Increased cancer incidence among patients with hidradenitis suppurativa – a Danish nationwide register study 1977–2017
DOI:
https://doi.org/10.2340/1651-226X.2024.26182Keywords:
Hidradenitis suppurativa, Cancer, Cancer risk, Registries, epidemiologyAbstract
Background: The chronic, inflammatory skin disease hidradenitis suppurativa (HS) (prevalence: 0.5%–1%, diagnostic delay: 7–10 years) primarily arises in younger adults and frequently coincides with autoimmune comorbidities and unhealthy life-styles (smoking and obesity). These factors are known to increase cancer risk, but despite this, information on cancer occurrence among HS patients is scarce.
Materials and methods: A nationwide retrospective register-based study assessing relative risk of cancer – overall and by anatomical site – following HS diagnosis expressed as standardized incidence ratios (SIRs), which is ratios between observed cases among all Danes diagnosed with HS since 1977 and expected cases based on cancer incidence rates of the entire Danish population during the same period.
Results: Participants consisted of a cohort of 13,919 Danes with HS, who during an average of 14.2 years of follow-up developed a total of 1,193 incident cancers, corresponding to a 40% increased risk (SIR = 1.4, 95% CI: 1.3 to 1.4, p < 0.001). Increased risks were observed for cancers of the respiratory system, oral cavity and pharynx, digestive organs and peritoneum, urinary tract, and the lymphatic tissues.
Interpretation: These findings underline an unmet need for health monitoring, lifestyle interventions and cancer screening if and when relevant.
Downloads
References
Jemec GB. Clinical practice. Hidradenitis suppurativa. N Engl J Med. 2012;366(2):158–64.
https://doi.org/10.1056/NEJMcp1014163 DOI: https://doi.org/10.1056/NEJMcp1014163
Andersen RK, Jemec GB. Treatments for hidradenitis suppurativa. Clin Dermatol. 2017;35(2):218–224.
https://doi.org/10.1016/j.clindermatol.2016.10.018 DOI: https://doi.org/10.1016/j.clindermatol.2016.10.018
Kjærsgaard Andersen R, Jørgensen IF, Reguant R, Jemec GBE, Brunak S. Disease trajectories for hidradenitis suppurativa in the Danish population. JAMA Dermatol. 2020;156(7):780–786.
https://doi.org/10.1001/jamadermatol.2020.1281 DOI: https://doi.org/10.1001/jamadermatol.2020.1281
Tzellos T, Zouboulis CC, Gulliver W, Cohen AD, Wolkenstein P, Jemec GB. Cardiovascular disease risk factors in patients with hidradenitis suppurativa: a systematic review and meta-analysis of observational studies. Br J Dermatol. 2015;173(5):1142–1155.
https://doi.org/10.1111/bjd.14024 DOI: https://doi.org/10.1111/bjd.14024
Shavit E, Dreiher J, Freud T, Halevy S, Vinker S, Cohen AD. Psychiatric comorbidities in 3207 patients with hidradenitis suppurativa. J Eur Acad Dermatol Venereol. 2015;29(2):371–376.
https://doi.org/10.1111/jdv.12567 DOI: https://doi.org/10.1111/jdv.12567
Aletaha D, Epstein AJ, Skup M, Zueger P, Garg V, Panaccione R. Risk of developing additional immune-mediated manifestations: a retrospective matched cohort study. Adv Ther. 2019;36(7):1672–1683.
https://doi.org/10.1007/s12325-019-00964-z DOI: https://doi.org/10.1007/s12325-019-00964-z
Jfri A, Nassim D, O’Brien E, Gulliver W, Nikolakis G, Zouboulis CC. Prevalence of hidradenitis suppurativa: a aystematic review and meta-regression analysis. JAMA Dermatol. 2021;157(8):924–931.
https://doi.org/10.1001/jamadermatol.2021.1677 DOI: https://doi.org/10.1001/jamadermatol.2021.1677
Kjaersgaard Andersen R, Clemmensen SB, Larsen LA, et al. Evidence of gene-gene interaction in hidradenitis suppurativa: a nationwide registry study of Danish twins. Br J Dermatol. 2022;186(1):78–85.
https://doi.org/10.1111/bjd.20654 DOI: https://doi.org/10.1111/bjd.20654
van Straalen KR, Prens EP, Willemsen G, Boomsma DI, van der Zee HH. Contribution of genetics to the susceptibility to hidradenitis suppurativa in a large, cross-sectional Dutch twin cohort. JAMA Dermatol. 2020;156(12):1359–62.
https://doi.org/10.1001/jamadermatol.2020.3630 DOI: https://doi.org/10.1001/jamadermatol.2020.3630
Deckers IE, Janse IC, van der Zee HH, et al. Hidradenitis suppurativa (HS) is associated with low socioeconomic status (SES): a cross-sectional reference study. J Am Acad Dermatol. 2016;75(4):755–9.e1.
https://doi.org/10.1016/j.jaad.2016.04.067 DOI: https://doi.org/10.1016/j.jaad.2016.04.067
Wertenteil S, Strunk A, Garg A. Association of low socioeconomic status with hidradenitis suppurativa in the United States. JAMA Dermatol. 2018;154(9):1086–8.
https://doi.org/10.1001/jamadermatol.2018.2117 DOI: https://doi.org/10.1001/jamadermatol.2018.2117
Acharya P, Mathur M. Hidradenitis suppurativa and smoking: a systematic review and meta-analysis. J Am Acad Dermatol. 2020;82(4):1006–11.
https://doi.org/10.1016/j.jaad.2019.10.044 DOI: https://doi.org/10.1016/j.jaad.2019.10.044
Garg A, Papagermanos V, Midura M, Strunk A, Merson J. Opioid, alcohol, and cannabis misuse among patients with hidradenitis suppurativa: a population-based analysis in the United States. J Am Acad Dermatol. 2018;79(3):495–500.e1.
https://doi.org/10.1016/j.jaad.2018.02.053 DOI: https://doi.org/10.1016/j.jaad.2018.02.053
Racanelli E, Jfri A, Gefri A, et al. Cutaneous squamous cell carcinoma in patients with hidradenitis suppurativa. Cancers (Basel). 2021;13(5):1153.
https://doi.org/10.3390/cancers13051153 DOI: https://doi.org/10.3390/cancers13051153
Lapins J, Ye W, Nyrén O, Emtestam L. Incidence of cancer among patients with hidradenitis suppurativa. Arch Dermatol. 2001;137(6):730–4.
Jung JM, Lee KH, Kim YJ, et al. Assessment of overall and specific cancer risks in patients with hidradenitis suppurativa. JAMA Dermatol. 2020;156(8):844–53.
https://doi.org/10.1001/jamadermatol.2020.1422 DOI: https://doi.org/10.1001/jamadermatol.2020.1422
Schmidt M, Pedersen L, Sørensen HT. The Danish civil registration system as a tool in epidemiology. Eur J Epidemiol. 2014;29(8):541–9.
https://doi.org/10.1007/s10654-014-9930-3 DOI: https://doi.org/10.1007/s10654-014-9930-3
Gjerstorff ML. The Danish Cancer Registry. Scand J Public Health. 2011;39(7 Suppl):42–5.
https://doi.org/10.1177/1403494810393562 DOI: https://doi.org/10.1177/1403494810393562
Schmidt M, Schmidt SA, Sandegaard JL, Ehrenstein V, Pedersen L, Sorensen HT. The Danish National Patient Registry: a review of content, data quality, and research potential. Clin Epidemiol. 2015;7:449–90.
https://doi.org/10.2147/CLEP.S91125 DOI: https://doi.org/10.2147/CLEP.S91125
Schmidt M, Schmidt SAJ, Adelborg K, et al. The Danish health care system and epidemiological research: from health care contacts to database records. Clin Epidemiol. 2019;11:563–91.
https://doi.org/10.2147/CLEP.S179083 DOI: https://doi.org/10.2147/CLEP.S179083
Rostgaard K. Methods for stratification of person-time and events – a prerequisite for Poisson regression and SIR estimation. Epidemiol Perspect Innov. 2008;5:7.
https://doi.org/10.1186/1742-5573-5-7 DOI: https://doi.org/10.1186/1742-5573-5-7
Tannenbaum R, Strunk A, Garg A. Association between gidradenitis suppurativa and lymphoma. JAMA Dermatol. 2019;155(5):624–5.
https://doi.org/10.1001/jamadermatol.2018.5230 DOI: https://doi.org/10.1001/jamadermatol.2018.5230
Makris GM, Poulakaki N, Papanota AM, Kotsifa E, Sergentanis TN, Psaltopoulou T. Vulvar, perianal and perineal cancer after hidradenitis suppurativa: a systematic review and pooled analysis. Dermatol Surg. 2017;43(1):107–15.
https://doi.org/10.1097/DSS.0000000000000944 DOI: https://doi.org/10.1097/DSS.0000000000000944
Rastogi S, Patel KR, Singam V, et al. Vulvar cancer association with groin hidradenitis suppurativa: a large, urban, midwestern US patient population study. J Am Acad Dermatol. 2019;80(3):808–10.
https://doi.org/10.1016/j.jaad.2018.10.008 DOI: https://doi.org/10.1016/j.jaad.2018.10.008
Zouboulis CC, Del Marmol V, Mrowietz U, Prens EP, Tzellos T, Jemec GB. Hidradenitis suppurativa/acne inversa: criteria for diagnosis, severity assessment, classification and disease evaluation. Dermatology. 2015;231(2):184–90.
https://doi.org/10.1159/000431175 DOI: https://doi.org/10.1159/000431175
Lamberg AL, Sølvsten H, Lei U, et al. The Danish Nonmelanoma Skin Cancer Dermatology Database. Clin Epidemiol. 2016;8:633–6.
https://doi.org/10.2147/CLEP.S99464 DOI: https://doi.org/10.2147/CLEP.S99464
Lamberg AL, Cronin-Fenton D, Olesen AB. Registration in the Danish Regional Nonmelanoma Skin Cancer Dermatology Database: completeness of registration and accuracy of key variables. Clin Epidemiol. 2010;2:123–36.
https://doi.org/10.2147/CLEP.S9959 DOI: https://doi.org/10.2147/CLEP.S9959
Braae Olesen A, Lei U, Jemec GB, Lamberg A. [Clinical database for non-melanoma skin cancer]. Ugeskrift Laeger. 2012;174(42):2546.
Cuenca-Barrales C, Molina-Leyva A. Sexuality in patients with hidradenitis suppurativa: beliefs, behaviors and needs. Int J Environ Res Public Health. 2020;17(23):8808.
https://doi.org/10.3390/ijerph17238808 DOI: https://doi.org/10.3390/ijerph17238808
Bechara FG, Sand M, Skrygan M, Kreuter A, Altmeyer P, Gambichler T. Acne inversa: evaluating antimicrobial peptides and proteins. Ann Dermatol. 2012;24(4):393–7.
https://doi.org/10.5021/ad.2012.24.4.393 DOI: https://doi.org/10.5021/ad.2012.24.4.393
Navrazhina K, Garcet S, Gonzalez J, Grand D, Frew JW, Krueger JG. In-depth analysis of the hidradenitis suppurativa serum proteome identifies distinct inflammatory subtypes. J Invest Dermatol. 2021;141(9):2197–207.
https://doi.org/10.1016/j.jid.2021.02.742 DOI: https://doi.org/10.1016/j.jid.2021.02.742
Shalom G, Freud T, Ben Yakov G, et al. Hidradenitis suppurativa and inflammatory bowel disease: a cross-sectional study of 3,207 patients. J Invest Dermatol. 2016;136(8):1716–8.
https://doi.org/10.1016/j.jid.2016.04.003 DOI: https://doi.org/10.1016/j.jid.2016.04.003
Kjaersgaard Andersen R, Saunte SK, Jemec GBE, Saunte DM. Psoriasis as a comorbidity of hidradenitis suppurativa. Int J Dermatol. 2020;59(2):216–20.
https://doi.org/10.1111/ijd.14651 DOI: https://doi.org/10.1111/ijd.14651
Schneeweiss MC, Merola JF, Schneeweiss S, Wyss R, Rosmarin D. Risk of connective tissue disease, morphoea and systemic vasculitis in patients with hidradenitis suppurativa. J Eur Acad Dermatol Venereol. 2021;35(1):195–202.
https://doi.org/10.1111/jdv.16728 DOI: https://doi.org/10.1111/jdv.16728
Miller IM, Ellervik C, Vinding GR, et al. Association of metabolic syndrome and hidradenitis suppurativa. JAMA Dermatol. 2014;150(12):1273–80.
https://doi.org/10.1001/jamadermatol.2014.1165 DOI: https://doi.org/10.1001/jamadermatol.2014.1165
World Health Organization. WHO report on cancer: setting priorities, investing wisely and providing care for all. Geneva: World Health Organization; 2020.
Cole DW, Fotouhi A, Fakhoury J, Daveluy S. An Internet-based survey study of patients with hidradenitis suppurativa: use of the Internet for disease-related information. J Am Acad Dermatol. 2020;83(3):905–7.
https://doi.org/10.1016/j.jaad.2019.12.024 DOI: https://doi.org/10.1016/j.jaad.2019.12.024
Saunte DM, Boer J, Stratigos A, et al. Diagnostic delay in hidradenitis suppurativa is a global problem. Br J Dermatol. 2015;173(6):1546–9.
https://doi.org/10.1111/bjd.14038 DOI: https://doi.org/10.1111/bjd.14038
Garg A, Neuren E, Cha D, et al. Evaluating patients’ unmet needs in hidradenitis suppurativa: results from the Global Survey Of Impact and Healthcare Needs (VOICE) Project. J Am Acad Dermatol. 2020;82(2):366–76.
https://doi.org/10.1016/j.jaad.2019.06.1301 DOI: https://doi.org/10.1016/j.jaad.2019.06.1301
Shukla N, Paul M, Halley M, et al. Identifying barriers to care and research in hidradenitis suppurativa: findings from a patient engagement event. Br J Dermatol. 2020;182(6):1490–2.
https://doi.org/10.1111/bjd.18818 DOI: https://doi.org/10.1111/bjd.18818
Bouazzi D, Theut Riis P, Jemec GBE. Emergency doctor’s ability to diagnose hidradenitis suppurativa. J Eur Acad Dermatol Venereol. 2020;34(11):e712–4.
https://doi.org/10.1111/jdv.16536 DOI: https://doi.org/10.1111/jdv.16536
Shalom G, Babaev M, Freud T, et al. Demographic and health care service utilization by 4417 patients with hidradenitis suppurativa. J Am Acad Dermatol. 2017;77(6):1047–1052.e2.
https://doi.org/10.1016/j.jaad.2017.10.001 DOI: https://doi.org/10.1016/j.jaad.2017.10.001
Santos JV, Lisboa C, Lanna C, Costa-Pereira A, Freitas A. Is the prevalence of hidradenitis suppurativa being overestimated in Europe? Or is the disease underdiagnosed? Evidence from a nationwide study across Portuguese public hospitals. Int J Dermatol. 2017;56(12):1491–2.
https://doi.org/10.1111/ijd.13703 DOI: https://doi.org/10.1111/ijd.13703
Theut Riis P, Pedersen OB, Sigsgaard V, et al. Prevalence of patients with self-reported hidradenitis suppurativa in a cohort of Danish blood donors: a cross-sectional study. Br J Dermatol. 2019;180(4):774–81.
https://doi.org/10.1111/bjd.16998 DOI: https://doi.org/10.1111/bjd.16998
Kristensen MH, Schmidt SAJ, Kibsgaard L, Hove H, Sommerlund M, Koppelhus U. Validity of first-time diagnoses of inherited ichthyosis in the Danish national patient registry and the Danish pathology registry. Clin Epidemiol. 2020;12:651–7.
https://doi.org/10.2147/CLEP.S232956 DOI: https://doi.org/10.2147/CLEP.S232956
Kristensen MH, Schmidt SAJ, Kibsgaard L, Mogensen M, Sommerlund M, Koppelhus U. Validity of first-time diagnoses of congenital epidermolysis bullosa in the Danish National Patient Registry and the Danish Pathology Registry. Clin Epidemiol. 2019;11:115–24.
https://doi.org/10.2147/CLEP.S184742 DOI: https://doi.org/10.2147/CLEP.S184742
Stovitz SD, Shrier I. Causal inference for clinicians. BMJ Evid Based Med. 2019;24(3):109–12.
https://doi.org/10.1136/bmjebm-2018-111069 DOI: https://doi.org/10.1136/bmjebm-2018-111069
Textor J, van der Zander B, Gilthorpe MS, Liskiewicz M, Ellison GT. Robust causal inference using directed acyclic graphs: the R package ‘dagitty’. Int J Epidemiol. 2016;45(6):1887–94. DOI: https://doi.org/10.1093/ije/dyw341
Kokolakis G, Wolk K, Schneider-Burrus S, et al. Delayed Diagnosis of Hidradenitis Suppurativa and Its Effect on Patients and Healthcare System. Dermatology. 2020;236(5):421-30. DOI: https://doi.org/10.1159/000508787
https://doi.org/10.2139/ssrn.3416695 DOI: https://doi.org/10.2139/ssrn.3416695
Published
How to Cite
License
Copyright (c) 2023 Rune Andersen, Klaus Rostgaard, Ole Pedersen, Gregor Borut Ernst Jemec, Henrik Hjalgrim
![Creative Commons License](http://i.creativecommons.org/l/by/4.0/88x31.png)
This work is licensed under a Creative Commons Attribution 4.0 International License.
Funding data
-
Novo Nordisk Fonden
Grant numbers NNF20SA0064340 -
LEO Fondet
Grant numbers LF 18002