Original Research

Stomatology

Oral cancer analysis in a Brazilian

city: interval between diagnosis
and treatment

Beatriz Afonso CHILITI(a) Abstract: In Brazil, there are 15,500 incident cases of oral cancer (OC)
Wladimir Gushiken de yearly, and early diagnosis is the main factor for a better prognosis. The
CAMPOS(a) objective of this study was to analyze the interval between the first
Camila de Barros GALLO(a) symptoms, diagnosis, and treatment commencement in patients with
Celso Augusto LEMOS(a) malignant neoplasms in the oral cavity, lips, and oropharynx diagnosed
between 2012–2018. Epidemiological data, duration, history of lesion,
(a)
Universidade de São Paulo – USP, School of
biopsy, and diagnosis were obtained from the medical records of these
Dentistry, Department of Stomatology, São patients, who were then contacted via phone and interviewed about
Paulo, SP, Brazil. their oncological treatment. The results were analyzed and expressed
as mean, median, and SD. Of 184 patients, most were men, white,
50–69 years old, smokers, and alcoholics. The longest interval was
between the first symptoms and first evaluation (a mean of 275 days).
The interval between the first appointment and the result of the biopsy
was shorter (13 days). Among the 85 patients interviewed, the interval
between the diagnosis, the first appointment at the oncological clinic
and treatment commencement was 55 days (mean) for patients using
private-sector health care, and 96 days (mean) for patients using public
health care. The interval was twice as long in the public health system
compared with the private sector, which highlights the inequality of
access to health care in Brazil. Delay in seeking health care after the
appearance of the first symptoms remains a major problem.
Declaration of Interests: The authors
certify that they have no commercial or
associative interest that represents a conflict Keywords: Mouth Neoplasms; Early Detection of Cancer; Delayed
of interest in connection with the manuscript. Diagnosis; Time-to-Treatment.

Corresponding Author: Introduction

Beatriz Afonso Chiliti
E-mail: [email protected]
Cancer is among the leading causes of death, second only to
cardiovascular diseases.1 Globally, OC accounted for approximately
150,000 deaths in 2015.2
https://doi.org/10.1590/1807-3107bor-2022.vol36.0073
In Brazil, OC is the 5th most common cancer in men (11,200 cases/year)
and the 12th most common cancer in women (3,500 cases/years).1 In 2016,
it was responsible for 0.46% of deaths in the country (6,088 people)1. In
Brazil’s southeast region, it is the 4th most common cancer in men and
the 13th most common cancer in women.1
Submitted: Mar 20, 2021
OC are malignant neoplasms of the tongue, gums, floor of the mouth,
Accepted for publication: September 9, 2021
Last revision: September 17, 2021 palate, and other unspecified mouth parts.3 OC has a multifactorial etiology,
with risk factors, such as smoking, excessive alcohol consumption, and

Braz. Oral Res. 2022;36:e073 1

 Oral cancer analysis in a Brazilian city: interval between diagnosis and treatment

exposure to solar radiation. Initially, the lesions are In the phone interview, patients were asked to
asymptomatic, which may account for the long time answer the following questionnaire, with their medical
it takes patients to seek professional care.1 data available in their hands, to avoid memory bias:
The risk of death from head and neck tumors a. When was the first appointment at the
increases with the waiting time between diagnosis oncological clinic?
and treatment.4 In approximately 4 weeks of waiting b. Where did you have the treatment? Public or
for radiotherapy, most patients develop significant private health care?
signs of tumor progression.5 So, the interval between c. When did you start treatment?
diagnosis and treatment is a determinant of the d. What was the proposed treatment?
prognosis of the disease. For patients who died, the questionnaire was
In Brazil, studies were published evaluating the answered by family members who agreed to
interval between the first sign or detection of the participate in the study. The questions were the
disease and the search for a professional. The interval same, but two more were added:
ranged from 18 days to 10 years.6,7,8 The mean interval a. What was the date of death?
ranged 197.88–2409 days. In all the studies, the interval b. What was the cause of death?
between the detection of the first symptom by the The data were divided into four moments: The
patient and the search for a professional was greater interval between the first sign/symptom of the lesion
than the interval between diagnosis and treatment. and the first appointment at the stomatology clinic,
In Brazil, in 2012, the 60-day law was established, the interval between the first appointment and the
whereby a patient diagnosed with malignant neoplasia biopsy result, the interval between the biopsy result
has the right to undergo the first treatment in the and the first appointment at the referred clinic, and
public health care system, within 60 days.10 the interval between the first appointment at the
The objective of this study was to evaluate the oncological clinic and treatment commencement.
interval between diagnosis and treatment of patients Whether the interval between the first appointment
diagnosed with cancer in the oral cavity, lips, and and treatment commencement satisfied the 60-day
oropharynx, evaluated at our stomatology clinic. law was also assessed.
All medical records accessed by the study had
Methodology authorization to use patient’s information for research
and all contacted patients agreed to participate.
Patients diagnosed with cancer in the oral cavity,
lips, and oropharynx at our stomatology clinic between Inclusion criteria
2012–2018 were selected. Patients were contacted Patients diagnosed and treated for cancer in the
via phone and, after accepting to participate in the oral cavity, lips, and oropharynx, with ICD-10 ranging
research and authorizing the recording of the call, an from 0.0 to 10.9, and were willing to participate in
interview was conducted. This study was approved the study.
by the Research Ethics Committee under reference
number 12482919.5.0000.0075. Exclusion criteria
The following were evaluated: the patient’s age, Patients diagnosed with potentially malignant
sex, race, predisposing habits (smoking, consumption disorders such as leukoplakias. Patients with
of alcoholic beverages), systemic diseases, first inconsistency/missing data in their medical records.
professional they looked for, history of the lesion
(first signs and symptoms), duration of the lesion, Results
staging of the lesion, location of the lesion, date of
first appointment, date of biopsy, date of biopsy result, Between 2012–2018, 209 patients were diagnosed
and date of referral. These data were retrieved from with cancer in the oral cavity, lips, and oropharynx
the patients’ medical records. at the School of Dentistry of the University of São

2 Braz. Oral Res. 2022;36:e073

 Chiliti BA, Campos WG, Gallo CB, Lemos CA

Table 1. Distribution of patients according to epidemiological

Paulo. Of these, 184 medical records were available data and medical history.
for evaluation and were included in the study, with Variables n %
25 records excluded due to inconsistency/missing data. Age (years)
From the 184 cases included in the study, we were 0–49 29 16
50–69 107 58
able to contact 94 patients. Of these, 9 patients refused
> 70 48 26
to participate in the study, while 85 agreed. Of the Sex
85 cases, 58 were the patients themselves, while in Male 121 66
27 cases, a family member was interviewed, because Female 63 34
Race
the patient had died. White 136 74
According to the epidemiological data in Table 1, Black 42 23
more than half of the patients were aged between Asian 6 3
50–69 years (58%), male (66%), white (74%), and were Habits
Smoking/alcohol 96 52
exposed to smoking and alcohol (52%). Most of the Nonsmoker/alcohol 44 24
patients looked for a private care dentist first (60%); Only smoking 35 19
the most frequent location of the cancer was the Only alcohol 9 5
First professional appointment
tongue (29%), the first sign was ulcer (54%), and the
Private care dentist 109 60
predominant diagnosis was squamous cell carcinoma Public care dentist 31 17
(88%). Of the 85 participants, most were treated with Physician 24 13
only surgery (41%). As regards the stage at the time Stomatology clinic 19 10
Location
of diagnosis, patients were predominantly in stage
Tongue 54 29
III (29.89%) (Figure). Floor of mouth 32 17
To assess the interval between diagnosis and Mandible 29 16
treatment, the information was divided into Palate 23 13
Lip 19 10
4 moments: T1 is the interval in days between the
Maxilla 17 9
first sign/symptom and the first appointment at the Buccal mucosa 7 4
stomatology clinic, T2 is the interval in days between Oropharynx 3 2
the first appointment and the result of the biopsy, First signs and symptoms
Ulcer 54 29
T3 the interval in days between the result of the
Nuisance / pain / burning 42 23
biopsy and the first appointment at the oncological Nodule 30 16
clinic and T4 the interval in days between the first Non healing oral aphthous ulcer 18 10
appointment at the oncological clinic and treatment Asymptomatic Growth 18 10
White and / or red lesion 18 10
commencement. T1 and T2 were calculated using
Verrucous lesion 4 2
the average time found in the medical records. Of Diagnosis
the 184 medical records, 8 were excluded due to Squamous cell carcinoma 162 88
primary diagnosis of leukoplakia, 2 were excluded Mucoepidermoid carcinoma 8 4
Adenoid Cystic Carcinoma 5 2
from T1 and 4 were excluded from T2 due to missing Verrucous Carcinoma 4 2
data. Whereas T3 and T4 were calculated using the Metastatic Carcinoma 2 1
average time reported by the 85 contacted study Basal-Cell carcinoma 1 1
participants after consulting their medical records; Clear-Cell Carcinoma 1 1
Myoepithelial Carcinoma 1 1
11 were treated in private health care, 74 were treated Treatment
in public health care and 4 did not start the treatment. Surgery 35 41
Data are summarized in Table 2. Surgery and radiotherapy 22 26
Surgery, radiotherapy and chemotherapy 10 12
Patients took 275 days (mean) (SD = 526.6) to have
Radiotherapy and chemotherapy 10 12
their first appointment at the Stomatology clinic, Palliative treatment 4 5
which took 13 days (mean) (SD = 8.4) to diagnose Radiotherapy 3 3
these patients. Those treated in private health care Chemotherapy 1 1

Braz. Oral Res. 2022;36:e073 3

 Oral cancer analysis in a Brazilian city: interval between diagnosis and treatment

OC Stage
in 2018.1 At the University of São Paulo’s School of
4.3% Dentistry, the Stomatology clinic diagnoses these
and other oral lesions, being one of the largest public
20.7%
centers for oral diagnosis in São Paulo. Biopsies are
sent to the Histopathology Service of the institution,
Stage I facilitating the exchange of information between the
26.6% professionals involved.
Stage II
29.9% In this study, most patients were men, white, and
Stage III aged between 50 and 69 years, like other studies.4,6,8
Stage IV Most patients were smokers or alcoholics, both of
18.5%
which were risk factors for head and neck cancer,
Not identified
especially if combined. 5 However, 24% denied
smoking and drinking alcohol, which differs from
Figure. Distribution of patients according to OC stage at diagnosis. other studies.4,6,8 This can be due partly to the
corresponding diagnosis of salivary gland cancer,
such as mucoepidermoid carcinoma and adenoid
waited 19 (mean) days (SD = 23.7) to have their first cystic carcinoma, which has little relation to smoking
appointment at the treatment center and for 36 days or alcohol consumption.8
(mean) (SD = 33.6) to start their treatment. Patients Squamous cell carcinoma was the most prevalent
treated in the Brazilian public health care system type of carcinoma (diagnosed in 88% of cases), as in
waited for 33 days (mean) (SD = 30) to have their first other Brazilian studies.8,9 Squamous cell carcinoma
appointment at the treatment center and for 63 days represents 90% of OC, followed by mucoepidermoid
(mean) (SD = 46.8) to start the treatment. carcinoma and adenoid cystic carcinoma,11 which
Of the 27 patients who died, 21 died due to cancer corroborates the result obtained in the present study.
while 6 died due to other health issues not related to The longest interval was for the patient to seek
cancer. Of the patients who died due to cancer, 67% professional care at the Stomatology clinic since the
died within1 year of the diagnosis, 28% died 2 to first perception of the lesion (T1), as in many similar
3 years after diagnosis, and 5% in 4 to 5 years after studies.6,7,12-15 Waiting times for patients to be treated
diagnosis. About these patients, 48% were diagnosed after diagnosis, among studies conducted in Brazil,
in stage IV, 43% were diagnosed in stage III, and 9% ranged from 457 to 71,18 days, mean 64, 31 days.6-9,16
were diagnosed in stage I. Compared to a study from Denmark,14 where the
waiting times for patients to be treated was 25 days,
Discussion implying that the Brazilian health care system has to
improve, and initiate the treatment earlier.
Cancer in the oral cavity, lips and oropharynx in Almost half of the patients were diagnosed at an
Brazil is considered a public health problem, with early stage (I or II) (Figure). Scott et al.11 concluded
more than 1,200 new cases in the city of São Paulo that there may be no association between delayed

Table 2. Data of the time gap (in days) between the first symptom of the lesions, diagnosis and treatment of patients.
T1 T2 T3 T4
Variable
Mean Median SD n Mean Median SD n Mean Median SD n Mean Median SD n
Private 19 10 23.7 11 36 30 33.6 11
275 105 526.6 174 13 9.5 8.4 172
Public 33 20 30 74 63 60 46.8 70
T1 the time gap in days between the first sign/symptom and the first appointment at the stomatology clinic; T2 the time gap in days between
the first appointment and the result of the biopsy; T3 the time gap in days between the result of the biopsy and the first appointment at the
oncological clinic; T4 the time gap in days between the first appointment at the treatment center and the start of treatment.

4 Braz. Oral Res. 2022;36:e073

 Chiliti BA, Campos WG, Gallo CB, Lemos CA

diagnosis and the stage of the disease as in their Additionally, the present study demonstrates that
study, 27% of patients were diagnosed at the first the interval between diagnosis and treatment does not
appearance of signs and symptoms, but with an fit the 60-day law, established in 2012.10 The interval
advanced stage of disease; and 19% of patients with corresponded to a mean of 96 days for patients to be
late head and neck cancer diagnosis had early stages attended in public health care.
of the disease.15 This may be because some people With the delayed start of treatment, carcinoma may
in the early stages of head and neck cancer may be progress, increasing its stage, affecting treatment, and
asymptomatic.1 In this study, 18% of patients were worsening prognosis.6,7,13 According to Kowalski and
asymptomatic at the time of diagnosis. Carvalho,15 for an advanced case with stage III or IV
Regarding the delay related to professionals (T2), to become a case where treatment is not possible, the
the interval for diagnosis in this study was 13 days, time taken was from 1 to 23 months with a median of
with the same result as the study by Lyhne et al.14 and 3 months, and for these cases to progress to death, the
represents the best time for diagnosis compared to all time taken was from 1 to 21 months with a median
other studies. As for the delay in the health system of 4 months. Thus, both early diagnosis and access to
(T3 + T4), the largest interval was that of the present treatment are important. Measures must be taken to
study, similar to the result of Le Campion et al.8 decrease the interval between diagnosis and treatment
carried out in Alagoas, Brazil. commencement for these patients, thereby reducing
Although 20 years passed between the Costa morbidity and mortality due to OC.
and Migliorati6 study, in a similar study conducted It is a consensus that early diagnosis of cancer
in our institution, and the present study, there was has a better prognosis, compared to cases of late
an increase of approximately 10 days for the patient diagnosis. Nevertheless, some studies have not shown
to start the treatment after diagnosis. This time better survival rates, even with early diagnosis.17,18
is related to the procedures that the patient goes The difference between the results of the studies can
through in the oncological clinic before starting be justified by several factors, including the study
the treatment itself, such as redoing the histological design and memory bias.19,20 A study showed that even
and immunohistochemical analysis, imaging tests, the memory of recent events has limited reliability.21
and laboratory tests for treatment planning. To Therefore, memory bias is an important bias to be
improve this delay, it would be necessary to have considered, especially in studies retrospectively
an integration between the diagnosis and treatment evaluating patients who have undergone treatments. To
centers, as already explained in another study,7 mitigate memory bias, a combination of data collection
there is no need to redo the histological analysis, methods, combining prospective and retrospective
immunohistochemistry, and imaging tests already data is a feasible alternative.18 In this study, to reduce
done at the diagnostic center, hence, reducing the memory bias, we retrieved retrospective information
time in the pre-treatment. from the patients’ medical records, combined with
There was a big difference in the interval between prospective information through the questionnaire.
diagnosis and first appointment at the treatment In the phone interview, we also asked patients to
site (T3) and first appointment until treatment answer the questions, with all their medical data in
commencement (T4) between patients treated by their hands, such as exams and appointments.
private-sector health care and public health care. There is also a need to train the health team to
The results of patients treated by private-sector identify these lesions, using strategies to motivate
health care correspond to approximately half the and involve the patient in the detection process22 and
time of patients treated by public health care. That even develop oncology education in undergraduate
indicates the need to improve organization and health courses.
infrastructure in public cancer care facilities to With the training of the health team to diagnose
reduce the diagnosis and treatment delay and, by these lesions, and the integration of the diagnosis
that, the mortality. and treatment center, the time for diagnosis and

Braz. Oral Res. 2022;36:e073 5

 Oral cancer analysis in a Brazilian city: interval between diagnosis and treatment

treatment of these patients may decrease, improving Conclusion

their prognosis.
The present study has some limitations. First, The interval between the first sign and symptom
as previously stated, besides all the effort to avoid of the disease and the first appointment at the
memory bias, it is still an important source of bias, Stomatology clinic was excessively long. Those
as the phone interview was a key source of data. who were treated in public health care took twice as
Another limitation might be the low response rate, as long to start treatment when compared to patients
we were able to contact only 94 patients from a total treated in private-sector health care, which shows the
of 184. This may be due mostly to the death of these inequality of access to health care in Brazil. There
patients, thus being a source of survivorship bias, was an improvement in early diagnosis at the School
affecting our results regarding survivability of OC. of Dentistry of the University of São Paulo.

References

1. Ministério da Saúde (BR), Instituto Nacional de Câncer - INCA. Estimate/2018 – Cancer Incidence in Brazil. Brasília, DF: Instituto de
Câncer, 2018.
2. Ghantous Y, Abu Elnaaj I. Global incidence and risk factors of oral cancer. Harefuah. 2017 Oct;156(10):645-9.
3. Chaturvedi AK, Anderson WF, Lortet-Tieulent J, Curado MP, Ferlay J, Franceschi S, et al. Worldwide trends in incidence rates for oral
cavity and oropharyngeal cancers. J Clin Oncol. 2013 Dec;31(36):4550-9. https://doi.org/10.1200/JCO.2013.50.3870
4. Harten MC, Hoebers FJ, Kross KW, Werkhoven ED, Brekel MW, Dijk BA. Determinants of treatment waiting times
for head and neck cancer in the Netherlands and their relation to survival. Oral Oncol. 2015 Mar;51(3):272-8.
https://doi.org/10.1016/j.oraloncology.2014.12.003
5. Jensen AR, Nellemann HM, Overgaard J. Tumor progression in waiting time for radiotherapy in head and neck cancer. Radiother Oncol.
2007 Jul;84(1):5-10. https://doi.org/10.1016/j.radonc.2007.04.001
6. Costa EG, Migliorati CA. [Oral cancer: how long does it take from detection of a lesion to the beginning of treatment]. Rev Bras
Cancerol. 2001;47(3):283-9. Portuguese. https://doi.org/10.32635/2176-9745.RBC.2001v47n3.2307
7. Silva MC, Marques EB, Melo LC, Bernardo JM, Leite IC. [Associated factors for the delay in the diagnoisis of
oral and oropharynx câncer in Juiz de Fora/MG]. Rev Bras Cancerol. 2009 out/dez;55(4):329-35. Portuguese.
https://doi.org/10.32635/2176-9745.RBC.2009v55n4.1563
8. Le Campion AC, Santos KC, Carmo ES, Silva Júnior FF, Peixoto FB, Ribeiro CM, et al. [Characterization of diagnostic delay
in oral and oropharyngeal cancer at two referral centers]. Cad Saúde Coletiva. 2016 abr/jun;24(2):178-84. Portuguese.
https://doi.org/10.1590/1414-462X201600020004
9. Santos VCB, Assis AMA, Silva LE, Ferreira SMS, Dias EP. Oral cancer: evaluation of the time from detection to treatment initiation at
oncology center of Maceió. Rev Bras Odontol. 2012;69(2):159-64. Portuguese. https://doi.org/10.18363/rbo.v69n2.p.159
10. Brasil. Lei Nº 12.732, de 22 de novembro de 2012. Dispõe sobre o primeiro tratamento de paciente com neoplasia maligna
comprovada e estabelece prazo para seu início. Diário Oficial União, 2012 Nov. 23.
11. Scott SE, Grunfeld EA, McGurk M. The idiosyncratic relationship between diagnostic delay and stage of oral squamous cell carcinoma.
Oral Oncol. 2005 Apr;41(4):396-403. https://doi.org/10.1016/j.oraloncology.2004.10.010
12. Petti S. Lifestyle risk factors for oral cancer. Oral Oncol. 2009 Apr-May;45(4-5):340-50.
https://doi.org/10.1016/j.oraloncology.2008.05.018
13. Montero PH, Patel SG. Cancer of the oral cavity. Surg Oncol Clin N Am. 2015 Jul;24(3):491-508.
https://doi.org/10.1016/j.soc.2015.03.006
14. Lyhne NM, Christensen A, Alanin MC, Bruun MT, Jung TH, Bruhn MA, et al. Waiting times for diagnosis and treatment
of head and neck cancer in Denmark in 2010 compared to 1992 and 2002. Eur J Cancer. 2013 May;49(7):1627-33.
https://doi.org/10.1016/j.ejca.2012.11.034
15. Kowalski LP, Carvalho AL. Influence of time delay and clinical upstaging in the prognosis of head and neck cancer. Oral Oncol.
2001 Jan;37(1):94-8. https://doi.org/10.1016/S1368-8375(00)00066-X
16. Peacock ZS, Pogrel MA, Schmidt BL. Exploring the reasons for delay in treatment of oral cancer. J Am Dent Assoc.
2008 Oct;139(10):1346-52. https://doi.org/10.14219/jada.archive.2008.0046

6 Braz. Oral Res. 2022;36:e073

 Chiliti BA, Campos WG, Gallo CB, Lemos CA

17. McGurk M, Chan C, Jones J, O’regan E, Sherriff M. Delay in diagnosis and its effect on outcome in head and neck cancer. Br J Oral
Maxillofac Surg. 2005 Aug;43(4):281-4. https://doi.org/10.1016/j.bjoms.2004.01.016
18. Gómez I, Seoane J, Varela-Centelles P, Diz P, Takkouche B. Is diagnostic delay related to advanced-stage oral cancer? A meta-analysis.
Eur J Oral Sci. 2009 Oct;117(5):541-6. https://doi.org/10.1111/j.1600-0722.2009.00672.x
19. Goy J, Hall SF, Feldman-Stewart D, Groome PA. Diagnostic delay and disease stage in head and neck cancer: a systematic review.
Laryngoscope. 2009 May;119(5):889-98. https://doi.org/10.1002/lary.20185
20. Gómez I, Warnakulasuriya S, Varela-Centelles PI, López-Jornet P, Suárez-Cunqueiro M, Diz-Dios P, et al. Is early
diagnosis of oral cancer a feasible objective? Who is to blame for diagnostic delay? Oral Dis. 2010 May;16(4):333-42.
https://doi.org/10.1111/j.1601-0825.2009.01642.x
21. Thompson CP. Memory for unique personal events: the roommate study. Mem Cognit. 1982 Jul;10(4):324-32.
https://doi.org/10.3758/BF03202424
22. Jornet PL, Garcia FJ, Berdugo ML, Perez FP, Lopez AP. Mouth self-examination in a population at risk of oral cancer. Aust Dent J.
2015 Mar;60(1):59-64. https://doi.org/10.1111/adj.12274

Braz. Oral Res. 2022;36:e073 7