Acta Dermato-Venereologica 99-10CompleteContent | Page 30
SHORT COMMUNICATION
929
Extreme Incidence of Skin Cancer in Kidney and Liver Transplant Recipients Living with High Sun
Exposure
Elsemieke I. PLASMEIJER 1,2# , Zainab JIYAD 1,3# , Mandy WAY 4 , Louise MARQUART 4 , Kyoko MIURA 1 , Scott CAMPBELL 5 ,
Nikky ISBEL 5 , Jonathan FAWCETT 6 , Lisa E. FERGUSON 1 , Marcia DAVIS 1 , David C. WHITEMAN 1 , H. Peter SOYER 7,8 , Peter
O’ROURKE 4 and Adele C. GREEN 1,9
1
Cancer and Population Studies Group, QIMR Berghofer Medical Research Institute, Locked Bag 2000 Royal Brisbane Hospital, Brisbane,
Queensland 4029, Australia, 2 Department of Dermatology, Erasmus Medical Centre, Erasmus University Rotterdam, Rotterdam, The
Netherlands, 3 Institute of Cardiovascular and Cell Sciences (Dermatology Unit), St George’s University of London, London, UK, 4 Statistics Unit,
QIMR Berghofer Medical Research Institute, 5 Department of Nephrology, 6 Queensland Liver Transplant Service, University of Queensland,
Princess, Alexandra Hospital, 7 Dermatology Research Centre, The University of Queensland, The University of Queensland Diamantina
Institute, 8 Department of Dermatology, Princess Alexandra Hospital, Brisbane, Queensland, Australia, and 9 CRUK Manchester Institute and
Faculty of Biology, Medicine and Health, University of Manchester, Manchester Academic Health Sciences Centre, Manchester, UK. E-mail:
[email protected]
#
These authors contributed equally
Accepted Jun 13, 2019; E-published Jun 14, 2019
Skin cancer is a major cause of morbidity and mortality in
organ transplant recipients (OTRs) but accurate data about
the extent of the problem are lacking. Cutaneous squamous
cell carcinoma (SCC) causes the greatest burden with es-
timated incidence in European OTRs 60 to 200 times the
general population rates (1, 2). Causes include immunosup-
pression and solar ultraviolet (UV) radiation, but oncogenic
viruses and carcinogenic drugs may also contribute (3).
Most studies report cumulative incidence and are not
transplant organ-specific. Annual incidence rates of SCC
and basal cell carcinoma (BCC) in kidney transplant re-
cipients have been published, but none in liver recipients
(4–7). Furthermore, previous studies have failed to assess
multiple skin cancers, though this is crucial for evaluating
true skin cancer burdens for health service planning. This
is especially true in countries like Australia with high
skin cancer rates but no standard surveillance programs
for OTRs (8–10). We therefore prospectively measured
incidence rates of SCC and BCC in high-risk kidney and
liver transplant recipients in Queensland.
The Skin Tumors in Allograft Recipients (STAR) study
cohort comprised adult (≥18 years) high-risk, single-organ
kidney and liver transplant recipients recruited at Princess
Alexandra Hospital, 2012–2014. High-risk OTRs were
defined as (i) white-skinned and (ii) either aged ≥ 40 years,
immunosuppressed ≥ 10 years, or having previous skin can-
cer or actinic keratosis (AK). Focus on this high-risk group
allowed characterization of OTRs who develop the bulk of
skin cancers. OTRs newly receiving systemic retinoid or
topical treatments and those with major co-morbidity were
excluded. The study had ethical approval; all participants
provided written informed consent. At recruitment, parti-
cipants completed questionnaires providing demographic
information and histories of sun exposure, treated skin
cancer, skin examination frequency and sun protection
(clothing, sunscreen). OTRs underwent full skin exami-
nations by trained physicians who recorded skin colour,
AKs and skin lesions on a body map, referring patients with
suspicious lesions for management (11). Prevalent tumours
identified at baseline (11) were excluded from analyses.
Full skin examinations were repeated annually, to mid-
2016. To ensure documentation of all new skin cancers,
several methods were employed: quarterly telephone calls
to participants about recent treatment; ‘treatment cards’ for
physicians to record skin cancer diagnoses; regular review
of public and private pathology databases.
Baseline characteristics were compared using Pearson’s
chi-squared test. Keratinocyte cancers (KC) included
SCC, BCC and intraepidermal carcinoma (IEC). Organ-
specific person-based IRs/1,000 person-year (py) were
determined by the first SCC or BCC during follow-up. To
account for multiple skin cancers per person we calculated
tumour-based incidence of cancers as total number of
SCCs [or BCCs]/total time in study. IRs were calculated
as crude rates and also age-standardized to the 2001 Aus-
tralian Population. To identify risk factors for multiple
SCCs and KCs, we used negative binomial regression
with offset to calculate incidence rate ratios (IRRs) and
95% CIs, adjusted for age and sex. Variables that defined
high-risk OTRs were excluded in multivariable analyses.
Analyses were performed using SAS 9.4.
Of 458 kidney and 276 liver transplant recipients who
were eligible, 289 kidney (63%) and 205 liver (74%) trans-
plant recipients were recruited. Main reasons for declining
were difficulty attending study clinics (due to distance/
time), or already having skin cancer monitoring by phy-
sician. Thirteen (3%) did not have baseline examination
and 5 (1%) were lost to follow-up, resulting in 476 OTRs
(281 kidney, 195 liver) analysed. Total follow-up varied
by organ: 637 py for kidney and 475 py for liver recipients
(3–36 months) (see Table SI 1 for baseline characteristics).
During follow-up, 265 OTRs developed 2,575 KCs (523
BCCs, 701 SCCs and 1351 IECs). Kidney recipients had
higher age-standardized SCC IRs (119 and 309/1,000 py,
person- and tumour-based respectively) than liver reci-
pients (corresponding IRs, 79 and 206/1,000 py) (Table
I), similarly for BCC. Seven OTRs (3 kidney, 4 liver)
developed melanoma and two, Merkel cell carcinoma.
Two Kaposi sarcomas, one sebaceous carcinoma, one
atypical fibroxanthoma occurred in 4 kidney recipients.
https://www.medicaljournals.se/acta/content/abstract/10.2340/00015555-3234
1
This is an open access article under the CC BY-NC license. www.medicaljournals.se/acta
Journal Compilation © 2019 Acta Dermato-Venereologica.
doi: 10.2340/00015555-3234
Acta Derm Venereol 2019; 99: 929–930