key: cord-0943767-q4u5t8zs
authors: Day, Andrew T.; Sher, David J.; Lee, Rebecca C.; Truelson, John M.; Myers, Larry L.; Sumer, Baran D.; Stankova, Lenka; Tillman, Brittny N.; Hughes, Randall S.; Khan, Saad A.; Gordin, Eli A.
title: Head and neck oncology during the COVID-19 pandemic: Reconsidering traditional treatment paradigms in light of new surgical and other multilevel risks
date: 2020-04-06
journal: Oral Oncol
DOI: 10.1016/j.oraloncology.2020.104684
sha: 04c9e6c0d1409a7c70326e1a2578ea9620897639
doc_id: 943767
cord_uid: q4u5t8zs

The COVID-19 pandemic demands reassessment of head and neck oncology treatment paradigms. Head and neck cancer (HNC) patients are generally at high-risk for COVID-19 infection and severe adverse outcomes. Further, there are new, multilevel COVID-19-specific risks to patients, surgeons, health care workers (HCWs), institutions and society. Urgent guidance in the delivery of safe, quality head and neck oncologic care is needed. Novel barriers to safe HNC surgery include: 1) imperfect presurgical screening for COVID-19; 2) prolonged SARS-CoV-2 aerosolization; 3) occurrence of multiple, potentially lengthy, aerosol generating procedures (AGPs) within a single surgery; 4) potential incompatibility of enhanced personal protective equipment (PPE) with routine operative equipment; 5) existential or anticipated PPE shortages. Additionally, novel, COVID-19-specific multilevel risks to HNC patients, HCWs and institutions, and society include: use of immunosuppressive therapy, nosocomial COVID-19 transmission, institutional COVID-19 outbreaks, and, at some locations, societal resource deficiencies requiring health care rationing. Traditional head and neck oncology doctrines require reassessment given the extraordinary COVID-19-specific risks of surgery. Emergent, comprehensive management of these novel, multilevel surgical risks are needed. Until these risks are managed, we temporarily favor nonsurgical therapy over surgery for most mucosal squamous cell carcinomas, wherein surgery and nonsurgical therapy are both first-line options. Where surgery is traditionally preferred, we recommend multidisciplinary evaluation of multilevel surgical-risks, discussion of possible alternative nonsurgical therapies and shared-decision-making with the patient. Where surgery remains indicated, we recommend judicious preoperative planning and development of COVID-19-specific perioperative protocols to maximize the safety and quality of surgical and oncologic care.

surgical risks are needed. Until this is achievedthese risks are managed, we temporarily favor nonsurgical therapy over surgery in most circumstancesfor most mucosal squamous cell carcinomas, wherein both surgery and nonsurgical therapy are both first-line options. Where surgery is traditionally preferred, we recommend multidisciplinary evaluation of multilevel surgical-risks, discussion of and possible alternative nonsurgical therapies alongside and shared-decision-making with the patient.

Where surgery remains indicated, we recommend judicious preoperative planning and development of COVID-19-specific perioperative protocols to maximize the safety and quality of surgical and oncologic care.

The COVID-19 pandemic demands reevaluation of current treatment paradigms in head and neck oncology. Severe acute respiratory syndrome (SARS)-Cov-2 has caused 896,450292,142 infections worldwide as of April 2March 22, 2020, [1] results in severe or critical illness in 20-30% of cases and has a case-fatality rate ranging from 1.42.3%-7.2%. [2] [3, 4] It disproportionately affects the elderly and individuals with comorbid conditions, which comprise a substantial portion of head and neck cancer (HNC) patients. [5, 6] Indeed, the case-fatality rate of individuals > 70 years of age has ranged from 8.0%-22.5%. [3, 4] Finally, a nationwide surge in COVID-19 hospital admissions is anticipated and threatens to overwhelm hospital capacity, with potential dire consequences for patients. [3, 4, 7, 8] Surgery has been a longstanding, first-line treatment option for HNC. However, emerging data demonstrate that head and neck oncologic surgery may be less advisable, and in some circumstances, imprudent, due to a confluence of extraordinary, co-occurring, rapidly-evolving, COVID-19-related circumstances. Therefore, head and neck oncology treatment doctrines must be reanalyzed for the welfare of patients, providers, health care workers (HCW), health care organizations and society.

There are now numerous, novel barriers to safe head and neck oncologic surgery. First, our ability to screen for and select COVID-19-negative patients for surgery is limited. Viral shedding and infection transmission occurs during incubation and the median incubation time of SARS-CoV-2 is five days. [9, 10] Indeed, itAmong COVID-19 positive patients who eventually develop symptoms, 99% will exhibit symptoms by day 14 takes 14 days for 99% of infected patients to develop symptoms. [9] AdditionallyMoreover, between 7-13% of COVID-19 patients are asymptomatic or minimally symptomatic [4] but may shed virus for weeks. Convalesced COVID-19 patients have exhibited prolonged viral shedding after complete symptom resolution. [11] [3] Unsatisfactory Further compounding the issue, SARS-CoV-2 testing also fails to adequately mitigateis insufficiently available and potentially insufficiently sensitive this problem. SARS-CoV-2 tests are insufficiently available and insufficiently sensitive. False negative test rates in symptomatic patients have ranged from 3-68% [12] [13] [14] but are more likely to be 16-24% according to the most highly-powered study to date (n=1014). [15] Investigators anticipate false negative test rates are likely to be highest near the beginning and end of the disease spectrum: in asymptomatic, infected patients and convalescing patients. [16, 17] Ultimately, COVID-19 positive patients may even elude a two-week quarantine with negative SARS-CoV-2 testing. Second, the virus replicates in the nasal cavity, nasopharynx and oropharynx, which are routine sites of head and neck surgery. [18, 19] Even a Moreover, asymptomatic patients have exhibited high viral loads at these sites. [18, 19] Third, SARS-CoV-2 is aerosolized, and can remain airborne for at least three hours. [20] and has been detected in airborne samples in the hallways of COVID-19 units. [21] Surgeries performed with general anesthesia involve multiple, In addition to the routine , multiple aerosol-generating procedures (AGPs) such as bag-valve mask ventilation and intubation. [22] These AGPs have been associated with that promote nosocomial virus infections transmissioduring previous coronavirus epidemics.n [22, 23] and accompany any surgery involving general anesthesia, [20] head Head and neck oncologic surgery often also often involves other additional, formal AGPs including such as nasogastric tube placement, tracheotomy, repeated endotracheal tube removal and replacement during total laryngectomy, and airway suctioning, which in some cases is continuous. [22] Routine use of cautery and suction in upper aerodigestive tract (UADT) surgery, such as transoral robotic surgery, is a continuous AGP. Cautery creates a plume of smoke often requiring constant airway suctioning to both facilitate visualization of the operative field and eliminate the odor of coagulated tissue. Common occurrences such as postAdditionally, post-extubation cough, cuff leak, inadvertent ventilatory circuit disconnection are common occurrences in HNC surgery also and presumed to be aerosol-generating events (AGEs).

Moreover, use of cautery in upper aerodigestive tract (UADT) surgery, such as transoral robotic surgery is a routine, often continuous, AGP. Cautery generates a plume of smoke often requiring constant airway suctioning to both facilitate visualization of the operative field and eliminate the odor of coagulated tissue. Therefore, we submit that head and neck oncologic surgeries involving the UADT are extraordinarily high-risk for COVID-19SARS-CoV-2 viral aerosolization and transmission to operating room personnel and viral aerosolization could jeopardize the safety of all operating room personnel. [22, 23] Although SARS-CoV-2 circulates in the blood of COVID-19-positive patients, [11] there is inadequate data to assess the risk of viral aerosolization in routine, non-UADT oncologic surgeries such as neck dissections, parotidectomies or thyroidectomies.

Fourth, use of necessarily enhanced personal protective equipment (PPE) may significantly impair or even prohibit execution of routine head and neck oncologic surgeries. We are not aware of any evidence to guide decision-making in this regard. As an example, use of the DaVinci console during transoral robotic surgery (TORS) may be difficult with goggles and potentially impossible with powered air-purifying respirators (PAPRs). Simultaneous useUse of goggles or a PAPR with loupes or an operative microscope for transoral laser microsurgery or microvascular anastomosis might also be challenging or impossible. Therefore, in circumstances in which enhanced PPE is necessary and use of routine operative equipment is not possible, selection of open surgical techniques for indicated oropharyngeal, hypopharyngeal or laryngeal cancers or regional-over free-tissue transfer may be necessary. These adjustments in surgical approach could result in compromised oncologic and functional surgical outcomes, presenting additional risk to patients.

Finally, many, if not most, hospitals have already described shortages in personal protective equipment (PPE). [24] Other hospitals are anticipating a surge of COVID-19 patients and corollary shortage in PPE. [7] Postoperative patients are highly likely to generate copious, aerosolized secretions for days to even weeks following surgery, which could present dramatic risks to additional hospital staffHCWs and personal caretakers in the setting of insufficient PPE. In conclusion, given the substantial risks of operating during this pandemic, head and neck oncology patients should be judiciously selected for surgery.

The risks of head and neck oncologic surgery must be assessed in light of their potential impact on patients, providers and HCWs, and health care institutions and society. The benefits of continued provision of standard of care oncologic surgeries are commonsense and will not be discussed further below. Serial, frequent reassessment of risk will be necessary. For example, there is now at least one ongoing randomized controlled trial of hydroxychloroquine for post-exposure prophylaxis (NCT04308668), which hopefully will accrue quickly and read out soon. If this study is positive, it may open new avenues that allow head and neck surgery to proceed more safely.

There are several new patient-level risks of head and neck oncologic surgery. HNC during the pandemic. These patients are often elderly and/or exhibit multiple comorbidities specifically associated with increased risk for and adverse outcomes in COVID-19 patients, including hypertension, diabetes, coronary artery disease, and chronic obstructive pulmonary disease. [5, 6] Patients may escape screening and undergo surgery with an ongoing asymptomatic or prodromal community-acquired COVID-19

infection. SARS-CoVv-2 negative patients who undergo surgery will be at increased risk for nosocomial COVID-19 infection via contact, droplet or airborne SARS-CoV-2 transmission.. [25] Head and neck oncologic surgery Surgical patients with community-acquired or nosocomial COVID-19 infections will be particularly susceptible to magnified adverse outcomes, including perioperative mortality rates of up to 22.5%. [4] In a recent nationwide study of COVID-19 patients in China, patients with a history of cancer were more likely to become infected with COVID-19. The 18 such COVID-19-positive patients with a history of cancer were more likely to require invasive ventilation with ICU admission or die (39%, 

There are also several HCW-level risks of performing head and neck oncologic surgery at this time. First, the high risk of infection and death among HCWs during this pandemic is welldocumented. [3, 4] As previously discussed, performing surgery on an asymptomatic or prodromal COVID-19 patient that eludes preoperative screening could be the source of a catastrophic COVID-19 outbreak among HCWs. Anecdotally, such tragedies have already occurred in China and Iran. Second, at a time when social distancing is imperative to prevent COVID-19 transmission, a surgery and hospital admission will require ongoing, close staff-staff, staff-patient, staff-caregiver and patient-caregiver proximity -often for days or, not uncommonly, 1-2 weeks.

Third, our understanding of the degree of SARS-CoV-2 virulence and COVID-19 transmission is inadequate and there is insufficient data to guide the appropriate level of PPE use touse of PPE prevent transmission of SARS-CoV-2 to operating room personnel, particularly in the operating room during surgeries involving prolonged AGPs. Numerous guidelines report N95 respirators sufficiently protect against airborne disease, including COVID-19. [28] [29] [30] [31] However, these guidelines address appropriate PPE for limited AGPs performed in clinic, the ICU and, in one guideline, tracheostomies. [30] Therefore, we cannot extrapolate from these positions and assume that this level of PPE is also appropriate for surgeries in which prolonged aerosol-generation within the UADT -sites of known viral replication -are routine. The CDC specifically states that "for patients with known or suspected COVID-19" undergoing AGPs, "health care providers in the room should wear N95 or higher-level respirators. [29] During the SARS 2003 outbreak, the CDC acknowledged that N95 respirators were the "minimum level of respiratory protection required for HCWs…performing AGPs" and that "healthcare facilities in some SARS-affected areas routinely used higher levels of respiratory protection," such as PAPRs "for AGPs on patients with SARS-CoV disease." [32] Therefore, there is urgent need for the publication of case reports or case series from areas with dense COVID-19 outbreaks regarding the level of respiratory protection required in these surgeries. The substantial uncertainty regarding the necessary level of PPE needed to safely execute these surgeries in unscreened, inadequately screened or even screened asymptomatic patients with false-negative tests represents a critical risk to all operating room staff.

Finally, HWCs caring for postoperative head and neck oncologic surgery patients with UADT malignancies may perform may undergo morenumerous daily AGPs requiring substantial amounts of enhanced PPEthan any other patients in the hospital and therefore will be heavy resource utilizers.

Patients requiring aundergoing a tracheostomy or laryngectomy routinely cough postoperatively and require will need regular, AGPs such as open suctioning. [33] Most other patients undergoing UADT surgeries routinely perform aerosol-generating self-suctioning. Therefore, a patients admitted with subclinical COVID-19 will present significant risk to providers and, HCWs in the operative and postoperative settings. and caregivers and will require a substantial amount of already limited PPE.

Head and neck oncologic surgeries present additional risks to health care systems and society.

The current trajectory of disease incidence in the United States suggest a nationwide surge in hospital admissions is imminent. [7, 8] Further, China and Italy have reported: PPE, ventilator, hospital bed and ICU shortages; [8, 34, 35] conversion of operating rooms to ICUs; [35] construction of temporary hospitals; [34] and even health care rationing. [35] In worst-case, nightmarish scenarios that are occurring have occurred in Italy, health care providers will have to ration ICU admissions or floor or ICU admissions or ventilator use and, in effect, decline needed care to COVID-19 patients with likely fatal consequences. [35] Surgery and subsequent admission of head and neck oncology patients will compete for valuable, limited hospital resources in real-time during the pandemic. [36] Additionally, the possibility of head and neck surgical oncology-related COVID-19 outbreaks described above have the potential to temporarily or permanently decimate the health care workforce. [3, 34, 35] 

Overview Novel barriers to safe head and neck oncologic surgery and corollary multilevel surgical risks necessitate urgent reevaluation of Given that the safety of head and neck oncologic surgery is compromised by the COVID-19 pandemic, head and neck oncology treatment treatment paradigms according to disease type and prior treatment. Traditional, standard of care treatments should be observed whenever reasonable. Deviation from the traditional standard of care may be appropriate or necessary in light of the current, extraordinary circumstances. These decisions are likely to be highly patient-, surgeon-, and institution-specific. For example, surgery may be impossible at institutions without available beds or ventilators. Therefore, in the context of the COVID-19 pandemic, we recommend multidisciplinary assessment of multilevel surgical risk and alternatives to surgery for each case followed by shared decision-making with the patient. require urgent reevaluation.

The collective multilevel risks of surgery vary according to patient-, HCW-, surgery-and postsurgery-specific factors and demand development of institutional risk-stratification protocols. [37] We describe a potential example of a risk-stratification algorithm in Table 1 Evaluation of COVID-19-specific, multilevel surgical risks will be necessary to make informed treatment decisions for head and neck oncology patients eligible for surgery. According to our example (Table 1) , we currently assume that most HCWs will present high-risk of COVID-19 transmission to patients and each other given the possibility of an asymptomatic disease presentation, their high likelihood of COVID-19 exposure, known inadequate PPE and insufficient SARS-CoV-2 testing nationally (Table 1) . We argue that multidisciplinary discussions should specifically attend to cases presenting high-risks of COVID-19 transmission during both surgery and/or post-surgery states in all patients -and particularly for high-risk patients. Practically, these high-risk designations will include most mucosal squamous cell carcinomas (SCCs) and sinonasal carcinomas along with ablations requiring regional-or especially free-tissue transfer. Primary surgery +/-adjuvant therapy and primary radiation +/chemotherapy are long-standing, first-line treatment options for head and neck cancers. These therapies often exhibit equivalent oncologic outcomes with unique treatment toxicity profiles. We review general head and neck oncology treatment considerations according to disease type, prior treatment, multilevel surgical risks and alternative therapies below. However, it will also present its own unique risks to patients and providers including:

immunosuppressive chemotherapy, [41] [42] [43] [44] [45] There may be exceptions to this general rule, particularly when adjuvant therapy is not anticipated. Importantly, these exceptions assume availability of hospital beds, ventilators and appropriate PPE, and compatibility of PPE with operative equipment. According to our example in Table   1 , a reliable, low-risk patient with a T1aN0 glottic or T1N0 tonsil SCC may present a one-time, high-risk of COVID-19 transmission intraoperatively to operating room personnel followed by medium-risk of COVID-19 transmission postoperatively. In such cases, the collective risks of a one-time surgery may be lower than the collective risks of daily presentation to an outpatient radiotherapy center for sevenweeks.

Patients with primary oral cavity, T4a laryngeal and advanced sinonasal cancers along with recurrent UADT malignancies requiring salvage surgery represent the principal head and neck oncologic treatment quandaries of the COVID-19 pandemic. In low-risk patients with oral cavity or sinonasal cancers for whom a brief postoperative admission is anticipated, the collective benefits of primary surgery may easily outweigh the collective risks. However, select advanced sinonasal cancer and a majority of oral cavity cancer, advanced laryngeal cancer and salvage surgery patients will require a prolonged hospital admission and/or tracheostomy or laryngectomy and/or free-tissue transfer.

Intraoperative and postoperative risk of SARS-CoV-2 transmission will be high in these settings. For these patients, the collective, multilevel risks of surgery should be weighed against the risks of traditionally substandard, alternative therapies and their corollary perceived compromises in oncologic efficacy. Primary surgery should remain the default treatment and should be chosen whenever reasonable. Conversely, multilevel surgical risks may sufficiently impair, or even prohibit, safe and efficacious surgery along with the safe care of patients postoperatively. In these circumstances, traditionally substandard alternative therapies discussed below may be preferable.

Conversely, traditional doctrines strongly favor surgery for some head and neck cancers including oral cavity, certain sinonasal, cutaneous, salivary gland and thyroid cancers, along with sarcoma. In patients who have failed nonsurgical therapy, salvage surgery is often the only remaining curative option, with few exceptions. For these cases we recommend: assessment of multilevel surgical risk; evaluation of alternatives to surgery and consideration of the corollary deviation from the standard of care and perceived degree of compromise in oncologic efficacy; multidisciplinary discussion; and shared decisionmaking with patients.

Despite the controversy surrounding its use independent of the COVID-19 pandemic, [46, 47] neoadjuvant chemotherapy  cetuximab or neoadjuvant chemotherapy  immunotherapy may be considered, in certain settings, at this time. In extenuating circumstances, primary radiation +/-chemotherapy may be selected for oral cavity, T4a laryngeal or advanced sinonasal SCC patients. Patients opting for nonsurgical therapy must be aware of the inferior oncologic outcomes and anticipated increased morbidity of this treatment compared to primary surgery. [53] [54] [55] [56] [57] [58] In certain salvage cases, definitive re-irradiation may be a reasonable alternative to surgery, particularly if the patient has experienced a prolonged disease-free interval. Re-irradiation +/-chemotherapy preserves the possibility of cure, although with substantial concomitant treatment toxicity. [59] [60] [61] Among some patients who later fail re-irradiation, a durable disease-free interval may allow for surgical salvage when the COVID-19-specific risks of surgery have been mitigated.

According to our example in Table 1 , surgery for most head and neck cutaneous, salivary and thyroid malignancies will present low-or medium-risk of SARS-CoV-2 transmission intraoperatively and postoperatively. Conversely, traditional surgery for certain patients may involve the UADT (e.g. minor salivary gland carcinomas) or free tissue transfer (e.g. temporal bone resection for a cutaneous or parotid malignancy). These patients may present high intraoperative and/or postoperative risk of SARS-CoV-2 transmission. Consequently, multidisciplinary evaluation of multilevel surgical risks and risks of alternative therapies of all cases alongside shared decision-making with patients will be necessary.

Assuming adequate hospital-based resources, surgery will likely maintain a principal role in the management of most low-risk patients with cutaneous, salivary and thyroid malignancies. More prolonged delays in surgery may also be considered in certain scenarios. For example, a several-week surgical delay for a patient with a low-grade salivary carcinoma is unlikely to impact their oncologic outcome. Delay of surgery for several weeks, or even months, with serial imaging may be reasonable for selectsome patients with conventional, well-differentiated papillary thyroid carcinomas. [62, 63] In select patients, the COVID-19-specific multilevel risks of surgery may outweigh the benefits.

In these cases, traditionally substandard, disease-specific alternative therapies may be considered. In patients with cutaneous SCC and basal cell carcinoma (BCC), the longstanding preference for primary surgery over primary radiation +/-chemotherapy is based primarily on low-level evidence and patient convenience. Accordingly, Primary radiation +/-chemotherapy will represent a primary option for select patients in whom surgery is generally indicated, particularly when the perceived compromise in oncologic outcomes is slight or the preference for surgery is based on low-level evidence. Despite the controversy surrounding its use independent of the COVID-19 pandemic, [39, 40] In select salvage cases, definitive re-irradiation may be a reasonable alternative to surgery. Reirradiation alone preserves the possibility of cure, although with substantial concomitant treatment toxicity. [46] [47] [48] Among some patients who fail re-irradiation, a prolonged interval between retreatment and disease progression may allow for surgical salvage when the COVID-19-specific risks of surgery have been mitigated.

In most circumstances, there is inadequate data to guide the use of neoadjuvant immunotherapy alone for head and neck cancer patients (NCT03952585), which would avoid the substantial risks of chemotherapy. pPatients with advanced cutaneous SCCs or BCCssquamous cell carcinomas could receive radical-intent radiotherapy. If or if not clearly curative, cemiplimab. [64] or vismodegib [65] may be considered. Neoadjuvant use of cemiplimab or vismodegib have not been adequately evaluated, [66] but may facilitate operative delays under extenuating circumstances. Similarly, there is limited evidence to guide the use of targeted biologic therapy alone in most scenarios. 59, 60 For example, vismodegib treatment may facilitate operative delays for patients requiring surgery for advanced basal cell carcinomas. 61 The length of definitive treatment delay would likely be unique to each circumstance, but using systemic treatment to open the window for a safer surgery should only be done if there is a viable "end date" at which point surgery can be performed.

Similarly, there is limited evidence to guide the use of targeted biologic therapy alone in rare salivary gland carcinomas. [67, 68] As previously noted, limited delays in "time sensitive" surgeries without additional therapy are acceptable. More prolonged delays in surgery may also be considered in certain scenarios. For example, a several-week surgical delay for a patient with a low-grade salivary carcinoma is unlikely to impact their oncologic outcome. Delay of surgery for several weeks, or even months, with serial imaging may be reasonable for select patients with papillary thyroid carcinomas. 62,63

Urgent head and neck oncologic surgery will still be the best treatment option for many patients after evaluation of multilevel risks, multidisciplinary discussion and shared decision-making with the patient. In these circumstances, institutions may reasonably employ a short-term delay in all nonemergent oncologic surgeries to ensure appropriate patient screening and perioperative planning for patient and HCW safety. The National Comprehensive Cancer Network implicitly supports two centers which are temporarily delaying oncologic surgery during this crisis. [36] For example, the Huntsman Cancer Institute advised rescheduling all "time-sensitive" but non-emergent surgeries (i.e. have to be performed within 48 hours) by a "few weeks." [69] In this interval, surgeons and institutions should rapidly develop COVID-19-specific protocols to provide safe, quality surgical care for head and neck oncology patients . Table 2 ). Some studies have questioned the efficacy of N95-respirators against airborne threats and specifically state: respirators may insufficiently protect against aerosolized small viruses [70, 71] and mask fit along with appropriate mask use are imperfect and prone to breaches in seal during routine clinical use. [71, 72] Conversely, other studies have cited the advantages of PAPRs including nonsignificant reduction in viral transmission compared to N95 respirators [70] along with improved comfort, complete head and neck covering, high-efficiency particulate air (HEPA) filtration. [73] [74] [75] According to another study, use of PAPRs protected 100% of operative personnel (n=124) throughout 41 "high-risk" procedures (including 15 tracheostomies) in "SARS-related patients"

during the 2003 outbreak. [37] Importantly, in this exercise we assume adequate PPE is available to all HCWs operatively and postoperatively. Access to PPE will need to be considered, and "contingency capacity" or "crisis/alternate" strategies may also need to be established. [76] In such circumstances, avoidance of surgery is preferred, especially for "high risk" patients, if possible.

Institutions will also need to develop novel preoperative protocols. Given the high attack rate [77] [78] [79] and prolonged aerosolization of this virus, [20] augmented infection control and containment training for OR, ICU and floor teams is necessary. [73, 80] Teams should seek to minimize AGPs and limit the length of these procedures whenever possible. For example, anesthesia may consider avoiding bag-mask ventilation, employing rapid sequence intubation techniques, and applying intratracheal or intravenous lidocaine to avoid postoperative coughing. [81, 82] specific multilevel risks of surgery and potential compromise in oncologic efficacy with deliveryrisks of alternative therapies in the context ofa multidisciplinary setting discussion andalong with shared patient-provider decision-making. Despite the amplified risks, surgery will still be indicated for many patients and appropriate preparation will be critical to ensure the safety of the patient, provider and all other involved HCWs. Legend AGE: aerosol-generating event; AGP: aerosol-generating procedure; TLM: transoral laser microsurgery; TORS: transoral robotic surgery *: Frequent, serial re-evaluation of patient-and surgical-risk will be required, particularly with anticipated improvements in management of patient-level risk. At the time of manuscript submission: there is known COVID-19 community spread with unknown disease prevalence; 1% of patients develop symptoms 14 days after exposure; among patients who develop symptoms, SARS-CoV-2 incubates for a median of five-days during which time viral shedding occurs; ~15% of COVID-19-positive individuals are asymptomatic or minimally symptomatic throughout the course of their disease; ~20% of patients with COVID-19 will have exhibit false negative SARS-CoV-2 tests. Therefore, there is justification for a conservative assessment of patient-risk for COVID-19. Despite this judicious approach, a "low-risk" patient could still be COVID-19 positive, particularly if the patient is not reliable, does not report breaches in quarantine or positive symptoms, or is asymptomatic with a false-negative test. Improved COVID-19 test sensitivity and faster specimen processing, analysis and result generation may be reasonably feasible and could substantially improve management of patient-level risk. **: Surgery-and post-surgery-specific risks may diverge according to this algorithm. For example, a patient undergoing a parotidectomy with neck dissection would present medium surgery-specific risk of COVID-19 transmission to operating room personnel and low-post-surgery-specific-risk of nosocomial COVID-19 or transmission to HCWs involved in postoperative care -assuming admission to a designated, COVID-19-free unit. A patient undergoing partial glossectomy for an early-stage oral cavity cancer and neck dissection without free tissue transfer would present high-surgery-specific risk of COVID-19 transmission to operating room personnel and medium post-surgery-specific risk of nosocomial COVID-19 or transmission to HCWs involved in postoperative care.

#: Cough, fever, shortness of breath, malaise, fatigue, headache, diarrhea, sore throat or rhinorrhea during quarantine or on the day of surgery PAPR Legend *: Frequent, serial re-evaluation of necessary surgical PPE according to patient-and surgical-risk will be required, particularly with improvements in management of patient-level risk. At the time of manuscript submission: there is reasonable justification for conservative PPE recommendations given the real possibility that a "low-risk" patient could still have COVID-19 (see Figure Table 1 , caption). Improved management of patient-level risk, such as improved SARS-CoV-2 test sensitivity, may allow for use of lower levels of PPE in the operating room. PAPR: powered air-purifying respirator; PPE: personal protective equipment

Estimates of the severity of coronavirus disease 2019: a model-based analysis. The Lancet Infectious diseases

Characteristics of and Important Lessons From the Coronavirus Disease 2019 (COVID-19) Outbreak in China: Summary of a Report of 72314 Cases From the Chinese Center for Disease Control and Prevention

Coronavirus Disease 2019 (COVID-19) in Italy

Clinical characteristics of 36 non-survivors with COVID-19 in Wuhan

Clinical course and risk factors for mortality of adult inpatients with COVID-19 in Wuhan, China: a retrospective cohort study

Impact of non-pharmaceutical interventions (NPIs) to reduce COVID19 mortality and healthcare demand. Imperial College COVID-19 Response Team

Critical Care Utilization for the COVID-19 Outbreak in Lombardy, Italy: Early Experience and Forecast During an Emergency Response

The Incubation Period of Coronavirus Disease 2019 (COVID-19) From Publicly Reported Confirmed Cases: Estimation and Application. Annals of internal medicine

Presumed Asymptomatic Carrier Transmission of COVID-19

Epidemiologic Features and Clinical Course of Patients Infected With SARS-CoV-2 in Singapore

Chest CT for Typical 2019-nCoV Pneumonia: Relationship to Negative RT-PCR Testing

False-Negative Results of Real-Time Reverse-Transcriptase Polymerase Chain Reaction for Severe Acute Respiratory Syndrome Coronavirus 2: Role of Deep-Learning-Based CT Diagnosis and Insights from Two Cases

Detection of SARS-CoV-2 in Different Types of Clinical Specimens

Correlation of Chest CT and RT-PCR Testing in Coronavirus Disease 2019 (COVID-19) in China: A Report of 1014 Cases

Positive RT-PCR Test Results in Patients Recovered From COVID-19

Potential preanalytical and analytical vulnerabilities in the laboratory diagnosis of coronavirus disease 2019 (COVID-19). Clinical chemistry and laboratory medicine

SARS-CoV-2 Viral Load in Upper Respiratory Specimens of Infected Patients. The New England journal of medicine

Nasopharyngeal shedding of severe acute respiratory syndromeassociated coronavirus is associated with genetic polymorphisms

Aerosol and Surface Stability of SARS-CoV-2 as Compared with SARS-CoV-1. The New England journal of medicine

Transmission Potential of SARS-CoV-2 in Viral Shedding Observed at the University of Nebraska Medical Center

Aerosol generating procedures and risk of transmission of acute respiratory infections to healthcare workers: a systematic review

Nosocomial Transmission of Emerging Viruses via Aerosol-Generating Medical Procedures

Challenges to the system of reserve medical supplies for public health emergencies: reflections on the outbreak of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) epidemic in China

Public health measures to control the spread of the severe acute respiratory syndrome during the outbreak in Toronto

Cancer patients in SARS-CoV-2 infection: a nationwide analysis in China

Prepare to adapt: Blood supply and transfusion support during the first 2 weeks of the 2019 Novel Coronavirus (COVID-19) pandemic affecting Washington State. Transfusion

Guidelines on the Management of Critically Ill Adults with Coronavirus Disease

Interim Infection Prevention and Control Recommendations for Patients with Suspected or Confirmed Coronavirus Disease 2019 (COVID-19) in Healthcare Settings

England aPH. COVID-19 guidance for infection prevention and control in healthcare settings; Adapted from Pandemic Influenza: Guidance for Infection prevention and control in healthcare settings

Care for Critically Ill Patients With COVID-19

Infection Control in Healthcare Facilities; Supplement I: Infection Control in Healthcare, Home, and Community Settings; Public Health Guidance for Community-Level Preparedness and Response to Severe Acute Respiratory Syndrome (SARS) Version 2/3

Use of lidocaine to prevent postoperative coughing after partial laryngectomy: comparison of three delivery methods. Drug design, development and therapy

COVID-19 and Italy: what next?

Facing Covid-19 in Italy -Ethics, Logistics, and Therapeutics on the Epidemic's Front Line. The New England journal of medicine

Managing Cancer Care During the COVID-19 Pandemic: Agility and Collaboration Toward a Common Goal

Infection control measures for operative procedures in severe acute respiratory syndrome-related patients

Epidemiological and clinical characteristics of 99 cases of 2019 novel coronavirus pneumonia in Wuhan, China: a descriptive study

Clinical findings in a group of patients infected with the 2019 novel coronavirus (SARS-Cov-2) outside of Wuhan, China: retrospective case series

How to improve adherence with quarantine: Rapid review of the evidence. medRxiv

COVID-19 rapid guideline: delivery of systemic anticancer treatments. NICE guideline

In Vitro Antiviral Activity and Projection of Optimized Dosing Design of Hydroxychloroquine for the Treatment of Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2)

First Case of 2019 Novel Coronavirus in the United States. The New England journal of medicine

Prophylactic and therapeutic remdesivir (GS-5734) treatment in the rhesus macaque model of MERS-CoV infection

Comparative therapeutic efficacy of remdesivir and combination lopinavir, ritonavir, and interferon beta against MERS-CoV

Looking beyond the CRT paradigm: why induction chemotherapy is worthy of pursuit

The never-ending story: finding a role for neoadjuvant chemotherapy in the management of head and neck cancer

Platinum-based chemotherapy plus cetuximab in head and neck cancer. The New England journal of medicine

Cisplatin, fluorouracil, and docetaxel in unresectable head and neck cancer. The New England journal of medicine

Induction cetuximab, paclitaxel, and carboplatin followed by chemoradiation with cetuximab, paclitaxel, and carboplatin for stage III/IV head and neck squamous cancer: a phase II ECOG-ACRIN trial (E2303)

Pembrolizumab alone or with chemotherapy versus cetuximab with chemotherapy for recurrent or metastatic squamous cell carcinoma of the head and neck (KEYNOTE-048): a randomised, open-label, phase 3 study

Randomized phase III trial of induction chemotherapy with docetaxel, cisplatin, and fluorouracil followed by surgery versus up-front surgery in locally advanced resectable oral squamous cell carcinoma

Primary Surgery vs Radiotherapy for Early Stage Oral Cavity Cancer. Otolaryngology--head and neck surgery : official journal of American Academy of Otolaryngology-Head and Neck Surgery

Primary radiotherapy in the treatment of stage I and II oral tongue cancers: importance of the proportion of therapy delivered with interstitial therapy

Treatment of oral cavity squamous cell carcinoma with adjuvant or definitive intensity-modulated radiation therapy

Use of Larynx-Preservation Strategies in the Treatment of Laryngeal Cancer

Primary total laryngectomy versus organ preservation for T3/T4a laryngeal cancer: a population-based analysis of survival

Total Laryngectomy Versus Larynx Preservation for T4a Larynx Cancer: Patterns of Care and Survival Outcomes

Salvage re-irradiation for recurrent head and neck cancer

ACR appropriateness criteria retreatment of recurrent head and neck cancer after prior definitive radiation expert panel on radiation oncology-head and neck cancer

Efficacy and toxicity of reirradiation using intensitymodulated radiotherapy for recurrent or second primary head and neck cancer

Guidelines of the American Thyroid Association for the Diagnosis and Management of Thyroid Disease During Pregnancy and the Postpartum

A Clinical Framework to Facilitate Risk Stratification When Considering an Active Surveillance Alternative to Immediate Biopsy and Surgery in Papillary Microcarcinoma

PD-1 Blockade with Cemiplimab in Advanced Cutaneous Squamous-Cell Carcinoma

Follow-Up of Patients With Complete Remission of Locally Advanced Basal Cell Carcinoma After Vismodegib Discontinuation: A Multicenter French Study of 116 Patients

A randomized phase II study evaluating vismodegib as neoadjuvant treatment of basal cell carcinoma preceding Mohs micrographic surgery: results and lessons learned. The British journal of dermatology

Targeted therapy for advanced salivary gland carcinoma based on molecular profiling: results from MyPathway, a phase IIa multiple basket study

NTRK fusion-positive cancers and TRK inhibitor therapy

The effects of exercise interventions on quality of life in clinical and healthy populations; a meta-analysis

Evaluation of a Novel Powered Airpurifying respirator (PAPR) vs. a N95 Respirator Mask for the Protection Against Influenza in a Human Exposure Model. Open Forum Infectious Diseases

Do N95 respirators provide 95% protection level against airborne viruses, and how adequate are surgical masks?

Comparison of performance of three different types of respiratory protection devices

To PAPR or not to PAPR? Canadian journal of respiratory therapy : CJRT = Revue canadienne de la therapie respiratoire : RCTR

Special article: personal protective equipment for care of pandemic influenza patients: a training workshop for the powered air purifying respirator

Health care worker protection in mass casualty respiratory failure: infection control, decontamination, and personal protective equipment

Checklist for Healthcare Facilities: Strategies for Optimizing the Supply of N95 Respirators during the COVID-19 Response

Early Transmission Dynamics in Wuhan, China, of Novel Coronavirus-Infected Pneumonia. The New England journal of medicine

Euro surveillance : bulletin Europeen sur les maladies transmissibles = European communicable disease bulletin

Secondary attack rate and superspreading events for SARS-CoV-2

How to train the health personnel for protecting themselves from novel coronavirus (COVID-19) infection during their patient or suspected case care

On-table extubation in neonates undergoing anoplasty: an experience of anesthetic management on the concept of fast-tracking anesthesia: A pilot study

Intravenous lidocaine to prevent postoperative airway complications in adults: a systematic review and meta-analysis

Identification and containment of an outbreak of SARS in a community hospital

Using an integrated infection control strategy during outbreak control to minimize nosocomial infection of severe acute respiratory syndrome among healthcare workers

Role of air distribution in SARS transmission during the largest nosocomial outbreak in Hong Kong

Protecting health care workers from SARS and other respiratory pathogens: a review of the infection control literature