Feasibility of clinical evaluation of individuals with increased risk for HPV-associated oropharynx cancer.

BACKGROUND: Human papillomavirus-associated oropharynx squamous cell carcinoma (HPV-OPSCC) has no known pre-malignant lesion. While vaccination offers future primary prevention, there is current interest in secondary prevention. The feasibility of clinical evaluation of individuals at increased risk for HPV-OPSCC is unclear. METHODS: Individuals with risk factors for HPV-OPSCC were enrolled in a prospective study (MOUTH). Participants positive for biomarkers associated with HPV-OPSCC were eligible for a clinical evaluation which comprised a head and neck examination and imaging with ultrasound and/or magnetic resonance imaging (MRI). This study was designed to evaluate feasibility of clinical evaluation in a screening study. RESULTS: Three hundred and eighty-four participants were eligible for clinical evaluation. Of the 384, 204 (53%) completed a head and neck examination or imaging. Of these, 66 (32%) completed MRI (n = 51) and/or ultrasound (n = 64) studies. CONCLUSIONS: Clinical evaluations, including head and neck examination and imaging, are feasible in the context of a screening study for HPV-OPSCC.

Prevalence of human papillomavirus in head and neck cancers at tertiary care centers in the United States over time.

BACKGROUND: Human papillomavirus (HPV) is responsible for a growing proportion of oropharyngeal squamous cell carcinomas (OPSCCs) among men and White individuals. Whether similar trends apply to women, non-Whites, and non-oropharyngeal squamous cell carcinomas (non-OPSCCs) is unknown. METHODS: This is a cross-sectional analysis combining 2 multi-institutional case series of incident head and neck squamous cell carcinoma (HNSCC) cases. Incident HNSCCs from 1995 to 2012 were enrolled retrospectively using banked tumor samples and medical record abstraction. Incident HNSCCs from 2013 to 2019 were enrolled prospectively. The prevalence of tumor HPV biomarkers was tested over 3 time periods (1995-2003, 2004-2012, and 2013-2019). Centralized testing was done for p16 immunohistochemistry (p16) and oncogenic HPV in situ hybridization (ISH). RESULTS: A total of 1209 incident cases of HNSCC were included. Prevalence of p16- and ISH-positive tumors increased significantly for oropharynx cancers over time. The majority were positive after 2013 for White patients (p16, 92%; P < .001; ISH 94%; P < .001), Black patients (p16, 72%; P = .021; ISH 67%; P = .011), and Hispanic patients (p16, 100%; P = .04; ISH 100%; P = .013). For women with OPSCC, the prevalence of p16- and ISH-positive tumors increased significantly to 82% (P < .001) and 78% (P = .004), respectively. For non-OPSCCs, there was increased p16 and ISH positivity overall with 24% p16 and 16% ISH positivity in the most recent time period (P < .001 for both). CONCLUSIONS: The majority of OPSCCs in US tertiary care centers are now p16 and ISH positive for all sex and race groups. In some populations in the United States, 91% of OPSCCs are now caused by HPV. Few non-OPSCCs are p16 and ISH positive.

Epidemiology of HPV Related Malignancies.

Human papillomavirus is the most common sexually transmitted infection in the world and had been linked to both anogenital and oropharyngeal cancers. It causes nearly 100% of cervical cancers and an increasing portion of oropharyngeal cancers. The geographical burden of cervical HPV infection and associated cancers is not uniform and is mainly found in low middle income countries in South America, Africa, and Asia. However, HPV-positive oropharyngeal cancer is rapidly becoming more prevalent in high middle income countries. With the development of vaccines which prevent HPV infection, the World Health Organization has designated the extirpation of HPV and its associated cancers a priority. Countries that have implemented adequate vaccine programs have shown a decrease in HPV prevalence. Understanding the epidemiology of HPV and its associated cancers is fundamental in improving vaccine programs and other health programs.

Effect of Perioperative Gabapentin Use on Postsurgical Pain in Patients Undergoing Head and Neck Mucosal Surgery: A Randomized Clinical Trial.

Importance: Effective postoperative pain management increases patient satisfaction, reduces cost, reduces morbidity, and shortens hospitalizations. Previous studies investigating multimodal pain therapy in otolaryngology patients focused on homogenous patient groups with short postoperative follow-up times. Objective: To investigate the effect of perioperative gabapentin treatment on postsurgical pain in patients undergoing head and neck mucosal surgery. Design, Setting, and Participants: Adults undergoing head and neck mucosal surgery from July 25, 2016, through June 19, 2017, were included in this double-blinded, placebo-controlled randomized clinical trial and randomized to receive gabapentin, 300 mg twice daily, or placebo before surgery and up to 72 hours after surgery. Main Outcomes and Measures: Primary outcome was hourly narcotic use calculated in morphine equivalents. Secondary outcomes included subjective visual analog scale pain scores captured for resting, coughing, and swallowing using a 0- to 100-mm scale (a 100-mm line anchored with no pain on the left end and worst possible pain on the right end). A change of 10 mm or more was deemed to be clinically meaningful. Additional secondary outcome measures included degree of pain control, patient satisfaction, and adverse effects. Results: Of the 110 patients randomized to receive gabapentin or placebo, 11 and 10 withdrew from each group, respectively. Ninety patients were then analyzed: 44 in the gabapentin group (mean [SD] age, 61.1 [10.0] years; 33 [75%] male; 40 [91%] white) and 46 in the placebo group (mean [SD] age, 60.9 [11.3] years; 35 [78%] male; 43 [94%] white). Both groups had similar self-reported levels of preoperative pain and narcotic effectiveness. A median difference of 0.26 mg/h of morphine (95% CI, -0.27 to 0.94 mg/h) was found between groups. After controlling for comorbidity and self-reported baseline pain levels, mixed model analysis found the difference in marginal means of visual analog scale scores between groups to be lower in the gabapentin group compared with the placebo group for all categories (rest difference, 7.9 mm; 95% CI, -0.4 to 16.2 mm; cough difference, 8.9 mm; 95% CI, -0.5 to 18.3 mm; swallow difference, 9.4 mm; 95% CI, -1.2 to 20.0 mm). More patients in the gabapentin group reported that pain was always well controlled than in the placebo group (difference, 9.2%; 95% CI, -21% to 3%). Gabapentin and placebo groups reported similar levels of satisfaction with pain control (difference, 2%; 95% CI, -11% to 15%). There was no clinically meaningful difference in reported nausea between the 2 groups (difference, 6%; 95% CI, -14% to 26%). Conclusion and Relevance: Perioperative gabapentin given 300 mg twice daily did not result in reduced narcotic use, but results were compatible with clinically meaningful reductions in pain scores. Satisfaction with pain control and adverse effects were similar between groups. Trial Registration: ClinicalTrials.gov Identifier: NCT02926573.

Intraoperative imaging during minimally invasive transoral robotic surgery using near-infrared light.

PURPOSE: The purpose of this study was to determine if the use of the FIREFLY imaging system could be an asset in transoral robotic surgery (TORS) for oropharyngeal squamous cell carcinoma (OPSCC). The system uses indocyanine green dye (ICG), which fluoresces when illuminated by near-infrared light from the Da Vinci robot. The system may improve visualization of tumor margins, highlight important vascular structures, and help identify the location of tumors and unknown primary head and neck cancers. METHODS: Six patients with OPSCC were enrolled in the study. Two of these cases were unknown primaries, one was base of tongue, and three were palatine tonsils. Each patient was given two 3ml doses of ICG, one at the beginning of the surgical case and one during resection of the tumor. The oropharynx was then visualized using the near-infrared light of the Da Vinci robot for a minute after injection. RESULTS: The FIREFLY system was unable to detect gross tumors, positive margins, unknown primaries, or vascular structures in any of the six subjects in the study. In addition, there were no adverse events or side effects in any of the subjects. CONCLUSION: The use of the FIREFLY system with indocyanine green fluorescence did not identify tumor boundaries, unknown primary head and neck cancers, or vascular structures in the oropharynx.

Survival of renal cell carcinoma metastatic to nonthyroid head and neck region: A systematic review.

OBJECTIVE: Metastasis of renal cell carcinoma to nonthyroid head and neck region is rare. Survival benefit for complete metastasectomy of more common renal cell foci has been reported in the literature. It is uncertain whether metastasectomy in nonthyroid head and neck region would provide a similar benefit. DATA SOURCES: We conducted a retrospective review of all renal cell metastases to the head and neck region treated in the past 15 years at an academic hospital, and a systematic review of all relevant reports with survival data in the literature between 1960 and 2016. REVIEW METHODS: An analysis of pooled data was performed to estimate overall survival. RESULTS: Six cases from our institution and 260 independent cases reported in the literature were included in the survival analyses (n = 266). The median follow-up time was 12 months (range 0-180 months). The overall median survival was 36 months (95% confidence interval [CI] 23.7-48.3). The median survival for those who underwent complete metastasectomy in the head and neck was significantly higher at 60 months (95% CI 41.1-78.9) than those who had incomplete or no metastasectomy (12 months, 95% CI 9.5-14.5). Multivariable Cox proportional hazards model estimated that, after controlling for potential confounders, complete metastasectomy remained associated with reduced risk of death (hazard ratio 0.44, 95% CI 0.29-0.69). CONCLUSION: Complete metastasectomy was associated with 4-year longer median overall survival than incomplete metastasectomy or no metastasectomy. Laryngoscope, 128:889-895, 2018.

A methodological assessment of studies that use voxel-based morphometry to study neural changes in tinnitus patients.

BACKGROUND: The scientific understanding of tinnitus and its etiology has transitioned from thinking of tinnitus as solely a peripheral auditory problem to an increasing awareness that cortical networks may play a critical role in tinnitus percept or bother. With this change, studies that seek to use structural brain imaging techniques to better characterize tinnitus patients have become more common. These studies include using voxel-based morphometry (VBM) to determine if there are differences in regional gray matter volume in individuals who suffer from tinnitus and those who do not. However, studies using VBM in patients with tinnitus have produced inconsistent and sometimes contradictory results. OBJECTIVE: This paper is a systematic review of all of the studies to date that have used VBM to study regional gray matter volume in people with tinnitus, and explores ways in which methodological differences in these studies may account for their heterogeneous results. We also aim to provide guidance on how to conduct future studies using VBM to produce more reproducible results to further our understanding of disease processes such as tinnitus. METHODS: Studies about tinnitus and VBM were searched for using PubMed and Embase. These returned 15 and 25 results respectively. Of these, nine met the study criteria and were included for review. An additional 5 studies were identified in the literature as pertinent to the topic at hand and were added to the review, for a total of 13 studies. RESULTS: There was significant heterogeneity among the studies in several areas, including inclusion and exclusion criteria, software programs, and statistical analysis. We were not able to find publicly shared data or code for any study. DISCUSSION: The differences in study design, software analysis, and statistical methodology make direct comparisons between the different studies difficult. Especially problematic are the differences in the inclusion and exclusion criteria of the study, and the statistical design of the studies, both of which could radically alter findings. Thus, heterogeneity has complicated efforts to explore the etiology of tinnitus using structural MRI. CONCLUSION: There is a pressing need to standardize the use of VBM when evaluating tinnitus patients. While some heterogeneity is expected given the rapid advances in the field, more can be done to ensure that there is internal validity between studies.

Reporting of Effect Size and Confidence Intervals in JAMA Otolaryngology-Head & Neck Surgery.

Importance: Effect sizes and confidence intervals (CIs) are critical for the interpretation of the results for any outcome of interest. Objective: To evaluate the frequency of reporting effect sizes and CIs in the results of analytical studies. Design, Setting, and Participants: Descriptive review of analytical studies published from January 2012 to December 2015 in JAMA Otolaryngology-Head & Neck Surgery. Methods: A random sample of 121 articles was reviewed in this study. Descriptive studies were excluded from the analysis. Seven independent reviewers participated in the evaluation of the articles, with 2 reviewers assigned per article. The review process was standardized for each article; the Methods and Results sections were reviewed for the outcomes of interest. Descriptive statistics for each outcome were calculated and reported accordingly. Main Outcomes and Measures: Primary outcomes of interest included the presence of effect size and associated CIs. Secondary outcomes of interest included a priori descriptions of statistical methodology, power analysis, and expectation of effect size. Results: There were 107 articles included for analysis. The majority of the articles were retrospective cohort studies (n = 36 [36%]) followed by cross-sectional studies (n = 18 [17%]). A total of 58 articles (55%) reported an effect size for an outcome of interest. The most common effect size used was difference of mean, followed by odds ratio and correlation coefficient, which were reported 17 (16%), 15 (13%), and 12 times (11%), respectively. Confidence intervals were associated with 29 of these effect sizes (27%), and 9 of these articles (8%) included interpretation of the CI. A description of the statistical methodology was provided in 97 articles (91%), while 5 (5%) provided an a priori power analysis and 8 (7%) provided a description of expected effect size finding. Conclusions and Relevance: Improving results reporting is necessary to enhance the reader's ability to interpret the results of any given study. This can only be achieved through increasing the reporting of effect sizes and CIs rather than relying on P values for both statistical significance and clinically meaningful results.

Mechanical Ventilation and ARDS in the ED: A Multicenter, Observational, Prospective, Cross-sectional Study.

BACKGROUND: There are few data regarding mechanical ventilation and ARDS in the ED. This could be a vital arena for prevention and treatment. METHODS: This study was a multicenter, observational, prospective, cohort study aimed at analyzing ventilation practices in the ED. The primary outcome was the incidence of ARDS after admission. Multivariable logistic regression was used to determine the predictors of ARDS. RESULTS: We analyzed 219 patients receiving mechanical ventilation to assess ED ventilation practices. Median tidal volume was 7.6 mL/kg predicted body weight (PBW) (interquartile range, 6.9-8.9), with a range of 4.3 to 12.2 mL/kg PBW. Lung-protective ventilation was used in 122 patients (55.7%). The incidence of ARDS after admission from the ED was 14.7%, with a mean onset of 2.3 days. Progression to ARDS was associated with higher illness severity and intubation in the prehospital environment or transferring facility. Of the 15 patients with ARDS in the ED (6.8%), lung-protective ventilation was used in seven (46.7%). Patients who progressed to ARDS experienced greater duration in organ failure and ICU length of stay and higher mortality. CONCLUSIONS: Lung-protective ventilation is infrequent in patients receiving mechanical ventilation in the ED, regardless of ARDS status. Progression to ARDS is common after admission, occurs early, and worsens outcome. Patient- and treatment-related factors present in the ED are associated with ARDS. Given the limited treatment options for ARDS, and the early onset after admission from the ED, measures to prevent onset and to mitigate severity should be instituted in the ED. TRIAL REGISTRY: ClinicalTrials.gov; No.: NCT01628523; URL: www.clinicaltrials.gov.