The frequency of different types of squamous cell carcinoma according to their triggering factors in patients with dark complexion skin

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Journal of Pakistan Association of Dermatologists. 2023;33(4):1535-1541.
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Address for correspondence
Professor Khalifa E Sharquie
Department of Dermatology, College of Medicine,
University of Baghdad, Iraqi and Arab Board of
Dermatology and Venereology,
Center of Dermatology and Venereology,
Baghdad Teaching Hospital, Medical City,
Medical Collection Office, P.O. BOX 61080,
Postal code 12114, Baghdad, Iraq.
Ph: 009647901468515
Email: ksharquieprof@yahoo.com
Original Article
The frequency of different types of squamous cell
carcinoma according to their triggering factors in
patients with dark complexion skin
Introduction
Squamous cell carcinoma (SCC) of the skin is
the second most common skin cancer,
characterized by atypical, faster growth of
squamous cells.1 Two major presuming
triggering factors: Firstly, endogenous mutagens
result in spontaneous variations of DNA, like
free radical damage due to depurination,
deamination, or reactive oxygen species.2
Secondly, exogenous mutagens like ultraviolet
sunlight, smoking, dietary components, and
Epigenetic alterations.3
The most common malignant proliferation of the
keratinocytes originating from the burn scar is
SCC, and it is an unavoidable probability.4 Deep
burns, unstable burned scars that commonly
ulcerate due to frequent trauma and those which
never cured completely, will advance into
malignant alteration. The lower limbs,
particularly around joints are commonly
affected.5,6 In Iraq, the occurrence of SCC
Khalifa E Sharquie, Thamir A Kubaisi*
Department of Dermatology, College of Medicine, University of Baghdad, Center of Dermatology,
Medical City Teaching Hospital, Iraq.
* Department of Dermatology, College of Medicine, University of Anbar; Anbar, Iraq.
Abstract
Objective To gather all patients with squamous cell carcinoma and try to classify them according to
their triggering factors.
Methods This is a cross-sectional study that was carried out during the period from 2014-2023
where all patients with squamous cell carcinoma were collected and analyzed into groups according
to their triggering factors. Nearly all patients were Fitzpatrick skin type III and IV. Full
demographic and clinical data were studied and evaluated. A histopathological assessment was
done as a confirmatory measure.
Results Full analysis and evaluation were carried out for 95 cases of squamous cell carcinoma and
classified into the following groups: lower lip sunlight-induced SCC in 44 (46.3%) cases, ordinary
SCC without triggering factor in 22 (23.1%), lichen planus induced SCC in 17 (17.89%) and burn-
induced in 12 (12.63%) patients with SCC.
Conclusion Cutaneous squamous cell carcinoma is not a common tumor but is frequently triggered
by sunlight exposure, lichen planus and old burn scar.
Key words
Squamous cell carcinoma; Triggering factors; Sunlight exposure; Lichen planus; Old burn scar.

Journal of Pakistan Association of Dermatologists. 2023;33(4):1535-1541.
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among old burn scars is about 6.97% of male
patients, where SCC is triggered by ulcerations,
frequent infection, recurrent trauma, and
contracture near the joints.7
Development of SCC over cutaneous lichen
planus (LP is rare with an estimated frequency
between 0.4 - 1.7%, the hypertrophic LP of the
lower legs is commonly involved.8 Concerning
mucosal LP, the most common type with risk of
SCC in 0.4-3.7% of females with oral LP. The
commonly affected sites are the tongue, buccal
mucosa, and gingiva.9 Sharquie provides new
observation regarding the malignant latency of
different types of LP, where all kinds of LP had
been accompanied by the development of
SCC.10
In a recent study,11 SCC of lower lips is not
uncommon progressively realized tumor in
middle age men that frequently present with
solitary nodular ulcerative vegetating lesion
without regional lymphadenopathy or distant
metastases. In only 16.66% of cases, preexisting
risk factors were observed.
SCC is the most common type of lip cancer,
affecting the vermilion portion, with a
distinguishing feature of being violently
metastatic and having a higher relapse.12
Epidemiological researches reveal that
individuals with lower lip malignancy are more
prevalent than those with upper lip.13 The well-
known cause for the advance of lip cancer is
heavy exposure to sunlight.11 Many studies
discovered that UVR activated immune
suppression in the skin over diverse signaling
molecules, including the Fas/FasL system,
interleukins, TNF, or initiation of apoptosis of T
cell.14 Ultraviolet radiation raises the TNF-α, IL-
6 and IL-10 points in epidermal skin cells, which
leads to down-regulating the actions of
Langerhans cells, thus impeding the immune
response of the involved skin.15
Also, it had been shown that autoimmune
diseases like pemphigus, vitiligo, alopecia
areata, lupus erythematosus and psoriasis had
decreasing frequencies of skin malignancies like
BCC and SCC. Hence these autoimmune
diseases are protective against these tumors but
through what mechanism? it is not well
elucidated.16-19 On the other hand, it has been
well elucidated that patients with kidney
transplants receiving cytotoxic therapy have a
great tendency to develop skin management
especially in cases with SCC.18,20
Over the last 10 years, Sharquie documented
interesting findings and published many studies,
regarding the different types of SCC and its
propagating factors, but without available
classification, like long-standing burn scars,7
lichen planus,10 lip cancer due to heavy exposure
to sunlight.11
Thus, initial diagnosis and treatment of SCCs,
and their premalignant conditions, are critical to
diminish the morbidity and mortality of this type
of skin cancer. The aim of the present work is to
do gathering trial for all patients with SCC and
challenging to classify them into groups
proportional to their provoking triggering
factors.
Patients and methods
This is a cross-sectional study that was carried
out in a dermatology private clinic, Baghdad,
Iraq, during the period from 2014-2023 where
all patients with SCC were collected and
analyzed into groups according to their
recognized triggering aspects. Full demographic
and clinical data were studied and evaluated.
Nearly all of them were skin types III and IV.
The name, age, gender, onset of disease, site of
SCC, associated skin illness or internal
problems, history of a long period of sun
exposure, or history of burn were recorded. All

Journal of Pakistan Association of Dermatologists. 2023;33(4):1535-1541.
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Figure 1 (A) Fifty-five years old man, (B) and
twenty years old male patient with SCC of the lower
lip, characterized by slowly growing nodular crusted
and verrucous lesions.
Figure 2 Sixty years old female patient, complaining
of lichen planus induced SCC at the base of the oral
cavity that is characterized by a slowly growing
nodular tumor, with Wickham striae of LP.
patients were immunocompetent and
nonsmokers but mostly had outdoor activities.
Cases of SCC that are not related to the theme of
the present work were excluded.
Biopsies from lesions were processed and
stained for HE stains and then histopathological
evaluation was carried out to confirm the clinical
diagnosis.
Written consent regarding publication and
photographs were taken from each subject
before enrollment in the study.
Results
Complete analysis and assessment were carried
out for 95 cases of SCC, 76 (80%) males and 19
(20%) females, with male to female ratio was 4:1.
The mean (ranged) ages were 42 (20-78) years.
They are classified into the following groups:
SCC of the lower lip, sunlight-induced in 44
(46.3%) cases, their ages ranged from 20-78
with a mean of 50 years, with 36 (83.7%) males
and 6 (13.6%) females and only two (4.65%)
patients showed associated solar keratosis of the
face (Figure 1).
Ordinary SCC without obvious triggering
factor This included 22(23.1%) patients, the
mean (ranged) ages were 50(24-60) years, 18
(81.8%) males and 4 (18.1%) females where
different sites were involved.
Lichen planus induced SCC in 17 (17.9%)
individuals, their ages ranged from 30-60years,
with 12 (70.6%) males and 5 (29.4%) females.
The type of lichen planus was an either oral
cavity, body lichen planus or lichen planus
actinicus. Oral SCC in 5 (29.4%) cases, all
males, SCC of the lips in 11 (64,7%) cases, 9
males (81.8%) and 2 (18.1%) females. While
one (5.8%) female case with foot involvement
(Figures 2, 3).
Burn-induced SCC in 12 (12.6%) patients, who
complained of long-standing burn scars, their
ages ranged from 25-50 years with a mean of 42
years, were 10 (83.3%) males and two (16.7%)
females. The sites involved were 5 (41.7%)
patients for the lower limbs and 5 (41.7%) cases
for the upper arms, one (10%) patient on the
buttock, and one (10%) case on the scalp. The
burn scars are characterized by deep, ulcerative,
located around the joints that had repeated
trauma, and sometimes with secondary infection
(Figure 4).
The clinical examination of the regional lymph
nodes and other parts of the body showed no
metastasis.

Journal of Pakistan Association of Dermatologists. 2023;33(4):1535-1541.
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Figure 3 Fifty years old male patient showing (A)
lichen planus of the leg, (B) SCC of the left foot.
Figure 4 Showing SCC of the lower limb, triggered
by a long-standing burn scar in 42 years old male
patient.
Discussion
SCC is the second non-melanoma skin cancer1
but unfortunately, they are managed separately
in clinical practice hence the actual incidence of
these different types of SCC is not well
established. The present study provides, for the
first time, an update on the frequency of SCC
according to the different triggering factors. This
is essentially required, as the risk factors of skin
cancer continues to rise dramatically, and this
needs to be judged to report the undergoing
changes in the biological mechanisms happening
in the human body. Few previous studies
reported the ratio of BCC to SCC was nearly
equal. However, an increasing incidence of SCC
in the studied population younger than 65 years
with heavy, chronic sunlight exposure may be an
underappreciated evolving trend.1, 21
The current study mentioned that the male-to-
female ratio in SCC was 4:1 and this could not
be well explained as most people whether males
or females have outdoor activities as they are
living in the sunny atmospheres all over the year
but males probably have more sunlight
exposure, especially among workers. Although
the people there have a dark complexion with
Fitzpatrick skin types III and 1V. This ratio is
considered to be slightly higher than many
preceding studies in other countries, where male
to female ratio was 2.85:1.22,23 But the ratio in
Iranian patients by Sadri's study was nearly
equal and was dissimilar from the present
work.24
One of the fixed causes for the development of
lower lip SCC is exposure to sunlight, because
of the longtime of exposure to the sunlight
compared to the upper lip which is sloping
downward and is protected by the nose region.11
In the present study, SCC of the lower lip, as
sunlight-induced SCC are reported up to 46.3%
of cases without closely related skin disease, like
solar keratosis as only 4.7% of patients showed
associated solar keratosis of the face.
Overall, chronic and cumulative exposure to
UVR is the single most significant etiological
environmental issue-induced skin carcinogenesis
for both non-melanoma skin cancer and
melanoma, the oncogenic pathway, mutation
ranges and tumor suppression genes are
relatively cell-specific.25 UVB is directly
absorbed by DNA and thus causes DNA injury
and changes in gene expression by intracellular
signaling transduction, which leads to skin
cancer. UVA irradiation can yield reactive
oxygen free radicals, which cause secondary
harm to DNA, and thus develop skin cancer.26,27
In the present work, ordinary SCC without

Journal of Pakistan Association of Dermatologists. 2023;33(4):1535-1541.
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obvious triggering factors is elucidated in 23.1%
of patients. The interpretation is related to other
exogenous mutagens including dietary
components, plus epigenetic alterations, leading
to changes in gene manifestation, and facilitating
inappropriate transcriptional initiation and
quieting of genes. Thus, enhancing the rate of
mutation, proliferation, and drop in cell death.
however, DNA repair passes through the wrong
way due to genetic or environmental aspects,
therefore mutations in tumor suppressor genes
and proto-oncogenes may happen, which lead to
the development of tumor.3,28
The current study demonstrated similar
information to what had been published by
Sharquie et al.,10 regarding the development of
SCC following all variants of LP, either directly
or with other additive influences. Herein, LP
derived SCC is observed in 17.9% of patients.
The oral cavity and actinic LP of the lips were
involved in 29.4%, and 64.7% of cases
respectively, while body lichen planus in 5.8%
of individuals. Especially when evaluating
poorly responding lesions or longstanding non-
healed LP. Though SCC as a complication of LP
is a sporadic and non-documented problem, this
observation should be kept in mind during daily
medical practice. But, on contrary, many
preceding kinds of researches suggest a greater
risk of malignant transformation in subjects with
oral LP. 29,30 World Health Organization (WHO)
describes oral LP as a potentially malignant
illness, and close monitoring of oral LP patients
was recommended.31
Also, this study showed that 12.6% of patients
are well recognized as burn-induced SCC. It was
somewhat higher than other published
studies.4,7,32 Our participants complained of
long-standing burn scars, where the main sites
involved are the lower limbs and the upper arms
in about 41.7% of patients for each site, while
nearly 10% of cases involved the buttock and
10% of cases for the scalp. The burn scars are
characterized by deep, ulcerative, located around
the joints getting repeated trauma, and
sometimes with secondary infection. The most
important correlation with the development of
SCC in burn scars is the early job time,
prolonged sunlight exposure during outdoor
work, and sunny climatic situation during the
whole year time.33 Important advice for patients
with old burn scars for preventing skin cancer
development is the avoidance of repeated
infection of the burned skin, protect the burn
scars from frequent trauma, and start medical
treatment like skin grafting for burn scars as
soon as possible.
Conclusion
This is the first study that documented the actual
frequency and incidence of different cutaneous
SCC according to their triggering factors. Their
frequency was lower lip sunlight-induced SCC
in 44(46.3%) cases, ordinary SCC without
triggering factor in 22(23.1%), lichen planus
induced SCC in 17(17.89%) and burn-induced in
12(12.63%) patients with SCC. It is essential to
treat and or prevent these triggering factors to
avoid these different SSC variants.
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