key: cord-0941642-srvz2ay0
authors: Ferrari, Marco; Paderno, Alberto; Giannini, Lorenzo; Cazzador, Diego; Ciardiello, Cristina; Carretta, Giovanni; Piazza, Cesare; Nicolai, Piero
title: COVID-19 screening protocols for preoperative assessment of head and neck cancer patients candidate for elective surgery in the midst of the pandemic: a narrative review with comparison between two Italian institutions
date: 2020-10-14
journal: Oral Oncol
DOI: 10.1016/j.oraloncology.2020.105043
sha: 7471853d46638d45423fde8b9f37c3beefca8d59
doc_id: 941642
cord_uid: srvz2ay0

Background Preoperative screening had a key role in planning elective surgical activity for head and neck cancer (HNC) during the COVID-19 pandemic. Methods All patients undergoing surgery for HNC at two Italian referral hospitals (University of Padua and National Cancer Institute [NCI]) during the peak of the COVID-19 epidemic in Italy were included. Accuracy of screening protocols was assessed. Results In the Padua protocol, 41 patients were screened by pharyngeal swab. The entire sample (100%) was admitted to surgery, diagnostic accuracy was 100%. In the NCI protocol, 23 patients underwent a telephone interview, blood test, and chest CT. Twenty patients (87%) were negative and were directly admitted to surgery. In the remaining 3 (13%), pharyngeal swab was performed. The screening was repeated until a negative chest CT was found. Diagnostic accuracy was 85%. Conclusions Dedicated screening protocols for COVID-19 allow to safely perform elective HNC surgery.

The COVID-19 pandemic has led to a progressive and significant strain on healthcare systems worldwide. The ideal management of COVID-19 patients has been improved and standardized by various reports dealing with risk-stratification, therapy, and follow-up. [1] [2] [3] However, optimized protocols for administration of routine activity in specific COVID-free surgical departments are still lacking. 4 Nonetheless, this is an essential point to take into consideration in preparation for the restart of conventional activity in the post-epidemic (or endemic) phase (so-called "Phase 2"). In this context, early identification of SARS-CoV-2 infected patients is the basis for adequate definition of subsequent planning in both in-and outpatient settings. However, etiological diagnosis is not always straightforward, especially when introduced in the framework of a screening protocol. In particular, nasal/nasopharyngeal and oropharyngeal swabs might be burdened by a high false negative rate. On the other hand, The aim of our retrospective study was to describe the screening and surgical activities of two Northern Italian (one in Lombardy and the other in Veneto regions) referral Institutions for management of head and neck cancer (HNC) during the peak phase (mid-March -mid-April 2020) of the COVID-19 epidemic, detailing their respective institutional COVID-19 screening protocols, related outcomes, and diagnostic accuracy.

The study included all patients undergoing surgery under general anesthesia for HNC at two Italian tertiary referral academic hospitals during the peak of the pandemic diffusion of to an internal "grey zone" of COVID-19 surveillance, submitted to further blood tests, chest CT, and nasal/nasopharyngeal swab while maintaining strict isolation.

The following data were extracted from institutional databases: patient-related including the 2-week post-discharge period) was considered as the gold standard evaluation (i.e. patients developing symptoms attributed to COVID-19 through nucleic acid-based test on respiratory secretions in this time frame were considered as "false negative" of the screening;

patients resulting positive at first screening who turned out to be negative at subsequent evaluations and did not develop COVID-19 throughout the perioperative period were considered as "false positive"). The choice of considering a 2-week time span to define results as either "false negative" or "true negative" was justified by: 1) the fact that during the inclusion period patients were instructed to maintain home isolation following discharge, as per governmental warning, and 2) the need to prioritize the negative (NPV) over the positive predictive value (PPV), being the selection of "true negatives" (i.e., non-infected patients) the main objective of the protocols. Sensitivity, specificity, PPV, NPV, and accuracy were calculated accordingly.

Between one for progression to distant lung metastases, and one for impossible laryngeal exposure of a T1b glottic cancer (therefore treated by radiation therapy). As a consequence, we performed 20 surgical procedures, of which 15 (75.0%) were major surgeries (7 with free flaps reconstruction), and 5 (25.0%) minor transoral tongue or laser-assisted laryngeal procedures.

None of these patients developed signs or symptoms of COVID-19 during hospitalization (range, 1-21 days; mean, 6). One patient presented mild fever and respiratory problems at 7 days after surgery that included segmental mandibulectomy, neck dissection, and free flap reconstruction. He therefore received chest CT (showing mild interstitial thickening) and

nasopharyngeal swab (negative for SARS-CoV-2). All patients underwent a postoperative follow-up visit at least 2 weeks after discharge or received a telephone call and did not refer COVID-19-related signs or symptoms.

Therefore, chest CT scan showed a sensitivity and PPV that were not assessable due to the lack of events. On the other hand, specificity, NPV, and accuracy were 85%, 100%, and 85%, respectively.

We herein describe two different screening protocols adopted for preoperative RT-PCR on swab was adopted, whereas a purely RT-PCR-based protocol was adopted where the pandemic was more contained. 5 With special reference to the Padua protocol, although a shorter time span between swab and surgery would have been preferable, it must be considered that both knowledge on timing of the infection and diagnostic resources (e.g. rapid test kits for urgent cases) were limited during the inclusion period. Moreover, it has been demonstrated that the rate of positive swab within 1 week from an initially negative test is low (3.5%) and mostly regards symptomatic subjects with worsening conditions. 6 While the relatively small number of patients does not allow making any definitive conclusions, both algorithms effectively selected non-infected patients in the preoperative phase, even during the pandemic peak of COVID-19 in one of the earliest and most involved areas of the European Union.

However, preoperative screening tools to be adopted for future triage of patients who are electively managed for HNC should be progressively refined in light of novel evidence and advances in the field of diagnostic testing, especially during the post-epidemic (endemic) phase, whose length and future impact on worldwide health care systems are far to be fully appreciated. Interestingly, it has been recently suggested that testing the asymptomatic population with a relatively inexpensive test (i.e. $50 or cheaper) might be cost-effective during the epidemic phases of the pandemic (i.e. with R e 1.6 or higher), otherwise providing a reduction in infections, deaths, and hospitalizations despite the non-cost-effectiveness.

Moreover, a test as cheap as $5 would be cost-effective even in the non-epidemic (endemic)

phase. If the cost could be reduced to $3 or less, then a test performed on a 14-day basis would be cost-effective regardless of R e value. 7 Since operating on patients affected by SARS-CoV-2 implies potentially dramatic consequences, 8 screening asymptomatic subjects prior to surgery is likely to provide a favorable cost-benefit, if not cost-effective, ratio.

To date, there is no clear-cut indication that blood chemistry can serve as a screening 

The role of CT in first-line diagnosis and screening of COVID-19 patients is a muchdebated topic. The proposed rationale is to speed-up diagnosis and prevent issues related to shortages of RT-PCR tests. However, data regarding this specific aspect are variable and should be carefully interpreted to identify the advantages and drawbacks. 13 Ai et al. evaluated the diagnostic performance of chest CT in 1014 cases during the Wuhan epidemic, highlighting its extremely high sensitivity (97%) and its potential in the routine screening of COVID-19 patients. 14 infection. However, its diagnostic accuracy remains unclear and is difficult to assess, especially in asymptomatic patients, given the lack of robust data. 17 Most evidence is based on a series of hospitalized COVID-19 patients and/or symptomatic patients, where reference standards for comparison of results are unclear. 18 The "threat" of false negative result is directly related to critical issues including site of sampling, sampling method, timing, and sampling safety for healthcare providers. A recent review on collection of respiratory specimens in symptomatic patients during the SARS, MERS, and H1N1 epidemics revealed that nasopharyngeal aspirate had the highest positive rate when performed within 2 weeks of onset of symptoms. 19 Combined sampling of nasal and oropharyngeal swabs was the safest method for medical staff. Results driven from experience in previous epidemics are yet to be validated in the current SARS-CoV-2 pandemic.

Rates of positivity with quantitative RT-PCR depends on the sampling site. Considering the upper respiratory tract, the highest positive rates in COVID-19 patients were found in nasal swabs (63% to 73%), followed by oropharyngeal swabs (32% to 61%). 20 These data reflect the results of Zou et al. on viral load of the upper respiratory tract, where higher viral loads were registered in the nasal cavity than in the oropharynx. 21 Among sampling of the lower respiratory tract, sputum collection was positive in 49% to 89% of cases, while bronchoalveolar lavage (BAL) had the highest diagnostic yield with 93% to 100% positivity. [22] [23] [24] Notably, selection bias might have affected the actual rates of positivity for BAL, considering that the collection procedure is generally performed in intubated patients, and thus in severe clinical scenarios for patients with COVID-19. Despite the higher diagnostic performance of lower respiratory tract specimens, the risk of exposure during sample collection and the technical demand of BAL advise against its routine use for screening. A reasonable balance between the above-mentioned issues is probably represented by nasal swab, which, as suggested by some authors, may be combined with oropharyngeal swabs or sputum collection to increase sensitivity. 18, 25 Time 

At the time of writing, serology for SARS-CoV-2 is gaining increasing interest, 27-29 as its theoretical utility ranges from a pre-treatment/pre-trial recruitment screening tool to a potential method to assess immunity on a large population-based scale. However, a number of limitations make serology a suboptimal tool to screen patients requiring oncologic surgery. One of the major drawbacks of serological assays is the time span required for detection of antibodies following infection, which is paramount for screening purposes: Pan et al.

demonstrated that sensitivity of serological immunochromatographic test takes almost one

week to increase from 11% within the first week following symptom onset to 93% thereafter. 30 If one considers that the incubation time of COVID-19 is estimated to be 6.4 days, 31 Some lines of evidence suggest that the degree of seroconversion is directly associated with severity of disease in terms of both clinical and biochemical manifestations. 35, 36 This further undermines the potential utility of serology in the screening of asymptomatic patients.

Moreover, non-uniformity among commercially available kits and potential cross-reactivity with respect to antibodies against non-SARS-CoV-2 coronaviruses further discourage the application of serology as preoperative screening method. 28 Considering that recent reports documented that IgG seroconversion occurs in almost all patients infected with SARS-CoV-2, 37 future elucidation about the role of antibodies in predicting immunity for COVID-19 will also be essential in the preoperative screening setting, as patients displaying IgG could be exempted from other expensive and time-consuming screening tests prior to surgery.

Although based on two small cohorts of patients, the present study suggests that different screening protocols for SARS-CoV-2 infection were effective for preoperative screening of HNC patients who were candidates for surgery. Even during the peak of the epidemic phase, pharyngeal swab alone or a combination of symptom evaluation, generic blood tests, and chest CT were able to adequately select patients for surgery, apparently including only those without COVID-19. However, each diagnostic test presents specific drawbacks in terms of accuracy and cost-related issues that must be placed into perspective when considering preoperative screening for elective surgery. In this view, further studies will need to assess a combination of various diagnostic methods aimed at optimizing diagnosis while maintaining a favorable cost-benefit ratio, especially in the post-epidemic (endemic) phase of COVID-19. Optimal integration and modulation of different screening strategies will be paramount to cope with the "silent threat" of asymptomatic endemic infections. 38 

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