10.5826/dpc.1303a65
Introduction: Solid organ transplant recipients (SOTR) are at an increased risk for developing keratinocyte carcinomas (KC). Four ultraviolet (UV) modifying factors have been identified that impact the incidence of KC: Fitzpatrick Skin Type (FST), race, sun exposure, and sun-protective factors. 
Objectives: We conducted a systematic review to summarize the association between UV modifying factors and the incidence of KC in SOTR. 
Methods: We systematically searched PubMed, Scopus, and Web of Science databases, and after screening for inclusion and exclusion criteria, we included 13 studies with 6,910 solid organ transplant recipients in our analysis. 
Results: Our review found that lower FST (I-II), white and Latinx populations, lack of regulated sunscreen application, and occupational and residential sun exposure are individual risk factors among solid organ transplant recipients for KC incidence. Although previous studies showed an increased SCC:BCC ratio, some studies found a contradictory increased BCC:SCC ratio. Limitations include few research studies that analyze these UV modifying factors and a lack of incorporating both varying immunosuppressant factors and transplantation follow-up times. 
Conclusions: These findings support the need for dermatological advice in increased risk patient demographic populations, lower FST and white and Latinx populations, and subsequently moderating sun exposure and protective factors.
text/xml
2160-9381
2688
en
Adel Haque
https://creativecommons.org/licenses/by-nc/4.0
Dermatology Practical & Conceptual
Sun exposure
Impact of UV Modifying Factors on the Incidence of Keratinocyte Carcinomas in Solid Organ Transplant Recipients: a Systematic Review
Text.Serial.Journal
https://dpcj.org/index.php/dpc
Review
2023-07-31
2022-07-06
2023-07-31
2023-08-24
e2023065
Dermatol Pract Concept
Introduction: Solid organ transplant recipients (SOTR) are at an increased risk for developing keratinocyte carcinomas (KC). Four ultraviolet (UV) modifying factors have been identified that impact the incidence of KC: Fitzpatrick Skin Type (FST), race, sun exposure, and sun-protective factors. 
Objectives: We conducted a systematic review to summarize the association between UV modifying factors and the incidence of KC in SOTR. 
Methods: We systematically searched PubMed, Scopus, and Web of Science databases, and after screening for inclusion and exclusion criteria, we included 13 studies with 6,910 solid organ transplant recipients in our analysis. 
Results: Our review found that lower FST (I-II), white and Latinx populations, lack of regulated sunscreen application, and occupational and residential sun exposure are individual risk factors among solid organ transplant recipients for KC incidence. Although previous studies showed an increased SCC:BCC ratio, some studies found a contradictory increased BCC:SCC ratio. Limitations include few research studies that analyze these UV modifying factors and a lack of incorporating both varying immunosuppressant factors and transplantation follow-up times. 
Conclusions: These findings support the need for dermatological advice in increased risk patient demographic populations, lower FST and white and Latinx populations, and subsequently moderating sun exposure and protective factors.
Adel Haque
2023/07/31
10.5826/dpc.1303a65
e2023065
Department of Medicine, Jefferson Health Northeast, Philadelphia, Pennsylvania
2160-9381
Sun exposure
en
e2023065
Ulrich C, Kanitakis J, Stockfleth E, Euvrard S. Skin Cancer in Organ Transplant Recipients-Where Do We Stand Today? Am J Transplant. 2008;8(11):2192-2198. DOI: 10.1111/j.1600-6143.2008.02386.x. PMID: 18782290.
Impact of UV Modifying Factors on the Incidence of Keratinocyte Carcinomas in Solid Organ Transplant Recipients: a Systematic Review
https://dpcj.org/index.php/dpc/article/download/2688/2238
Impact of UV Modifying Factors on the Incidence of
 Keratinocyte Carcinomas in Solid Organ Transplant
          Recipients: A Systematic Review
                 Syed Minhaj Rahman1, Fahad Ahmed2, Amir Amanullah3, Adel Haque4


1 Department of Dermatology, University of Rochester School of Medicine and Dentistry, Rochester, New York
2 Department of Dermatology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania
3 Department of Dermatology, Lewis Katz School of Medicine, Temple University, Philadelphia, Pennsylvania
4 Department of Medicine, Jefferson Health Northeast, Philadelphia, Pennsylvania



Key words: keratinocyte, organ transplant recipient, ultraviolet radiation, Fitzpatrick Skin Type, sun exposure
Citation: Rahman SM, Ahmed F, Amanullah A, Haque A. Impact of UV Modifying Factors on the Incidence of Keratinocyte Carcinomas
in Solid Organ Transplant Recipients: A Systematic Review. Dermatol Pract Concept. 2023;13(3):e2023065.
DOI: https://doi.org/10.5826/dpc.1303a65
Accepted: January 11, 2023; Published: July 2023
Copyright: ©2023 Rahman et al. This is an open-access article distributed under the terms of the Creative Commons Attribution-
NonCommercial License (BY-NC-4.0), https://creativecommons.org/licenses/by-nc/4.0/, which permits unrestricted noncommercial use,
distribution, and reproduction in any medium, provided the original authors and source are credited.
Funding: None.
Competing interests: None.
Authorship: All authors have contributed significantly to this publication.
Corresponding author: Syed Minhaj Rahman, BA, Department of Dermatology, University of Rochester School of Medicine and Dentistry,
1188 Mount Hope Ave, Apt 503 Rochester, NY 14620 Telephone: (718)-598-4637 E-mail: minhaj_rahman@urmc.rochester.edu




  ABSTRACT             Introduction: Solid organ transplant recipients (SOTR) are at an increased risk for developing kerati-
                       nocyte carcinomas (KC). Four ultraviolet (UV) modifying factors have been identified that impact the
                       incidence of KC: Fitzpatrick Skin Type (FST), race, sun exposure, and sun-protective factors.
                       Objectives: We conducted a systematic review to summarize the association between UV modifying
                       factors and the incidence of KC in SOTR.
                       Methods: We systematically searched PubMed, Scopus, and Web of Science databases, and after
                       screening for inclusion and exclusion criteria, we included 13 studies with 6,910 solid organ ­transplant
                       recipients in our analysis.
                       Results: Our review found that lower FST (I-II), white and Latinx populations, lack of regulated
                       ­sunscreen application, and occupational and residential sun exposure are individual risk factors
                        among solid organ transplant recipients for KC incidence. Although previous studies showed an in-
                        creased SCC:BCC ratio, some studies found a contradictory increased BCC:SCC ratio. Limitations
                        include few research studies that analyze these UV modifying factors and a lack of incorporating both
                        varying immunosuppressant factors and transplantation follow-up times.
                       Conclusions: These findings support the need for dermatological advice in increased risk patient
                       ­demographic populations, lower FST and white and Latinx populations, and subsequently moderating
                        sun exposure and protective factors.



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Introduction                                                      prospective cohort, case-control, and observational studies
                                                                  to summarize the association between UV modifying fac-
Keratinocyte carcinomas (KC) are non-melanoma skin can-           tors and the incidence of KC in SOTR. The results of this
cers (NMSC) consisting of basal cell carcinomas (BCC) and         study will help clinicians better assess what pertinent, signif-
squamous cell carcinomas (SCC) [1]. KCs are the most preva-       icant risk factors to be aware of when treating adult SOTR
lent cancer worldwide with 20-25% of KCs being SCC [2,3].         and monitoring for the development of KC. Results of this
Solid organ transplant recipients (SOTR) have an increased        study will allow us to lead a discussion regarding skin phe-
risk of developing KC and these patients are at a 65-250 in-      notype, race, and UV protection/exposure and better guide
creased risk for cutaneous SCC than the general population        ­physicians treating SOTR adults.
[4-6]. Specifically, a recent Delphi consensus survey found
that male thoracic organ recipients aged 50 or older at the
time of transplant are at the highest risk for developing skin    Methods
cancer [7]. There are several UV modifying factors that can
                                                                  Study Identification
impact KC incidence in SOTR, however, the 4 major vari-
                                                                  A systematic literature search using PubMed and Scopus
ables are: Fitzpatrick skin type (FST), race, sunscreen use,
                                                                  databases was performed. This search included all years
and sun exposure.
                                                                  through April 2022 and consisted of the search terms:
    The FST classifies 6 skin complexions and reactions
                                                                  “­
                                                                   organ transplantation” OR “organ graft” OR “organ
to sun exposure ranging from very light skin, burns easily,
                                                                  ­transplant recipients” AND “skin cancer” OR “squamous
and never tans (FST I) to very dark skin, never burns, and
                                                                  cell carcinomas” OR “basal cell carcinomas” OR “cutaneous
tans profusely (FST VI) [8]. Although there are overlapping
                                                                  squamous cell carcinoma” OR “nonmelanoma skin cancer”
factors in FST and race, several other factors should be ac-
                                                                  OR “keratinocyte carcinoma” AND “skin tone” OR “skin
counted for such as: environmental, geographic, and socio-
                                                                  color” OR “Fitzpatrick skin type” OR “sunscreen” or “sun
economic factors. All of these factors impact the association
                                                                  protective factors”. Additionally, we searched the reference
between race and KC incidence.
                                                                  lists of selected studies. The search was conducted adhering
    Aside from FST, sun exposure and sun protective actions
                                                                  to the updated 2020 standards of the Preferred Reporting
are major contributors to skin cancer incidence [9]. Sun ex-
                                                                  Items for Systematic Reviews and Meta-analysis (PRISMA)
posure and sunburn can be used indirectly as tools to as-
                                                                  statement [18].
sess skin cancer risk as it accounts for UV exposure amount
and skin sensitivity [10]. Although some studies show that
continuously high sun exposure is more closely associated
                                                                  Eligibility Criteria
with an increase in SCC incidence, other studies have also        Two reviewers (SR and FA) selected studies that met the
reported a positive association between sunburn history and       following inclusion criteria: i) the population of interest -
KC incidence [11-15].                                             adult solid organ transplant recipients, including FST or
    Sunscreen is a primary photoprotective factor against         skin tone identification, race, sunscreen behaviors, or sun
UV radiation that absorbs environmental UV rays to pro-           exposure; ii) the outcomes of interest - cutaneous squamous
tect the skin [16]. A trial conducted in Queensland, Australia    cell carcinomas, basal cell carcinomas, or non-melanoma
found that daily morning use of broad-spectrum sun protec-        skin cancers; and iii) observational or interventional study
tion factor (SPF)-16 sunscreen on the head, neck, arms, and       designs (cross-sectional studies, cohort studies, case stud-
hands of healthy individuals decreased both the number of         ies, cases series, or randomized controlled trials). Studies
individuals with SCCs and the incidence of SCC tumors up          were excluded if there was no record of UV modifying
to 8 years post-cessation of intervention [17]. However, this     risk factors. Any disagreement was resolved by a third re-
same protective factor for regular use of sunscreen was not       viewer (AA).
significant in reducing BCC incidence.
                                                                  Data Extraction
                                                                  A total of 480 studies were screened and 13 were included.
Objectives
                                                                  Information was collected on study design, data source,
To the author best knowledge, there is a lack of systematic re-   number of participants, selection criteria, and outcomes of
views that assess the impact of UV modifying factors on skin      interest including SCC, BCC, KC, and overall NMSC inci-
cancer incidence in the adult SOTR population. Although           dence based on our 4 UV modifying risk factors. FST and
there is substantial evidence suggesting immunosuppression        race data collected and analyzed is presented in Table 1. Sun
increases the risk of SOTR developing KC, this systematic re-     exposure and sunscreen data collected and analyzed is pre-
view will synthesize the evidence from retrospective cohort,      sented in Table 2.



2                                                                            Review | Dermatol Pract Concept. 2023;13(3):e2023065
                                                                   Table 1. Studies examining keratinocyte carcinoma risk variables, Fitzpatrick skin type, and race in solid organ transplant recipients.

                                                                         Study
                                                        KC Risk        Author(S)                     Data Collection   Number of                                      UV Modifying
                                                        Variable       And Year                      Location (Year    Subjects in                     Type of        Risk Variables
                                                        Studied        Published      Study Design      Ranges)        Study         KC Reported    Transplant(S)       Reported                 Risk Type/Data
                                                       FST           Gogia et al     Retrospective   USA - CA          556           317 cSCC      Kidney, heart,    FST               SCC HR (95% CI)
                                                                     2013            Cohort          2004-2008                                     lung, pancreas,   I                 3.47 (1.46-8.28)
                                                                                                                                                   and liver         II                2.63 (1.16-5.92)
                                                                                                                                                                     III               2.79 (1.24-6.30)
                                                                                                                                                                     IV                2.07 (0.91-4.70)
                                                                                                                                                                     V                 1.58 (0.66-3.81)
                                                                     Moloney et al   Observational   Ireland           270           44 SCC and    Kidney            FST %             SCC                   BCC
                                                                     2005            cohort          (2000-2001)                     22 BCC                          I                 52.3%                 54.5%
                                                                                                                                                                     II                25.0%                 27.3%




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                                                                                                                                                                     III               18.2%                 18.2%
                                                                                                                                                                     IV                4.5%                  0%
                                                                     De Rosa et al   Retrospective   Australia         94            -             Heart and lung    FST               Carcinoma type - HR (95% CI)
                                                                     2019            Cohort                                                                          III-VI            NMSC - 0.60 (0.35-1.02)
                                                                                                                                                                                       SCC - 0.57 (0.33-1.00)
                                                                                                                                                                     I-II              BCC - 0.55 (0.29-1.02)
                                                                                                                                                                                       NMSC - 1*
                                                                                                                                                                                       SCC - 1*
                                                                                                                                                                                       BCC - 1*

                                                                     Ng et al 2014   Prospective     Australia         142           253 cSCC      Kidney            FST               Carcinoma type - accrual (SD)
                                                                                     cohort          (2004-2009)                     and 88 BC                       I                 NMSC - 2.37 (±3.25)
                                                                                                                                                                                       SCC - 1.76 (±2.70)
                                                                                                                                                                     II                BCC - 0.61 (±1.66)
                                                                                                                                                                                       NMSC - 3.05 (±8.88)
                                                                                                                                                                                       SCC - 2.41 (±7.48)
                                                                                                                                                                     III               BCC - 0.64 (±1.60)
                                                                                                                                                                                       NMSC - 0.80 (±1.57)
                                                                                                                                                                                       SCC - 0.60 (±1.40)
                                                                                                                                                                     IV                BCC - 0.20 (±0.49)
                                                                                                                                                                                       NMSC - 0.45 (±2.85)
                                                                                                                                                                                       SCC - 0.40 (±1.75)
                                                                                                                                                                                       BCC - 0.05 (±0.16)




3
                                                                                                                                                                                                             Table1 continues
4
                                                         Table 1. Studies examining keratinocyte carcinoma risk variables, Fitzpatrick skin type, and race in solid organ transplant recipients. (continued)

                                                                           Study
                                                         KC Risk         Author(S)                             Data Collection     Number of                                                  UV Modifying
                                                         Variable        And Year                              Location (Year      Subjects in                               Type of          Risk Variables
                                                         Studied         Published         Study Design           Ranges)          Study               KC Reported        Transplant(S)         Reported                    Risk Type/Data
                                                                       Garcia et al      Prospective +        Mediterranean        289                 41 cSCC and      Kidney               FST                 Relative NMSC HR (95% CI)
                                                                       2013              Retrospective        Region                                   91 BCC                                I-II                1*
                                                                                         cohort               (1996-2010)                                                                    ≥III                0.5 (0.27-0.92)
                                                                       Ducroux et al     Retrospective        1996-2008            371                 50 KC (cSCC      Lung                 FST                 NMSC OR (95% CI)
                                                                       2014              cohort               (France)                                 and/or BCC)                           I-III               10.91 (1.45-81.77)
                                                                                                                                                                                             IV-VI               1*
                                                                       Caforio et al     Prospective          Italy                300                 53 SCC and       Heart                FST                 NMSC HR (95% CI)
                                                                       2000              Cohort                                                        37 BCC                                II                  2.6 (± 1-7)
                                                                                                                                                                                             III-IV              1*
                                                        Race           Dusendang         Case-control         USA - CA             3308 OTR vs         -                Heart, kidney,       Race                cSCC HR (95% CI)
                                                                       et al 2022                             (2009-19)            65,883 no OTR                        liver, lung, and     White               1.00*
                                                                                                                                                                        pancreas             AA                  0.04 (0.02-0.07)
                                                                                                                                                                                             Asian American      0.07 (0.05-0.09)
                                                                                                                                                                                             Latinx              0.23 (0.18-0.29)
                                                                                                                                                                                             Other               0.52 (0.41-0.65)
                                                       AA = African American; BCC = basal cell carcinoma; CI = confidence interval; cSCC = cutaneous squamous cell carcinoma; FST = Fitzpatrick skin type; HR = Hazard Ratio; KC = keratinocyte carcinoma;
                                                       NMSC = non-melanoma skin cancer; OR = Odds Ratio; SCC = squamous cell carcinoma; SD = standard deviation; * = hazard or odds ratio in reference to this value.




Review | Dermatol Pract Concept. 2023;13(3):e2023065
                                                                     Table 2. Studies examining keratinocyte carcinoma risk variables, sunscreen, and sun exposure in solid organ transplant recipients.
                                                          KC Risk        Study Author(S)                              Data Collection      Number of                                              UV Modifying
                                                          Variable          and Year                                  Location (Year       Subjects In                            Type of         Risk Variables
                                                          Studied           Published            Study Design            Ranges )            Study          KC Reported        Transplant(S)        Reported                 Risk Type/Data
                                                        Sunscreen       Savoia et al 2011     Retrospective         Italy (1997-2010)          282        99 Skin cancers     Kidney              SS Use             Neoplasm HR (95%)
                                                                                              cohort                                                      - 70 NMSC                               Yes                1.00*
                                                                                                                                                          (47 BCC and                             No                 1.25 (0.56-2.79)
                                                                                                                                                          23 SCC)                                 Risk Factors       No sunscreen use (P = 0.0252)
                                                                                                                                                                                                  significant link   Outdoor job (P = 0.0413)




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                                                                        Ulrich et al 2009     Case-control          Berlin, Germany            120        19 NMSC (BCC        Heart, kidney,   SS Use                P
                                                                                                                                                          and SCC) (8         and liver tx (20 cSCC                  P < 0.01
                                                                                                                                                          SCC, 11 BCC)        each)            BCC                   Not significant
                                                        Sun Exposure    Vadnerkar et al       Retrospective         USA - Pittsburgh,          543        17 SCC              Lung                Risk factor:       SCC P value
                                                                        2010                  Cohort                PA                                                                            Residence in       P = 0.0001
                                                                                                                    (2003-2008)                                                                   region with high
                                                                                                                                                                                                  sun exposure
                                                                        Caforio et al 2000    Prospective           Italy                      300        53 SCC and 37       Heart               Risk factor:       SCC HR (95% CI)
                                                                                              Cohort                                                      BCC                                     high sunlight      7.6 (2.5-22.8)
                                                                                                                                                                                                  exposure           P
                                                                                                                                                                                                                     P = 0.0003
                                                                        Rodriguez-Acosta      Case-control          Mexico                     140        59 SCC and 19       Kidney and          Risk factor:       NMSC OR (95% CI) (P)
                                                                        et al 2015                                  (2011-2012)                           BCC                 liver               total sun burden   19 (3-120) (P < 0.001)
                                                                                                                                                                                                  (recreational +
                                                                                                                                                                                                  occupational)
                                                                        Iannacone et al       Prospective           Queensland,                495        135 NMSC (41        Kidney and          Risk factor:       NMSC PR (95% CI)
                                                                        2016                  Cohort                Australia                             cSCC, 50 BCC,       liver               Born in            2.38 (1.28-4.42)
                                                                                                                    (2012-2014)                           77 Bowen)                               Australia
                                                       HR = Hazard Ratio; KC = keratinocyte carcinoma; NMSC = non-melanoma skin cancer; OR = Odds Ratio; PR = Prevalence Ratio; SS = Sunscreen.




5
Results                                                                    patients older than age 18 and collected one of the four
                                                                           UV modifying factors. These studies included solid organ
Thirteen studies were selected for review after assessing                  transplants of the: kidney, heart, lung, liver, and pancreas.
a total of 480 full-text studies. Overall, the 13 studies in-              Dates for incorporated studies ranged from 2000 to 2022
cluded 6910 patients with solid organ transplantations in                  (Figure 1).




          Figure 1. Flowchart of the identification of eligible studies.



6                                                                                        Review | Dermatol Pract Concept. 2023;13(3):e2023065
   All 13 studies provide adequate data supporting in-            NMSC incidence and found that higher tumor accrual rates
creased risk for KC associated with one of the four UV mod-       in both FST I (1.76 SCC/patient per year, 0.61 BCC/patient
ifying risk factors. Seven studies explored FST impact and        per year) and FST II (2.41 SCC/patient per year, 0.64 BCC/
found that SOTR with lower FST (FST I and II) have an             patient per year) compared to FSTs III, IV, and V [22]. A simi-
increased incidence of KC. One study identified the impact        lar association was reported in an Italian cohort study where
race has on KC incidence; the results indicated that white        FST II was found to be a significant risk factor (HR=2.60)
SOTR patients had a higher KC incidence than non-white            in NMSC incidence in heart SOTR compared to FSTs III, IV,
SOTR. Within the non-white population, Latinx SOTR had            and V [23]. Although the Australian study noted both SCC
the highest KC incidence. Two studies examined the impact         and BCC, it is vital to point out the increased SCC:BCC r­ atio
of sunscreen application and suggested that controlled ap-        (2.86:1), an association comparable with previous studies
plication of sunscreen can significantly reduce KC incidence      [24,25]. Additionally, FST I patients specifically had a much
in SOTR. Lastly, four studies explored sun exposure as a UV       higher SCC:BCC ratio compared to other FSTs. It is imper-
modifying factor and found that both occupational sun ex-         ative for clinicians to keep this increased SCC:BCC ratio in
posure and residence sun exposure are major contributors to       mind when treating SOTR patients as this impacts the regu-
KC incidence in SOTR.                                             larity of skin screenings and requires more patient-centered
                                                                  treatment plans.
The Impact of FST on KC in SOTRs                                     A retrospective and prospective follow-up study exam-
This systematic review explores the incidence of KC in adult      ined the risk factors for NMSC in renal transplant patients.
solid organ transplant recipients of UV modifying risk fac-       Lighter FSTs (I and II) were associated with a significantly
tors, including FST. Seven studies supported an increased         greater risk of NMSC compared to FST ≥III (HR 0.50 +/-
risk in KC for lighter skin FSTs (FST I-II).                      0.27-0.92, P = 0.026) [26]. Interestingly, Garcia et al found
   A major cohort study by Gogia et. al examined 556 or-          an increased BCC:SCC ratio (2.21:1) which conflicts with
gan transplant recipients with skin cancer history between        the studies previously mentioned. This inverse relationship
2004 and 2008 and recorded patient demographics, trans-           between lower FST and higher risk of NMSC in renal trans-
plant type, and FST [19]. SCC incidence and FST displayed         plant patients was also supported by Savoia et al (BCC:SCC
an inverse relationship ie the risk of SCC increased with         ratio 2.1:1) [27].
each incremental decrease in FST. FST I patients had a 1.67-         Lower FST has been shown in numerous studies to be
fold increased risk in developing SCC compared to FST IV          a significant risk factor for incidence of NMSC, and more
patients, but a FST I patients had an even higher, 3.47-fold      specifically, KC, in SOTR. Although previous studies have
risk increase when compared to FST VI patients [19]. This         shown an overall increased SCC:BCC ratio, some studies
trend continued over a 15-year period where SCC incidence         have found a surprisingly increased BCC:SCC ratio. There
of FST I participants was 68% compared to 27% in FST              is a need for additional well-designed prospective studies to
VI participants. However, the 15-year SCC incidence rates         be included in the literature to further distinguish the factors
for FST II and FST III participants were 66% and 63%, re-         which affect varying SCC and BCC ratios.
spectively, indicating that fair skin types were more likely to
have to develop SCC than the overall population. This trend       The Impact of Race on KC in SOTR
was observed in an earlier study examining skin cancer de-        Although race is associated with FST, many environmental,
velopment in renal transplant recipients. Out of the 44 sub-      socioeconomic, genetic, and patient outcome factors con-
jects that developed squamous cell carcinomas, 52.3% were         tribute to race as a distinct identifier. Along with FST, race
of FST I while 25.0% were of FST II [20]. The remaining           also contributes to SCC incidence in SOTR. A retrospective
22.7% were of FST III and FST IV. The results of this study       cohort study examining the incidence of SCC in SOTR from
were also suggestive that SCC were more probable to de-           2009 to 2019 found that the annual incidence rate of SCC in
velop in lighter skin type individuals. Furthermore, an Aus-      white SOTR was 4.70% compared to 0.38% in non-white
tralian retrospective cohort study that traced 94 heart and/or    SOTR (African American, Asian American, Latinx, Multiple/
lung transplant patients reported results that also supported     Other, or Unknown) [28]. Additionally, white SOTR were
this trend. Compared to FSTs I-II, FSTs III-VI had a 0.57-fold    more likely to have a history of skin cancers than non-white
decreased risk of developing SCC [21]. Although these stud-       SOTR. This trend was consistent with Kang et al and could
ies reiterated similar trends, some of the variability in SCC     be the result of earlier diagnoses or a greater chance to get a
incidence can likely be attributed to the variability in world-   diagnosis [28,29]. Latinx SOTR also had an increased SCC
wide sun exposure levels and various UV modifying factors.        incidence compared to other non-white groups [28]. Our
   FST also impacts BCC incidence in SOTR. A 60-month             search was limited to one study that examined race associa-
prospective Australian study examined FST impact on               tion with KC incidence in SOTR.



Review | Dermatol Pract Concept. 2023;13(3):e2023065                                                                            7
    Overall, white SOTR had a significantly higher incidence      The Impact of Sun Exposure on KC in SOTR
rate of SCC than non-white SOTR while the Latinx popula-          In addition to sun protective factors, sun exposure has been
tion had an increased SCC incidence when compared to the          shown to be a major contributor to SCC in SOTR. For exam-
remaining non-white group.                                        ple, Queensland, Australia is known for its excessive sunlight
                                                                  exposure [33]. One study of SOTRs found that Australia
The Impact of Sun Protective Factors                              SOTRs had a 10-year NMSC incidence of 70%, compared
on KC in SOTR                                                     to SOTRs in Italy (10%) and Northern Europe (20%) [34].
Sun protective factors, such as sunscreen, are major contrib-     Additionally, this study also found that cumulative amounts
utors to SCC incidence in SOTR. In a 24-month prospec-            of sun exposure strongly predicted the risk of NMSC in both
tive case-control study of 120 patients, treatment groups         the Italian and Australian cohorts [34]. Moreover, the geo-
were divided into a sunscreen group and a control group           graphic impact of Australia sun exposure on NMSC was
to explore the impact of regular application of >60 SPF           supported by Iannacone et al. The authors reported that
sunscreen on SCC incidence in SOTR. The study included            patients born in Australia had a 2.38 prevalence ratio for
heart, kidney, and liver organ transplant recipients (OTR).       NMSC compared to those born outside of Australia [35].
After the 24-month phase, no new invasive SCC occurred               A separate retrospective case-cohort study (1:3 case-to-
in the sunscreen group while control patients developed 8         control ratio) in Pittsburgh examined the impact of high-
new invasive SCC (P < 0.01) (5 heart OTR, 3 kidney OTR,           level sun exposure on SCC incidence in single and double
and 0 liver OTR) [30]. This trend was also supported by an        lung OTR (N = 543). High-level sun exposure was defined
Australian study of 1383 immunocompromised non-SOTR               as residence south of 35° latitude with high to very high UV
patients, demonstrating a similar trend found in both SOTR        indexes. The authors found that residing in high-level sun ex-
and non-SOTR populations [30,31]. Although the initial            posure areas was an independent risk factor for SCC in lung
SOTR case-control study supported the potential protective        OTR (P = 0.0001) [36]. Additionally, 94% of the patients
benefits of sunscreen in decreasing the incidence of SCC, it is   who developed SCC presented on sun-exposed parts of the
imperative to note that a 24-month period is too narrow to        body and this finding may be explained by the impact sun
determine the full development of NMSC.                           exposure has on the increased risk for SCC.
    Lastly, in a single-center retrospective study in Italy,         In addition to residential sun exposure, Savoia et al retro-
Savoia et al examined risk factors for skin cancers in kid-       spective study reported that outdoor occupation was one of two
ney OTR. They found that the two exogenous risk factors           exogenous risk factors significantly associated with skin can-
that were significantly associated with skin cancers were the     cer incidence [27]. Additional studies have also reported sim-
lack of sunscreen use (P = 0.0252) and outdoor occupation         ilar conclusions regarding the association between increased
(P = 0.0413) [27]. Although this controlled trial suggested       outdoor labor and increased risk of skin cancer. A case-control
that sunscreen is a protective factor against SCC in SOTR,        study in Mexico displayed that greater than 20 hours per week
a retrospective study examining NMSC incidence in kidney          of occupational sun exposure was a significant risk factor as-
OTR found that self-reported sunscreen was not a signifi-         sociated with increased NMSC incidence (P < 0.01) [37]. An-
cant protective factor in NMSC incidence [32]. This compar-       other study examined the risk factors for skin cancers in heart
ison highlights the importance of educating SOTR patients         transplant recipients and found that cumulative increased sun
on daily appropriate usage of sunscreen and emphasizing the       exposure during work was independently associated with an
use of higher sunscreen strength to best achieve the potential    increased risk of SCC (P = 0.0003) [23].
reduced risks of the development of SCC.
    Overall, sunscreen may be an effective protective fac-        Limitations
tor to reduce the incidence of NMSC in SOTR. However,             This systematic review has several limitations. The first lim-
due to the limited number of supporting studies, we cannot        itation is the high disparity in quantifiable variables to validly
draw conclusions regarding sunscreen potential protective         measure the effect of UV modifying factors reported in studies.
benefits. Further studies are required to understand the as-      Seven studies supported FST as a risk factor for skin cancer, but
sociation between sunscreen and NMSC development. Addi-           only one study supported race as a risk factor for cancer, even
tionally, although SPF was not a controlled variable, further     though both race and FST are factors determined by skin phe-
research is required to determine the effect of varying SPF       notype. Therefore, we require more standardized protocols for
intensities in reducing NMSC incidence in SOTR. Future,           SOTR studies that monitor KC to collect demographics such
prospective studies interested in this relationship should        as race to further support its impact on increased KC incidence.
also explore determining an adequate cut-off point for SPF        Additionally, we were unable to account for the effect of time
strength that is associated with a significantly decreased risk   from SOTR status to KC presentation, and how this would be
for NMSC.                                                         related to various UV modification habits in SOTR patients.



8                                                                             Review | Dermatol Pract Concept. 2023;13(3):e2023065
   Lastly, although we analyzed the influence of exoge-            SOTR in comparison to kidney SOTR [39]. Gjersvik et al
nous factors on the development of NMSC, our review                further confirmed this finding by displaying a 2.8-fold
did not account for the impact of immunosuppression.               higher risk [40]. The increased risk can be explained by
Pharmacological immunosuppression is necessary for                 the elevated immunosuppressive dosage by heart SOTR
post-operative SOTR and is deemed the biggest risk factor          compared to kidney SOTR [39]. Additionally, numerous
contributing to NMSC incidence in SOTR [38]. NMSC                  studies have concluded that NMSC incidence increases in
incidence rates are proportional to the type of organ              proportion to immunosuppressive duration [26,33,41,42].
transplant, immunosuppressant type, dosage, and dura-              We presented immunosuppressive drugs, percent distribu-
tion of the drug [39]. A single-center Norwegian study             tion of drug types, and median time of immunosuppres-
found a 3-fold higher risk of developing SCC in heart              sion for all included patients in Table 3.

         Table 3. Immunosuppressive drugs, percent distribution of drug types, and median time
                  of immunosuppression from studies included in retrospective analysis.
                                                                                              % of
           Study                              Type of Immunosuppressant                       SOTR           Median time
 Gogia et al 2013             NR                                                            NR          NR
 Moloney et al 2005           Cyclosporine, Azathioprine, and Prednisolone                  NR          NR
 De Rosa et al 2019           NR                                                            NR          8.4 years (range:
                                                                                                         0.4-27 years)
 Dusendang et al 2022         Mycophenolate mofetil and Tacrolimus                          93%         15 months
                              Other Mycophenolate                                           53%         4 months
                              Other Tacrolimus                                              44%         4 months
 Savoia et al 2011            Tacrolimus                                                    58.9%       7.2 years
                              Cyclosporine                                                  36.2%
                              Azathioprine, Mycophenolate, and Sodium mofetil               NR
 Ng et al 2014                Calcineurin inhibitors (Cyclosporine or Tacrolimus),          53%         11.6 years
                              Mycophenolate mofetil, and Prednisolone                                   (+/- 8.2 years)
                              Azathioprine, Mycophenolate mofetil, and Prednisolone         27%
 Garcia et al 2013            Mycophenolate, mTOR-Sirolimus, and/or Everolimus              6.2%        NR
                              inhibitors
                              Tacrolimus and Mycophenolate                                  66.4%
                              Cyclosporine and Mycophenolate                                25.6%
                              Older regimens and Azathioprine                               1.7%
 Ducroux et al 2014           Cyclosporine                                                  19.5%       8.2 years
                              Tacrolimus                                                    95.7%
                              Sirolimus                                                     20.8%
 Caforio et al 2000           Cyclosporin A and Azathioprine                                79.3%       NR
                              Cyclosporin A, Azathioprine, and prednisone                   20.7%
 Ulrich et al 2009            Cyclosporine, Prednisolone, and Mycophenolate or              33.3%       24 months
                              Azathioprine
                              Tacrolimus, Mycophenolate, and Prednisolone                   33.3%
                              Tacrolimus                                                    33.3%
 Vadnerkar et al 2010         Calcineurin inhibitor, Mycophenolate, and Prednisolone        88.2%       NR
                              Voriconazole                                                  23.5%       6 months
                              Voriconazole                                                  76.5%       > 6 months
 Rodriguez-Acosta et al       Cyclosporine, Azathioprine, and Prednisolone                  NR          NR
 2015
 Iannacone et al 2016         Calcineurin inhibitor, Antiproliferative agent, and           53.5%       8.9 years
                              Corticosteroid
                              Calcineurin inhibitor with or without Corticosteroid          35.5%
NR = not reported ; SOTR = solid organ transplant recipients.



Review | Dermatol Pract Concept. 2023;13(3):e2023065                                                                        9
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Review | Dermatol Pract Concept. 2023;13(3):e2023065                                                                                            11
