Automated Surgical Approach Planning for Complex Skull Base Targets: Development and Validation of a Cost Function and Semantic At-las.

Successful multidisciplinary treatment of skull base pathology requires precise preoperative planning. Current surgical approach (pathway) selection for these complex procedures depends on an individual surgeon's experiences and background training. Because of anatomical variation in both normal tissue and pathology (eg, tumor), a successful surgical pathway used on one patient is not necessarily the best approach on another patient. The question is how to define and obtain optimized patient-specific surgical approach pathways? In this article, we demonstrate that the surgeon's knowledge and decision making in preoperative planning can be modeled by a multiobjective cost function in a retrospective analysis of actual complex skull base cases. Two different approaches- weighted-sum approach and Pareto optimality-were used with a defined cost function to derive optimized surgical pathways based on preoperative computed tomography (CT) scans and manually designated pathology. With the first method, surgeon's preferences were input as a set of weights for each objective before the search. In the second approach, the surgeon's preferences were used to select a surgical pathway from the computed Pareto optimal set. Using preoperative CT and magnetic resonance imaging, the patient-specific surgical pathways derived by these methods were similar (85% agreement) to the actual approaches performed on patients. In one case where the actual surgical approach was different, revision surgery was required and was performed utilizing the computationally derived approach pathway.

Residency Selection in Otolaryngology: Past, Present, & Future.

OBJECTIVES: To examine the otolaryngology residency selection process, including past experiences based on the medical literature and survey analysis of our present practices to generate recommendations for future selection system design. METHODS: A mixed-methods study, including a scoping review and a cross-sectional survey, was completed. Four databases were assessed for articles on otolaryngology residency selection published from January 1, 2016 through December 31, 2020. A 36-question survey was developed and distributed to 114 otolaryngology program directors. Descriptive and thematic analysis was performed. RESULTS: Ultimately, 67 of 168 articles underwent data abstraction and assessment. Three themes surfaced during the analysis: effectiveness, efficiency, and equity. Regarding the survey, there were 62 participants (54.4% response rate). The three most important goals for the selection process were: (1) to fit the program culture, (2) to make good colleagues, and (3) to contribute to the program's diversity. The three biggest 'pain points' were as follows: (1) Large volume of applications, (2) Lack of reliable information about personal characteristics, and (3) Lack of reliable information about a genuine interest in the program. CONCLUSIONS: Within this study, the depth and breadth of the literature on otolaryngology residency selection have been synthesized. Additionally, baseline data on selection practices within our specialty has been captured. With an informed understanding of our past and present, we can look to the future. Built upon the principles of person-environment fit theory, our proposed framework can guide research and policy discussions regarding the design of selection systems in otolaryngology, as we work to achieve more effective, efficient, and equitable outcomes. LEVEL OF EVIDENCE: N/A Laryngoscope, 133:2929-2941, 2023.

Intersectionality of Race, Ethnicity, and Gender in the Otolaryngology Match From 2013 to 2019.

OBJECTIVES: Racial, ethnic, and gender disparities in the otolaryngology-head and neck surgery (OHNS) match have been described individually, but not intersectionally. Intersectionality recognizes how multiple forms of discrimination (e.g., sexism, racism) can have a combined effect. The objective of this study was to analyze racial, ethnic, and gender disparities in the OHNS match using an intersectional approach. METHODS: Cross-sectional evaluation of data from otolaryngology applicants from the Electronic Residency Application Service (ERAS) and of corresponding otolaryngology residents from the Accreditation Council for Graduate Medical Education (ACGME) from 2013 to 2019. Data were stratified by race, ethnicity, and gender. The Cochran-Armitage tests assessed trends over time in the proportions of applicants and corresponding residents. Chi-square tests with Yates' continuity correction were performed to evaluate differences between the aggregate proportions of applicants and corresponding residents. RESULTS: The proportion of White men in the resident pool was increased compared to the applicant pool (ACGME 0.417, ERAS 0.375; Δ + 0.042; 95% CI 0.012 to 0.071; p = 0.03). This was also the case for White women (ACGME 0.206, ERAS 0.175; Δ + 0.031; 95% CI 0.007 to 0.055; p = 0.05). In contrast, there was a smaller proportion of residents compared to applicants among Multiracial men (ACGME 0.014, ERAS 0.047; Δ - 0.033; 95% CI -0.043 to -0.023; p < 0.001) and Multiracial women (ACGME 0.010, ERAS 0.026; Δ - 0.016; 95% CI -0.024 to -0.008; p < 0.001). CONCLUSION: The findings of this study imply that White men have a persistent advantage, while several racial, ethnic, and gender minorities are disadvantaged in the OHNS match. Further research is necessary to examine why these differences exist in residency selection, including evaluation during the screening, reviewing, interviewing, and ranking stages. Laryngoscope, 133:2558-2563, 2023.

Defining the Performance of Clinician's Ability to Screen for Laryngeal Mass From Voice.

OBJECTIVE: Defining a clinician's ability to perceptually identify mass from voice will inform the feasibility, design priorities, and performance standards for tools developed to screen for laryngeal mass from voice. This study defined clinician ability of and examined the impact of expertise on screening for laryngeal mass from voice. STUDY DESIGN: Task comparison study between experts and nonexperts rating voices for the probability of a laryngeal mass. SETTING: Online, remote. METHODS: Experts (voice-focused speech-language pathologists and otolaryngologists) and nonexperts (general medicine providers) rated 5-s/i/voice samples (with pathology defined by laryngoscopy) for the probability of laryngeal mass via an online survey. The intraclass correlation coefficient (ICC) estimated interrater and intrarater reliability. Diagnostic performance metrics were calculated. A linear mixed effects model examined the impact of expertise and pathology on ratings. RESULTS: Forty clinicians (21 experts and 19 nonexperts) evaluated 344 voice samples. Experts outperformed nonexperts, with a higher area under the curve (70% vs 61%), sensitivity (49% vs 36%), and specificity (83% vs 77%) (all comparisons p < .05). Interrater reliability was fair for experts and poor for nonexperts (ICC: 0.48 vs 0.34), while intrarater reliability was excellent and good, respectively (ICC: 0.9 and 0.6). The main effects of expertise and underlying pathology were significant in the linear model (p < .001). CONCLUSION: Clinicians demonstrate inadequate performance screening for laryngeal mass from voice to use auditory perception for dysphonia triage. Experts' superior performance indicates that there is acoustic information in a voice that may be utilized to detect laryngeal mass based on voice.

Implementing a "Distance Traveled" Question to Improve Resident Diversity: Process and Feasibility.

Increasing diversity in the physician workforce is important to improving racial and ethnic disparities in health outcomes in the United States. We describe the implementation of a "distance traveled" question (DTQ) in our residency application process. For the 2021-2022 cycle, all applicants to the University of Washington otolaryngology residency program were allowed to complete an optional DTQ. Responses were shared with the application review committee. Following the distribution of interview invites, an anonymous survey was sent to all faculty reviewers. The response rate was 26 of 36 (72%). Among respondents, 20 (77%) felt that the DTQ helped them learn something new about the applicant, and 19 (73%) reported that the DTQ influenced their decision making about the applicant. Thus, a DTQ may provide faculty with new and influential information regarding residency applicants.

The impact of the COVID-19 pandemic on medical student education: Implementation and outcome of a virtual general surgery curriculum.

BACKGROUND: Due to the COVID-19 pandemic, medical schools were forced to adapt clinical curricula. The University of Washington School of Medicine created a hybrid in person and virtual general surgery clerkship. METHODS: The third year general surgery clerkship was modified to a 4-week in person and 2-week virtual clerkship to accommodate the same number of learners in less time. All students completed a survey to assess the impact of the virtual clerkship. RESULTS: The students preferred faculty lectures over national modules in the virtual clerkship. 58.6% indicated they would prefer the virtual component before the in-person experience. There was no change from previous years in final grades or clerkship exam scores after this hybrid curriculum. CONCLUSIONS: If the need for a virtual general surgery curriculum arises again in the future, learners value this experience at the beginning of the clerkship and prefer faculty lectures over national modules.

Evidence of Specialty-Specific Gender Disparities in Resident Recruitment and Selection.

BACKGROUND: Specialty-specific gender disparities are multifactorial, yet one area that is lacking from this discussion is the impact of recruitment and selection. OBJECTIVE: Customized data reports were utilized to compare trends in the gender representation of applicants and residents within 11 surgical and medical specialties between 2013 and 2018. METHODS: Applicant data was obtained from the Electronic Residency Application Service (ERAS) and resident data from the Accreditation Council for Graduate Medical Education (ACGME). Eleven specialties with the highest number of applications per applicant were included (dermatology, emergency medicine, general surgery, neurological surgery, obstetrics and gynecology [OB/GYN], orthopedic surgery, otolaryngology, plastic surgery, radiation oncology, radiology, urology). A Cochran-Armitage trend test assessed for changes in the proportion of females within the total applicant group and the corresponding matched resident group. A t test was utilized to compare the mean proportion of females for ERAS and ACGME data. RESULTS: Otolaryngology, plastic surgery, radiation oncology, and urology had no significant changes over the study period. Dermatology, general surgery, and orthopedic surgery demonstrated increased gender diversity in applicants over time, while OB/GYN demonstrated decreased gender diversity. General surgery and neurological surgery showed increased gender diversity in resident representation over time. Emergency medicine and radiology had increased gender diversity, and OB/GYN had decreased gender diversity in matched residents compared to applicants. CONCLUSIONS: Our findings provide baseline data, but also illustrate evident gaps in our understanding and attempts to improve gender diversity. A multifaceted approach to obtaining and assessing data from all stages of residency recruitment and selection is necessary to support these efforts.

Computer-Aided Rhinoplasty Using a Novel "navigated" Nasal Osteotomy Technique: A Pilot Study.

OBJECTIVE: To describe the surgical technique of navigation-guided nasal osteotomies and assess feasibility of this technique for treating complex nasal bone deformities in reconstructive rhinoplasty. METHODS: A retrospective chart review was performed in order to identify patients who underwent computer-aided rhinoplasty from August 2014 to February 2017. Inclusion criteria were nasal bone deformities on computed-tomography (CT) that correlated with specific nasal complaints. All patients underwent computer-aided rhinoplasty with navigation-guided nasal osteotomies using a standard navigation system. Osteotomies were performed using real-time visualization on the navigation screen. Additional soft tissue procedures were performed as needed. Medical records were reviewed for presenting symptoms, radiologic and operative findings, and postoperative course. Cosmetic outcomes were subjectively based on patients' standard 6-view photo-documentation from pre- and post-operative timepoints. RESULTS: Twenty-one patients were included in the study; 8 were revision cases and 3 had mild-to-moderate hemifacial microsomia. Fifteen were completely closed procedures. No cases were opened because of inadequate visualization or difficulty accessing bony pathology. Mean (range) follow up was 98.6 (6-559) days. There were no intra-operative complications, unplanned admissions or re-admissions, or iatrogenic cosmetic complications (ie, "inverted V" or "saddle nose" deformities). Two patients required revision. One was after suffering nasal trauma within 4 weeks of initial rhinoplasty. The second underwent further correction of a deformity that required a costochondral graft. Both experienced good final results. CONCLUSIONS: Computer-aided rhinoplasty is safe and feasible for treating complex nasal deformities using standard navigation systems.

A Novel Curriculum for Medical Student Training in LGBTQ Healthcare: A Regional Pathway Experience.

BACKGROUND: Lesbian, gay, bisexual, transgender, and queer (LGBTQ) individuals face considerable health disparities, often due to a lack of LGBTQ-competent care. Such disparities and lack of access to informed care are even more staggering in rural settings. As the state medical school for the Washington, Wyoming, Alaska, Montana, and Idaho (WWAMI) region, the University of Washington School of Medicine (UWSOM) is in a unique position to train future physicians to provide healthcare that meets the needs of LGBTQ patients both regionally and nationally. OBJECTIVE: To describe our methodology of developing a student-driven longitudinal, region-wide curriculum to train medical students to provide high-quality care to LGBTQ patients. METHODS: A 4-year LGBTQ Health Pathway was developed and implemented as a student-led initiative at the UWSOM. First- and second-year medical students at sites across the WWAMI region are eligible to apply. Accepted Pathway students complete a diverse set of pre-clinical and clinical components: online modules, didactic courses, longitudinal community service/advocacy work, a scholarly project, and a novel clinical clerkship in LGBTQ health developed specifically for this Pathway experience. Students who complete all requirements receive a certification of Pathway completion. This is incorporated into the Medical Student Performance Evaluation as part of residency applications. RESULTS: The LGBTQ Health Pathway is currently in its fourth year. A total of 43 total students have enrolled, of whom 37.3% are based in the WWAMI region outside of Seattle. Pathway students have completed a variety of scholarly projects on LGBTQ topics, and over 1000 hours of community service/advocacy. The first cohort of 8 students graduated with a certificate of Pathway completion in spring 2020. CONCLUSIONS: The LGBTQ Health Pathway at UWSOM is a novel education program for motivated medical students across the 5-state WWAMI region. The diverse milestones, longitudinal nature of the program, focus on rural communities, and opportunities for student leadership are all strengths and unique aspects of this program. The Pathway curriculum and methodology described here serve as a model for student involvement and leadership in medical education. This program enables medical students to enhance their training in the care of LGBTQ patients and provides a unique educational opportunity for future physicians who strive to better serve LGBTQ populations.

Content-specific auditing of a large scale anatomy ontology.

Biomedical ontologies are envisioned to be usable in a range of research and clinical applications. The requirements for such uses include formal consistency, adequacy of coverage, and possibly other domain specific constraints. In this report we describe a case study that illustrates how application specific requirements may be used to identify modeling problems as well as data entry errors in ontology building and evolution. We have begun a project to use the UW Foundational Model of Anatomy (FMA) in a clinical application in radiation therapy planning. This application focuses mainly (but not exclusively) on the representation of the lymphatic system in the FMA, in order to predict the spread of tumor cells to regional metastatic sites. This application requires that the downstream relations associated with lymphatic system components must only be to other lymphatic chains or vessels, must be at the appropriate level of granularity, and that every path through the lymphatic system must terminate at one of the two well known trunks of the lymphatic system. It is possible through a programmable query interface to the FMA to write small programs that systematically audit the FMA for compliance with these constraints. We report on the design of some of these programs, and the results we obtained by applying them to the lymphatic system. The algorithms and approach are generalizable to other network organ systems in the FMA such as arteries and veins. In addition to illustrating exact constraint checking methods, this work illustrates how the details of an application may reflect back a requirement to revise the design of the ontology itself.

A sequence-oriented comparison of gene expression measurements across different hybridization-based technologies.

Over the last decade, gene expression microarrays have had a profound impact on biomedical research. The diversity of platforms and analytical methods available to researchers have made the comparison of data from multiple platforms challenging. In this study, we describe a framework for comparisons across platforms and laboratories. We have attempted to include nearly all the available commercial and 'in-house' platforms. Using probe sequences matched at the exon level improved consistency of measurements across the different microarray platforms compared to annotation-based matches. Generally, consistency was good for highly expressed genes, and variable for genes with lower expression values as confirmed by quantitative real-time (QRT)-PCR. Concordance of measurements was higher between laboratories on the same platform than across platforms. We demonstrate that, after stringent preprocessing, commercial arrays were more consistent than in-house arrays, and by most measures, one-dye platforms were more consistent than two-dye platforms.

Faculty Benefits From Medical Student Learning Communities: A Junior and Senior Faculty Members' Perspectives.

Medical school learning communities have many benefits for students. In this perspective, the authors briefly describe how learning communities have benefited them as faculty. These include finding other like-minded faculty, improving communication and clinical skills, career advancement through scholarly work associated with the learning community, and above all, developing mutually beneficial relationships with students. Here, they offer viewpoints from junior and senior faculty members on how the learning community has positively affected them.

Otosyphilis: Resurgence of an Old Disease.

OBJECTIVES: To describe the clinical characteristics of patients presenting with a new diagnosis of otosyphilis over the past 10 years in a large, urban, safety-net hospital affiliated with a large county sexually transmitted disease clinic. METHODS: Retrospective case series. A chart review was performed of all patients who presented to an adult otolaryngology clinic with a new diagnosis of syphilis and hearing loss from January 2008 to December 2017. RESULTS: Twelve patients met the criteria for "suspected" or "likely" otosyphilis based on Centers for Disease Control and Prevention definitions. The average age was 48 years (range 19-59). All were male. Nine (75%) were men who have sex with men. Eight (67%) were positive for human immunodeficiency virus. One (8%) presented with primary, nine (75%) with secondary, and two (17%) with early latent syphilis. Seven (58%) presented with bilateral audiogram-confirmed hearing loss, two (17%) with unilateral hearing loss, and three (25%) with suspected hearing loss based on fluctuating symptoms. Nine (75%) presented with tinnitus and two (17%) with vertigo. The median duration of otologic symptoms prior to presentation was 2 weeks (range: 0-16 weeks). All presented within the last 2 years surveyed. CONCLUSION: We have seen an increase in the number of otosyphilis cases in our clinic. We suspect otosyphilis may be underdiagnosed and emphasize the importance of screening for syphilis in patients with new audiologic symptoms of vertigo, tinnitus, or hearing loss. LEVEL OF EVIDENCE: 4 Laryngoscope, 129:1680-1684, 2019.

A Computer Simulation Model to Analyze the Application Process for Competitive Residency Programs.

BACKGROUND: The residency match process for competitive specialties hinders programs' ability to holistically review applications. OBJECTIVE: A computer simulation model of the residency application process was created to test the hypotheses that (1) it is advantageous to medical students to apply to the maximum number of programs under the current system, and (2) including a medical student's residency program preferences at the beginning of the application process improves the efficiency of the system for applicants and programs as quantified by the number of interview invitations received. METHODS: The study was conducted in 2016 using 2014 Otolaryngology Match data. A computer model was created to perform simulations for multiple scenarios to test the hypotheses. Students were assigned scores representing easy and hard metrics and program preferences, simulating a mixture of individual student preference and general program popularity. RESULTS: We modeled a system of 99 otolaryngology residency programs with 292 residency spots and 460 student applicants. While it was individually advantageous for an applicant to apply to the maximum number of programs, this led to a poor result for the majority of students when all applicants undertook the strategy. The number of interview invitations improved for most applicants when preference was revealed. CONCLUSIONS: Offering applicants an option to provide program preference improves the practical number of interview invitations. This enables programs to review applicants holistically-instead of using single parameters such as United States Medical Licensing Examination scores-which facilitates a selection of applicants who will be successful in residency.

Trends in female leadership at high-profile otolaryngology journals, 1997-2017.

OBJECTIVES: To determine the proportion and relative advancement of women in leadership positions at high-impact otolaryngology journals. METHODS: Nine clinical otolaryngology journals were selected based on high impact factor and subspecialty representation (journal impact factor, 2016: 1.16-2.95). The proportion of women editorial board members associate and/or section editors, and/or editor-in-chief was measured from 1997 to 2017. Comparisons were made to the proportion of women otolaryngology faculty at U.S. medical schools in 2017. RESULTS: From 1997 to 2017, female editorial board membership increased from 7.2% (range: 0.0%-12.8%) to 17.7% (range: 10.9%-38.9%) (P = 0.0001). In 2017, the proportion of female editorial board members was significantly less than the proportion of female academic otolaryngology faculty (17.7% vs. 27.7%, P = 0.0001), and there was threefold variation between journals. From 1997 to 2017, the proportion of female associate and/or section editors increased from 9.3% (range: 0.0-27.3) to 20.9% (range: 5.3% to 45.5%) (P = 0.09). In 2017, the proportion of female associate and/or section editors was not significantly different than the proportion of female associate or full professor academic otolaryngology faculty (20.9% vs. 19.5%, P = 0.73), but there was ninefold variation between journals. CONCLUSION: Women were underrepresented on eight of nine otolaryngology editorial boards but appropriately represented at the associate and/or section editorship level. There was remarkable variation in representation at individual journals, which may provide future opportunities to examine best practices. Disparity exists in leadership at the most senior level of these high-profile otolaryngology journals: none had women editor-in-chiefs. LEVEL OF EVIDENCE: NA Laryngoscope, 129:2031-2035, 2019.

Does Attending Surgeon Presence at the Preinduction Briefing Improve Operating Room Efficiency?

OBJECTIVE: To examine if attending surgeon presence at the preinduction briefing is associated with a shorter time to incision. STUDY DESIGN: Retrospective cohort study and survey. SETTING: Tertiary academic medical center. SUBJECTS AND METHODS: A retrospective cohort study was conducted of 22,857 operations by 141 attending surgeons across 12 specialties between August 3, 2016, and June 21, 2018. The independent variable was attending surgeon presence at the preinduction briefing. Linear regression models compared time from room entry to incision overall, by service line, and by surgeon. We hypothesized a shorter time to incision when the attending surgeon was present and a larger effect for cases with complex surgical equipment or positioning. A survey was administered to evaluate attending surgeons' perceptions of the briefing, with a response rate of 68% (64 of 94 attending surgeons). RESULTS: Cases for which the attending surgeon was present at the preinduction briefing had a statistically significant yet operationally minor reduction in mean time to incision when compared with cases when the attending surgeon was absent. After covariate adjustment, the mean time to incision was associated with an efficiency gain of 1.8 ± 0.5 minutes (mean ± SD; P < .001). There were no statistically significant differences in the subgroups of complex surgical equipment and complex positioning or in secondary analysis comparing service lines. The surgeon was the strongest confounding variable. Survey results demonstrated mild support: 55% of attending surgeons highly prioritized attending the preinduction briefing. CONCLUSION: Attending surgeon presence at the preinduction briefing has only a minor effect on efficiency as measured by time to incision.

Comparison of Micro-Computed Tomography and Clinical Computed Tomography Protocols for Visualization of Nasal Cartilage Before Surgical Planning for Rhinoplasty.

IMPORTANCE: There is no imaging standard to model nasal cartilage for the planning of rhinoplasty procedures. Preoperative visualization of cartilage may improve objective evaluation of nasal deformities, surgical planning, and surgical reconstruction. OBJECTIVES: To evaluate the feasibility of visualizing nasal cartilage using high resolution micro-computed tomography (CT) compared with the criterion standard of pathologic findings in a cadaveric specimen and to evaluate its accuracy compared with various clinical CT protocols. DESIGN, SETTING, AND PARTICIPANTS: Anatomic study at the University of Washington using single human cadaveric nasal specimens performed from July 10, 2017, to March 30, 2018. INTERVENTIONS: A micro-CT acquisition with 60-micron resolution was obtained of a nasal specimen. The specimen was then scanned with 5 different clinical CT protocols to span both clinical care and machine limits. The specimen was then sectioned in 5-mm axial slices for pathologic analysis. MAIN OUTCOMES AND MEASURES: Micro-CT images were registered to pathologic specimen cross-sections using a graphite fiducial system. Cartilage substructures were manually segmented and analyzed. A library of matched images across the micro-CT and various clinical CT protocols was then developed. Region of interest analysis was performed for each of the cartilage structures and their boundaries on clinical CT protocols and micro-CT, with the outcome of mean (SD) density using Hounsfield units. RESULTS: A single human cadaveric nasal specimen was used to obtain the following results. Lower lateral cartilage, upper lateral cartilage, and septal cartilage were accurately delineated on the micro-CT images compared with pathologic findings. The mean absolute deviation from pathologic findings was 0.30 mm for septal cartilage thickness, 0.98 mm for maximal upper lateral cartilage length, and 1.40 mm for maximal lower lateral cartilage length. On clinical CT protocols, only septal cartilage was well discriminated from boundary. Higher radiation dose resulted in more accurate density measurements of cartilage, but it did not ultimately improve ability to discriminate cartilage. CONCLUSIONS AND RELEVANCE: The results of this anatomic study may represent a notable step toward advancing knowledge of the capabilities and pitfalls of nasal cartilage visualization on CT. Nasal cartilage visualization was feasible on the micro-CT compared with pathologic findings. Future research may further examine the barriers to accurately visualizing upper lateral cartilage and lower lateral cartilage, a prerequisite for clinical application. LEVEL OF EVIDENCE: NA.

Angiogenic heterogeneity in head and neck squamous cell carcinoma: biological and therapeutic implications.

The literature contains numerous references describing heterogeneity for tumor phenotypes including cell proliferation, invasiveness, metastatic potential, and response to therapies. However, data regarding angiogenic heterogeneity are limited. In this study, we investigated the degree of intertumoral angiogenic heterogeneity present in head and neck squamous cell carcinomas (HNSCC). In addition, we investigated the biological relevance that this heterogeneity may have in the context of cytokine directed antiangiogenic therapy. Keratinocytes were harvested from HNSCC specimens using laser capture microdissection (LCM). Gene expression profiling of the RNA extracted from these specimens demonstrated variability in the expression of angiogenesis-related genes. Hierarchical clustering and principal component analyses (PCA) demonstrated the presence of unique patient clusters, suggesting that there may be two potentially distinct pathways by which HNSCC induce angiogenesis. Immunohistochemistry for VEGF, IL-8/CXCL8, HGF, and FGF-2, cytokines that play functional roles in HNSCC angiogenesis was performed on the original patient samples as well as a larger panel of normal, dysplastic and HNSCC specimens to validate the heterogeneous expression observed in the gene expression profiling studies. Finally, the therapeutic response of HNSCC tumor xenografts to anti-VEGF therapy was found to be dependent on the amount of VEGF produced by the tumor cells. These findings support the hypothesis of intertumoral angiogenic heterogeneity. They imply that there are differences with regard to the specific molecular mechanisms by which individual tumors within the same histological type induce angiogenesis. Moreover, they demonstrate the need for a more in-depth understanding of the variability of the angiogenic phenotype within a given type of neoplasm when designing cytokine targeted antiangiogenic therapies. Finally, they suggest that studies in conjunction with the ongoing clinical trials that explore the correlation between target expression and clinical outcome are warranted.