with infertility. METHODS: Peer-reviewed publications from PubMed published from 1980 through February 2016 were identified that related to sexual dysfunction and infertility in men and women. MAIN OUTCOME MEASURES: Pathophysiology and management approach of erectile dysfunction, Peyronie's disease, low libido, ejaculatory disorders in men, and GPPPD and low sexual desire in women and how each etiology contributes to sexual dysfunction and infertility in the couple. RESULTS: Treating the infertile couple with sexual dysfunction involves addressing underlying conditions such as psychogenic erectile dysfunction, low testosterone, Peyronie's disease in men, and GPPPD and low sexual desire in women. Psychogenic erectile dysfunction can be successfully treated with phosphodiesterase inhibitors. Low testosterone is often identified in men with infertility, but testosterone therapy is contraindicated in men attempting conception. Men with Peyronie's disease have a new treatment option to address their penile curvature-collagenase Clostridium histolyticum injection directly into the penile plaque. GPPPD is a broad disorder that includes vulvodynia and vaginismus and can be treated with topical lubricants and moisturizers. We must address psychosocial factors in women with low sexual desire. Flibanserin and transdermal testosterone (off-label) are novel therapies for women with low sexual desire. CONCLUSION: Sexual dysfunction in a couple with infertility is a complex issue. Management of infertility and sexual dysfunction should involve appropriate medical therapy and addressing the psychosocial concerns of the couple.