Appendix Table 1. Oral cancers and oral precancerous lesions in

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Appendix Table 1. Oral cancers and oral precancerous lesions in noninflammatory bowel disease patients.
Author
Drug(s)
Patient(s)
Underlying
disease
HIV+
Location of oral Ca
Histology of oral
Ca
Candidiasis &
leukoplakia
Comments
Hilton et al.1
152
Epstein et al.2
HAART
(HIV therapy
scheme)
IS
HIV +
cohort
Immunosu
ppressed
vs HC
1
HIV+
Oral cavity
Malignant
HIV+
Renal Tx
Controls
Panuveitis
EBV-DNA(+) more
in Tx than HIV
CMV(-),
HPV-DNA (+) more
in HIV+
BCC adenoCa
Oral lichen
planus (OLP)
OLP
SCC
OLP
Areas of Tacrolimus
application
Tongue
(left side)
Oral cavity
Geographical
variation
Hairy
leukoplakia
more in men
After 52
months of CyA
5 ys after
topical use
5 ys after
topical use
Successful
treatment
Amatuna et al.3
IS
Ramchandani et al.4
CyA
Mattsson et al.5
1
Chaklader et al.7
Tacrolimus
topical
Tacrolimus
topical
CyA
Yamamoto et al.8
CyA
1
Psoriasis
Oral cavity
AdenoCa
Koo et al.9
CyA
1
Psoriasis
B-cell lymphoma
Horie et al.10
MTX
60
M
RA
Maxillary sinus,
orbit, palate
Gingival ulcer
Naidu et al.11
MTX
1
RA
Many oral ulcers
EBV+ Hodgkinlymphoma like
Ishida et al.12
MTX
76
F
RA
Gingiva
Hanakawa et al.13
MTX
67
M
RA
Oropharyngeal
Lymphoproliferative
disorder (LPD)EBV+
LPD
Attard et al.14
MTX
1
RA
Pastor-Nieto et al.15
MTX
79
F
RA
Oral mucocutaneous ulcer
Oral ulcer
LPD
(probable)
EBV+ - LPD
Gono et al.16
MTX
1
RA
Right
submandibullar
Diffuse large B-cell
Mok et al.17
AZA
1
RA
Parotid gland
Dojcinov et al.18
AZA or MTX or
CyA
26
16 / 26 with oral
ulcers
Hasegawa et al.19
Allogenic BMT
557
BMT
Various
autoimmune
diseases
Hematology
related Ca
Lymphoepithelioma
-like Ca
Large B-cell blasts
Schmigelow et al.20
MTX or AZA
children
ALL
Noguchi et al.21
IS
67
M
Malignant
Lymphoma
Demarosi et al.22
AZA + CyA +
Prednisone
+colchicine
53
F
Chien et al.23
AZA
GVHD
Cohort
1997-2010
BMT
(for NonHodgkin
lymphoma)
BMT
Becker et al.6
56
F
1
Oral cavity
Labial
SCC
SCC
Diffuse B-cell
lymphoma EBV+
Increased incidence
of oral Ca and
NMSC
Oral Ca
(as secondary
cancer)
Left buccal mucosa
SCC
Oral
SCC arising from
GVHD-induced
lesion s
Oral cavity
(+esophagus)
Ca SIR=14.18
SCC
Uncomplicated
Remission
after MTX
withdrawal
Differential
diagnosis with
Hodgkin
lym[phoma
DD with large
B-cell
lymphoma
Remission
after MTX
withdrawal
uncomplicated
Remission
after MTX
withdrawal
CHOP as no
remission
after MTX
withdrawal
Long-term
AZA use
EBV+
as secondary
malignancies
Increased
incidence of
second Ca
Died postsurgery of
sepsis
16 cases
reported
Need for oral
screening
Risk increased
with
cumulative
doses of AZA
Raut et al.24
IS
1
BMT
Gingival ulcer
Malignant
lymphoma EBV+
IS to prevent
GVHD
Allen et al.25
IS
1
BMT
Lower lip
(vermillion zone)
Verruciform
xanthoma
Surgery
De Araujo et al.26
AZA+CyA
+Tacrolimus
+Prednisone
IS
43 GVHD
BMT
Oral
SCC
10
BMT
Oral
Hairy leukoplakia
Koharazawa et al.28
CyA +
Prednisone
31
M
BMT -GVHD
SCC both
Curtis et al.29
Chronic GVHD
therapy
183
501
BMT
vs
HC
2 cancers
(1 mandibulargingival, 1 palate)
Buccal cavity (or
skin)
P<0.001
GCHDprolonged
multidrug
EBV+ in 2
HPV+ in 3
3rd Ca
esophagus
Byun et al.30
IS
1
BMT-GVHD
tongue
SCC
Abbas et al.31
IS
1
HSCT
gingival
Kaposi sarcoma
Gummert et al.32
Tripple IS
AZA + CyA +
PrednIsone
45
M
Heart Tx
Tonsils
Tonsilar SCC
Rinaldi et al.33
AZA + CyA +
PrednIsone
474
Heart Tx
Oral cavity
N=55
(6.5% of all Ca)
Schmid-Westhanen
et al.34
IS
50
20
Oral lesions
EBV+ only in Tx not
in HC
O’ Connell et al.35
IS
Rhinow et al.36
Azathioprine
AZA+CyA
42
M
32/F
56/M
Heart Tx
vs
HC
Heart Tx
Wimmer et al.37
CyA vs
Tacrolimus
609
Heart Tx
Myasthenia
gravis
Liver Tx
Labial pappula
(lower lip)
Both Maxillary ridge
alveolar / right
edentulous ridge
-Oropharyngeal
(6.9% n=6/609)
Acantholytic
keratosis
Diffuse large B-cell
(NHL) lymphoma
EBV+
NMSC (44.8%)
Saigal et al.38
IS
1,140
Liver Tx
2 oropharyngeal
SCC
Broughton et al.39
IS
275
pediatric
Liver Tx
Tonsils (5/13 with
changes at
tonsillectomy,
Tonsillar
hyperplasia to large
cell lymphoma
Jain et al.40
Tacrolimus
Liver Tx
IS
Liver Tx
Oropharyngeal
(X25.5 > general
population)
Oropharyngeal =7
SCC (de novo)
Jain et al.41
185 ALD
vs 649
non-ALD
1,000
Helenius-Hieblich et al.42
IS
84
Liver Tx
Oral lesions
Maraki et al.43
IS
1
Liver Tx
Tongue
OLP
Candida
Hairy leukoplakia
In situ Ca
Hernandes et al.44
FK506
+prednisone
1
M
Liver Tx
-GVHD
Mouth floor Ca
SCC
(started from
leukoplakia)
Nure et al.45
Tacrolimus
+MMF
+ prednisone
Tacrolimus
225
Liver Tx
1 Tonsillar
1 Tongue
SCC both
1
Liver Tx
Oral ulcers
GVHD-like lession
et al.s
Epstein et al.27
Bunetel et al.46
AZA major risk
factor for SCC
SCC
Especially
when
combined to
CyA/steroids
Also KS in
respiratory
Pre-existing
Ca? 1 month
after Tx,
smoke/alcohol
Role of AZA
and duration of
IS
uncomplicated
24 ys on AZA
7 wks after Tx
Tacrolimus- is
risk factor for
oral Ca
Increased in
alcoholic livers
Recommend
tonsillectomy if
increased size
of tonsils
In non-ALD Ca
risk not
increased
x 7.6 higher
than expected
More in Tx
than controls
(43% vs 15%)
Brush biopsy
Rapid
progression
in 4 months of
leukoplakia to
SCC
Plus 2
esophageal, 1
larynx Ca
Due to
tacrolimus
Concentini et al.47
AZA+CyA
59
M
Tx RenalPancreas
2 oral cancers
-SCC
-Spinocellular
Keogh et al.48
IS
1
Renal Tx
Oral
NHL
Quniby et al.49
CyA
1
Renal Tx
gingiva
Kaposi sarcoma
Rosa-Gare et al.50
AZA + CyA +
Prednisone
CyA
190
Renal Tx
Oral lesions
1
Renal Tx
Oral
Singh et al.52
AZA or CyA +
PrednIsone
31
with Ca
Renal Tx
-6/31 oral Ca (20%
of all Ca)
More on combo
AZA+CyA
Gingival overgrowth
Candidiasis
Leukoplakia
Lingual SCC,
larynx, parotid Ca,
tonsillar lymphoma
Siegal et al.53
CyA
1
Renal Tx
oral
Kaposi sarcoma
King et al.54
IS
160
Renal Tx
oral leukoplakia=21
King et al.55
IS
159
160
Renal Tx
vs
HC
Oral lesions more in
Tx vs HC p<0.005)
Zmonarski et al.56
AZA + CyA +
Prednisone
CyA
2
Renal Tx
Hard palate
Of 21, 13
dysplastic and 2
progressed in SCC
Hairy leukoplakia
Candidiasis
Gingival
hyperplasia
Kaposi sarcoma
28
M
1
Renal Tx
Gingiva
Renal Tx
Gingival
(+skin)
Al-Mohaya et al.51
Pan et al.57
Extramedullary
plasmatocytoma
Kaposi sarcoma
Vlasic-Matas et al.58
AZA + CyA +
Prednisone
Varga et al.59
CyA
1
Renal Tx
Oral
Siegal et al.60
CyA
1
Renal Tx
Bilinska-Petry et al.61
AZA + CyA +
Prednisone
CyA +
Prednisone
25
M
500
Renal Tx
Gingival
(+skin)
Lingual Ca
Renal Tx
6 oral (1.2%)
Van Zuuren et al.63
IS
1
Renal Tx
Lip Ca
De Visscher et al.64
IS
6
Renal Tx
Lower lip
SCC
Gallagher et al.65
1
Renal Tx
Head and neck
8
King et al.66
CyA or AZA
+prednisone
IS
160
Renal Tx
Dysplasrtic or
malignant
Van Leeuwen et al.67
IS
8,162
Renal Tx
Lip lesions
increased risk
Lip Ca (n=203)
Darling et al.68
IS
1
Renal Tx
Oral cavity
Kaposi sarcoma
Mihalov et al.69
IS
674
Madeleine et al.70
Tacrolimus
187,699 Tx
Tx
(solid organ)
Tx
(solid organs)
Lip Ca and skin Ca
increased risk
Oropharyngeal
(risk x2.1)
SCC
(HPV related)
Karagas et al.71
Oral steroids
592 BCC
Tx
Risk x2.31
NMSC
Lopez-Pintor et al.62
SCC
(arising from
gingival overgrowth)
Kaposi sarcoma
AZA stopped
surgery-fatal,
ex smoker
Reduced IS
gingival
hyperplasia
preceding
Not a Ca study
uncomplicated
Without
drawing IS
prolonged
survival
alive
uncomplicated
In month 7
Regress tumor
after stop AZA
and low CyA
uncomplicated
After CMV
infection
SCC
More men
affected,
sunlight
exposure
Mainly
increased in
Tx period
uncomplicated
Higher risk in
Heart Tx
Increase
incidence of
HPV-related
Ca
IS-related Ca
281 SCC
by oral
corticoids
Reduced CyA
dose
Rolland et al.72
CyA
2
Tx
Gingiva
Rushing et al.73
IS
2
Tx
Oral
Post-Tx LPD
(DD gingival
overgrowth)
Hairy leukoplakia
Qunibi et al.74
CyA
2
Tx
Gingival
Kaposi sarcoma
Thomas et al.75
IS
1
Tx
Lower lip
SCC
Vargas et al.76
IS
8
Tx
Tongue
Verma et al.77
AZA
1
Tx
Oral lichen planus
fibroproliferative
polyps of tongue
benign
Chaiben et al.78
IS
1
Tx
Lower lip
keratoacanthoma
Successful
treatment
uncomplicated
Lindelof et al.79
IS
5356
Tx
NMSC
Higher for men
Väkevä L et al.80
CyA (n=272)
3
Kujken et al.81
Switch from
AZA to CyA
Tx
(eczema)
Tx
Increased risk x
108.6
Mouth cancer
Alexander et al.82
IS
8,000
Penn et al.83
IS
6,934
Tx
HC
Tx
Miranda et al.84
IS
1
SLE
surgery
IS-related
Medium CyA
dose
Better reduce
IS dose
Not reduced oral
malignancies
Lip Ca (7% Tx vs
0,3% HC)
Lip Ca (Pediatric
29% > 13% adults)
Oral cavity
uncomplicated
SCC
Hairy leukoplakia
Abbreviations used in the Table: ALD=alcoholic liver disease,
ALL=acute lymphoid leukemia, AZA=azathioprine, BMT=bone marrow
transplantation, BSC=basal cell cancer, Ca=Cancer, CyA=cyclosporine,
GVHD=graft versus host disease, HSCT=Hemopoietic stem cell
transplantation,
HC=healthy
controls,
IS=immunosuppression,
LPD=Lymphoproliferative
disease
MMF=mycophenolate
mofetil,
MTX=methotrexate, NMSC=non-melanoma skin cancer, OLP=oral lichen
planus, RA=rheumatoid arthritis, SCC=squamous cell cancer,
SLE=systemic lupus erythematosus, Tx=transplantation.
uncomplicated
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