SUPPLEMENTARY MATERIAL
Mortality in cancer patients previously diagnosed with herpes zoster in the
hospital setting: a nationwide cohort study
Sigrun Alba Johannesdottir Schmidt;1 Gitte Vrelits Sørensen;1 Erzsébet Horváth-Puhó;1 Lars
Pedersen;1 Niels Obel;2 Karin L. Petersen;3 Henrik Carl Schønheyder;1,4 and Henrik Toft Sørensen1
1
Department of Clinical Epidemiology, Aarhus University Hospital, Olof Palmes Allé 43-45, 8200 Aarhus N, Denmark;
2
Department of Infectious Diseases, Copenhagen University Hospital, Rigshospitalet, Blegdamsvej 9, 2100 Copenhagen
Ø, Denmark; 3California Pacific Medical Center Research Institute, 475 Brannan Street, Suite 220, San Francisco, CA
94107, USA; 4Department of Clinical Microbiology, Aalborg University Hospital, Mølleparkvej 10, 9000 Aalborg,
Denmark
CONTENT

Supplementary Materials and Methods. Detailed description of data sources used in the study

Table S1. International Classification of Diseases (ICD) codes used in the study

Table S2. Selected characteristics of persons diagnosed with herpes zoster and subsequent
cancer and a matched cancer cohort, Denmark 1982-2011

Table S3. Mortality following haematological cancer among patients with a prior diagnosis of
herpes zoster compared with a matched cancer cohort, by study characteristics, Denmark
1982-2011

Table S4. Mortality following immune-related cancer among patients with a prior diagnosis
of herpes zoster compared with a matched cancer cohort, by study characteristics, Denmark
1982-2011

Table S5. Mortality following smoking- and alcohol-related cancer among patients with a
prior diagnosis of herpes zoster compared with a matched cancer cohort, by study
characteristics, Denmark 1982-2011

Table S6. Mortality following cancers at ‘all other sites’ among patients with a prior diagnosis
of herpes zoster compared with a matched cancer cohort, by study characteristics, Denmark
1982-2011

Table S7. Mortality following cancer among patients with a prior diagnosis of herpes zoster
compared with a matched cancer cohort, Denmark 1982-2011
Supplementary Materials and Methods. Detailed description of data sources used in the study
In Denmark, the National Health Service provides universal tax-supported healthcare, guaranteeing
unfettered access to general practitioners, outpatient specialty clinics, and hospitals, as well as partial
reimbursement of most prescribed medications (Johannesdottir et al., 2012; Schmidt, Pedersen, &
Sørensen, 2014). Our study was based on information from the Civil Registration System, the Danish
Cancer Registry (DCR), the Danish National Patient Registry (DNPR), and the Danish National
Health Service Prescription Database, which we describe in detail in the following.
The Danish Civil Registration System, established in 1968, contains information on sex,
residence, and dates of death and emigration for all Danish residents (Schmidt et al., 2014). The
registry assigns a unique Civil Personal Register number to all Danish residents at birth or upon
immigration (Schmidt et al., 2014), which permitted accurate and unambiguous linkage of all
registries used in this study. Furthermore, we used the Civil Registration System to identify all
emigrants and decedents during follow-up.
The DCR contains records of all incident cases of malignant neoplasms in Denmark since 1943
and provides details on morphology, histology, and cancer stage at diagnosis (Gjerstorff, 2011).
Throughout our study period, tumours were classified according to the topography and histology
codes in the third revision of the International Classification of Diseases for Oncology (ICD-O-3)
and the tenth revision of the International Classification of Diseases (ICD-10) (Gjerstorff, 2011).
Staging was classified according to Summary Staging as “local”, “regional”, or “distant” from 1943
through 2003, and thereafter according to the 6th revised version of the International Union against
Cancer’s international TNM classification of malignant tumours (Gjerstorff, 2011). Ann Arbour
staging of non-Hodgkin’s and Hodgkin’s lymphomas was available starting in 2004. Until then no
clinically meaningful stage categorization was available for haematological cancers. In the present
study, we used the Summary Staging classification with the TNM and Ann Arbour groupings
translated as follows: localised (TNM: T1–4, N0, M0; Ann Arbour I), regional (TNM: T1–4, N1–3,
M0; Ann Arbour II, IIe), distant (TNM: T1–4, N1–3, M1; Ann Arbour IIs, III-IV), or
unknown/missing. We grouped cancers into subgroups of haematological cancers, immune-related
cancers, smoking- and alcohol-related cancers, and cancers at all other sites (Boffetta & Hashibe,
2006; Boyle, 1997; Nasca, 2001).
The DNPR provides information on all hospital inpatient admissions to non-psychiatric units
since 1977, and on all outpatient clinic (ambulatory) and emergency room visits since 1995 (Lynge,
Sandegaard, & Rebolj, 2011). Patient contacts in general practice are not included in the registry.
Each hospital discharge or outpatient visit is recorded with one primary diagnosis and one or more
secondary diagnoses classified according to a modified Danish version of ICD-8 through 1993 and
ICD-10 thereafter (Lynge et al., 2011). Surgical information is coded according to a Danish
classification (1977 through 1995) and a Danish version of the Nordic Medico-Statistical Committee
(NOMESCO) Classification of Surgical Procedures (from 1996 on) (Lynge et al., 2011).
We used the DNPR to retrieve each patient’s entire hospital diagnosis history between 1977
and the date of cancer diagnosis (inclusive). We categorised levels of comorbidity using the Charlson
Comorbidity Index (CCI) (Charlson, Pompei, Ales, & MacKenzie, 1987). The CCI is a validated
instrument used to predict risk of death from comorbid diseases by weighting 19 major disease
categories based on the relative risk of death (Charlson et al., 1987; Ording & Sørensen, 2013). We
computed a CCI score for each study subject, classifying the level of comorbidity as none (0),
moderate (1), severe (2), or very severe (≥3). In addition, we used a history of any autoimmune
disease, solid organ transplantation, autologous or allogeneic stem cell or bone marrow
transplantation, HIV infection, and other conditions associated with low white blood cell count
(lymphopenia, leukopenia, agranulocytosis, aplastic anaemia, and Felty’s syndrome) as a proxy
measure for immune dysregulation. For stem cell or bone marrow transplantation, solid organ
transplantation, and other conditions associated with a low white blood cell count, we included only
diagnoses made before the date of cancer diagnosis, to ensure that they were not a consequence of the
cancer.
The Danish National Health Service Prescription Database includes information on all
reimbursed prescriptions redeemed at community and outpatient pharmacies with complete coverage
since January 1, 2004 (Johannesdottir et al., 2012). Each time a prescription is redeemed at a
pharmacy, relevant information including the Civil Personal Register number, the date, and the type
and quantity of drug prescribed (according to the Anatomical Therapeutic Chemical Classification
System) is transmitted to the database (Johannesdottir et al., 2012). We used the Prescription
Database to retrieve information on prescriptions for immunosuppressive drugs (TNF-alpha
inhibitors, systemic glucocorticoids, other) redeemed within six months before the cancer diagnosis.
The group of other immunosuppressive drugs included e.g. methotrexate, azathioprine, calcineurin
inhibitors, other biological agents, and intestinal-acting aminosalicylic acid. For identification of
treatment with TNF-alpha inhibitors, we also used treatment codes in the DNPR. To ensure at least
six months of prescription history for all cancer patients, the analysis including presence/absence of
immunosuppressive therapy was restricted to cancer patients diagnosed in July 2004 or later.
References
Boffetta, P., & Hashibe, M. (2006). Alcohol and cancer. The Lancet Oncology, 7(2), 149–156.
Boyle, P. (1997). Cancer, cigarette smoking and premature death in Europe: a review including the
Recommendations of European Cancer Experts Consensus Meeting, Helsinki, October 1996.
Lung Cancer, 17(1), 1–60.
Charlson, M. E., Pompei, P., Ales, K. L., & MacKenzie, C. R. (1987). A new method of classifying
prognostic comorbidity in longitudinal studies: development and validation. Journal of Chronic
Diseases, 40(5), 373–383.
Gjerstorff, M. L. (2011). The Danish Cancer Registry. Scandinavian Journal of Public Health, 39(7
Suppl), 42–45.
Johannesdottir, S. A., Horvath-Puho, E., Ehrenstein, V., Schmidt, M., Pedersen, L., & Sørensen, H.
T. (2012). Existing data sources for clinical epidemiology: The Danish National Database of
Reimbursed Prescriptions. Clinical Epidemiology, 4, 303–313.
Lynge, E., Sandegaard, J. L., & Rebolj, M. (2011). The Danish National Patient Register.
Scandinavian Journal of Public Health, 39(7 Suppl), 30–33.
Nasca, P. C. (2001). Immunity and cancer risk. In P. C. Nasca & H. Pestides, Fundamentals of
Cancer Epidemiology (pp. 225–273). Gaithersburg, NY: Aspen Publishers, Inc.
Ording, A. G., & Sørensen, H. T. (2013). Concepts of comorbidities, multiple morbidities,
complications, and their clinical epidemiologic analogs. Clinical Epidemiology, 5, 199–203.
Schmidt, M., Pedersen, L., & Sørensen, H. T. (2014). The Danish Civil Registration System as a tool
in epidemiology. European Journal of Epidemiology, 29(8), 541–549.
Table S1. Registry codes used in the study
Hospital diagnosis of herpes zoster, all diagnoses
Herpes zoster, uncomplicated
Herpes zoster, complicated
Herpes zoster, localized
Herpes zoster, disseminated
Immunosuppressive drugs
Any of the following within prior 6 months:
TNF-alpha inhibitors
Systemic and intestinal-acting glucocorticoids
Other immunosuppressive agents including e.g.
methotrexate, azathioprine, calcineurin inhibitors,
other biological agents, and intestinal-acting
aminosalicylic acid.
Comorbidities associated with immune
dysregulation
Autologous or allogeneic stem cell or bone marrow
transplantation
Solid organ transplantation
HIV (broader than s19 from CCI)
Primary immunodeficiency
Other conditions with low white blood cell count
(lymphopenia, leukopenia, agranulocytosis, aplastic
anaemia, and Felty’s syndrome)
Any autoimmune disease
Autoimmune diseases
Haematological system
Autoimmune haemolytic anaemia
Herpes zoster alius definitus: ICD-8: 053.08
Herpes zoster: ICD-8: 053.09
Herpes zoster without complication: ICD-10: B02.9
Herpes zoster ophthalmicus: ICD-8: 053.00
Herpes zoster oticus: ICD-8: 053.01
Meningoencephalitis herpes zoster: ICD-8: 053.02
Herpes zoster generalisatus: ICD-8: 053.03
Herpes zoster encephalitis: ICD-10: B02.0
Herpes zoster meningitis: ICD-10: B02.1
Herpes zoster with other complication of nervous system: ICD10: B02.2
Herpes zoster in eye: ICD-10: B02.3
Herpes zoster disseminated: ICD-10: B02.7
Herpes zoster with other complication: ICD-10: B02.8
Herpes zoster ophthalmicus: ICD-8: 053.00
Herpes zoster oticus: ICD-8: 053.01
Herpes zoster in eye: ICD-10: B02.3
Herpes zoster alius definitus: ICD-8: 053.08
Herpes zoster: ICD-8: 053.09
Herpes zoster without complication: ICD-10: B02.9
Meningoencephalitis herpes zoster: ICD-8: 053.02
Herpes zoster generalisatus: ICD-8: 053.03
Herpes zoster encephalitis: ICD-10: B02.0
Herpes zoster meningitis: ICD-10: B02.1
Herpes zoster with other complication of nervous system: ICD10: B02.2
Herpes zoster disseminated: ICD-10: B02.7
Herpes zoster with other complication: ICD-10: B02.8
Treatment codes BOHJ18A, or procedures coded with
additional relevant ATC codes (L04AB, L04AA11, L04AA12,
L04AA16, or L04AA17)
ATC: H02AB, A07EA
Any of the other ATC codes within L04A (excluding
L04AA07) L01BB01, V02CA01, or V02CA02, and A07EC
Treatment codes: BOQE1-BOQE7, BOQF0, BOQF1-2; ICD10: Z948C1-Z948C2
Danish Classification of Surgical Procedures: 322.09, 322.29,
322.50, 356.09, 472.70, 472.79, 488.40, 488.49, 574.80,
574.90; NOMESCO Classification of Surgical Procedures: FQ,
GDG, JLE, JJC, KAS
ICD-8: 079.83, Y40.49, Y41.49; ICD-10: B20-B24, F02.4
ICD-10: D80-D84, D89
ICD-8: 284, 288; 712.19; ICD-10: D61, D70, D728D, D728H,
M050
See below
ICD-8: 283.90; ICD-10: D59.0, D59.1
Idiopathic thrombocytopenic purpura
Endocrine system
Graves’ disease
Autoimmune thyroiditis
Addison´s disease
Diabetes type I
Central nervous/ neuromuscular system
Multiple sclerosis
Myasthenia gravis
Gastrointestinal/hepatobiliary system
Pernicious anemia
Coelic disease
Crohn´s disease
Ulcerative colitis
Primary biliary cirrhosis
Skin
Atopic dermatitis
Pemphigus/pemphigoid
Dermatitis herpetiformis
Psoriasis
Vitiligo
Connective tissue diseases
Rheumatoid arthritis
Juvenile rheumatoid arthritis
Ankylosing spondylitis
Polymyositis/dermatomyositis
Systemic- and subacute cutaneous lupus
erythematosus
Systemic scleroderma
Mixed connective tissue disease
Sjögren´s syndrome
Sarcoidosis
Vasculitis syndromes including polymyalgia
rheumatica
Pulmonary system
Idiopathic fibrosing alveolitis (pulmonary fibrosis)
Ocular diseases
Iridocyclitis
Any autoimmune disease
Charlson Comorbidity Index
Score 1
Myocardial infarction
Congestive heart failure
Peripheral vascular disease
Cerebrovascular disease
Dementia
Chronic pulmonary disease
Connective tissue disease
Ulcer disease
Mild liver disease
ICD-8: 287.10; ICD-10: D69.3
ICD-8: 242.00, 242.01, 242.08, 242.09; ICD-10: E05.0
ICD-8: 244.01, 245.03; ICD-10: E06.3
ICD-8: 255.10; ICD-10: E27.1
ICD-8: 249; ICD-10: E10
ICD-8: 340; ICD-10: G35
ICD-8: 733.09; ICD-10: G70.0
ICD-8: 281.00, 281.01, 281.08, 281.09; ICD-10: D51.0
ICD-8: 269.00; ICD-10: K90.0
ICD-8: 563.01, 563.02, 563.09; ICD-10: K50, M07.4
ICD-8: 563.19, 569.04; ICD-10: K51, M07.5
ICD-8: 571.90; ICD-10: K74.3
ICD-8: 691.00; ICD-10: L20
ICD-8: 694.00-694.03, 694.05; ICD-10: L10.0, L10.1, L10.2,
L10.4, L12.0
ICD-8: 693.08, 693.09; ICD-10: L13.0
ICD-8: 696.09, 696.10, 696.19; ICD-10: L40, M07.0-M07.3
ICD-8: 709.01; ICD-10: L80
ICD-8: 712.19, 712.29, 712.39, 712.59; ICD-10: M05, M06,
G73.7D, I32.8A, I39.8E, I41.8A, I52.8A
ICD-8: 712.09; ICD-10: M08
ICD-8: 712.49; ICD-10: M45, H221B
ICD-8: 716.09, 716.19; ICD-10: M33
ICD-8: 734.19; ICD-10: M32, G05.8A, G73.7C, I32.8B,
I39.8C, L93.1, L93.2, N08.5A, N16.4B
ICD-8: 734.00-734.09; ICD-10: M34.0-34.9
ICD-8: 734.91; ICD-10: M35.1
ICD-8: 734.90; ICD-10: M35.0, G73.7A, N16.4A
ICD-8: 135.99; ICD-10: D86, G53.2, H22.1A, I41.8B, K77.8B,
M63.3
ICD-8: 287.09, 446.09-446.99; ICD-10: D69.0B, I77.6, L95,
M30-M31, M35.3, M35.6, M79.3, N08.5B-N08.5E
ICD-8: 517.01; ICD-10: J841A, J841B, J841C
ICD-8: 364; ICD-10: H200, H201
Any of the codes listed above
ICD-8: 410; ICD-10: I21, I22, I23
ICD-8: 427.09, 427.10, 427.11, 427.19, 428.99, 782.49; ICD10: I50, I11.0, I13.0, I13.2
ICD-8: 440, 441, 442, 443, 444, 445; ICD-10: I70, I71, I72,
I73, I74, I77
ICD-8: 430-438; ICD-10: I60-I69, G45, G46
ICD-8: 290.09-290.19, 293.09; ICD-10: F00-F03, F05.1, G30
ICD-8: 490-493, 515-518, ICD-10: J40-J47, J60-J67, J68.4,
J70.1, J70.3, J84.1, J92.0, J96.1, J98.2, J98.3
ICD-8: 712, 716, 734, 446, 135.99; ICD-10: M05, M06, M08,
M09, M30, M31, M32, M33, M34, M35, M36, D86
ICD-8: 530.91, 530.98, 531-534; ICD-10: K22.1, K25-K28
ICD-8: 571, 573.01, 573.04; ICD-10: B18, K70.0-K70.3,
Diabetes type 1 and 2
Score 2
Hemiplegia
Moderate to severe renal disease
Diabetes with end organ damage
Any tumour
Leukaemia
Lymphoma
Score 3
Moderate to severe liver disease
Score 6
Metastatic solid tumour
AIDS
Cancers
Haematological cancers
Hodgkin’s lymphoma
Non-Hodgkin’s lymphoma excl. leukaemia and
myelomatosis
Multiple myeloma and malignant plasma cell
neoplasms
Leukaemia
Malignant neoplasm of lymphoid, hematopoietic and
related tissues, unspecified
Immune-related cancers
Liver including intrahepatic bile ducts*
Malignant melanoma including those located in anus
and anal canal (morphological code 872-879)
Non-melanoma skin cancers
Kaposi’s sarcoma
Cervix
Anus and anal canal excl. malignant melanomas
(morphologic code 872-879) and basal cell cancers
(morphologic code 809)
External female genitals excluding basal cell
carcinomas (morphological code 809)
Smoking- and alcohol-related cancers
Lip
Tongue
Mouth
Tonsil and pharynx
Other and poorly specified location in lip, oral cavity,
and pharynx
Larynx
Other and poorly specified location in airways and
respiratory organs
Oesophagus
Stomach
Colon incl. rectosigmoid junction
Rectum
Pancreas
K70.9, K71, K73, K74, K76.0
ICD-8: 249.00, 249.06, 249.07, 249.09, 250.00, 250.06,
250.07, 250.09; ICD-10: E10.0, E10.1, E10.9, E11.0, E11.1,
E11.9
ICD-8: 344; ICD-10: G81, G82
ICD-8: 403, 404, 580-583, 584, 590.09, 593.19, 753.10-753.19,
792; ICD-10: 12, I13, N00-N05, N07, N11, N14, N17-N19,
Q61
ICD-8: 249.01-249.05, 249.08, 250.01-250.05, 250.08; ICD10: E10.2-E10.8, E11.2-E11.8
ICD-8: 140-194; ICD-10: C00-C75
ICD-8: 204-207; ICD-10: C91-C95
ICD-8: 200-203, 275.59; ICD-10: C81-C85, C88, C90, C96
ICD-8: 070.00, 070.02, 070.04, 070.06, 070.08, 573.00,
456.00-456.09; ICD-10: B15.0, B16.0, B16.2, B19.0, K70.4,
K72, K76.6, I85
ICD-8: 195-198, 199; ICD-10: C76-C80
ICD-8: 079.83; ICD-10: B21-B24
C81
C82-85, C88
C90
C91-C95
C96
C22
ICD-10: C43
ICD-10: C44
C46, B210
C53
ICD-10: C21
ICD-10: C51
ICD-10: C00
ICD-10: C01-02
ICD-10: C03-06
ICD-10: C09-C13
ICD-10: C14
ICD-10: C32
ICD-10: C39
ICD-10: C15
ICD-10: C16
ICD-10: C18-C19
ICD-10: C20
ICD-10: C25
Lung, bronchus and trachea
Kidney
Renal pelvis
Ureter
Urinary bladder
All other sites
Salivary gland
Small intestine
Gallbladder and bile ducts
Other and ill-defined cancers of digestive organs
Nasal cavity, middle ear and accessory sinuses
Thymus
Heart and mediastinum
Pleura incl. mesothelioma pleura
Bone and articular cartilage
Mesothelioma
Peripheral nerves and autonomic nervous system
Retroperitoneum and peritoneum, and malignant
neoplasm of other connective and soft tissue
Breast
Vagina excluding basal cell carcinomas
(morphological code 809)
Uterus
Ovary and fallopian tube
Placenta
Other and unspecified female genital organs
Penis excluding basal cell carcinomas
(morphological code 809)
Prostate
Testis
Other and unspecified cancers in male genital organs
excluding basal cell carcinomas (morphological code
809)
Other and unspecified urinary organs
Eye and adnexa
Meninges
Brain including hypophysis, corpus pineale, and
ductus craniopharyngealis
Spinal cord, cranial nerves and other parts of central
nervous system
Endocrine glands and related structure
Metastasis and unspecified cancer in lymph nodes
(only if there is no primary tumor coded)
Malignant neoplasm of other, ill-defined, or
unspecified sites
Malignant neoplasms of independent (primary)
multiple sites
ICD-10: C33-C34
ICD-10: C64
ICD-10: C65
ICD-10: C66
ICD-10: C67
C07-C08
C17
C23-C24
C26
C30-C31
C37
C381-383, C388
C384, C450
C40-C41
C45.1-C45.9
C47
C48-C49
C50
C52
C54-C55
C56, C570-574
C58
C577-579
C60
C61
C62
C63
C68
C69
C70
C71
C72
C73-C75
C77-79 (only if there is no primary tumor coded)
C76, C80
C97
ATC = Anatomical Therapeutic Chemical; ICD = International Classification of Diseases
*Liver cancer is also considered alcohol-related but is here included with immune-related cancers due to hepatitis.
Table S2. Selected characteristics of persons diagnosed with herpes zoster and subsequent cancer and a matched cancer cohort, Denmark 1982-2011
Haematological cancers
Immune-related cancers
Smoking & alcohol-related
cancers
Herpes zoster
Matched
Herpes zoster
Matched
Herpes zoster Matched cohort
cohort
cohort
n (%)
n (%)
n (%)
n (%)
n (%)
n (%)
244 (100.0)
2,255 (100.0) 741 (100.0)
7,201 (100.0)
994 (100.0)
9,557 (100.0)
Total
Age at cancer diagnosis (years)
Range
22–94
20–95
23–100
21–102
41–98
40–99
Median (interquartile range)
76 (69–83)
76 (69–82)
78 (69–84)
78 (69–84)
78 (71–84)
78 (71–83)
Age groups
0-59
32 (13.1)
247 (11.0)
99 (13.4)
859 (11.9)
58 (5.8)
533 (5.6)
60-69
43 (17.6)
389 (17.3)
107 (14.4)
1,108 (15.4)
159 (16.0)
1,608 (16.8)
70-79
84 (34.4)
849 (37.6)
226 (30.5)
2,311 (32.1)
357 (35.9)
3,532 (37.0)
≥80
85 (34.8)
770 (34.1)
309 (41.7)
2,923 (40.6)
420 (42.3)
3,884 (40.6)
Sex
Women
124 (50.8)
1,138 (50.5)
436 (58.8)
4,246 (59.0)
521 (52.4)
4,984 (52.2)
Men
120 (49.2)
1,117 (49.5)
305 (41.2)
2,955 (41.0)
473 (47.6)
4,573 (47.8)
Calendar period of cancer diagnosis
1982–1994
109 (44.7)
1,014 (45.0)
226 (30.5)
2,181 (30.3)
384 (38.6)
3,749 (39.2)
1995–2011
135 (55.3)
1,241 (55.0)
515 (69.5)
5,020 (69.7)
610 (61.4)
5,808 (60.8)
a
Cancer stage at diagnosis
Localised
27 (11.1)
215 (9.5)
580 (78.3)
5,876 (81.6)
336 (33.8)
2,960 (31.0)
Regional
21 (8.6)
222 (9.8)
25 (3.4)
209 (2.9)
238 (23.9)
2,274 (23.8)
Distant
37 (15.2)
312 (13.8)
18 (2.4)
113 (1.6)
246 (24.7)
2,609 (27.3)
Unknown/missing
159 (65.2)
1,506 (66.8)
118 (15.9)
1,003 (13.9)
174 (17.5)
1,714 (17.9)
Charlson Comorbidity Index levelb
None
95 (38.9)
1,334 (59.2)
347 (46.8)
4,948 (68.7)
432 (43.5)
5,808 (60.8)
Moderate
58 (23.8)
388 (17.2)
164 (22.1)
1,386 (19.2)
272 (27.4)
2,167 (22.7)
Severe
43 (17.6)
344 (15.3)
90 (12.1)
513 (7.1)
156 (15.7)
954 (10.0)
Very severe
48 (19.7)
189 (8.4)
140 (18.9)
354 (4.9)
134 (13.5)
628 (6.6)
Comorbidities with immune dysregulation,
69 (28.3)
241 (10.7)
191 (25.8)
681 (9.5)
176 (17.7)
728 (7.6)
overall
Any autoimmune disease
55 (22.5)
205 (9.1)
149 (20.1)
641 (8.9)
171 (17.2)
712 (7.5)
Solid organ transplantation
4 (1.6)
1 (0.0)
35 (4.7)
10 (0.1)
3 (0.3)
2 (0.0)
All other sites
Herpes zoster
n (%)
775 (100.0)
Matched
cohort
n (%)
7,230 (100.0)
18–98
78 (70–84)
16–99
77 (70–84)
67
127
248
333
(8.6)
(16.4)
(32.0)
(43.0)
620
1,239
2,413
2,958
(8.6)
(17.1)
(33.4)
(40.9)
485 (62.6)
290 (37.4)
4,529 (62.6)
2,701 (37.4)
301 (38.8)
474 (61.2)
2,794 (38.6)
4,436 (61.4)
250
162
165
198
(32.3)
(20.9)
(21.3)
(25.5)
2,438
1,446
1,558
1,788
(33.7)
(20.0)
(21.5)
(24.7)
362
205
117
91
(46.7)
(26.5)
(15.1)
(11.7)
4,909
1,425
551
345
(67.9)
(19.7)
(7.6)
(4.8)
145 (18.7)
139 (17.9)
4 (0.5)
573 (7.9)
565 (7.8)
2 (0.0)
Table S2. Selected characteristics of persons diagnosed with herpes zoster and subsequent cancer and a matched cancer cohort, Denmark 1982-2011
Haematological cancers
Immune-related cancers
Smoking & alcohol-related
cancers
Herpes zoster
Matched
Herpes zoster
Matched
Herpes zoster Matched cohort
cohort
cohort
n (%)
n (%)
n (%)
n (%)
n (%)
n (%)
Stem cell or bone marrow transplantation
1 (0.4)
3 (0.1)
–
–
–
–
Human immunodeficiency virus
5 (2.0)
11 (0.5)
17 (2.3)
30 (0.4)
4 (0.4)
–
Primary immunodeficiency
2 (0.8)
2 (0.1)
3 (0.4)
6 (0.1)
2 (0.2)
5 (0.1)
Otherc
10 (4.1)
25 (1.1)
3 (0.4)
8 (0.1)
1 (0.1)
15 (0.2)
9 (3.7)
45 (2.0)
42 (5.7)
230 (3.2)
52 (5.2)
318 (3.3)
Immunosuppressive drugs, overalld
Systemic glucocorticoids
9 (3.7)
41 (1.8)
38 (5.1)
184 (2.6)
45 (4.5)
290 (3.0)
TNF-alpha inhibitors
–
–
–
2 (0.0)
–
–
Other
1 (0.4)
8 (0.4)
16 (2.2)
70 (1.0)
11 (1.1)
49 (0.5)
Setting of herpes zoster diagnosise
Inpatient
204 (83.6)
–
606 (81.8)
–
839 (84.4)
–
Outpatient
25 (10.2)
–
83 (11.2)
–
102 (10.3)
–
Emergency room
15 (6.1)
–
52 (7.0)
–
53 (5.3)
–
Severity of herpes zoster
Complicated
60 (24.6)
–
193 (26.0)
–
263 (26.5)
–
Uncomplicated
184 (75.4)
–
548 (74.0)
–
731 (73.5)
–
Extent of herpes zoster
Disseminated
29 (11.9)
–
75 (10.1)
–
89 (9.0)
–
Localised
215 (88.1)
–
666 (89.9)
–
905 (91.0)
–
Follow-up (years)
Median (interquartile range)
1.28 (0.27–
1.42 (0.23-4.88)
3.99 (1.79–
4.64 (2.22–
0.64 (0.13–
0.55 (0.12–2.20)
3.80)
7.39)
9.05)
2.39)
Range
0–26.85
0–28.54
0–25.38
0–30.46
0–21.98
0–30.55
Total
720
7,800
4,050
45,710
2,050
19,530
a
All other sites
Herpes zoster
n (%)
–
4 (0.5)
1 (0.1)
1 (0.1)
25 (3.2)
24 (3.1)
–
3 (0.4)
Matched
cohort
n (%)
–
–
3 (0.0)
10 (0.1)
167 (2.3)
148 (2.0)
–
36 (0.5)
635 (81.9)
79 (10.2)
61 (7.9)
–
–
–
196 (25.3)
579 (74.7)
–
–
69 (8.9)
706 (91.1)
–
–
1.85 (0.27–
5.01)
0–30.71
2,660
2.08 (0.31–
5.42)
0–30.71
27,780
Stage defined according to Summary Staging as follows: Localised (T1-4, N0, M0; Ann Arbour I), regional (T1-4, N1-3, M0; Ann Arbour IIs, II-IIe), distant (T1-4, N1-3, M1; Ann Arbour IIs, III-IV) and
unknown or missing.
b Four levels of comorbidity were defined based on Charlson Index scores of 0 (none), 1 (moderate), 2 (severe), and 3 or more (very severe).
cOther immunosuppressive conditions include lymphopenia, leukopenia, agranulocytosis, aplastic anaemia, and Felty’s syndrome.
dAmong patients diagnosed with cancer in July 2004 or later.
eAmong patients diagnosed with herpes zoster in 1995 or later.
Table S3. Mortality following haematological cancer among patients with a prior diagnosis of herpes zoster (n=244) compared with a matched cancer cohort (n=2,255), by study
characteristics, Denmark 1982-2011
0–1 year of follow-up
>1 year of follow-up
Mortality rate (per 1,000 PY)
Adjusted MRR (95%
Mortality rate (per 1,000 PY)
Adjusted MRR (95% CI)*
CI)*
Herpes zoster
Matched cohort
Herpes zoster
Matched cohort
Time between
herpes zoster and
cancer diagnoses
0–365 days
652 (391–912)
611 (527–695)
0.82 (0.52–1.29)
158 (92–224)
142 (122–161)
0.88 (0.50–1.57)
>365 days
637 (501–774)
647 (602–692)
0.91 (0.72–1.15)
211 (166–255)
144 (134–155)
1.33 (1.01–1.75)
Sex
Women
590 (428–752)
644 (588–700)
0.86 (0.65–1.16)
197 (148–247)
163 (148–177)
1.13 (0.86–1.49)
Men
694 (514–874)
634 (577–691)
0.96 (0.72–1.26)
197 (141–253)
126 (114–138)
1.30 (0.96–1.77)
Age at cancer
diagnosis
15–59 years
654 (323–985)
241 (176–307)
2.01 (1.07–3.75)
138 (63–213)
41 (32–51)
2.65 (1.28–5.50)
60–69 years
303 (124–482)
345 (281–410)
0.69 (0.37–1.29)
101 (55–146)
115 (98–132)
0.80 (0.50–1.30)
70-79 years
621 (421–821)
627 (563–691)
0.85 (0.61–1.20)
204 (141–267)
171 (154–189)
1.11 (0.80–1.54)
≥80 years
904 (640–1169)
1,076 (977–1,174)
0.86 (0.65–1.16)
528 (355–700)
351 (309–393)
1.41 (0.98–2.03)
Calendar period of
cancer diagnosis
1982–1994
805 (596–1014)
830 (759–901)
0.93 (0.70–1.22)
229 (166–292)
171 (155–186)
1.13 (0.84–1.52)
1995–2011
521 (378–665)
507 (461–553)
0.87 (0.65–1.17)
176 (130–221)
124 (112–135)
1.25 (0.94–1.66)
Stage at cancer
diagnosis
Local
562 (230–893)
390 (296–484)
1.00 (0.52–1.94)
179 (88–269)
102 (83–121)
1.10 (0.63–1.91)
Regional
545 (189–901)
787 (641–933)
0.69 (0.35–1.36)
212 (92–332)
121 (95–146)
1.85 (0.94–3.65)
Metastatic
1,126 (666–1586)
1,089 (932–1,245)
0.97 (0.62–1.51)
244 (111–376)
197 (161–234)
0.97 (0.53–1.77)
Unknown/missing
580 (439–721)
587 (541–633)
0.91 (0.70–1.18)
192 (147–238)
151 (139–164)
1.21 (0.94–1.56)
Charlson
Comorbidity Index
level
None
465 (308–621)
546 (499–592)
0.78 (0.55–1.11)
204 (150–257)
134 (123–144)
1.28 (0.97–1.69)
Moderate
876 (568–1185)
810 (697–923)
1.09 (0.75–1.60)
140 (73–206)
193 (161–224)
1.01 (0.60–1.69)
Severe
Very severe
Comorbidity with
immune
dysregulation
Yes
No
Immunosuppressive
drugs†
Yes
No
Setting of herpes
zoster diagnosis‡
Inpatient
Outpatient clinic
Emergency room
Severity of herpes
zoster
Uncomplicated
Complicated
Extent of herpes
zoster
Localised
Disseminated
582 (305–859)
843 (519–1167)
651 (547–756)
1,072 (875–1,270)
0.90 (0.54–1.50)
0.80 (0.52–1.23)
206 (111–302)
262 (141–383)
128 (106–150)
233 (170–295)
1.11 (0.67–1.84)
1.11 (0.63–1.98)
1,050 (729–1372)
517 (393–641)
856 (708–1,004)
616 (574–657)
1.09 (0.75–1.57)
0.78 (0.61–1.00)
202 (111–293)
196 (155–237)
142 (109–175)
144 (134–154)
1.19 (0.68–2.10)
1.21 (0.97–1.51)
321 (-124–766)
431 (205–657)
777 (436–1,170)
393 (327–460)
0.34 (0.07–1.60)
0.99 (0.56–1.75)
–
253 (125–382)
167 (51–283)
126 (101–151)
–
1.81 (1.02–3.20)
625 (364–886)
548 (190–907)
250 (-33–532)
602 (519–685)
371 (283–459)
281 (181–382)
0.89 (0.57–1.40)
1.18 (0.57–2.44)
1.03 (0.29–3.64)
181 (102–260)
87 (11–162)
116 (14–218)
129 (109–148)
100 (76–125)
85 (57–112)
1.10 (0.67–1.79)
0.65 (0.25–1.68)
1.59 (0.53–4.74)
625 (488–762)
688 (433–943)
673 (625–720)
546 (474–618)
0.86 (0.68–1.08)
1.05 (0.70–1.57)
221 (174–267)
140 (81–198)
147 (136–158)
133 (116–151)
1.25 (0.99–1.58)
1.00 (0.64–1.59)
645 (516–774)
607 (264–950)
677 (633–722)
407 (323–492)
0.87 (0.70–1.07)
1.52 (0.82–2.82)
207 (166–248)
140 (57–223)
152 (141–162)
103 (84–123)
1.19 (0.96–1.47)
1.85 (0.94–3.63)
Abbreviations: CI = confidence interval; MRR = mortality rate ratios
*Mortality rate ratios were calculated with Cox proportional hazard regression adjusted for the same set of variables (age at diagnosis, sex, Charlson Comorbidity Index level, cancer stage, and calendar period at
cancer diagnosis) in each stratified analysis.
‡Restricted to herpes zoster patients diagnosed in 1995 or later and their corresponding matched cancer cohort members because of the availability of outpatient clinic and emergency room diagnoses.
Table S4. Mortality following immune-related cancer among patients with a prior diagnosis of herpes zoster (n=741) compared with a matched cancer cohort (n=7,201), by study
characteristics, Denmark 1982-2011
0–1 year of follow-up
>1 year of follow-up
Mortality rate (per 1,000 PY)
Adjusted MRR (95%
Mortality rate (per 1,000 PY)
Adjusted MRR
CI)*
(95% CI)*
Herpes zoster
Matched cohort
Herpes zoster
Matched cohort
Time between herpes zoster and cancer
diagnoses
0–365 days
188 (93–283)
123 (99–147)
1.15 (0.62–2.11)
138 (99–177)
95 (87–104)
1.41 (1.00–1.97)
>365 days
126 (98–154)
108 (99–116)
0.91 (0.70–1.17)
111 (99–123)
84 (81–87)
1.09 (0.96–1.24)
Sex
Women
118 (84–151)
107 (97–117)
0.88 (0.65–1.19)
116 (101–130)
86 (82–90)
1.11 (0.97–1.27)
Men
156 (110–202)
113 (101–126)
0.81 (0.58–1.13)
110 (92–128)
85 (81–90)
1.13 (0.94–1.35)
Age at cancer diagnosis
15–59 years
117 (48–186)
53 (37–68)
0.95 (0.41–2.20)
45 (29–62)
15 (12–17)
1.33 (0.79–2.24)
60–69 years
68 (18–119)
64 (49–79)
0.76 (0.34–1.69)
72 (50–93)
41 (37–46)
1.80 (1.30–2.49)
70-79 years
128 (80–176)
113 (99–127)
0.74 (0.49–1.12)
100 (82–118)
84 (79–89)
0.94 (0.77–1.15)
≥80 years
166 (119–214)
142 (128–156)
1.00 (0.73–1.35)
203 (175–232)
180 (171–188)
1.07 (0.92–1.25)
Calendar period of cancer diagnosis
1982–1994
188 (128–247)
139 (122–155)
1.02 (0.71–1.46)
118 (101–136)
94 (90–99)
1.00 (0.85–1.17)
1995–2011
111 (81–140)
97 (88–106)
0.77 (0.58–1.03)
110 (95–125)
79 (75–82)
1.27 (1.10–1.47)
Stage at cancer diagnosis
Local
96 (70–121)
73 (66–80)
0.89 (0.66–1.20)
111 (99–123)
84 (81–87)
1.15 (1.03–1.30)
Regional
458 (159–757)
653 (523–783)
0.74 (0.35–1.54)
345 (150–540)
148 (115–181)
1.65 (0.83–3.26)
Metastatic
2,217 (1095–3340)
1,672 (1,312–2,031)
1.57 (0.89–2.77)
436 (-168–1041)
197 (113–282)
0.88 (0.11–7.37)
Unknown/missing
138 (68–207)
162 (136–188)
0.68 (0.39–1.17)
106 (74–138)
91 (82–100)
0.95 (0.68–1.32)
Charlson Comorbidity Index level
None
85 (53–116)
78 (70–86)
0.99 (0.67–1.46)
88 (75–101)
72 (69–74)
1.08 (0.93–1.27)
Moderate
159 (95–222)
136 (116–156)
1.12 (0.73–1.71)
137 (108–166)
130 (121–140)
1.11 (0.88–1.39)
Severe
159 (73–246)
188 (149–228)
1.02 (0.56–1.86)
147 (106–187)
166 (146–187)
1.00 (0.72–1.39)
Very severe
213 (133–294)
379 (308–449)
0.58 (0.37–0.89)
172 (132–213)
197 (166–229)
1.03 (0.76–1.39)
Comorbidity with immune dysregulation
Yes
134 (80–187)
128 (100–156)
0.69 (0.42–1.11)
112 (89–136)
108 (96–121)
0.95 (0.74–1.22)
No
133 (102–165)
108 (99–116)
0.97 (0.75–1.25)
114 (101–127)
84 (81–87)
1.15 (1.01–1.29)
Immunosuppressive drugs†
Yes
105 (2–208)
102 (58–145)
1.42 (0.47–4.30)
102 (39–166)
111 (81–141)
0.90 (0.42–1.96)
No
Setting of herpes zoster diagnosis‡
Inpatient
Outpatient clinic
Emergency room
Severity of herpes zoster
Uncomplicated
Complicated
Extent of herpes zoster
Localised
Disseminated
98 (58–138)
75 (64–86)
0.81 (0.52–1.27)
96 (70–122)
70 (64–77)
1.08 (0.80–1.44)
120 (69–172)
89 (23–154)
81 (2–160)
73 (61–86)
76 (57–95)
103 (74–132)
1.09 (0.68–1.77)
0.49 (0.21–1.14)
0.63 (0.21–1.83)
120 (92–147)
102 (61–142)
78 (37–119)
78 (71–84)
68 (58–77)
60 (49–71)
1.37 (1.06–1.76)
1.25 (0.80–1.94)
1.04 (0.58–1.87)
131 (100–162)
140 (85–195)
105 (96–114)
123 (106–139)
0.84 (0.64–1.10)
0.88 (0.58–1.35)
110 (97–123)
126 (101–151)
84 (81–87)
91 (85–97)
1.09 (0.96–1.24)
1.26 (1.02–1.56)
129 (100–157)
177 (77–277)
108 (100–117)
119 (93–145)
0.81 (0.63–1.03)
1.29 (0.70–2.40)
111 (100–123)
153 (97–209)
85 (82–88)
95 (84–107)
1.10 (0.99–1.23)
1.60 (1.07–2.38)
Abbreviations: CI = confidence interval; MRR = mortality rate ratios
*Mortality rate ratios were calculated with Cox proportional hazard regression adjusted for the same set of variables (age at diagnosis, sex, Charlson Comorbidity Index level, cancer stage, and calendar period at
cancer diagnosis) in each stratified analysis.
‡Restricted to zoster patients diagnosed in 1995 or later and their corresponding matched cancer cohort members because of the availability of outpatient clinic and emergency room diagnoses.
Table S5. Mortality following smoking- and alcohol-related cancer among patients with a prior diagnosis of herpes zoster (n=994) compared with a matched cancer cohort
(n=9,557), by study characteristics, Denmark 1982-2011
0–1 year of follow-up
>1 year of follow-up
Mortality rate (per 1000 PY)
Adjusted MRR (95%
Mortality rate (per 1000 PY)
Adjusted MRR
CI)*
(95% CI)*
Herpes zoster
Matched cohort
Herpes zoster
Matched cohort
Time between herpes zoster and cancer
diagnoses
0–365 days
1,091 (852–1,330)
1,275 (1,188–1,361)
0.92 (0.72–1.17)
158 (108–207)
206 (184–227)
0.74 (0.48–1.14)
>365 days
994 (907–1,081)
1,066 (1,036–1,096)
0.82 (0.75–0.91)
233 (206–260)
197 (190–205)
0.98 (0.83–1.15)
Sex
Women
1,083 (965–1,202)
1,135 (1,095–1,175)
0.91 (0.81–1.02)
207 (174–239)
187 (177–197)
1.03 (0.87–1.22)
Men
926 (814–1,038)
1,047 (1,007–1,086)
0.85 (0.75–0.97)
235 (199–271)
212 (200–223)
0.99 (0.84–1.17)
Age at cancer diagnosis
15–59 years
723 (455–991)
610 (532–688)
1.03 (0.68–1.55)
97 (51–144)
125 (106–144)
0.84 (0.50–1.43)
60–69 years
699 (541–857)
740 (689–792)
0.92 (0.73–1.17)
152 (111–193)
145 (132–157)
0.88 (0.66–1.18)
70-79 years
1,026 (888–1,164)
1,117 (1,070–1,164)
0.89 (0.77–1.03)
222 (183–262)
199 (187–211)
1.03 (0.86–1.25)
≥80 years
1,183 (1,041–1,325)
1,362 (1,309–1,414)
0.85 (0.75–0.96)
333 (276–391)
273 (257–290)
1.09 (0.91–1.31)
Calendar period of cancer diagnosis
1982–1994
1,172 (1,024–1,319)
1,337 (1,285–1,390)
0.82 (0.72–0.94)
220 (184–257)
202 (191–214)
1.03 (0.86–1.22)
1995–2011
915 (818–1,013)
958 (926–991)
0.93 (0.83–1.04)
220 (188–252)
196 (186–205)
0.99 (0.85–1.16)
Stage at cancer diagnosis
Local
484 (398–570)
478 (449–506)
0.90 (0.75–1.09)
186 (158–214)
151 (144–159)
1.10 (0.94–1.30)
Regional
986 (823–1,149)
954 (903–1,005)
0.94 (0.79–1.12)
221 (170–272)
252 (234–270)
0.88 (0.69–1.12)
Metastatic
2,367 (2,045–2,690)
2,455 (2,353–2,557)
0.91 (0.79–1.06)
457 (296–618)
572 (509–635)
0.82 (0.56–1.20)
Unknown/missing
1,170 (953–1,387)
1,492 (1,407–1,576)
0.75 (0.62–0.91)
312 (226–397)
245 (220–269)
1.18 (0.87–1.60)
Charlson Comorbidity Index level
None
876 (764–988)
969 (936–1,002)
0.89 (0.78–1.01)
199 (168–230)
176 (168–184)
1.05 (0.89–1.24)
Moderate
944 (796–1,093)
1,208 (1,144–1,271)
0.79 (0.67–0.94)
222 (177–268)
239 (220–258)
0.97 (0.78–1.21)
Severe
1,272 (1,023–1,521)
1,407 (1,298–1,515)
0.92 (0.74–1.13)
272 (189–356)
274 (239–309)
1.14 (0.81–1.60)
Very severe
1,362 (1,085–1,638)
1,617 (1,467–1,766)
0.96 (0.77–1.20)
307 (197–417)
417 (347–487)
0.74 (0.50–1.11)
Comorbidity with immune dysregulation
Yes
1,057 (856–1,257)
1,219 (1,108–1,330)
0.89 (0.72–1.10)
190 (135–245)
230 (197–264)
0.76 (0.54–1.07)
No
996 (906–1,085)
1,082 (1,053–1,111)
0.88 (0.80–0.97)
226 (199–253)
197 (189–204)
1.05 (0.93–1.19)
Immunosuppressive drugs†
Yes
967 (602–1,331)
1,452 (1,251–1,653)
0.66 (0.44–1.00)
175 (66–283)
278 (196–360)
0.66 (0.31–1.41)
No
Setting of herpes zoster diagnosis‡
Inpatient
Outpatient clinic
Emergency room
Severity of herpes zoster
Uncomplicated
Complicated
Extent of herpes zoster
Localised
Disseminated
763 (624–903)
760 (715–805)
1.01 (0.83–1.23)
199 (143–256)
201 (184–219)
0.97 (0.72–1.30)
971 (792–1,149)
813 (583–1,043)
973 (619–1,327)
856 (803–910)
838 (761–915)
893 (786–999)
1.13 (0.93–1.38)
1.00 (0.74–1.35)
0.91 (0.62–1.35)
210 (150–271)
154 (87–222)
202 (83–321)
183 (167–200)
199 (174–224)
193 (159–227)
1.05 (0.77–1.43)
0.76 (0.48–1.22)
0.86 (0.45–1.62)
968 (875–1,061)
1,119 (948–1,289)
1,141 (1,108–1,175)
961 (911–1,011)
0.80 (0.72–0.89)
1.15 (0.98–1.35)
248 (218–279)
154 (117–191)
208 (199–217)
176 (164–189)
1.04 (0.91–1.19)
0.91 (0.71–1.18)
982 (898–1,066)
1,279 (958–1,600)
1,103 (1,074–1,133)
979 (892–1,065)
0.85 (0.78–0.93)
1.27 (0.97–1.66)
225 (200–250)
160 (82–238)
199 (191–207)
194 (169–219)
1.02 (0.91–1.15)
0.69 (0.41–1.17)
Abbreviations: CI = confidence interval; MRR = mortality rate ratios
*Mortality rate ratios were calculated with Cox proportional hazard regression adjusted for the same set of variables (age at diagnosis, sex, Charlson Comorbidity Index level, cancer stage, and calendar period at
cancer diagnosis) in each stratified analysis.
‡Restricted to zoster patients diagnosed in 1995 or later and their corresponding matched cancer cohort members because of the availability of outpatient clinic and emergency room diagnoses.
Table S6. Mortality following cancers at ‘all other sites’ among patients with a prior diagnosis of herpes zoster (n=775) compared with a matched cancer cohort (n=7,230), by study
characteristics, Denmark 1982-2011
0–1 year of follow-up
>1 year of follow-up
Mortality rate (per 1000 PY)
Adjusted MRR
Mortality rate (per 1000 PY)
Adjusted MRR
(95%
CI)*
(95% CI)*
Herpes zoster
Matched cohort
Herpes zoster
Matched cohort
Time between herpes zoster and cancer
diagnoses
0–365 days
434 (283–584)
518 (463–574)
0.69 (0.46–1.03)
164 (114–214)
119 (107–132)
1.45 (0.97–2.16)
>365 days
523 (459–587)
498 (478–518)
0.94 (0.81–1.08)
157 (139–175)
134 (128–139)
1.01 (0.87–1.17)
Sex
Women
467 (396–538)
468 (444–491)
0.92 (0.78–1.08)
140 (121–158)
114 (109–120)
1.08 (0.93–1.24)
Men
588 (483–693)
558 (525–592)
0.91 (0.75–1.10)
213 (174–253)
178 (167–189)
1.10 (0.90–1.34)
Age at cancer diagnosis
15–59 years
161 (61–261)
98 (72–123)
1.91 (0.94–3.87)
55 (32–77)
43 (37–49)
1.00 (0.62–1.61)
60–69 years
230 (142–318)
231 (202–260)
0.82 (0.54–1.24)
107 (79–135)
80 (72–87)
1.20 (0.90–1.59)
70-79 years
502 (399–605)
488 (455–520)
0.87 (0.70–1.09)
171 (139–202)
144 (135–153)
1.04 (0.85–1.26)
≥80 years
780 (659–900)
799 (758–840)
0.90 (0.76–1.07)
282 (235–330)
256 (241–270)
1.03 (0.86–1.23)
Calendar period of cancer diagnosis
1982–1994
716 (598–835)
613 (578–648)
0.97 (0.81–1.17)
167 (141–193)
161 (152–169)
1.04 (0.88–1.23)
1995–2011
401 (337–466)
436 (414–458)
0.86 (0.72–1.02)
151 (129–173)
111 (105–116)
1.13 (0.96–1.32)
Stage at cancer diagnosis
Local
222 (160–285)
175 (158–193)
1.12 (0.83–1.52)
125 (105–146)
101 (95–106)
1.06 (0.89–1.27)
Regional
197 (124–270)
300 (269–331)
0.62 (0.42–0.92)
147 (117–178)
126 (117–136)
1.05 (0.84–1.32)
Metastatic
1,672 (1,373–1,971)
1,630 (1,535–1,726)
0.90 (0.74–1.09)
517 (350–683)
363 (327–400)
1.23 (0.86–1.74)
Unknown/missing
708 (561–854)
653 (607–699)
0.97 (0.77–1.21)
209 (159–258)
176 (162–189)
1.00 (0.77–1.28)
Charlson Comorbidity Index level
None
378 (306–449)
407 (387–428)
1.00 (0.82–1.21)
122 (103–141)
115 (110–120)
1.07 (0.91–1.26)
Moderate
619 (489–749)
665 (614–717)
0.97 (0.78–1.22)
184 (145–223)
186 (170–202)
1.05 (0.83–1.33)
Severe
639 (462–816)
800 (705–895)
0.74 (0.54–1.00)
224 (165–284)
256 (221–291)
0.79 (0.58–1.07)
Very severe
737 (514–960)
980 (841–1,120)
0.75 (0.53–1.05)
311 (212–410)
264 (214–315)
1.40 (0.95–2.06)
Comorbidity with immune dysregulation
Yes
455 (328–582)
575 (501–650)
0.73 (0.53–0.99)
190 (146–234)
135 (116–155)
1.24 (0.93–1.66)
No
524 (458–591)
494 (475–514)
0.95 (0.83–1.09)
151 (133–170)
131 (127–136)
1.06 (0.93–1.20)
Immunosuppressive drugs†
Yes
315 (63–567)
630 (476–784)
0.42 (0.18–1.00)
208 (64–351)
138 (89–188)
1.58 (0.62–4.02)
No
Setting of herpes zoster diagnosis‡
Inpatient
Outpatient clinic
Emergency room
Severity of herpes zoster
Uncomplicated
Complicated
Extent of herpes zoster
Localised
Disseminated
269 (189–348)
336 (307–365)
0.71 (0.52–0.97)
112 (78–146)
102 (91–112)
0.86 (0.62–1.19)
435 (308–563)
319 (176–462)
130 (34–225)
453 (410–496)
486 (424–548)
251 (205–296)
0.98 (0.71–1.34)
0.67 (0.42–1.08)
0.42 (0.20–0.92)
149 (103–194)
143 (87–199)
105 (60–150)
119 (106–131)
97 (82–111)
86 (74–99)
1.01 (0.72–1.41)
1.33 (0.85–2.07)
1.03 (0.65–1.65)
543 (472–614)
424 (320–528)
500 (478–522)
502 (464–541)
0.94 (0.81–1.08)
0.80 (0.62–1.04)
160 (140–180)
153 (121–185)
133 (128–139)
127 (118–137)
1.07 (0.94–1.23)
1.07 (0.85–1.35)
521 (458–584)
411 (235–586)
498 (478–518)
528 (461–596)
0.90 (0.79–1.03)
0.92 (0.58–1.44)
157 (139–175)
169 (111–228)
132 (127–137)
133 (116–150)
1.05 (0.93–1.19)
1.24 (0.85–1.82)
Abbreviations: CI = confidence interval; MRR = mortality rate ratios
*Mortality rate ratios were calculated with Cox proportional hazard regression adjusted for the same set of variables (age at diagnosis, sex, Charlson Comorbidity Index level, cancer stage, and calendar period at
cancer diagnosis) in each stratified analysis.
†Restricted to cancer diagnoses made in 2005 or later because of the availability of prescription data.
‡Restricted to zoster patients diagnosed in 1995 or later and their corresponding matched cancer cohort members because of the availability of outpatient clinic and emergency room diagnoses.
Table S7. Mortality following cancer among patients with a prior diagnosis of herpes zoster (n=2,754) compared
with a matched cancer cohort (n=26,243), Denmark 1982-2011*
0–1 year of follow-up
>1 year of follow-up
Unadjusted MRR
Adjusted MRR
Unadjusted
Adjusted MRR
(95% CI)†
(95% CI)‡
MRR (95% CI)†
(95% CI)‡
Haematological cancers
Non-Hodgkin’s lymphoma
1.16 (0.83–1.63)
0.97 (0.68–1.37)
1.20 (0.81–1.78)
1.14 (0.77–1.71)
Hodgkin’s lymphoma
3.62 (0.93–14.10)
3.70 (0.30–45.64)
1.05 (0.31–3.57)
0.88 (0.18–4.43)
Multiple myeloma
0.93 (0.59–1.47)
0.94 (0.59–1.49)
1.27 (0.76–2.12)
1.16 (0.67–1.99)
Leukaemia
0.82 (0.59–1.13)
0.72 (0.52–1.00)
1.37 (0.91–2.06)
1.31 (0.86–2.01)
Immune-related cancers
Liver including intrahepatic
0.76 (0.46–1.27)
0.76 (0.45–1.28)
–
–
bile ducts
Malignant melanoma
2.06 (0.89–4.81)
1.48 (0.49–4.46)
1.37 (0.80–2.35)
1.17 (0.64–2.13)
Non-melanoma skin cancers
1.22 (0.89–1.67)
0.86 (0.62–1.19)
1.26 (1.11–1.43)
1.08 (0.95–1.23)
Kaposi’s sarcoma
1.11 (0.39–3.13)
0.89 (0.25–3.12)
1.35 (0.22–8.37)
3.79 (0.19–76.03)
Cervix
1.35 (0.70–2.61)
1.11 (0.54–2.31)
2.58 (1.33–4.99)
3.19 (1.59–6.38)
Anus and anal canal
2.80 (0.66–11.81)
–
2.92 (0.72–11.93)
2.99 (0.42–21.17)
External female genitals
0.80 (0.17–3.70)
0.29 (0.04–1.94)
2.79 (1.10–7.12)
3.62 (1.14–11.48)
Smoking- & alcohol-related
cancers
Mouth
1.63 (0.60–4.38)
1.49 (0.48–4.65)
1.80 (0.57–5.68)
1.86 (0.52–6.68)
Tonsil and pharynx
0.72 (0.21–2.47)
0.79 (0.21–2.99)
1.04 (0.40–2.71)
0.93 (0.34–2.54)
Larynx
0.69 (0.15–3.16)
0.48 (0.10–2.26)
1.61 (0.68–3.85)
1.16 (0.41–3.26)
Oesophagus
0.95 (0.61–1.50)
0.78 (0.49–1.24)
16.90 (1.93–
63.07 (2.31–1,721.4)
148.28)
Stomach
0.66 (0.48–0.91)
0.60 (0.43–0.84)
1.12 (0.55–2.31)
1.05 (0.45–2.41)
Colon
0.93 (0.75–1.15)
0.90 (0.72–1.13)
1.11 (0.87–1.41)
1.00 (0.78–1.28)
Rectum
0.84 (0.57–1.24)
0.71 (0.47–1.08)
0.99 (0.68–1.43)
0.93 (0.63–1.37)
Pancreas
0.79 (0.61–1.03)
0.69 (0.53–0.91)
2.23 (0.53–9.31)
1.88 (0.38–9.22)
Lung, bronchus and trachea
0.99 (0.86–1.14)
0.95 (0.82–1.10)
0.81 (0.55–1.19)
0.81 (0.54–1.21)
Kidney
0.83 (0.53–1.31)
0.80 (0.50–1.29)
1.10 (0.60–2.01)
1.24 (0.66–2.33)
Urinary bladder
0.98 (0.68–1.41)
0.84 (0.57–1.22)
0.65 (0.40–1.06)
0.51 (0.31–0.85)
All other sites
Gallbladder and bile ducts
1.01 (0.56–1.83)
0.83 (0.43–1.59)
–
–
Pleura
0.73 (0.32–1.63)
0.52 (0.19–1.38)
0.78 (0.07–8.88)
–
Retroperitoneum,
1.04 (0.38–2.79)
1.39 (0.43–4.52)
2.33 (0.62–8.70)
6.00 (1.08–33.30)
peritoneum, and other
connective and soft tissue
Breast
0.89 (0.64–1.25)
0.78 (0.54–1.11)
1.38 (1.15–1.67)
1.19 (0.98–1.44)
Uterus
0.74 (0.34–1.65)
0.59 (0.23–1.54)
1.28 (0.82–2.02)
0.92 (0.56–1.53)
Ovary and fallopian tube
0.86 (0.54–1.37)
0.81 (0.50–1.31)
1.15 (0.66–2.02)
0.92 (0.51–1.65)
Prostate
0.93 (0.69–1.27)
0.79 (0.57–1.08)
0.98 (0.77–1.25)
0.88 (0.68–1.13)
Brain
1.02 (0.62–1.66)
0.88 (0.52–1.48)
0.80 (0.16–3.85)
0.78 (0.15–4.10)
Endocrine glands
1.08 (0.36–3.22)
1.31 (0.40–4.28)
3.80 (0.74–19.53)
4.15 (0.33–52.46)
Metastasis and unspecified
0.99 (0.76–1.31)
0.93 (0.70–1.23)
0.70 (0.17–2.99)
0.90 (0.13–6.41)
cancer in lymph nodes
Malignant neoplasm of
1.61 (1.12–2.30)
1.50 (1.04–2.18)
–
–
other, ill-defined, or
unspecified sites
Abbreviations: CI = confidence interval; MRR = mortality rate ratios
*Only cancer types with ten or more herpes zoster cohort members are presented.
†Mortality rate ratios calculated with stratified Cox proportional hazard regression and thus adjusted for age at diagnosis, sex, calendar
period at cancer diagnosis, and cancer type by study design
‡Additionally adjusted for Charlson Comorbidity Index level and cancer stage