1. Photosensitizing Antihypertensive Drug Use and Risk of Cutaneous Squamous Cell Carcinoma
K.A. Su,1,2 L.A. Habel,3 N.S. Achacoso,3 G.D. Friedman,3 M.M. Asgari1,2
1 Massachusetts General Hospital, Harvard Medical School, Boston, M.A., U.S.A.
2 Harvard Pilgrim Health Care Institute, Harvard Medical School, Boston, M.A., U.S.A.
3 Kaiser Permanente Northern California, Oakland, C.A., U.S.A.
British Journal of Dermatology. DOI: /bjd.16713

2. Dr. Katherine A. Su

3. Introduction What’s already known?
Certain antihypertensive drugs are photosensitizing, heightening reactivity of the skin to sunlight.
Photosensitizing antihypertensive drugs may act as carcinogens by triggering:
phototoxic reactions: produce DNA damage
photoallergic reactions: produce chronic inflammation
Photosensitizing antihypertensive drugs have been associated with lip cancer, but their impact on cutaneous squamous cell carcinoma (cSCC) risk is unclear.

4. Objective
To examine the association between antihypertensive drug use and cSCC risk among a cohort of non- Hispanic whites with hypertension enrolled in a comprehensive integrated healthcare delivery system in northern California.

5. Methods Study Design: Retrospective cohort study, 1997-2012
Study Setting: Kaiser Permanente Northern California
Study Population: 28,357 non-Hispanic whites with hypertension enrolled in the Research Program in Genes and Environmental Health

6. Methods Exposure: Pharmacy-dispensed antihypertensive drug
Photosensitizing
Alpha-2 receptor agonists
Diuretics (loop, potassium-sparing, thiazide, combination)
Unknown photosensitizing
Angiotensin converting enzyme inhibitors
Calcium channel blockers
Vasodilators
Other combinations
Non-photosensitizing
Alpha-blockers
Beta-blockers
Central agonists
Angiotensin receptor blockers

7. Methods Outcome: Pathologically-verified cSCC
Statistical Analysis: Cox modelling
Covariates:
Age
Sex
Cigarette use
Charlson Comorbidity Index
Healthcare utilization
Surveillance measure
Length of health plan membership
Survey year
Prior cSCC
Prior actinic keratosis
Prior photosensitizing antihypertensive drug use

8. Results: Cohort characteristics
Overall
(n=28,357)
Ever use of
Non-use of ADs (n=1,530)
Photosensitizing ADs (n=17,946)
Non-photosensitizing ADs (n=19,092)
Unknown
photosensitizing ADs (n=17,345)
Age (at cohort entry): Mean (±SD)
69.1 (10.6)
69.3 (10.4)
69.9 (10.2)
70.1 (10.2)
67.9 (12.7)
Sex, n (%)
Male
12,382 (43.7)
7,268 (40.5)
8,952 (46.9)
8,193 (47.2)
652 (42.6)
Female
15,975 (56.3)
10,678 (59.5)
10,140 (53.1)
9,152 (52.8)
878 (57.4)
Prior cSCC, n (%)
Yes
2,228 (7.9)
1,329 (7.4)
1,487 (7.8)
1,352 (7.8)
217 (14.2) No
26,129 (92.1)
16,617 (92.6)
17,605 (92.2)
15,993 (92.2)
1,313 (85.8)
Prior photosensitizing AD use, n (%)
20,994 (74.0)
16,189 (90.2)
14,244 (74.6)
12,921 (74.5)
791 (51.7)
7,363 (26.0)
1,757 (9.8)
4,848 (25.4)
4,424 (25.5)
(48.3)
AD: antihypertensive drug

9. Results: Hazard ratios for cSCC among cohort members
Treatment (after cohort entry)
cSCC, n (%)
Person-years of follow-up
Unadjusted HR (95% CI)
Adjusted HR (95% CI)
Overall (n=28,357)
3,010 (100)
144,215
Non-use of ADs (n=1,530)
371 (12.3)
19,222
1.00 (Reference)
Ever use of photosensitizing ADs (n=17,946)
1,720 (57.1)
76,881
1.21 (1.12, 1.31)
1.17 (1.07, 1.28)
Ever use of non-photosensitizing ADs (n=19,092)
1,862 (61.9)
83,414
1.23 (1.14, 1.33)
0.99 (0.91, 1.07)
Ever use of unknown photosensitizing ADs (n=17,345)
1,717 (57.0)
73,300
1.35 (1.25, 1.46)
1.11 (1.02, 1.20)
AD: antihypertensive drug

10. AD: antihypertensive drug
Results: Hazard ratios for cSCC based on number of prescriptions for ADs filled
Treatment (after cohort entry)
cSCC cases,
n (%)
Person-years of follow-up
Unadjusted HR
(95% CI)
Adjusted HR
Non-use of ADs
371 (12.3)
19,222
1.00 (Reference)
Use of photosensitizing ADs
1-7 fills
862 (28.6)
40,173
1.17 (1.06, 1.28)
1.12 (1.02, 1.24)
8-15 fills
610 (20.3)
27,071
1.21 (1.09, 1.35)
1.19 (1.06, 1.34)
16+ fills
248 (8.2)
9,637
1.42 (1.21, 1.66)
1.41 (1.20, 1.67)
Use of non-photosensitizing ADs
768 (25.5)
36,284
1.18 (1.07, 1.30)
0.99 (0.89, 1.09)
625 (20.8)
27,326
1.27 (1.14, 1.41)
1.02 (0.92, 1.14)
469 (15.6)
19,804
1.30 (1.14, 1.47)
0.95 (0.83, 1.07)
Use of unknown photosensitizing ADs
782 (26.0)
34,182
1.33 (1.21, 1.46)
1.12 (1.02, 1.23)
561 (18.6)
23,649
1.37 (1.23, 1.53)
1.12 (1.01, 1.25)
374 (12.4)
15,469
1.38 (1.21, 1.57)
1.06 (0.93, 1.21)
AD: antihypertensive drug

11. Discussion
This large cohort study examined the association between antihypertensive drug use and cSCC risk.
This study suggests that use of photosensitizing antihypertensive drugs is associated with a 17% higher risk of cSCC compared with non-use.
There was a modest increase in cSCC risk with increasing number of prescriptions for photosensitizing antihypertensive drugs.

12. Conclusions What does this study add?
This study provides support for an increased cSCC risk among individuals treated with photosensitizing antihypertensive drugs.
Patients taking photosensitizing antihypertensive drugs may benefit from education on safe sun practices and closer screening for cSCC.

13. Ninah S. Achacoso (not pictured)
Research Team
Katherine A. Su
Laurel A. Habel
Gary D. Friedman
Maryam M. Asgari
Ninah S. Achacoso (not pictured)

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