Laserterapy for Treatment of Oral Mucositis in

Patients with Head and Neck Cancer

Mariane de Lourdes Hernandes Martins Peres 
Medical School of São José do Rio Preto (FAMERP)
Eny Maria Goloni-Bertollo 
Medical School of São José do Rio Preto (FAMERP)
Erika Cristina Pavarino 
Medical School of São José do Rio Preto (FAMERP)
Mariah Cristina Antunes do Nascimento 
Medical School of São José do Rio Preto (FAMERP)
Marcia Maria Urbanin Castanhole-Nunes 
Medical School of São José do Rio Preto (FAMERP)
Ana Livia Silva Galbiatti-Dias 
(

analiviagalbiattidias@gmail.com
)
Medical School of São José do Rio Preto (FAMERP)

Research Article

Keywords: Laser Therapy, Stomatitis, Head and Neck Neoplasm

Posted Date: May 31st, 2023

DOI: https://doi.org/10.21203/rs.3.rs-2976830/v1

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Abstract
We investigate patients undergoing treatment for head and neck cancer (HNC) who had mucositis. The
most were male, literate, white, smokers and and alcoholics. Mucositis is associated with age over 65
years and alcohol (age:OR:0.52;CI:0.37 0.74;p = 0.000/Alcohol:OR:1.90;CI:1.25–2.87;p = 0.002). There is
significance for oropharyngeal site (OR:1.58;CI:1.02–2.43;p = 0.039), advanced clinical stage
(OR:2.39;CI:1.18–4.85;p = 0.016) and chemotherapy (OR:0.61;CI: 0.41–0.91;p = 0.016) with mucositis.
Grade 1 mucositis was present in 55.2% of patients, followed by 23.6% with grade 2 and 21.1% with
grade 3. A total of 57.09% of patients with mucositis were submitted to lasertherapy and the mean time
between the beginning of the treatment and the complaint of mucositis was six months; the mean time
between the complaint of mucositis and the beginning of lasertherapy was 33 days. Normality test
showed that there is a difference in the groups: mucositis Initial degree (K2 = 55.17;<0.000 1), number of
lasertherapy (K2 = 112.2; p < 0.0001) and current degree (K2 = 45.50; p < 0.0001). There was significance
of the initial and current degrees of mucositis (R = 0.41;p < 0.0001). Pearson's correlation was negative
between mucositis current degree and the number of lasertherapy (R= -0.1423;p = 0.072). Patients with
mucositis are male, with 65 years, white, literat, smokers and alcoholics. Oropharyngeal cancer and
advanced stage are more likely to develop mucositis in the casuistic evaluated. Lasertherapy is effective
in treatment of mucositis and can contribute to better life quality for patients with mucositis after
treatment for HNC.

INTRODUCTION
Head and neck cancer (HNC) occupies the fifth position in the list of the most frequent neoplasias with
incidence of 780.000 new cases and 450,000 deaths per year in worldwide. This tumor type corresponds
to tumors located in the oral cavity, sinuses, the three portions of the pharynx and the three portions of
the larynx [1]. The estimative of the National Cancer Institute for the triennium 2020–2022 are 11,180
cases in men and 4,010 in women in Brazil for oral cavity cancer, with an estimated risk of 10.69 new
cases per 100,000 men and, for women, corresponds to 3.71 for every 100 thousand women. For
laryngeal cancer, the number of new cases expected for Brazil in the 2020–2022 period is 6,470 in men
and 1,180 in women. The estimated risk will be 6.20 new cases per 100,000 men and 1.06 new cases per
100,000 women [2].

The treatment option for HNC is defined according to stage of the disease, anatomical location and
surgical accessibility and may consist of surgery, radiotherapy and/or chemotherapy, used in
combination or isolated [3] [4] [5]. The most common side effects are nausea, vomiting, diarrhea,
increased susceptibility to infection, anemia, hair loss, fatigue, numbness in hands and feet, hearing loss,
kidney damage, bleeding problems, malaise, dizziness and mucositis [6].

Mucositis is an inflammatory alteration in the mucosa that appears in about 40 percent of patients who
are undergoing chemotherapy or radiotherapy and cause discomfort/pain and can change the nutritional
health of patients affecting directly and negatively in cancer treatment, as it can causes interruption of

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the treatment [7] [8] [9] [10] [11] [12]. It is classified according to the World Health Organization (WHO) into
four degrees of severity; Grade 0 (no changes), Grade 1 (erythema, irritation, pain), Grade 2 (erythema,
ulcers, solid diet), Grade 3 (ulcers, liquid diet), and Grade 4 (inability to eat) [8] [12] [13].

Despite studies to establish a proactive and therapeutic approach to oral mucositis, the treatment is still
essentially palliative, based on the use of topical anesthetics, anti-inflammatory drugs, topical and
systemic antimicrobial agents when necessary [10] [14]. However, studies have demonstrated that the
utilization of low power laserterapy can be effective in the prevention and treatment of oral mucositis or
applied to existing mucositis deficiencies to accelerate the healing process of the lesion, in order to
improve the quality [11] [12] [13] [14] [15]. It acts by generating biological effects through photophysical
and biochemical processes, increasing cellular metabolism. It stimulates mitochondrial activity, thus
presenting an anti-inflammatory, analgesic and also mucosal healing action [16].

Laser teraphy is an extension of light, which has projections stimulated by radiation, which have their
own characteristics in order to reduce or prevent the lesion [17]. Several studies have investigated the
potential benefit of low-level laser for the prevention and treatment of oral mucositis [3] [18] [19] [20] [21]
[22]. The present study aims to investigate the epidemiological profile of patients who presented
mucositis after treatment for HNC; to verify the association of clinical parameters with the development
of mucositis, in addition to verifying the therapeutic efficacy of Laser Therapy in improving mucositis.

METHODOLOGY
The study was approved by the Ethics Committee in Research with Human Beings of the Faculty of
Medicine of São José do Rio Preto, in accordance with CNS Resolution No. 466 of 2012 and CNS
Operational Standard No. 001 of 2013.

This is a cross-sectional, observational, descriptive study describing a population of head and neck
patients undergoing chemotherapy from 2015 to 2020 at a University Hospital. All data from the present
study were obtained through analysis of medical records.

This is a retrospective study that describes a population of patients with head and neck cancer from
2016 to 2020 at a University Hospital. Exploratory field research, with the purpose of evaluating the
effectiveness of laser therapy in the treatment of mucositis in patients with head and neck cancer. All
data in the present study were obtained through analysis of medical records. For the composition of the
sample, patients undergoing treatment for head and neck cancer and who during the study period met the
eligibility criteria were selected: Patients of both sexes, over 18 years old, undergoing oncological
treatment, who had mucositis lesions .

From the selected sample, a retrospective analysis of the medical records was carried out. The analysis
sought data such as: patient identification and sociodemographic data (gender, age, education,
occupation, marital status and risk factors), clinical data, primary site of the tumor, tumor stage, presence
of metastasis, stage cancer clinic, type of treatment, date of initiation of treatment) and dental clinical
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data (time between the beginning of treatment and the onset of the mucositis lesion, time between the
onset of mucositis and the beginning of laser application, number of sessions types of laser therapy used
and clinical outcome of mucositis after laser therapy. The information collected was guaranteed secrecy,
which ensures the privacy and anonymity of the subjects regarding the confidential data involved in the
research.

Based on the information obtained from the medical records, a descriptive statistical analysis, frequency
tables and cross tables were performed, with the objective of verifying aspects relevant to the research.
The collected data were analyzed using the statistical programs MiniTAB (version 14.0), GraphPad Instat
3.10 (2009) and Microsoft Excel (2016). Descriptive statistical analysis was performed based on
calculations of measures of central tendency, dispersion and frequency counts. Frequency comparisons
were performed using Pearson's Chi-square Test and Multiple Logistic Regression, with a p value ≤ 0.05
considered statistically significant and the results are presented as Odds Ratio (OR) and confidence
intervals of 95% (CI 95%). Odds Ratio was used for risk analysis.

Multiple Logistic Regression was used to verify demographic and clinical variables. The construction of
the demographic statistical analysis spreadsheet was carried out considering: Patients with mucositis
(reference: patients without mucositis), gender (reference: female), race (reference: non-white), literacy
level (reference: literate), habit smoker (reference: non-smokers) and alcoholic habit (reference: non-
alcoholics), using the MiniTab program for Windows (Version 14.0).

Regarding the construction of the statistical analysis of the clinical variables, the following were
considered: primary tumor site, oral cavity (reference: other), oropharynx (reference: other), hypopharynx
(reference: other), nasopharynx (reference: other), nasal cavity (reference: other). other), larynx (reference:
other), occult primary site (reference: other), T3, T4 (reference: Tis, T0, T1 and T2), N1, N2, N3 (reference:
N0), M1 (reference: M0 ) and III/IV (reference: I/II) and type of treatment, considering chemotherapy
(reference: other), radiotherapy (reference: other), chemotherapy/radiotherapy (reference: other),
surgery/chemotherapy/radiotherapy (reference: other), surgery/radiotherapy (reference: other), and
surgery/chemotherapy (reference: other). For the analysis of the correlation between the degree of
mucositis, number of laser applications and current degree of mucositis, the D'Agostino Normality Test
and correlation between Pearson's variables were verified using the Statistical Program GraphPad 8.0.

RESULTS
A total, 586 medical records of patients diagnosed with head and neck cancer were analyzed. Of these,
282 (48.1%) had mucositis during or after cancer treatment and 304 (51.8%) did not have mucositis. The
results regarding sociodemographic and clinical variables of patients with head and neck cancer are
described in Tables 1 and 2, respectively.

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 Table 1
Distribution in Odds Ratio (OR) of the presence of mucositis and demographic variables related to head
and neck cancer (age, sex, race, education, smoking and alcohol consumption).
Variable Patients with mucositis Patients witout mucositis OR (IC 95%) P value

  Patients (n = 282) Patients (n = 304)    

  n (%) n (%)    

Age        

< 65 153 (54.2) 116 (38.1) 1.00 (Ref)  

≥ 65 129 (45.7) 188 (61.8) 0.52 (0.37-0,74) < 0,05*

Gender        

Female 45 (15.9) 50 (16.4) 1.00 (Ref)  

Male 237 (84.0) 254 (83.5) 0.86 (0.53–1.40) 0.543

Skin Color        

No-White 27 (9.57) 40 (13.1) 1.00 (Ref)  

White 255 (90.4) 264 (86.8) 0.61 (0.36–1.05) 0.074

literacy level        

Literate 260 (92.1) 266 (87.5) 1.00 (Ref)  

Iliterate 22 (7.80) 38 (12.5) 0.71 (0.40–1.25) 0.231

Smoking habit        

No 56 (19.8) 65 (21.3) 1.00 (Ref)  

Yes 226 (80.1) 239 (78.6) 0.80 (0.49–1.31) 0.377

Etilist habit        

No 92 (32.6) 137 (45.0) 1.00 (Ref)  

Yes 190 (67.3) 167 (54.9) 1.90 (1.25–2.87) 0.002*

OR data were adjusted for age, gender, skin color, literacy level, smoking and drinking habits. p < 0.05 was
considered significant in the multiple logistic regression model.

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 Table 2
Odds Ratio (OR) distribution of mucositis and clinical variables related to head and neck cancer
Variables Patients with Patients witout OR (IC 95%) P
mucositis mucositis value

  Patients (n = 282) Patients (n = 304)    

  n (%) n (%)    

Primary site        

Oral cavity 124 (43.9) 112 (36.8) 1.35 (0.97– 0.074

1.88)

Larinx 60 (21.2) 93 (30.5) 1.62 (0.99– 0.067

1.65)

Oropharinx 58 (20.5) 43 (14.1) 1.58 (1.02– 0.039*

2.43)

Hipofarinx 22 (7.8) 29 (9.53) 0.81 (0.45– 0,464

1.44)

Nasal cavity 7 (2.4) 15 (4.93) 0.49 (0.20– 0.128

1.23)

Nasofarinx 7 (2.4) 6 (1.97) 1.27 (0.42– 0.672

3.82)

Hidden Primary Site 4 (1.4) 6 (1.97) 0.61 (0.18– 0.438

2.12)

Tumoral stage        

Tis/ T0/ T1/ T2 123 (43.6) 165 (54.2) 1.00 (Ref)  

T3/T4 159 (56.3) 139 (45.7) 0.86 (0.46– 0.645

1.62)

Nodal stage        

N0 177 (62.7) 212 (69.7) 1.00 (Ref)  

N1/N2/N3 105 (37.2) 92 (30.2) 0.69 (0.47– 0.062

1.02)

Metastasis        

M0 282 (100.0) 302 (99.3) 1.00 (Ref)  

M1 0 (0) 2 (0.65) 0.00 (0.00 – 0.999

*)

AJCC clinical stage        

I/II 97 (34.3) 145 (47.6) 1.00 (Ref)  

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 Variables Patients with Patients witout OR (IC 95%) P
mucositis mucositis value

  Patients (n = 282) Patients (n = 304)    

  n (%) n (%)    

III/IV 185 (65.6) 159 (52.3) 2.39 (1.18– 0.016*

4.85)

Treatment        

Chemoterapy and 150 (53.1) 105 (34.5) 1.33 (0.96– 0,087

radiotherapy 1.85)

Radiotherapy 53 (18.7) 68 (22.3) 0.78 (0.52– 0,240

1.18)

Chemoterapy 50 (17.7) 79 (25.9) 0.61 (0.41– 0,016*

0,91)

Surgery/Chemoterapy and 13 (4.6) 1 (0.32) 1.75 (0.56– 0,333

radiotherapy 5.40)

Surgery/radiotherapy 11 (3.9) 10 (3.2) 1.19 (0.50– 0,691

2.85)

Surgery/ Chemoterapy 5 (1.7) 41 (13.4) 0.81 (0.18– 0,779

3.64)

OR data were adjusted for primary site, tumor stage, nodal stage, metastasis stage, and AJCC clinical
stage. p < 0.200 was considered significant in the chi-square test.

Of the 282 patients undergoing treatment who had oral mucositis, a total of 57.09% (n = 161) underwent
low-level laser application to improve the side effect. The most frequent grade of mucositis was grade 1
(n = 89; 55.2%), followed by grade 2 (n = 38; 23.6%) and grade 3 (n = 34; 21.2%).

The mean time between the start of cancer treatment and the complaint of mucositis was six months (± 
12 months) (Fig. 1) and the mean time between the complaint of mucositis and the first laser application
was 33 days (± 47 days). (Fig. 2)

The average number of laser therapy sessions in the patients was eight applications. Regarding the
clinical outcome of mucositis (initial and current) with the number of laser therapy sessions. The
Normality test showed that there is a significant difference (p < 0.05) in the groups: Initial mucositis grade
(K2 = 55.17; p < 0.0001), number of laser therapy sessions (K2 = 112.2; p < 0.0001) and current mucositis
grade (K2 = 45.50; p < 0.0001). When performing the correlation and comparison of the initial and current
degrees of mucositis, there was statistical significance (R = 0.41; p < 0.0001), that is, there was an
improvement in the clinical outcome of the patients after the laser therapy sessions. Pearson's correlation
was negative between the current degree of mucositis and the number of laser therapy sessions (R=
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-0.1423; p = 0.072). Although the result did not show significance, there is a negative correlation between
the two groups, that is, the greater the number of laser therapy sessions, the better the clinical outcome of
the current mucositis. (Fig. 3)

DISCUSSION
In the present study, it was possible to evaluate 586 patients with head and neck cancer treated from
January 2016 to May 2020 at a university hospital in the northwest of the State of São Paulo. Of these,
48.1% had the mucositis side effect after treatment for head and neck cancer. It was found that patients
with HNC aged 65 years or older are less likely to have mucositis, corroborating data from the literature
that show that mucositis has a higher incidence in younger patients. This fact can be explained because
younger patients have a greater capacity for epithelial cell mitotic activity compared to older patients, in
whom the mitotic activity of epithelial cells is reduced. In addition, studies show that the relationship
between the rate of cell duplication and the severity of the damage caused by some type of treatment
suggests that the greater the age, the lower the severity of side effects [17] [23]. Our study also found that
patients with an alcohol habit are more susceptible to the onset of mucositis. Alcohol intake can damage
your teeth and contribute to a variety of oral diseases, including stomatitis, malnutrition and mucositis.
The knowledge these relationships will allow the dentist to question patients about their social habits and
provide guidance to encourage a healthy lifestyle [24]. Patients with HNC who smoke and drink alcohol
are more likely to have mucositis, and other factors such as age, sex, genetic predisposition, oral health
and hygiene, oral microflora, normality and salivary secretory function and diet can influence the
appearance of mucositis.[3] [11] [12] [13] [14] [15] [16] [17] [18] [19] [20] [21] [22] [25] [26].

Regarding the profile and sociodemographic data of patients with oral mucositis, it was observed that the
majority are male, aged 65 or over less, white skin color, literate and with alcohol and tobacco habits,
corroborating data from the literature [17] [26] [27] [28]. Oral mucositis may arise after treatment for the
various types of cancer due to the rupture of the epithelial cells lining the gastrointestinal tract that divide
rapidly leaving the mucosal tissue open to ulceration and infection23. There are individuals who are more
susceptible to the appearance of mucositis and factors related to the treatment, such as type of radiation,
drug used and daily doses are generally related to the effects on normal tissues and the appearance of
mucositis. Age, clinical and dental condition are factors inherent to each patient, which have been
associated with the presence of oral mucositis [24] [26] [27] [29] [30].

Head and neck cancer can be occur three to five times more often in men than in women. Low education,
poverty, and social disadvantage are important prognostic considerations for HNC patients. As a result, a
lower socioeconomic level and black race have a worse prognosis, however, these differences are still not
fully explained by demographic data and comorbidities regardless of the presence of mucositis [31] [32].

Regarding clinical parameters, our study demonstrated that patients with oropharyngeal primary site are
more likely to develop mucositis than patients with other primary sites 26. The oropharynx includes the
base of the tongue (the back of the tongue), the soft palate, the tonsils and the pillars and the lateral and

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posterior walls of the throat and, according to data in the literature, injuries diagnosed after treatment of
head and neck cancer compromise in its the oropharynx, as well as our study. Furthermore, tumors
located in the oropharynx region had worse survival rates [28] [33].

Our study also confirmed that patients with head and neck cancer at a more advanced clinical stage
(III/IV) are more likely to develop mucositis. Data show that patients with advanced cancer have a variety
of oral problems and these can have a significant impact on physical well-being, social and
psychological can limit the daily activities of these patients, therefore, an initial dental evaluation is
extremely important [34]

Regarding the treatment, our results showed that chemotherapy treatment was significantly associated
with the appearance of mucositis, as well as the studies by Menezes et al. (2014)[35] Santos et al.(2019)
[36] and Schirmer et al. ( 2012) [29] found that each cycle of chemotherapy implies a risk of mucositis
and patients who presented this condition in a cycle are at greater risk of re-presenting it in subsequent
cycles, respectively. This fact occurs due to the adverse effects caused by the chemotherapy treatment,
because in the oral cavity, the chemotherapy does not act selectively for neoplastic cells, also affecting
the lining epithelium of the mucosa of the oral cavity Cacelli et al., 2009 [28]. In chemotherapy, the
medication acts on cells with neoplastic characteristics, that is, cells that have the characteristic of
constant mitosis.

According to Sonis et al. (2004) [37], mucositis is described as a complex biological process, which can
be divided into five sequential phases characterized as initiation, signaling, amplification, ulceration with
inflammation and healing. In the initiation phase, signs and symptoms common to oral mucositis are still
unnoticed. The signaling (message generation phase) and amplification phases follow. The ulceration
phase with inflammation is characterized by the loss of mucosal integrity, resulting in all the symptoms
of oral mucositis. At this stage, there is a risk of opportunistic infections due to the access of bacteria,
fungi or viruses to deeper tissues, which consequently increases the chances of pronounced systemic
infections and even septic shock, representing the most pronounced form of the pathology. In the end, in
healing, proliferation, differentiation and migration of epithelial cells are observed. It occurs through
increased release of growth factors, increased neovascularization and collagen formation, causing the
reestablishment of mucosal integrity [17] [26].

The World Health Organization (WHO) classifies oral mucositis into five different grades: grade 0 -
indicates absence of the disease; grade I - presence of painless ulcer, erythema or mild sensitivity; grade II
- presence of painful erythema, edema or ulcers that do not interfere with the patient's swallowing; grade
III –existence of ulcers that interfere with the patient's ability to ingest solid foods; and grade IV -
symptoms so severe that the patient requires enteral or parenteral[17] [38].

Regarding the development of mucositis, after starting treatment, the average time of the complaint was
six months and grade 1 was the most frequent, corroborating with other studies, in which mucositis
manifests itself during the first and second week of chemotherapy sessions. It may appear at the
beginning of treatment and is generally characterized as an area of ​generalized redness that is replaced
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by regions of ulceration covered by a pseudomembrane, which may be generalized or localized and,
generally, colonized by bacteria. Mucositis lesions usually appear three to 15 days after the start of
treatment, being noticeable earlier in patients undergoing chemotherapy. Mucositis induced by
chemotherapy usually lasts for a week and resolves within 21 days after administration of chemotherapy.
Each chemotherapy cycle implies a risk of mucositis and those patients who presented this condition in
one cycle are at greater risk of re-presenting it in subsequent cycles [17] [26] [35].

Treatmen risk factors also include the specific sites and surface area/volume of the irradiated head and
neck mucosa, the radiation dose accumulation rate, the specific concomitant chemotherapy agent used
and its dose schedules [26] [35].

More serious problems can be triggered by mucositis, as the ulcerated oral epithelium allows the entry of
microorganisms into the oral cavity, which can cause local and systemic infections. As a result of oral
pain, patients tend to become dehydrated and malnourished [26] [35] .

Our study showed that after complaining of mucositis, the mean time to start treatment with laser
therapy was ± 47 days. We know that the use of low-intensity laser has been successful in many cases,
due to its stimulating actions on cell activity, the release of growth factors by macrophages, the
proliferation of keratinocytes and angiogenesis. Such effects may accelerate the wound healing process
due, in part, to the reduction in the duration of acute inflammation, resulting in faster tissue repair [17] [38]
.

Low intensity laser is one of the therapeutic methods used to prevent or treat oral mucositis, this therapy
has the ability to induce various biological effects, such as analgesia and modulation of the
inflammatory process. It involves photobiomodulation of cell metabolism with intense but non-
destructive light irradiation. The laser acts on cellular enzymes that increase the oxidative chain
mechanism in mitochondria (cellular power), which results in an increase in the production of adenosine
triphosphate (ATP), producing intracellular reactive oxygen species. Many diferente wavelengths act on
different tissue levels. The laser also stimulates the capacity for proliferation and migration of
fibroblasts, collagen synthesis and angiogenesis, favoring tissue repair. In addition, an analgesic effect
was attributed to the laser due to the depolarization of cell membranes, boost of cyclooxygenase activity
and increased production of endorphins. [26] [39].

Regarding the clinical outcome and treatment of mucositis with laser therapy, more than 50% of the
patients underwent low-level laser application, and the average obtained was eight laser applications.
The present study showed a significant decrease in the degree of mucositis after laser therapy, showing
the effectiveness of low-intensity laser, as patients had a favorable evolution of their signs and
symptoms[12] [30] [36]. In the study by Rezk-Allah et al.10 (2019) [12] there was a 48% decrease in grade
3 mucositis before treatment with 0% low-level laser, after treatment. The study by Cavalcanti et al.
(2018) [26] showed that most lesions remitted within seven days or had no recurrence, which proves the
effectiveness of low-intensity laser in the prevention and treatment of mucositis and its importance as an
additional adjuvant method in the routine of patients undergoing antineoplastic treatment.
Page 10/17
Thefore it is necessary to establish educational, preventive and curative strategies aimed at oral health
before, during and after treatment to solve and / or decrease the discomfort of patients [3] [26] [8] .

CONCLUSION
The epidemiological profile of patients undergoing treatment for head and neck cancer who presented
mucositis after treatment in the casuistic evaluated are male, with a mean age of 65 years, white, literate,
smokers and drinkers. Patients with oropharyngeal primary site and advanced stage for head and neck
cancer are more likely to develop mucositis. Chemotherapy treatment is significantly associated with the
appearance of mucositis. Initial mucositis presents grade 1 as the most frequent, with the average time
between the start of treatment and the complaint of mucositis being ± six months and the time between
the complaint of mucositis and the beginning of laser therapy being ± 33 days. The mean number of
laser therapy sessions casuistic evaluated is eight times and, after the laser therapy sessions, there is an
improvement in the clinical evolution of the mucositis. Laser therapy is significantly effective in the
clinical outcome of mucositis.

Declarations
Conflicts of Interest

The authors declare no conflicts of interest regarding the publication of this paper.

Acknowledgments

Medical School of São José do Rio Preto (FAMERP)

Ethics approval statement: Accordance statement with a named standard that your research was carried
out in line with Ethics Committee for Research with Human Beings of the Medical School of São José do
Rio Preto (FAMERP), in accordance with CNS Resolution No. 466 of 2012 and Operational Norm No. 001
of 2013 of the CNS.

Author Contributions Statement

Study concept and design: Mariane, Ana Livia, Eny and Erika

Data acquision: Mariane and Mariah

Methdology: Mariane, Mariah and Marcia

Manuscript preparation: Mariane,Marcia and Mariah

Manuscript rewiew: Ana Livia, Eny and Erika

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Figures
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Figure 1

Time between the date of diagnosis and the appearance of mucositis in patients with head and neck
cancer (in months).

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Figure 2

Time between the onset of mucositis and the beginning of laser therapy in patients with head and neck
cancer (in days).

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Figure 3

Pearson's correlation of the clinical outcome of mucositis in relation to the initial (A) and current degree
(B) of mucositis in the patients.

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