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\begin{document}

\title{Respiratory and pulmonary complications in head and neck cancer
patients: An evidence-based review for the COVID-19 era}



\author[1]{Stephen Y. Kang, MD}%
\affil[1]{The James Cancer Hospital and Solove Research Institute}%


\vspace{-1em}



  
  \date{June 14, 2024}


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\selectlanguage{english}
\begin{abstract}
\textbf{Background}: Pulmonary complications and infections frequently
affect patients with head and neck squamous cell carcinoma (HNSCC).
Common characteristics can predispose these patients to the development
of severe respiratory illness, which may be particularly relevant during
the~ 2019 coronavirus disease (COVID-19) pandemic. \textbf{Methods:} A
scoping review was performed to assess the impact of pulmonary
comorbidities and adverse respiratory outcomes in HNSCC patients.
\textbf{Results}: Advanced age, history of tobacco and alcohol abuse,
and cardiopulmonary comorbidities are significant risk factors for the
development of adverse respiratory outcomes. Treatment~ toxicities from
radiation or chemoradiation therapy significantly increase these risks.
~\textbf{Conclusion}: Respiratory complications are a frequent cause of
morbidity and mortality among HNSCC patients, and the COVID-19 pandemic
may disproportionately affect this population.~ Interventions designed
to decrease smoking and alcohol use, improve oral hygiene, and
aggressively manage medical comorbidities are important to the long-term
management and health of these patients. ~%
\end{abstract}%



\sloppy




Dustin A. Silverman, MD\textsuperscript{1}*; Chen Lin,
MD\textsuperscript{1}*; Akina Tamaki, MD\textsuperscript{1} ; Sidharth
V. Puram, MD, PhD \textsuperscript{2} ; Ricardo L. Carrau, MD
\textsuperscript{1} ; Nolan B. Seim, MD \textsuperscript{1} ; Antoine
Eskander, MD, ScM\textsuperscript{3} ; James W.~ Rocco, MD, PhD
\textsuperscript{1} ; Matthew O. Old, MD \textsuperscript{1} ; Stephen
Y. Kang, MD\textsuperscript{1}

\par\null

\textbf{Author Affiliations}: 1 Department of Otolaryngology-Head \&
Neck Surgery, Division of Head \& Neck Oncology, The Ohio State
University, James Cancer Center and Solove Research Institute, Columbus,
OH, USA~ 2 Department of Otolaryngology-Head \& Neck Surgery and
Department of Genetics, Washington University School of Medicine, Ear,
Nose \& Throat Center, 4921 Parkway Place, 11th Floor, St. 14 Louis, MO
63110

Department of Otolaryngology-Head and Neck Surgery, Sunnybrook Health
Sciences Center, 16 2075 Bayview Avenue, Suite M1-102, Toronto, ON, M4N
3M5

*These authors contributed equally to this manuscript

Word Count: 3188

Funding: None

Conflicts of Interest: Antoine Eskander MD, ScM is a paid consultant for
Bristol-Myers and has received research support from Merck. ``None
declared'' for all remaining authors.

\textbf{Corresponding Author:}

Stephen Y. Kang, MD

Department of Otolaryngology--Head \& Neck Surgery

The James Cancer Hospital and Solove Research Institute

460 W 10th Avenue, 5th Floor

Columbus, OH 43210

Telephone: 614-685-6778 40 Fax: 614-293-7292 (Attn: Elaine Ortiz)

\href{mailto:Stephen.kang@osumc.edu}{\nolinkurl{Stephen.kang@osumc.edu}}
~

\par\null

\textbf{ABSTRACT}:~

\textbf{Background}: Pulmonary complications and infections frequently
affect patients with head and neck squamous cell carcinoma (HNSCC).
Common characteristics can predispose these patients to the development
of severe respiratory illness, which may be particularly relevant during
the~ 2019 coronavirus disease (COVID-19) pandemic.

\textbf{Methods:} A scoping review was performed to assess the impact of
pulmonary comorbidities and adverse respiratory outcomes in HNSCC
patients.

\textbf{Results}: Advanced age, history of tobacco and alcohol abuse,
and cardiopulmonary comorbidities are significant risk factors for the
development of adverse respiratory outcomes. Treatment~ toxicities from
radiation or chemoradiation therapy significantly increase these risks.

~\textbf{Conclusion}: Respiratory complications are a frequent cause of
morbidity and mortality among HNSCC patients, and the COVID-19 pandemic
may disproportionately affect this population.~ Interventions designed
to decrease smoking and alcohol use, improve oral hygiene, and
aggressively manage medical comorbidities are important to the long-term
management and health of these patients. ~

\subsubsection*{}

{\label{682229}}

\textbf{INTRODUCTION:}

The novel severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)
and associated 2019 coronavirus disease (COVID-19) pandemic has created
unique challenges for all healthcare providers and patients.
Complications resulting from COVID-19 infection are significant, and
immunocompromised patients, including cancer patients, appear
particularly susceptible. Limited data regarding the effect on
immunocompromised patients is available. Early reviews indicate that
severe respiratory events including pneumonia, need for mechanical
ventilation, intensive care unit (ICU) admission, and increased risk of
death may be experienced by a significant proportion of patients with
cancer.\textsuperscript{1,2}

Patients with head and neck squamous cell carcinoma (HNSCC) share common
characteristics, namely upper aerodigestive tumors, advanced age,
history of tobacco and alcohol abuse, and multiple cardiopulmonary
comorbidities which predispose to severe adverse respiratory outcomes.
Moreover, potential toxicities conferred by chemotherapy and radiation
therapy (RT) have been demonstrated to significantly increase rates of
dysphagia, aspiration, and pneumonia within this
population.\textsuperscript{3-6} Recent studies have sought to identify
sources of mortality and characterize long-term morbidity following
HNSCC treatment.\textsuperscript{6-8} An understanding of the various
adverse respiratory outcomes experienced among head and neck patients
following treatment, particularly during the COVID-19 pandemic, is
critical in treatment algorithms and medical decision-making.

A scoping review\textsuperscript{9} was performed to assess the impact
of pneumonia, aspiration pneumonitis, and other select viral and
bacterial infectious etiologies in patients with HNSCC. An appraisal of
risk factors, sources of competing mortality, pathophysiology, and
respiratory outcomes is also provided.

\subsection*{COVID-19 and Cancer}

{\label{595072}}

Cancer patients and immunocompromised hosts are particularly susceptible
to lung infection. The spectrum of various infectious etiologies ranges
widely from viral, bacterial, and fungal pathogens; however, patients'
unique treatment regimens and resulting immunologic deficits predispose
patients to particular infections.\textsuperscript{10-14} In the setting
of SARS-CoV-2 and the COVID-19 pandemic, increased emphasis is being
placed upon the treatment and protection of those with cancer who may be
at increased risk to develop severe and potentially life-threatening
respiratory infections.\textsuperscript{15}

Following the COVID-19 outbreak, the Italian National Institute of
Health established a surveillance program to collect information on all
patients with reverse transcriptase-polymerase chain reaction (RT-PCR)
confirmed SARS-CoV-2 infection. Among the Italian population, the
overall case fatality rate (CFR) was 7.2\% (1625 deaths/22,512 cases) as
of March 15, 2020.\textsuperscript{16} In a subsample of 355 patients,
20.3\% were noted to have active cancer in addition to multiple
comorbidities.\textsuperscript{17} Although a higher mean age (79.5 \selectlanguage{ngerman}±
8.1 years) was observed within this cohort, separate analyses have
reported a fatality rate approximating 20\% in patients aged 80 and
older.\textsuperscript{18} While CFR estimates and degrees of morbidity
may vary based upon testing strategies and population demographics,
cancer patients and elderly individuals appear at higher risk for
adverse outcomes from COVID-19 infection.

Early reports from China indicate that infected cancer patients have a
3.5 times higher risk of requiring ICU admission, mechanical
ventilation, or death compared to individuals without
cancer.\textsuperscript{1} Zhang et al. noted a strong association
between anti-cancer therapy and risk of severe effects from COVID-19
infection (HR 4.079, \emph{p} = 0.037) with 6 of 28 (21.4\%) COVID-19
patients having received immunosuppressive treatment within the last 14
days.\textsuperscript{2} In a separate prospective analysis of 1,590
patients with laboratory-confirmed COVID-19 disease, Liang et al.
discovered that 18 (1\%) patients had a history of cancer, a rate which
appears to be higher than the overall cancer incidence within the
Chinese population (0.29\%) according to 2015 epidemiologic
data.\textsuperscript{1} Of the 16 patients with a known oncologic
treatment, 25\% underwent surgery or received chemotherapy within the
past month. Compared to patients without cancer in this study, oncology
patients were older (mean 63.1 years vs. 48.7 years) and more likely to
have a history of smoking (22\%). Notably, these characteristics are
also shared among a large proportion of patients with HNSCC. In a
multivariable model, cancer history was associated with the highest risk
for severe events (OR 5.4, \emph{p} \textless{} 0.01). Older age, while
not significant, was the only risk factor associated with increased risk
for severe events in the cancer group (OR 1.43). Critics of this
analysis argue that exposure to an infectious source, rather than an
association with cancer, is the most important comorbid factor given
that 12 of the 18 patients had recovered from their initial cancer
treatments (e.g. surgery or chemotherapy) and were without obvious
immunosuppression.\textsuperscript{19} The response, by Wang and Zhang,
further notes that a higher median patient age of those with cancer
(63.1 vs. 48.7) in addition to increased comorbidities, remain
significant factors associated with worse COVID-19 outcomes. These
findings have been supported by prior COVID-19
analyses.\textsuperscript{20-22}

Although data regarding the impact of prior viral outbreaks on patients
with HNSCC is lacking, the decision to proceed with anti-cancer therapy,
including surgery, in the current context of COVID-19 should be
carefully considered given the risk of severe respiratory complications,
immunosuppression, and death within this cohort. A recent review of 34
asymptomatic patients who underwent various elective surgeries during
the COVID-19 incubation period exemplifies these
risks.\textsuperscript{23} All 34 patients went on to develop COVID-19
pneumonia shortly after surgery (median time to COVID-19 onset, 3.5
days), with 15 (44\%) requiring ICU admission. Ultimately, half of those
(7/15) patients died in the ICU. The risks of treatment delay and impact
on tumor progression should be carefully weighed given the potential for
devastating outcomes should surgery be pursued, even among asymptomatic
patients. Strategies to temporize tumor growth, such as induction
chemotherapy, may also predispose to severe COVID-19 complications
following immunosuppression. Further, treatment of HNSCC must be
balanced with the current local operational environment and resources to
achieve maximum patient and staff safety while minimizing morbidity.

\subsection*{Pulmonary Comorbidities in
HNSCC}

{\label{255021}}

Recently, an increased focus on competing causes of mortality among
patients with HNSCC has been observed, with respiratory causes of
particular interest.\textsuperscript{6,7,24} As advances in treatment
modalities improve disease control and survival, the estimated number of
HNSCC survivors is expected to increase.\textsuperscript{25} As a
result, clinicians will be required to consider longer-term treatment
effects and identify patients at highest risk for noncancer-related
morbidity and mortality. Multiple studies have shown increases in
adverse pulmonary outcomes among HNSCC patients compared to the general
population.\textsuperscript{3,6,8,26-30} The prevalence of respiratory
comorbidities in HNSCC patients approximates 10 to 15\%, nearly twice as
common as healthy controls.\textsuperscript{29,30} Moreover, a
significant percentage (21\%) of head and neck cancer patients have
moderate to severe comorbidities, second only to patients with lung
(40\%) and colorectal (25\%) cancer, with a significant relationship
between comorbidity severity and overall survival (\emph{p} \textless{}
0.0013).\textsuperscript{31}

An analysis by Rose et al. of 34,568 patients with nonmetastatic
squamous cell carcinoma identified through the Surveillance Epidemiology
and End Results (SEER) registry found that the most frequent causes of
noncancer mortality included cardiovascular disease (28.2\%), chronic
obstructive pulmonary disease (COPD, 8.5\%), and cerebrovascular disease
(5.6\%); lung cancer was the most common cause of second primary cancer
mortality (45.8\%) (Table 1).\textsuperscript{7} On multivariable
analysis, increased risk of noncancer mortality was associated with
higher age, black race, unmarried status, localized disease, and
nonsurgical treatment.\textsuperscript{7} Comparable results have been
reported through other analyses of competing mortality, examining
noncancer/comorbidity mortality and second primary cancer
mortality.\textsuperscript{8,26,27} In a population-based review of
23,494 patients, Shen et al. also found cardiovascular diseases, lung
cancer, COPD, and cerebrovascular disease to be the most frequent causes
of competing death with rates of 28.3\%, 10.4\%, 8.5\%, and 5.7\%,
respectively.\textsuperscript{8} These data demonstrate a
disproportionate impact on the pulmonary system and increasing mortality
that respiratory comorbidities may confer. Prior series have
demonstrated that a large proportion of patients continue to smoke both
during and after therapy. As expected, smokers have lower rates of
treatment response and poorer survival compared to non-smoking
counterparts, particularly if smoking continues during and after
treatment.\textsuperscript{32-38}

\subsection*{Susceptibility to Adverse Respiratory
Outcomes}

{\label{895984}}

Patients with HNSCC are at high risk for poor respiratory outcomes due
to underlying respiratory comorbidities. Kawakita et al. performed the
first population-based analysis designed to compare the incidence of
respiratory disease in HNSCC patients compared to the general
population. In a study of 1901 head and neck cancer patients within the
Utah Cancer Registry matched to 7796 noncancer patients, the authors
discovered that risks of respiratory infection (HR 1.63), COPD and
bronchiectasis (HR 2.65), and aspiration pneumonitis (HR 6.21) were
higher among head and neck cancer survivors, even after adjusting for
baseline smoking status.\textsuperscript{6} Interestingly, this
increased risk persisted more than 5 years after diagnosis
(\textbf{Table 1} ).\textsuperscript{6} Specifically, risks of COPD and
aspiration pneumonitis were more than 3-times higher among this
population. Moreover, the authors demonstrated that triple modality
therapy was the strongest risk factor for aspiration pneumonia. Age at
diagnosis, baseline body mass index, sex, smoking status, treatment
modality, primary tumor site, and stage were also identified as
significant risk factors for adverse respiratory outcomes.

The risk of severe pulmonary complications remains elevated in both the
immediate and long-term perioperative period. In a review of 3932
patients from a national database who underwent head and neck surgical
procedures, postoperative pneumonia was the most common medical
complication (3.26\%) and was associated with a mortality rate of 10.9\%
(OR for mortality, 4.4).\textsuperscript{39} Buitelaar et al. showed
comparable outcomes in a retrospective series of 469 patients undergoing
primary major head and neck ablation with cardiovascular (12\%) and
respiratory (11\%) complications being the most frequent. Significant
risk factors for pulmonary complications included preexisting pulmonary
disease, prior myocardial infarction, and ASA
grade.\textsuperscript{40}The incidence of new respiratory comorbidities
including pneumonia, asthma, and COPD has been found to be highest
within the first 6 to 12 months following treatment and remains nearly
two-fold higher compared to non-cancer patients. Similar findings were
reported by Baxi et al. who demonstrated that mortality from COPD,
pneumonia, and influenza continued to rise among HNSCC survivors who had
lived at least 3 years after diagnosis (Table 1).\textsuperscript{3}

These findings highlight several key considerations. First, early
dysphagia intervention programs may be useful in mitigating the adverse
functional impacts of surgery and radiation-induced fibrosis and prevent
aspiration pneumonitis.\textsuperscript{41} Second, adherence to smoking
cessation is critical to reducing the risk of recurrence, second primary
malignancies, and comorbid respiratory
diseases.\textsuperscript{42}Finally, in general, frequent disease
surveillance and multidisciplinary care should remain central to the
treatment and prevention of adverse pulmonary outcomes among higher risk
HNSCC survivors.

\subsection*{Pathophysiology of radiation and smoking-related
injury}

{\label{753038}}

\subsubsection*{\texorpdfstring{\emph{Radiation
Effects}}{Radiation Effects}}

{\label{299285}}

RT is one of the primary treatment modalities in HNSCC. RT is believed
to place HNSCC patients at increased risk of respiratory infection by
two mechanisms: 1. damage to respiratory tract cilia and 2. alteration
of the microbial landscape of the upper aerodigestive tract. RT to the
ciliated epithelium in the upper respiratory tract results in cellular
changes that negatively affect mucociliary clearance. In a
histopathological study of irradiated nasal mucosa in an animal model,
Ohashi et al. observed a progressive decline in the number of cilia as
epithelial metaplasia occurred several weeks after
radiation.\textsuperscript{43} At the end of 8 weeks, there was complete
loss of cilia.\textsuperscript{43} Similar histological findings of
epithelial change and ciliary loss have been observed in irradiated
larynx and nasopharynx tissue from
humans.\textsuperscript{44,45}Functional studies of cilia by measuring
nasal secretion transport times have shown significantly slower
transport in irradiated adults and children compared to healthy
controls.\textsuperscript{46,47} Many patients who have been treated
with radiation go on to develop chronic
sinusitis.\textsuperscript{44,48}

RT has also been shown to alter the microbial landscape of the oral
cavity and oropharynx. Radiation to the salivary glands causes reduction
in salivary flow and subsequent
xerostomia.\textsuperscript{49,50}Coinciding with decreased saliva in
patients treated with radiation for HNSCC, Brown et al. showed
significantly altered oral flora including increases in
\emph{Streptococcus mutans} , \emph{Lactobacillus} ,\emph{Candida} , and
\emph{Staphylococcus} .\textsuperscript{49}Additional studies on the
immunologic impact of these changes have shown alterations in the amount
of immunoglobulin A (IgA), which plays a principal role in the local
immune response, against virulent streptococcus species. Specifically,
there was an increase in IgA activity against \emph{Streptococcus
pneumoniae} , a common cause of lower and upper respiratory tract
infections, suggesting increased infections by this species in this
population.\textsuperscript{50} Thus, it is possible that the impact of
RT on oral flora may ultimately lead to downstream effects on the
microbiology of respiratory infections.

\subsubsection*{\texorpdfstring{\emph{Smoking
Effects}}{Smoking Effects}}

{\label{117864}}

The strong association between smoking and squamous cell carcinoma of
the head and neck is well established.\textsuperscript{51} Smoking
induces changes to the respiratory epithelium and immune system, which
ultimately puts patients at increased risk of developing respiratory
infections. ~Some of the changes that occur at the epithelial level
include cell transformation, respiratory barrier disruption, mucous
production, and transport alterations.\textsuperscript{52} Squamous
metaplasia occurs throughout the respiratory tract with an increase in
inflammatory cells and polymorphonuclear
leukocytes.\textsuperscript{52}Respiratory epithelium is normally quite
impermeable due to tight cell-to-cell junctions; however, these are
disrupted by smoke and leads to an increase in lung
permeability.\textsuperscript{52} Additionally, smoking alters
respiratory secretions and transport by increasing the volume of mucous
while also slowing mucociliary clearance in the upper and lower
respiratory pathways.\textsuperscript{52}

Smoking also alters cellular and humoral immune responses. In heavy
smokers, CD4 T cell populations are decreased while CD8 cells are
increased.\textsuperscript{53} CD4 cells play a role in stimulating
other immune cells including macrophages, B cells, and immunoglobulins;
therefore, lower numbers of CD4 cells in smokers may increase their
susceptibility to pulmonary infections.\textsuperscript{53}Additionally,
smokers have been found to have decreased neutrophil function, increased
immunosuppressive effects of macrophages, and decreased proinflammatory
cytokines.\textsuperscript{53} In the humoral immune system,
immunoglobulin populations of IgA, IgG, and IgM have all been found to
be lower than nonsmokers, thus predisposing to
infection.\textsuperscript{53}

\subsubsection*{Viral and Bacterial Pneumonia in
HNSCC}

{\label{269066}}

Risks of viral and bacterial pneumonia are increased among HNSCC
patients receiving chemotherapy and/or radiotherapy given the presence
of unique risk factors (e.g. depressed immune function, older age,
malnutrition, smoking and alcohol abuse, tumor location, and
comorbidities).\textsuperscript{8,26,54-56} Pulmonary viral infections
frequently occur in patients with impaired cellular immunity, with
cytomegalovirus and herpes group viruses being common
sources.\textsuperscript{11} Influenza, parainfluenza, respiratory
syncytial virus, rhinovirus, and adenovirus, are also recognized as
frequent pulmonary pathogens, particularly among immunocompromised
cancer patients with respiratory illness.\textsuperscript{10,12,57,58}

Bacterial co-infection and secondary insults in HNSCC patients can lead
to severe respiratory complications. Influenza-bacterial and
rhinovirus-pneumococcal pneumonia have been associated with increased
mortality.\textsuperscript{59} \emph{Streptococcus pneumoniae}
and\emph{Staphylococcus aureus} are also commonly observed, accounting
for as many as 35\% and 28\% of co-infections,
respectively.\textsuperscript{60} The type of bacterial pneumonia in
cancer patients depends on multiple factors including mechanism and
duration of the underlying immunologic defect and whether the infection
is community acquired or nosocomial.

In a review of healthcare-associated infections in HNSCC patients
treated with chemotherapy and/or RT, respiratory tract infections were
most common.\textsuperscript{55} \emph{Pseudomonas
aeruginosa}represented the majority of gram-negative organisms (49\%)
compared to gram-positive pathogens (35\%), where \emph{Staphylococcus
aureus}predominated. Smoking, malnutrition, and presence of a
tracheostomy tube are significant risk factors for nosocomial infections
in this population.\textsuperscript{55,61} A prospective analysis by
Panghal et al. revealed that HNC patients treated with chemoradiation
(CRT) are prone to oral cavity bacterial infections, especially
with\emph{Staphylococcus aureus} .\textsuperscript{62} Common oral
flora, including anaerobes, are commonly responsible for lower
respiratory infections, particularly in patients with dysphagia and
aspiration.\textsuperscript{63,64}

\subsubsection*{Aspiration Pneumonia and
Pneumonitis}

{\label{653426}}

Among HNSCC patients, the etiology of aspiration, pneumonia, and
pneumonitis is multifactorial and remains an important and often
under-recognized source of morbidity and mortality during and following
completion of treatment. In a retrospective analysis of 374 patients who
received organ preservation therapy for locally advanced HNSCC, risk
factors for aspiration pneumonia included poor oral hygiene, advanced
N-classification, inpatient treatment, and
hypoalbuminemia.\textsuperscript{65} Treatment breaks occurred far more
often in patients with aspiration pneumonia versus those without (36\%
vs. 3\%, respectively; \emph{p} \textless{} 0.01), which ultimately
affected survival (Table 1).\textsuperscript{65} Kawai et al. reported
similar findings and found that 21\% (65 of 305) of patients developed
pneumonia at a median of 161 days following treatment; chronic alcohol
consumption, poor oral hygiene, hypoalbuminemia, coexisting malignancies
(mainly esophageal and gastric cancer), and use of sleeping pills were
independent predictors.\textsuperscript{66} Rates of post-treatment
pneumonia range from 5 to 25\%, with concurrent CRT having the largest
influence on its development in most
studies.\textsuperscript{5,6,65-72}The sequela can be devastating with
30-day mortality rates of 20 to 30\%.\textsuperscript{24,73-75} The
range in incidence of pneumonia among studies could partly be explained
by patient demographics and length of follow up. In a retrospective
study of 15,894 Taiwanese patients with HNSCC by Chu et al., the authors
reported a lower incidence of pneumonia (5\%) within 90 days of RT
initiation.\textsuperscript{67} However, only 15\% of the cohort was
older than age 65, in contrast to studies with a higher proportions of
elderly patients.\textsuperscript{65-67}

While the risk of pneumonia in patients treated with CRT is
significantly elevated during and soon after treatment, this risk
continues to be elevated several years after
therapy.\textsuperscript{6,75} In an analysis of 3,513 patients, Xu et
al. found that nearly one-quarter of elderly patients developed
aspiration pneumonia within 5 years of CRT, with a 1 year and 5 year
cumulative incidence of 15.8\% and 23.8\% for patients with head and
neck malignancies, compared to 3.6\% and 8.7\% for noncancer controls,
respectively.\textsuperscript{75} A 42\% increased risk of death was
also observed (\emph{p} \textless{} 0.001) after controlling for
confounding factors. The authors showed that independent risk factors
for aspiration pneumonia included hypopharyngeal and nasopharyngeal
tumors, increased comorbidities, older age at diagnosis, and treatment
at a teaching hospital.

Notably, both of the studies from Xu et al.\textsuperscript{75} and Chu
et al.\textsuperscript{67} separately identified an increased risk of
aspiration pneumonia among patients receiving care at a teaching
institution. This finding likely reflects a higher concentration of
sicker patients with a higher degree of medical complexity at academic
teaching institutions. This is important to note as many of our HNSCC
population will undergo treatment at higher volume, academic centers
burdened by the COVID-19 pandemic.

\subsubsection*{Oral Hygiene}

{\label{258116}}

Poor oral hygiene has also been separately demonstrated as an
independent risk factor for the development of HNSCC and has been
associated with poorer overall survival in several
series.\textsuperscript{76-80} In addition to the mechanism of
pathogenic oral cavity and oropharyngeal bacteria in the development of
carcinoma and pneumonia, improved oral hygiene may also reduce
mortality. Decrease in mortality may be associated with decreased
pneumonia incidence and severity as well as the oncologic benefits
conferred through routine dental and oral cavity
surveillance.\textsuperscript{81-83} This further underscores the
importance of maintaining a healthy oral cavity, particularly in older
patients and those with previously treated
HNSCC.\textsuperscript{65,66,84} In all, increased attention should be
paid to modifiable risk factors including smoking, oral hygiene, and
nutrition status in order to mitigate aspiration risks.

\textbf{CONCLUSIONS} :

Primary COVID-19 infections are more likely to cause pulmonary
complications (and mortality) in men, older patients, those with
underlying prior or current cancers, and patients with concomitant lung
conditions (such as COPD and prior smoking). Patients with head and neck
cancer share similar attributes with those at highest risk for adverse
outcomes with COVID-19 infection.\textsuperscript{3-6} Toxicities from
CRT have been demonstrated to significantly increase rates of aspiration
and pneumonia within this cohort.\textsuperscript{6-8} HNSCC patients
are at increased risk for a variety of viral and bacterial pulmonary
infections, which depend upon the underlying mechanism of
immunosuppression. Interventions designed to decrease smoking and
alcohol use, improve oral hygiene, maximize nutrition, and treat
underlying medical comorbidities are central to the short and long-term
management of patients with HNSCC, especially during the COVID-19 era.

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1. Liang W, Guan W, Chen R, et al. Cancer patients in SARS-CoV-2
infection: a nationwide analysis in China. \emph{The Lancet
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2. Zhang L, Zhu F, Xie L, et al. Clinical characteristics of
COVID-19-infected cancer patients: A retrospective case study in three
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journal of the European Society for Medical Oncology.} 2020.

3. Baxi SS, Pinheiro LC, Patil SM, Pfister DG, Oeffinger KC, Elkin EB.
Causes of death in long-term survivors of head and neck
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4. Ferrier MB, Spuesens EB, Le Cessie S, Baatenburg de Jong RJ.
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