Outcomes of Cerebral Venous Thrombosis due to Vaccine-Induced Immune Thrombotic Thrombocytopenia After the Acute Phase.

BACKGROUND: Cerebral venous thrombosis (CVT) due to vaccine-induced immune thrombotic thrombocytopenia (VITT) is a severe condition, with high in-hospital mortality rates. Here, we report clinical outcomes of patients with CVT-VITT after SARS-CoV-2 (severe acute respiratory syndrome coronavirus 2) vaccination who survived initial hospitalization. METHODS: We used data from an international registry of patients who developed CVT within 28 days of SARS-CoV-2 vaccination, collected until February 10, 2022. VITT diagnosis was classified based on the Pavord criteria. Outcomes were mortality, functional independence (modified Rankin Scale score 0-2), VITT relapse, new thrombosis, and bleeding events (all after discharge from initial hospitalization). RESULTS: Of 107 CVT-VITT cases, 43 (40%) died during initial hospitalization. Of the remaining 64 patients, follow-up data were available for 60 (94%) patients (37 definite VITT, 9 probable VITT, and 14 possible VITT). Median age was 40 years and 45/60 (75%) patients were women. Median follow-up time was 150 days (interquartile range, 94-194). Two patients died during follow-up (3% [95% CI, 1%-11%). Functional independence was achieved by 53/60 (88% [95% CI, 78%-94%]) patients. No new venous or arterial thrombotic events were reported. One patient developed a major bleeding during follow-up (fatal intracerebral bleed). CONCLUSIONS: In contrast to the high mortality of CVT-VITT in the acute phase, mortality among patients who survived the initial hospitalization was low, new thrombotic events did not occur, and bleeding events were rare. Approximately 9 out of 10 CVT-VITT patients who survived the acute phase were functionally independent at follow-up.

The nasal valve: new insights on the static and dynamic NV with MR-imaging.

PURPOSE: We assessed the static nasal valve angle with MR imaging in healthy subjects and evaluated the complex mechanism of nasal valve dynamics during physiologic and forced inspiration. METHODS: In 17 healthy subjects, measurements of the static nasal valve angle were conducted on MR scans, using a TSE Axial T2-weighted sequence and a 3 mm slice thickness. The dynamic changes of nasal valve movement were detected using MR Cine-imaging techniques. RESULTS: The static median angle of the nasal valve was found to be 28.6° with a range of 12.7°-39.3°. The median degree of nasal valve collapse during forced inspiration was 68% (range 20-99%) of the baseline (static nasal valve angle). In the moderately forced inspiration (3 s) the median nasal valve angle declined to 76% of the baseline angle (range 42-100%). In the physiologic or unforced inspiration, the median nasal valve angle was reduced to 86.3% of the baseline angle (range 52-100%). CONCLUSION: MRI, as a non-invasive tool, is a reliable method for evaluation of the static nasal valve angle and for the illustration of the complex nasal valve dynamics.

Transoral laser microsurgery in early glottic cancer involving the anterior commissure.

PURPOSE: Treatment modalities for glottic cancer comprise surgery, (chemo-)radiation, and combined treatment options. Glottic cancer involving the anterior commissure (AC) requires special preoperative assessment and surgical skills, as it is commonly considered a risk factor for local recurrence. The aim of this study is to analyze the oncological effectiveness of transoral laser microsurgery (TLM) in the early glottic cancer involving the AC. METHODS: We retrospectively analyzed the data of all patients with primary, early staged (T1-2) glottic squamous cell carcinoma who were treated between 2004 and 2014. Patients were preferably treated by TLM (rather than open surgical techniques) if appropriated transoral exposure of the endolarynx was ensured. Voice outcomes were not assessed. RESULTS: 186 patients with early glottic cancer were included, 143 were treated by TLM and 43 by other therapy modalities [OT open surgical techniques (n = 32) or primary (chemo-)radiation (n = 11)], respectively. In 84 patients (59%) of the TLM cohort, the AC was involved (OT cohort n = 29 (73%), p = 0.143). The 1-, 3-, and 5-year local control rates after TLM were 91%, 86%, and 81% in patients without AC infiltration and 84%, 74%, and 70% in patients with AC infiltration, respectively, showing no statistical difference (p = 0.180). The 5-year disease-free survival and laryngeal preservation rate (LPR) did not differ with regard to AC infiltration (p = 0.215 and p = 0.261). Comparing the treatment modalities, the 5-year LPR was 90% for TLM and 83% for OT regardless of infiltration of the AC (p = 0,653 and p = 0.267, respectively). CONCLUSION: TLM is an effective surgical treatment for early glottic cancer with AC involvement in patients with adequate transoral laryngeal exposure.

Prognostic value of the lymph node ratio in oropharyngeal carcinoma stratified for HPV-status.

OBJECTIVE: Lymph node ratio (LNR) was shown to be a prognostic factor in laryngeal and oral cavity primaries. The purpose of this study was to investigate the impact of the lymph node ratio in oropharyngeal squamous cell carcinoma (OPSCC) with a high incidence of HPV-related disease. Therefore, the role of LNR was evaluated as an additional predictive parameter to the 8th edition of AJCC TNM staging system. METHODS: From December 2009 to August 2015, patients diagnosed with primary oropharyngeal squamous cell carcinoma were prospectively enrolled. After tumor resection with uni- or bilateral neck dissection, patients with ≥ 1 nodal metastasis (pN+) were eligible for a retrospective LNR analysis. RESULTS: 137 patients underwent tumor resection with uni- or bilateral neck dissection. The proportion of HPV-associated disease was 42%. Most patients (n = 96; 70%) presented with involved neck nodes. In p16-positive OPSCC, the rate of pN + cases was significantly increased compared to p16-negative OPSCC (86% vs. 58%, p = 0.007). Patients with LNR ≤ 10% had a significant better overall survival (OS) and disease-specific survival (DSS). However, when stratified for p16-status, LNR ≤ 10% had a significant impact on OS only for HPV-associated tumors (p = 0.027), whereas LNR of ≤ 10% was not a significant predictor for better OS in p16-negative OPSCC (p = 0.143). CONCLUSION: The LNR with a cut-off value of 10% serves as an additional prognostic parameter in HPV-related OPSCC and may help to improve risk stratification in combination with the revised AJCC 8th edition TNM classification.

Head and neck reconstruction in the elderly patient: a safe procedure?

Demographic changes strongly affect industrialized countries. While free tissue transfer was initially believed to be beneficial only for younger patients, there is an increasing number of elderly patients requiring microvascular operations in our aging society. Medical and surgical risks for head and neck cancer patients over a certain age who undergo free tissue transfer has hardly been investigated. A retrospective mono-center cohort study was performed. All patients with the age 75 or higher undergoing microvascular operations were reviewed. Patient characteristics including the ASA-status, the ACE-27-score, flap survival and postoperative medical and surgical complications were evaluated. The Clavien-Dindo-classification system for postoperative complications was applied to assess the severity of the complications. A total of 31 patients with an average age of 78.8 years were included. 4 patients suffered from venous congestion and had to undergo revision surgery. All flaps could successfully be salvaged. Higher ASA-status and ACE-score were significantly associated with postoperative medical and surgical complications and a higher severity of the complications. However , neither age nor operating time had influence on the complication rate. Microvascular free tissue transfer can be performed with a high degree of security in selected elderly patients. However, serious medical complications remain a concern, correlating strongly with high ASA and ACE-score. Careful patient selection is mandatory to reduce complications to a minimum.

Management of locoregional recurrence in cutaneous squamous cell carcinoma of the head and neck.

Cutaneous squamous cell carcinomas often affect elderly patients. Follow-up monitoring is difficult in these patients due to their multi-morbidity and reduced compliance. Tumour recurrence is consequently diagnosed in advanced tumour stages. Surgical therapy with curative intention often requires extended resections. The study at hand should determine whether surgical concepts are warranted in this collective. Sixty-seven patients who underwent surgical procedure due to recurrent disease of cutaneous head and neck squamous cell carcinoma were included. The cohort was divided in patients with/without adjuvant therapeutic regimens. Data were assessed retrospectively. Complete tumour resection was achieved in 85 % of our patients. Patients with adjuvant treatment demonstrated a favorable 5-year-recurrence-free interval (78 vs 30 %) and overall survival (79 vs 46 %). Complete surgical resection of advanced recurrent head and neck cutaneous squamous cell carcinomas is possible and yields favorable results in terms of survival, especially if combined with adjuvant treatment.

Bilateral Keloid Formation after Otoplasty in the Presence of Prolonged Mask Wearing.

Prominent ears are the most frequently observed congenital deformity of the head and neck. Various techniques have been proposed for their aesthetic correction. Typically, surgical treatment for protruding ears involves a combination of suture, cutting, and scoring techniques. Herein, we present the clinical case of an 11-year-old child who developed bilateral keloid formations 12 months after otoplasty. Keloids and hypertrophic scars can result from extensive retroauricular skin excisions that do not allow for tension-free wound closure. In addition, skin tension and friction on immature surgical scars are common risk factors for keloid formation. To comply with school guidelines aimed at reducing the transmission of SARS-CoV-2, the patient has consistently worn FFP2 masks with ear loops positioned behind the concha. Although masks play a critical role in preventing the spread of infectious diseases, they can lead to friction in the postauricular area. In light of the presented case, it is important to examine potential cofactors that may contribute to keloid formation after otoplasty, as well as suggest a strategy to safeguard the retroauricular scar.

Risk and course of COVID-19 in immunosuppressed patients with myasthenia gravis.

BACKGROUND: Patients with myasthenia gravis (MG) are potentially prone for a severe COVID-19 course, but there are limited real-world data available on the risk associated with COVID-19 for patients with MG. Here, we investigate whether current immunosuppressive therapy (IST) influences the risk of SARS-CoV-2 infection and COVID-19 severity. METHODS: Data from the German myasthenia gravis registry were analyzed from May 2020 until June 2021 and included patient demographics, MG disease duration, comorbidities, current IST use, COVID-19 characteristics, and outcomes. Propensity score matching was employed to match MG patients with IST to those without, and multivariable binary logistic regression models were used to determine associations between IST with (1) symptomatic SARS-CoV-2 infection and (2) severe COVID-19 course, as measured by hospitalization or death. RESULTS: Of 1379 patients with MG, 95 (7%) patients (mean age 58 (standard deviation [SD] 18) presented with COVID-19, of which 76 (80%) received IST at time of infection. 32 patients (34%) were hospitalized due to COVID-19; a total of 11 patients (12%) died. IST was a risk factor for hospitalization or death in the group of COVID-19-affected MG patients (odds ratio [OR] 3.04, 95% confidence interval [CI] = 1.02-9.06, p = 0.046), but current IST was not associated with a higher risk for SARS-CoV-2 infection itself. DISCUSSION: In this national MG cohort study, current IST use was a risk factor for a severe disease course of COVID-19 but not for SARS-CoV-2 infection itself. These data support the consequent implementation of effective strategies to prevent COVID-19 in this high-risk group. TRIAL REGISTRATION INFORMATION: German clinical trial registry ( https://www.drks.de ), DRKS00024099, first patient enrolled: February 4th, 2019.

Diabetes, Hypertension, Atrial Fibrillation and Subsequent Stroke-Shift towards Young Ages in Brunei Darussalam.

Southeast Asia harbors a young population of more than 600 million people. Socioeconomic transition within the last decades, driven by globalization and rapid economic growth, has led to significant changes in lifestyle and nutrition in many countries of this region. Hence, an increase in the number of non-communicable diseases is seen in most populations of Southeast Asia. Brunei Darussalam is the smallest country in this region, with a population of around 400,000 inhabitants. Vast hydrocarbon resources have transformed Brunei into a wealthy industrialized country within the last few decades. We compared the age distribution and prevalence of cardiovascular risk factors in ischemic stroke patients between the only stroke unit in Brunei Darussalam and a tertiary stroke center from Frankfurt/Germany. Between 2011 and 2016, a total number of 3877 ischemic stroke patients were treated in both institutions. Even after adjusting for age due to different population demographics, stroke patients in Brunei were younger compared to their German counterparts. The prevalence of hypertension and diabetes mellitus was significantly higher in young age groups in Brunei, whereas no difference was observed for older patients. The rapid socioeconomic transition might be a significant risk factor for the development of non-communicable diseases, including stroke.

Frequency and syndrome specificity of antibodies to aquaporin-4 in neurological patients with rheumatic disorders.

BACKGROUND: A new autoantibody (termed NMO-IgG, or AQP4-Ab) has recently been described in patients with neuromyelitis optica (NMO) and its formes frustes, longitudinally extensive transverse myelitis (LETM) and recurrent optic neuritis (rON). However, AQP4-Ab has been found also in patients with co-existing rheumatic diseases such as systemic lupus erythematosus (SLE) or Sjögren's syndrome (SS), conditions which are characterized by broad, polyspecific B cell activation. OBJECTIVES: In this study, we aimed at evaluating the syndrome specificity and frequency of AQP4-Ab in patients with rheumatic diseases and neurological symptoms. METHODS: For this purpose, serum samples from 109 neurological patients with established connective tissue disorders (CTD) (n = 54), possible CTD (n = 42), or vasculitis (n = 13) were analysed for the presence of AQP4-Ab by a cell-based assay employing recombinant human AQP4. RESULTS: AQP4-Ab was detectable in 31/40 (78%) patients with CTD and NMO spectrum disorders (median titre, 1:1000) but in none of the samples obtained from patients with CTD or vasculitis and neurological disorders other than NMO, LETM, or rON (n = 69). CONCLUSION: The high syndrome specificity of the antibody for neuromyelitis optica spectrum disorders (NMOSDs) in patients with CTD supports the concept of AQP4-Ab being involved in the pathogenesis of these neurological conditions, and argues against AQP4-Ab simply being part of the polyclonal B cell activation generally associated with rheumatic diseases. Moreover, the finding that AQP4-Ab is present in patients with CTD and co-existing NMOSD with approximately the same frequency as in patients without CTD strengthens the case of CTD and AQP4-Ab positive NMOSD representing two co-existing yet distinct entities in the majority of patients.

Better be prepared: the spectrum of neuropsychiatric impairment among Libyan war victims transferred to Germany for trauma rehabilitation.

BACKGROUND: The current Libyan civil war has originated many casualties, imposing medical challenges. War injuries are complex, requiring specialized knowledge and interdisciplinary assessment for adequate patient and intercultural management. METHODS: This retrospective study analyzed records of 78 Libyan patients admitted from July 2016 to November 2017 to neurological and trauma surgical departments of Krankenhaus Nordwest, Frankfurt, Germany. Issues of system preparation of the hospital, demographics, injury patterns and therapies were analyzed. The chi-squared test was used to analyze differences in injury patterns in explosion and gunshot injuries. RESULTS: Seventy-seven of seventy-eight patients were male (mean age 30.6 years). The patients received primary and secondary treatment in Tunisia (n = 39), Libya (n = 36) and Turkey (n = 23). Forty-eight patients had gunshot injuries, 37 explosion injuries, 11 both. Preparation for management of injuries included hygienic and isolation protocols, organization of interpreters and intercultural training. Patients presented with a broad variety of neurological, psychiatric and trauma surgical injuries. Fifty-six patients had sensory, 47 motor deficits. Nine reported headache, 5 vertigo, 13 visual impairment, 28 psychiatric symptoms. Eighteen patients had central nervous damage, 50 peripheral nervous damage. Central nervous damage was significantly more common in gunshot than explosion injuries (p = 0.015). Peripheral nervous damage was more common in explosion than gunshot injuries (p < 0.1). Fifty-one patients had polytrauma and 49 suffered from fractures. Therapy included surgical interventions (n = 56) and physiotherapy. Structured rehabilitation programs were often indicated. CONCLUSION: Specialized knowledge about war injuries and their management including hospital preparation and planning regarding infrastructure may be required anytime. Injuries include a broad variety of neurological, psychiatric and trauma surgical injuries. Therefore, an interdisciplinary approach is crucial.

Rippling muscle disease: variable phenotype in a family with five afflicted members.

We report a family with rippling muscle disease (RMD) who had an autosomal dominant mode of inheritance. The father, mother, and one daughter proved to be heterozygous, and two sons were homozygous for the A92T mutation of the caveolin-3 gene. The cardinal features of RMD, particularly percussion-induced rapid contractions, muscle mounding, and muscle rippling, varied considerably among these subjects. Moreover, all examined individuals showed muscle weakness; however, the patterns were inconsistent.

Exposure of NK cells to intravenous immunoglobulin induces IFN gamma release and degranulation but inhibits their cytotoxic activity.

The mechanisms underlying the modulation of Natural Killer (NK) cell functions by intravenous immunoglobulin (IVIg) are poorly understood. Using an ex vivo whole blood assay system we demonstrate that IVIg suppresses NK cell cytotoxicity. This was paralleled by IVIg-induced degranulation of CD56(bright), CD16(positive) NK cells, reduced expression of CD16 and elevated IFN gamma release. To assess whether these findings also occur in vivo we analyzed whole blood before and after IVIg therapy of patients. Following IVIg treatment the number of NK cells in peripheral blood dropped significantly. We observed reduced CD16 expression, elevated IFN gamma-amounts in plasma, reduced NK cell cytotoxicity, and granzyme B release into the plasma, confirming our in vitro data. These effects on the functions of NK cells describe a novel immunomodulatory effect of IVIg. The in vitro assays employed here could represent informative test systems to monitor effects of in vivo IVIg treatment at an individual level.

Aquaporin-4 antibody positive longitudinally extensive transverse myelitis following varicella zoster infection.

Longitudinally extensive transverse myelitis (LETM) is a condition shown to confer high risk of conversion into neuromyelitis optica (NMO). Increasing evidence from immunological and histopathological studies suggests that LETM is an autoimmune disorder caused by pathogenic antibodies to aquaporin-4 (AQP4-Ab), the most abundant water channel in the CNS, at least in a subset of patients. However, cases of infectious or parainfectious NMO/LETM (mostly associated with herpes zoster) have been repeatedly reported in the previous literature, raising the question of aetiological diversity in NMO/LETM. Here we present a case of acute LETM in a 63-year-old patient occurring two weeks after reactivation of varicella zoster virus (VZV). Serological testing revealed antibodies to AQP4. Plasma exchange was paralleled by disappearance of AQP4-Ab and sustained clinical improvement. Our observations provide further evidence for a pathogenic role of AQP4-Ab in LETM and suggest that AQP4-Ab associated auto-immunity should be considered also in apparently infectious/parainfectious settings.

Chemoradiation and local recurrence of head and neck squamous cell carcinoma and the risk of carotid artery blowout.

BACKGROUND: Carotid blowout syndrome (CBS) is a rare but life-threatening complication of head and neck squamous cell carcinoma (HNSCC). Chemoradiation (CRT) may make CBS more likely, but so far no longitudinal analysis of different treatment strategies has been conducted. METHODS: In the present study, 1072 patients with HNSCC were divided into groups depending on whether they had experienced CBS. Disease-related data were analyzed using chi-square test, Fisher exact test, and Student's t test. Survival rates were calculated using Kaplan-Meier test, log-rank test, and the Cox regression analysis for forward selection. RESULTS: Thirty-six patients suffering from CBS demonstrated significantly advanced T status (P = .001) and UICC stage (P = .004) when compared with unaltered counterparts. After adjustment for UICC stage, OS was comparable in both groups, whereas the mean recurrence-free survival (RFS) rate was better in unaltered patients (67 vs 24 months; P < .0001). Cox regression for forward selection revealed local recurrence (hazard ratio [HR], 1.9; P < .0001), T status (HR, 1.9; P = .03), and CRT (HR, 2.0; P < .0001) as independent risk factors for mortality related to CBS. CONCLUSION: CBS is a rare event in patients with HNSCC demonstrating reduced OS/RFS. Advanced T status, C/RT, and the recurrence of local tumors increase the risk of CBS-associated death.

Long-term Outcome for Open and Endoscopically Resected Sinonasal Tumors.

OBJECTIVE: Endoscopic resection of sinonasal cancer has become an alternative to open craniofacial surgery and leads to safe and satisfying results in emerging numbers. Randomized study data comparing outcomes between approaches are missing. Hence, it remains unclear which subgroups of patients might profit most from each technique. We aimed to identify such patient and tumor characteristics and gather information for future prospective study design. STUDY DESIGN: Case series with chart review. SETTING: Tertiary academic center. SUBJECTS AND METHODS: This study is based on a retrospective chart review of 225 patients undergoing open craniofacial or endoscopic resection for sinonasal malignancy between 1993 and 2015 at Munich University Hospital. Statistical analyses include t test, chi-square, Kaplan-Meier charts, and univariate and multivariate analyses. RESULTS: The sample size was similar between the endoscopic and open surgery groups. Tumors were significantly larger in patients who underwent open craniofacial resection. The risk of notable bleeding ( P = .041) was lower and hospital stay shorter ( P = .001) for endoscopic interventions of all tumor stages. Rates of overall ( P = .024) and disease-specific ( P = .036) survival were significantly improved for endoscopic cases; improved recurrence-free survival rates did not achieve statistical significance ( P = .357). For cases matched for tumor size, this improvement was confirmed for T3 tumors ( P = .038). Regional and distant metastatic tumor spread generally worsened survival in both surgical subgroups. Multivariate Cox regression analysis revealed independent prognosticators for overall survival. CONCLUSION: Endoscopic tumor resection remains a suitable option for distinct indications and showed improved outcome in intermediate-stage tumors in our collective. Further randomized studies acknowledging the here-identified factors are needed to improve future therapy guidelines and patient care.

Is Perineural Invasion of Head and Neck Squamous Cell Carcinomas Linked to Tobacco Consumption?

Perineural invasion (PNI) is an underrecognized path of cancer spread, and its causes and mechanisms are poorly understood. Recent research indicates a mutual attraction of neuronal and cancer cells, largely dependent on neurotrophic factors and their receptors. Interestingly, the release of neurotrophic factors occurs upon cigarette smoke/nicotine exposure in a dose-dependent manner, and serum levels correlate with current smoking, number of smoking years, and smoking severity. Among cell types capable of neurotrophic factors secretion are lung and oral fibroblasts. In our study of 178 patients with head and neck squamous cell carcinoma, tumors of current and former smokers showed PNI significantly more often than tumors of never smokers. Moreover, PNI was a marker for aggressive tumor growth. Surprisingly, PNI was more significant for survival than p16 status. Our study warrants further research on PNI in head and neck squamous cell carcinoma with special emphasis on the impact of tobacco consumption to identify suitable candidates for therapeutic interventions.

Therapy Testing in a Spheroid-based 3D Cell Culture Model for Head and Neck Squamous Cell Carcinoma.

Current treatment options for advanced and recurrent head and neck squamous cell carcinoma (HNSCC) enclose radiation and chemo-radiation approaches with or without surgery. While platinum-based chemotherapy regimens currently represent the gold standard in terms of efficacy and are given in the vast majority of cases, new chemotherapy regimens, namely immunotherapy are emerging. However, the response rates and therapy resistance mechanisms for either chemo regimen are hard to predict and remain insufficiently understood. Broad variations of chemo and radiation resistance mechanisms are known to date. This study describes the development of a standardized, high-throughput in vitro assay to assess HNSCC cell line's response to various therapy regimens, and hopefully on primary cells from individual patients as a future tool for personalized tumor therapy. The assay is designed to being integrated into the quality-controlled standard algorithm for HNSCC patients at our tertiary care center; however, this will be subject of future studies. Technical feasibility looks promising for primary cells from tumor biopsies from actual patients. Specimens are then transferred into the laboratory. Biopsies are mechanically separated followed by enzymatic digestion. Cells are then cultured in ultra-low adhesion cell culture vials that promote the reproducible, standardized and spontaneous formation of three-dimensional, spheroid-shaped cell conglomerates. Spheroids are then ready to be exposed to chemo-radiation protocols and immunotherapy protocols as needed. The final cell viability and spheroid size are indicators of therapy susceptibility and therefore could be drawn into consideration in future to assess the patients' likely therapy response. This model could be a valuable, cost-efficient tool towards personalized therapy for head and neck cancer.

Impact of comorbidity and anemia in patients with oropharyngeal cancer primarily treated with surgery in the human papillomavirus era.

BACKGROUND: Comorbidity and anemia strongly influence treatment and outcome of oropharyngeal squamous cell carcinomas (SCCs), but respective data are frequently lacking in clinical studies. We evaluated 149 cases of oropharyngeal SCC primarily treated with surgery regarding the impact of these factors on disease-free survival (DFS) and overall survival (OS). METHODS: Data were recorded during treatment and follow-up visits. Human papillomavirus (HPV) association of oropharyngeal SCC was detected by p16 immunohistochemistry. RESULTS: Patients with p16-positive disease were significantly less comorbid and anemic, and treated more aggressively. Comorbidity and anemia, but not p16 status, significantly influenced DFS and had more impact on OS than p16 status. CONCLUSION: In our study, p16-positive seems a good surrogate marker for healthier patients. Patients with p16-positive disease showed improved survival, but this was limited to none/mild comorbid and/or nonanemic individuals in this group. On the basis of our results, we strongly suggest the inclusion of these factors in risk stratification for clinical studies. © 2016 Wiley Periodicals, Inc. Head Neck 39: 7-16, 2017.