ORIGINAL ARTICLE

Personal history of psoriasis and risk of

nonmelanoma skin cancer (NMSC)
among women in the United States:
A population-based cohort study
Hongji Dai, PhD,a,b,c Wen-Qing Li, PhD,d,e Abrar A. Qureshi, MD, MPH,d,e,f and Jiali Han, PhDa,b,c,f
Tianjin, China; Indianapolis, Indiana; Providence, Rhode Island; and Boston, Massachusetts

Background: To our knowledge, no prospective studies have examined the association between personal
history of psoriasis and risk of nonmelanoma skin cancer.

Objective: We sought to examine this association based on 2 prospective cohorts, the Nurses’ Health Study
and Nurses’ Health Study II.

Methods: Diagnoses of nonmelanoma skin cancer, including basal cell carcinoma and squamous cell
carcinoma (SCC), were obtained by self-reported questionnaires. Information on clinician-diagnosed
psoriasis and diagnosis year was collected and validated with a supplementary questionnaire.

Results: After 2,487,941 and 2,478,148 person-years of follow-up, we documented 1725 SCC cases and
16,075 basal cell carcinoma cases, respectively. For the combined cohorts, personal history of psoriasis was
associated with an elevated risk of SCC, with a multivariate-adjusted relative risk (RR) of 1.51 (95%
confidence interval [CI] 1.11-2.05). The associations appeared stronger with increasing psoriasis severity,
with RR of 1.42 (95% CI 0.94-2.15) in the mild psoriasis group and RR of 1.99 (95% CI 0.74-5.32) in the
moderate to severe psoriasis group (P trend = .03). There was no association between psoriasis and the risk
of basal cell carcinoma (RR 0.95; 95% CI 0.75-1.18).

Limitations: Lack of treatment data may bias the result.

Conclusion: Personal history of psoriasis may be associated with an increased risk of SCC. Further
investigations are warranted to understand the underlying mechanisms. ( J Am Acad Dermatol http://
dx.doi.org/10.1016/j.jaad.2016.05.021.)

Key words: basal cell carcinoma; cohort study; nonmelanoma skin cancer; psoriasis; squamous cell
carcinoma.

P soriasis is a chronic inflammatory disorder
that mainly affects skin and is characterized
by excessive growth and aberrant differenti-
ation of keratinocytes. There is increasing awareness
that psoriasis is more than a skin disorder and that it
has important systemic manifestations that it shares
with other chronic diseases, including metabolic
syndrome, depression, and cancer.1
Previous studies suggest that patients with psori-
asis seem to be at an increased risk of developing
certain cancers (eg, lymphoma and skin cancer),
especially patients with long psoriasis duration and

From the Department of Epidemiology and Biostatistics, National
Clinical Research Center for Cancer, Key Laboratory of Cancer
Prevention and Therapy of Tianjin, Tianjin Medical University
Cancer Institute and Hospitala; Department of Epidemiology,
Richard M. Fairbanks School of Public Health,b and Melvin and
Bren Simon Cancer Center,c Indiana University; Department of
Dermatology, Warren Alpert Medical School,d and Department
of Epidemiology, School of Public Health,e Brown University,
Providence; and Channing Division of Network Medicine,
Department of Medicine, Brigham and Women’s Hospital and
Harvard Medical School, Boston.f
Funding sources: This study was supported by the National Institutes
of Health grants [R01 CA186107, CA87969, and CA176726].
Conflicts of interest: None declared.
Accepted for publication May 5, 2016.
Reprint requests: Jiali Han, PhD, Department of Epidemiology,
Richard M. Fairbanks School of Public Health, Indiana
University, 714 N Senate Ave, Indianapolis, IN 46202. E-mail:
jialhan@iu.edu.
Published online July 15, 2016.
0190-9622/$36.00
Ó 2016 by the American Academy of Dermatology, Inc.
http://dx.doi.org/10.1016/j.jaad.2016.05.021

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n 2016

possibly severe disease.2,3 Squamous cell carcinoma Identification of NMSC and covariates
(SCC) was shown to be associated with severe Diagnoses of NMSC were obtained by self-
psoriasis, especially for those treated with psoralen reported questionnaires biannually. With partici-
and ultraviolet (UV)A,3-5 cyclosporine,6 metho- pants’ permission, medical records of SCC cases
trexate,7 or other radiation therapies. However, it is were reviewed and verified by primary pathology
unclear if the treatments for psoriasis or the disease reports. Medical records were not obtained for
itself explain this association. For most patients with self-reported cases of basal cell carcinoma (BCC),
mild psoriasis, their cancer because previous reports
risk is unclear. demonstrated the high valid-
CAPSULE SUMMARY
This study aimed to pro- ity of self-report of BCC.13,14
spectively investigate the as- d Patients with severe psoriasis are at an Covariates obtained from
sociation between a personal increased risk of developing certain questionnaires in both co-
history of psoriasis and risk cancers. horts in the 1980s included
of incident nonmelanoma body mass index, exercise,
skin cancer (NMSC), based
d Our cohort study suggests that mild alcohol intake, smoking
on a prospective analysis of psoriasis is associated with an elevated status, family history of
the Nurses’ Health Study risk of squamous cell carcinoma, but not melanoma, number of severe
(NHS) and NHS II, at the basal cell carcinoma. sunburns, mole count on the
population level. d Providers should be aware of increased left arm, natural hair color,
skin cancer risk among patients with and UV index at birth, age
psoriasis. 15 years, and age 30 years.
METHODS According to the state of
Study population residence, the UV index at
Participants were from 2 birth and age 15 and 30 years was categorized into 1
ongoing prospective cohort studies: the NHS and of 3 ranges (#5, 6, or $7). We do not have Fitzpatrick
NHS II. In brief, the NHS was established in 1976 skin types for the participants.
when 121,701 married, female registered nurses who
were 30 to 55 years of age and living in the United Statistical analysis
States were enrolled using a mailed questionnaire. Participants who reported NMSC that occurred
The NHS II was established in 1989 when 116,671 before the beginning of follow-up were excluded.
female nurses aged 25 to 42 years completed a Person-years of follow-up for each participant
mailed questionnaire. Details of these cohorts have were calculated from the return date of baseline
been described previously.8,9 questionnaire (1996 for NHS and 1991 for NHS II) to
The protocol for this study was approved by the the date of diagnosis of BCC or SCC, or the cut-off
Institutional Review Board at Brigham and Women’s date (June 2012 for NHS, and June 2011 for NHS II),
Hospital and the Harvard School of Public Health. whichever came first.
Cox proportional hazards analysis was conducted
to estimate the age- and multivariate-adjusted
Assessment of exposure relative risks (RR) and 95% confidence intervals
A personal history of psoriasis was assessed by (CI) for the association between psoriasis and
self-reported questionnaire. In 2008, the NHS incident NMSC. Risk of BCC and SCC were calculated
participants were asked whether they had psoriasis separately. Covariates in the multivariable analysis
diagnosed by a medical provider and the date of included age, body mass index, exercise, and other
diagnosis. In 2005, NHS II participants were asked skin cancererelated factors. An indicator was
the same questions. Self-reported psoriasis was created for the missing data of each covariate. The
confirmed using the Psoriasis Screening Tool10 and combined RRs were calculated by pooling the RRs of
validated by mailed questionnaires. The confirmed NHS and NHS II using a random-effect meta-analysis
cases are participants who confirmed the diagnosis model.
on the supplementary questionnaire and met criteria Further analyses were performed according to
for psoriasis. Involved body surface area was also severity of psoriasis, which was categorized as
measured using the palm in the following categories: none/very little psoriasis, mild psoriasis (#2 palms),
none/very little psoriasis and 1 to 2, 3 to 4, 5 to 10, 11 or moderate to severe psoriasis (3-$4 palms).
to 20, or more than 20 palm areas.11,12 Participants Trend tests were carried out using medians
who have information on psoriasis serve as the base in different categories. The median values for
population. the categories was 0 for none/very little psoriasis,
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Abbreviations used:
BCC: basal cell carcinoma
CI: confidence interval
NHS: Nurses’ Health Study
NMSC: nonmelanoma skin cancer
RR: relative risk
SCC: squamous cell carcinoma
UV: ultraviolet
1 for mild psoriasis, and 3 for moderate to severe
psoriasis.
All statistical analyses were conducted using
software (SAS, Version 9.2, SAS Institute, Cary, NC).
All statistical tests were 2-tailed, and the significance
level was set at P less than .05.
RESULTS
A total of 157,934 participants were enrolled in
our study, including 63,054 from the NHS and 94,880
from the NHS II. The percent of personal history of
psoriasis at baseline was 1.8% and 1.6% in the NHS
and NHS II, respectively. Characteristics of the
participants according to the diagnosis of psoriasis
at the beginning of the follow-up are listed in Table I.
Women in the NHS II were much younger than those
in the NHS. Compared with psoriasis-free women,
patients with psoriasis were more likely to have
higher body mass index, smoking and alcohol
consumption, and blistering or painful sunburn.
From NHS, 1204 SCC cases and 8899 BCC cases
were documented after 742,172 and 737,081
person-years of follow-up, respectively. From
NHS II, 521 SCC cases and 7176 BCC cases
were documented after 1,745,769 and 1,741,067
person-years of follow-up, respectively. The propor-
tion of SCC among those with NMSC was 11.9% in the
NHS and 6.8% in the NHS II. Overall, women with a
personal history of psoriasis were at increased risk of
developing SCC. There was a borderline significantly
increased risk among patients with psoriasis in the
NHS and a statistically significantly increased risk
among patients with psoriasis in the NHS II.
Compared with women with no psoriasis, the age-
and multivariate-adjusted RRs of SCC were 1.43 (95%
CI 0.98-2.08) and 1.37 (95% CI 0.94-2.00) for psoriatic
women in the NHS and 1.87 (95% CI 1.10-3.17) and
1.84 (95% CI 1.08-3.13) for psoriatic women in the
NHS II. In the meta-analysis of the results from 2
cohorts, the age- and multivariate-adjusted RRs of
SCC were 1.56 (95% CI 1.15-2.12) and 1.51 (95% CI
1.11-2.05). No significant association was found for
risk of BCC (Table II).
We further performed an analysis according to
severity of psoriasis in the study population. The
Dai et al 3
NHS II study participants had no data on severity of
psoriasis. For NHS, there was an increased risk of
SCC according to the severity of psoriasis. The age-
and multivariate-adjusted RRs of SCC in the mild
psoriasis group were 1.52 (95% CI 1.01-2.30) and
1.42 (95% CI 0.94-2.15), respectively, and in
the moderate to severe psoriasis group were 1.89
(95% CI 0.71-5.05) and 1.99 (95% CI 0.74-5.32),
respectively. Although this positive association was
modest, there was a trend toward increased risk of
psoriasis with increasing psoriasis severity (P for
trend 0.03) (Table III).
DISCUSSION
During follow-up of more than 16 years, we found
psoriasis was associated with an increased risk of
SCC. The associations appeared stronger with
increasing severity of psoriasis. No association was
found for BCC. This result is consistent with our
previous finding, which suggested an increased risk
of melanoma and kidney cancer for patients with
psoriasis.15
Previous studies have noted a significantly
increased risk of SCC among hospitalized patients,
who usually have severe disease.4,6,16,17 To our
knowledge, there have been few examinations
based on a well-characterized cohort study.
For patients with less-severe psoriasis, there is
some evidence for a slightly increased risk
for lymphoproliferative cancers and NMSCs.2,18
However, these studies compared only to individuals
with hypertension, not the overall population or
separate SCC and BCC, which may bias the result.
In the current study, our large sample size enabled
us to separate the risk of BCC and SCC. We found a
relatively higher ratio of BCC to SCC (9:1) in our
cohort study, compared with the historical report
(4:1),19 which might reflect age and gender
differences. There are clear differences between
BCC and SCC in their etiology and pathogenesis.20
For example, intermittent UV exposure and
exposure during childhood was causative for the
development of BCC, whereas chronic UV exposure
is more closely associated with SCC. Squamous cells
have a lower tolerance for DNA damage and a lower
apoptotic threshold, which makes apoptosis a
predominant protective mechanism against SCC.
Psoriasis lesions are characterized by accelerated
epidermal proliferation and the infiltration of
inflammatory cells into the papillary dermis. The
less-differentiated basal cells are less likely than
squamous cells to undergo apoptosis. Another
reason for this difference could be gene mutation
during tumor progression. SCC is associated with
4 Dai et al J AM ACAD DERMATOL
n 2016

Table I. Age-standardized baseline characteristics of women according to history of psoriasis in the Nurses’
Health Study and Nurses’ Health Study II cohorts
NHS NHS II
Characteristics No psoriasis, n = 61,917 Psoriasis, n = 1137 No psoriasis, n = 93,372 Psoriasis, n = 1508
Mean age, y (SD)* 62.6 (6.8) 62.1 (6.5) 36.1 (4.7) 36.7 (4.7)
Body mass index, kg/m2 (SD) 26.9 (5.3) 27.8 (5.7) 24.6 (5.3) 25.9 (6.4)
Physical activity, MET-h/wk (SD) 18.0 (21.8) 16.9 (20.5) 20.8 (26.8) 18.6 (24.9)
Alcohol consumption, g/d (SD) 4.9 (8.8) 6.0 (10.4) 3.1 (6.0) 3.6 (7.8)
Current smoker, % 10 12 12 17
Family history of melanoma, % 5 6 4 4
No. of sunburns $6, % 7 7 10 12
No. of moles $6, % 4 4 21 20
Blistering or painful burn, % 13 16 23 27
Red-blonde hair, % 14 15 20 22
UV-index at age 15 y $7, % 12 11 24 23
UV-index at age 30 y $7, % 18 18 31 32
UV-index at birth $7, % 12 11 23 23

Characteristics of participants without squamous and basal cell carcinoma at the beginning of follow-up (return date of the 1996 and 1991
questionnaires, respectively, for NHS and NHS II).
MET, Metabolic equivalent; NHS, Nurses’ Health Study; UV, ultraviolet.
*Value is not age adjusted.

Table II. Relative risk of incident nonmelanoma skin cancer according to psoriasis
Person-y/cases
Psoriasis No psoriasis RR (95% CI)* RR (95% CI)y
NHS
SCC 12,011/28 730,161/1176 1.43 (0.98-2.08) 1.37 (0.94-2.00)
BCC 11,927/158 725,154/8741 1.07 (0.92-1.26) 1.06 (0.90-1.24)
NHS II
SCC 21,812/14 1,723,957/507 1.87 (1.10-3.17) 1.84 (1.08-3.13)
BCC 21,767/87 1,719,300/7089 0.82 (0.67-1.02) 0.83 (0.67-1.03)
Combined
SCC 33,823/42 2,454,118/1683 1.56 (1.15-2.12) 1.51 (1.11-2.05)
BCC 33,694/245 2,444,454/15,830 0.95 (0.74-1.21) 0.95 (0.75-1.18)

BCC, Basal cell carcinoma; CI, confidence interval; NHS, Nurses’ Health Study; RR, relative risk; SCC, squamous cell carcinoma.
*Adjusted for age.
y
Adjusted for age, body mass index (\21.0, 21.0-22.9, 23.0-24.9, 25.0-26.9, 27.0-29.9, 30.0-32.9, 33.0-34.9, 35.0-39.9, or $40.0 kg/m2), exercise
(\3.0, 3.0-8.9, 9.0-17.9, 18.0-26.9, or $27.0 metabolic equivalent h/wk), alcohol intake (no, \4.9, 5.0-14.9, or $15.0 g/d), smoking status
(never, past, and current with 1-14, 15-24, or $25 cigarettes/d), family history of melanoma (yes or no), nevi counts on extremity,
susceptibility to burn, hair color, number of severe or blistering sunburns, and ultraviolet index at birth, age 15 y, and age 30 y.

Table III. Relative risk of squamous cell carcinoma according to severity of psoriasis in Nurses’ Health Study
Person- y Cases RR (95% CI)* RR (95% CI)y
No psoriasis 730,161 1176 1.00 1.00
Mild psoriasis 9292 23 1.52 (1.01-2.30) 1.42 (0.94-2.15)
Moderate-severe psoriasis 1317 4 1.89 (0.71-5.05) 1.99 (0.74-5.32)
P trend 0.02 0.03

Nurses’ Health Study II data were not shown because study participants did not have data on the severity of psoriasis.
CI, Confidence interval; RR, relative risk.
*Adjusted for age.
y
Adjusted for age, body mass index (\21.0, 21.0-22.9, 23.0-24.9, 25.0-26.9, 27.0-29.9, 30.0-32.9, 33.0-34.9, 35.0-39.9, or $40.0 kg/m2), exercise
(\3.0, 3.0-8.9, 9.0-17.9, 18.0-26.9, or $27.0 metabolic equivalent h/wk), alcohol intake (no, \4.9, 5.0-14.9, or $15.0 g/d), smoking status
(never, past, and current with 1-14, 15-24, or $25 cigarettes/d), family history of melanoma (yes or no), nevi counts on extremity,
susceptibility to burn, hair color, number of severe or blistering sunburns, and ultraviolet index at birth, age 15 y, and age 30 y.
J AM ACAD DERMATOL
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UV-induced TP53 mutations and is more dependent
on sunlight than BCC or melanoma.21
Our study has several strengths. First, our findings
were based on 2 large prospective cohort studies
with a large sample size and long follow-up. Second,
we were able to thoroughly adjust for the previously
identified risk factors for skin cancer and identified a
personal history of psoriasis as an independent risk
factor for SCC in women. Third, unlike previous data
based on cancer statistics (which provided a sample
of only 9.6% of the population), our data are more
likely to estimate the true incidence of NMSC. Based
on our results, we recommend health providers
should be aware of increased skin cancer risk
when treating patients with psoriasis, even mild
psoriasis. One limitation of this study is that
treatment for patients with psoriasis was not
recorded in our cohorts. Although most patients
were in mild condition in this study, it is possible that
some patients may have received oral or injectable
treatment, which could be carcinogenic. The
stronger association with severe psoriasis could be
a result of the additional effect from the treatment.
In conclusion, this study conducted in 2 large
cohort studies examined the association between
personal history of psoriasis and the risk of incident
NMSC. Patients with mild psoriasis had an increased
risk of developing SCC, and the risk increased with
disease severity. Further investigation into the
mechanisms underlying this association identified
in this study is warranted.
We would like to thank the participants and staff of the
NHS and NHS II for their valuable contributions and the
following state cancer registries for their help: AL, AZ, AR,
CA, CO, CT, DE, FL, GA, ID, IL, IN, IA, KY, LA, ME, MD, MA,
MI, NE, NH, NJ, NY, NC, ND, OH, OK, OR, PA, RI, SC, TN,
TX, VA, WA, WY. The authors assume full responsibility for
analyses and interpretation of these data.
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