Patients with integrated HPV16 in head and neck cancer show poor survival.

OBJECTIVES: We previously reported identifying three categories of HPV16-positive head and neck tumors based on The Cancer Genome Atlas (TCGA) RNA and DNA sequence data. Category 1 had truly integrated HPV16 genomes, category 2 had simple episomal genomes, and category 3 had novel episomes that were a hybrid between viral and human DNA. Using our categorization, we investigated in this study survival of patients with integrated HPV16 tumors versus patients with episomal HPV16 tumors. MATERIALS AND METHODS: The TCGA RNA-Seq sequence reads were used to quantify HPV E2 and E7 gene expression, which was used as a marker for HPV integration. RESULTS: The results demonstrate that integration is associated with poor survival; those patients with integrated HPV tumors fared no better than non-HPV tumors in their five-year survival. Integrated HPV in tumors was found strikingly to be prevalent in patients born earlier while episomal HPV was prevalent in patients born later. We also observed a fairly constant incidence of all HPV forms among head and neck cancer patients over the last eight years of this study (2006-2013). CONCLUSION: We propose our characterization of HPV integrated and episomal state is more accurate than previous studies that may have mischaracterized the hybrid HPV-human DNA episomes as integrated. The state of integrated HPV is associated with a poor clinical outcome. Results suggest that the incidence of integrated HPV among all HPV forms peaked and is decreasing. We discuss the importance of our findings for the management of HPV positive head and neck cancer.

Integration of Human Papillomavirus Genomes in Head and Neck Cancer: Is It Time to Consider a Paradigm Shift?

Human papillomaviruses (HPV) are detected in 70-80% of oropharyngeal cancers in the developed world, the incidence of which has reached epidemic proportions. The current paradigm regarding the status of the viral genome in these cancers is that there are three situations: one where the viral genome remains episomal, one where the viral genome integrates into the host genome and a third where there is a mixture of both integrated and episomal HPV genomes. Our recent work suggests that this third category has been mischaracterized as having integrated HPV genomes; evidence indicates that this category consists of virus-human hybrid episomes. Most of these hybrid episomes are consistent with being maintained by replication from HPV origin. We discuss our evidence to support this new paradigm, how such genomes can arise, and more importantly the implications for the clinical management of HPV positive head and neck cancers following accurate determination of the viral genome status.

Elimination of pain improves specificity of clinical diagnostic criteria for adult chronic rhinosinusitis.

OBJECTIVE: Determine whether the elimination of pain improves accuracy of clinical diagnostic criteria for adult chronic rhinosinusitis. STUDY DESIGN: Retrospective cohort study. METHODS: History, symptoms, nasal endoscopy, and computed tomography (CT) results were analyzed for 1,186 adults referred to an academic otolaryngology clinic with presumptive diagnosis of chronic rhinosinusitis. Clinical diagnosis was rendered using the 1997 Rhinosinusitis Taskforce (RSTF) Guidelines and a modified version eliminating facial pain, ear pain, dental pain, and headache. RESULTS: Four hundred seventy-nine subjects (40%) met inclusion criteria. Among subjects positive by RSTF guidelines, 45% lacked objective evidence of sinonasal inflammation by CT, 48% by endoscopy, and 34% by either modality. Applying modified RSTF diagnostic criteria, 39% lacked sinonasal inflammation by CT, 38% by endoscopy, and 24% by either modality. Using either abnormal CT or endoscopy as the reference standard, modified diagnostic criteria yielded a statistically significant increase in specificity from 37.1% to 65.1%, with a nonsignificant decrease in sensitivity from 79.2% to 70.3%. Analysis of comorbidities revealed temporomandibular joint disorder, chronic cervical pain, depression/anxiety, and psychiatric medication use to be negatively associated with objective inflammation on CT or endoscopy. CONCLUSION: Clinical diagnostic criteria overestimate the prevalence of chronic rhinosinusitis. Removing facial pain, ear pain, dental pain, and headache increased specificity without a concordant loss in sensitivity. Given the high prevalence of sinusitis, improved clinical diagnostic criteria may assist primary care providers in more accurately predicting the presence of inflammation, thereby reducing inappropriate antibiotic use or delayed referral for evaluation of primary headache syndromes. LEVEL OF EVIDENCE: 4. Laryngoscope, 127:1011-1016, 2017.

Advances in head and neck fine-needle aspiration and ultrasound technique for the pathologist.

The success of fine-needle aspiration (FNA) biopsy in the evaluation of head and neck (H&N) masses has already been established. Herein we outline the most recent advancement for the pathologist who performs traditional palpation-guided FNA (PGFNA) in the H&N while also incorporating ultrasound-guided FNA (UGFNA) into their practice. We provide an overview of the educational and training opportunities in H&N ultrasound and UGFNA with emphasis on the advantages and limitations for the pathologist. Throughout are useful clinical and technical pearls, many of which may also interest those who practice PGFNA, including local anesthesia use and FNA procedures in pediatric patients.

Risk factors for hazardous events in olfactory-impaired patients.

IMPORTANCE: Normal olfaction provides essential cues to allow early detection and avoidance of potentially hazardous situations. Thus, patients with impaired olfaction may be at increased risk of experiencing certain hazardous events such as cooking or house fires, delayed detection of gas leaks, and exposure to or ingestion of toxic substances. OBJECTIVE: To identify risk factors and potential trends over time in olfactory-related hazardous events in patients with impaired olfactory function. DESIGN, SETTING, AND PARTICIPANTS: Retrospective cohort study of 1047 patients presenting to a university smell and taste clinic between 1983 and 2013. A total of 704 patients had both clinical olfactory testing and a hazard interview and were studied. On the basis of olfactory function testing results, patients were categorized as normosmic (n = 161), mildly hyposmic (n = 99), moderately hyposmic (n = 93), severely hyposmic (n = 142), and anosmic (n = 209). INTERVENTIONS: Patient evaluation including interview, examination, and olfactory testing. MAIN OUTCOMES AND MEASURES: Incidence of specific olfaction-related hazardous events (ie, burning pots and/or pans, starting a fire while cooking, inability to detect gas leaks, inability to detect smoke, and ingestion of toxic substances or spoiled foods) by degree of olfactory impairment. RESULTS: The incidence of having experienced any hazardous event progressively increased with degree of impairment: normosmic (18.0%), mildly hyposmic (22.2%), moderately hyposmic (31.2%), severely hyposmic (32.4%), and anosmic (39.2%). Over 3 decades there was no significant change in the overall incidence of hazardous events. Analysis of demographic data (age, sex, race, smoking status, and etiology) revealed significant differences in the incidence of hazardous events based on age (among 397 patients <65 years, 148 [37.3%] with hazardous event, vs 31 of 146 patients ≥65 years [21.3%]; P < .001), sex (among 278 women, 106 [38.1%] with hazardous event, vs 73 of 265 men [27.6%]; P = .009), and race (among 98 African Americans, 41 [41.8%] with hazardous event, vs 134 of 434 whites [30.9%]; P = .04). CONCLUSIONS AND RELEVANCE: Increased level of olfactory impairment portends an increased risk of experiencing a hazardous event. Risk is further impacted by individuals' age, sex, and race. These results may assist health care practitioners in counseling patients on the risks associated with olfactory impairment.

Genes involved in radiation therapy response in head and neck cancers.

OBJECTIVES: This is a pilot study designed to identify gene expression profiles able to stratify head and neck squamous cell carcinoma (HNSCC) tumors that may or may not respond to chemoradiation or radiation therapy. STUDY DESIGN: We prospectively evaluated 14 HNSCC specimens, arising from patients undergoing chemoradiotherapy or radiotherapy alone with curative intent. A complete response was assessed by clinical evaluation with no evidence of gross tumor after a 2-year follow-up period. METHODS: Residual biopsy samples from eight complete responders (CR) and six nonresponders (NR) were evaluated by genome-wide gene expression profiling using HG-U133A 2.0 arrays. Univariate parametric t-tests with proportion of false discoveries controlled by multivariate permutation tests were used to identify genes with significantly different gene expression levels between CR and NR cases. Six different prediction algorithms were used to build gene predictor lists. Three representative genes showing 100% crossvalidation support after leave-one-out crossvalidation (LOOCV) were further validated using real-time QRT-PCR. RESULTS: We identified 167 significant probe sets that discriminate between the two classes, which were used to build gene predictor lists. Thus, 142 probe sets showed an accuracy of prediction ranging from 93% to 100% across all six prediction algorithms. The genes represented by these 142 probe sets were further classified into different functional networks that included cellular development, cellular movement, and cancer. CONCLUSIONS: The results presented herein offer encouraging preliminary data that may provide a basis for a more precise prognosis of HNSCC, as well as a molecular-based therapy decision for the management of these cancers.

A new clinical olfactory function test: cross-cultural influence.

OBJECTIVE: To investigate whether a new clinical olfactory test, the Odor Stick Identification Test for Japanese (OSIT-J), can be used to assess olfactory function cross-culturally in a US patient population. DESIGN: Cross-sectional prospective study. SETTING: A university medical center otolaryngology clinic. PATIENTS: Fifty US patients presenting with complaints of olfactory dysfunction from December 2004 to January 2006. INTERVENTIONS: Olfactory testing and patient interview. MAIN OUTCOME MEASURES: Comparison of test results obtained with the OSIT-J, the Connecticut Chemosensory Clinical Research Center (CCCRC) olfactory function test, and patients' self-reported level of olfactory function. Patients' opinions regarding the 2 test methods were also recorded. RESULTS: The mean +/- SD time required to administer the OSIT-J (8 +/- 1 minutes) was shorter than that required for the standard CCCRC test (21 +/- 6 minutes). Significant Spearman rank correlations were found between the OSIT-J and CCCRC test scores (r(s) = 0.80, P<.001, n = 50), and patients' self-reported level of olfactory function (r(s) = 0.73, P<.001, n = 50). Although 3 of the 13 odors used in the OSIT-J were not familiar to US subjects, patients reported that the OSIT-J was easier, more interesting, and the odors used more pleasant than the CCCRC test. CONCLUSIONS: Olfactory function tests developed in different countries should be evaluated to determine if a cross-cultural bias exists among test odorants. Although a cultural bias was detected for a few odorants, this study demonstrates that a modified version of the OSIT-J can be used to assess olfactory function in US patients.

Toxic effects on gustatory function.

A large number of substances and disease processes may impact the sense of taste. Toxic substances may cause taste dysfunction from their effects on the gustatory system from the salivary gland, to the taste bud, to the central neural pathways. A number of external toxins, including industrial compounds, tobacco, and alcohol, may adversely affect taste, most commonly through local effects in the oral cavity. Blood-borne toxins, such as medications and those present in autoimmune and other systemic disorders (e.g. renal or liver failure), have access to all parts of the gustatory system, and thus may exhibit varied effects on taste function. An understanding of these potential toxins and their impact on gustation will help physicians better recognize, and potentially limit the impact of such taste alterations on their patients.

Effects of head injury on olfaction and taste.

Traumatic events such as motor vehicle accidents, falls, or assaults can lead to dysfunction in olfaction or gustation. Mechanisms of posttraumatic olfactory dysfunction include direct injury to the sinonasal tract or olfactory epithelium, shearing effect on olfactory fibers at the cribriform plate, or brain contusion or intraparenchymal hemorrhage. Posttraumatic gustatory dysfunction is rare, but may occur as a result of direct injury to the tongue, injury to cranial nerves VII or IX, or brain contusion or hemorrhage. Evaluation of head-injured patients presenting with olfactory or gustatory complaints should include a thorough history, including assessment for pre-and posttraumatic chemosensory dysfunction and potential mechanisms of injury, complete head and neck examination including nasal endoscopy and cranial nerve testing, and focused radiographic imaging, usually CT of the sinuses and skull base. Formal olfactory and gustatory testing may be performed using various techniques, although in cases potentially involving litigation, methodologies able to detect malingering should be used. Treatable causes of chemosensory disturbance, most notably conductive olfactory losses caused by chronic rhinosinusitis or nasal obstruction, should be ruled out. In the event of neurosensory deficits, recovery may occur up to 12 to 18 months after the traumatic event. All patients should be counseled regarding the risks of their chemosensory deficits, and given suggestions for appropriate compensatory strategies.

Hazardous events associated with impaired olfactory function.

OBJECTIVE: To evaluate the risk of olfactory-related hazardous events in patients with impaired olfactory function. DESIGN: Retrospective cohort study. SETTING: A university-based clinic for smell and taste disorders. PATIENTS: A total of 445 patients who underwent olfactory testing between 1983 and 2001. INTERVENTIONS: Patient interview, olfactory testing. MAIN OUTCOME MEASURES: (1) Frequency of olfactory-related hazardous events including cooking incidents (ie, burning pots or pans), undetected fires, undetected gas leaks, and ingestion of spoiled foods or toxic substances; (2) level of olfactory function (anosmia; severe, moderate, or mild hyposmia; or normosmia) as determined by olfactory testing. RESULTS: Olfactory testing revealed that 76% of patients had some degree of impairment; 30% had complete anosmia. Thirty-seven percent of patients with olfactory impairment but only 19% of patients without impairment experienced at least 1 olfactory-related hazardous event. Of the hazardous events reported by impaired patients, cooking-related incidents were most common, representing 45%, with ingestion of spoiled food (25%), inability to detect a gas leak (23%), and inability to smell a fire (7%) reported less frequently. There was a significant correlation between frequency of hazardous events and degree of olfactory impairment (Cochran-Armitage trend test, P<.001): at least 1 hazardous event was reported by 45.2% of patients with anosmia, 34.1% with severe hyposmia, 32.8% with moderate hyposmia, 24.2% with mild hyposmia, and 19.0% of patients with with normal olfaction by testing. CONCLUSION: Patients with impaired olfactory function are more likely to experience olfactory-related hazardous events than those with normal olfactory function.

Image-guided endoscopic transsphenoidal drainage of select petrous apex cholesterol granulomas.

OBJECTIVE: Explore the indications and advantages of image-guided transsphenoidal endoscopic drainage of select petrous apex cholesterol granulomas. STUDY DESIGN: Case report and literature review. SETTING: Tertiary referral center. CONCLUSIONS: Image-guided endoscopic transsphenoidal drainage of cholesterol granulomas is the procedure of choice for petrous apex cholesterol granulomas that abut the sphenoid sinus and are accessible through its posterior wall.