Assessment of Incidence Rate and Risk Factors for Keratoacanthoma Among Residents of Queensland, Australia.

Importance Keratoacanthoma (KA) is a common and generally benign keratinocyte skin tumor. Reports of the incidence rates of KA are scant. In addition, the risk factors for KA are not well understood, although associations with UV radiation exposure and older age have been described. Objective To investigate the incidence rate of KA and the risk factors for developing KA. Design, Setting, and Participants The study included data from 40 438 of 193 344 randomly selected residents of Queensland, Australia, who participated in the QSkin Sun and Health (QSkin) prospective population-based cohort study. All participants completed a baseline survey between 2010 and 2011 and were ages 40 to 69 years at baseline. Histopathologic reports of KA were prospectively collected until June 30, 2014, through data linkage with pathologic records. Cox proportional hazards models were used to identify risk factors associated with KA while controlling for potential confounding variables. Data were analyzed from January 2 to April 8, 2020. Exposures Demographic characteristics, phenotypes, UV radiation exposure, medical history, and lifestyle. Results Among 40 438 participants (mean [SD] age, 56 [8] years; 18 240 men [45.1%]), 596 individuals (mean [SD] age, 62 [6] years; 349 men [58.6%]) developed 776 KA tumors during a median follow-up period of 3.0 years (interquartile range, 2.8-3.3 years). The person-based age-standardized incidence rate for KA in the age-restricted cohort was 409 individuals per 100 000 person-years (based on the 2001 Australian population). Risk factors after adjustment for potential confounders were older age (age ≥60 years vs age <50 years; hazard ratio [HR], 6.38; 95% CI, 4.65-8.75), male sex (HR, 1.56; 95% CI, 1.33-1.84), fair skin (vs olive, dark, or black skin; HR, 3.42; 95% CI, 1.66-7.04), inability to tan (vs ability to tan deeply; HR, 1.69; 95% CI, 1.19-2.40), previous excisions of keratinocyte cancers (ever had an excision vs never had an excision; HR, 6.28; 95% CI, 5.03-7.83), current smoking (vs never smoking, HR, 2.02; 95% CI, 1.59-2.57), and high alcohol use (≥14 alcoholic drinks per week vs no alcoholic drinks per week; HR, 1.42; 95% CI, 1.09-1.86). Conclusions and Relevance This is, to date, the first large prospective population-based study to report the incidence rate and risk factors for KA. The high person-based incidence rate (409 individuals per 100 000 person-years) highlights the substantial burden of KA in Queensland, Australia. Furthermore, the study's findings suggest that older age (≥60 years), male sex, UV radiation-sensitive phenotypes, indications of high sun exposure (eg, previous keratinocyte cancer excisions), smoking, and high alcohol use are independent risk factors for the development of KA.

[1]  I. Zalaudek,et al.  The detection rate of human papillomavirus in well‐differentiated squamous cell carcinoma and keratoacanthoma: is there new evidence for a viral pathogenesis of keratoacanthoma? , 2019, The British journal of dermatology.

[2]  Kishwer S Nehal,et al.  Update on Keratinocyte Carcinomas. , 2018, The New England journal of medicine.

[3]  R. Sinclair,et al.  Epidemiology of skin cancer in the mature patient. , 2017, Clinics in dermatology.

[4]  D. Whiteman,et al.  Cigarette Smoking and the Risks of Basal Cell Carcinoma and Squamous Cell Carcinoma. , 2017, The Journal of investigative dermatology.

[5]  A. Qureshi,et al.  Alcohol intake and risk of nonmelanoma skin cancer: a systematic review and dose–response meta‐analysis , 2017, The British journal of dermatology.

[6]  A. Green,et al.  Cutaneous squamous cell carcinoma: an epidemiological review , 2017, The British journal of dermatology.

[7]  Maciej Liskiewicz,et al.  Robust causal inference using Directed Acyclic Graphs: the R package , 2018 .

[8]  C. Baykal,et al.  Management of keratoacanthoma in patients with xeroderma pigmentosum: a challenge for clinicians , 2016, Journal of the European Academy of Dermatology and Venereology : JEADV.

[9]  R. Schwartz,et al.  Keratoacanthoma (KA): An update and review. , 2016, Journal of the American Academy of Dermatology.

[10]  D. Hohl,et al.  Keratoacanthoma: a distinct entity? , 2016, Experimental dermatology.

[11]  Fan Xiang,et al.  Incidence of nonmelanoma skin cancer in relation to ambient UV radiation in white populations, 1978-2012: empirical relationships. , 2014, JAMA dermatology.

[12]  R. Carr,et al.  Follicular squamous cell carcinoma is an under-recognised common skin tumour , 2014 .

[13]  J. Maize,et al.  Keratoacanthoma Clinical Behavior: A Systematic Review , 2014, The American Journal of dermatopathology.

[14]  Joseph P Houghton,et al.  Histopathologists’ approach to keratoacanthoma: a multisite survey of regional variation in Great Britain and Ireland , 2014, Journal of Clinical Pathology.

[15]  D. Whiteman,et al.  A meta-analysis of pigmentary characteristics, sun sensitivity, freckling and melanocytic nevi and risk of basal cell carcinoma of the skin. , 2013, Cancer epidemiology.

[16]  F. Song,et al.  Smoking and risk of skin cancer: a prospective analysis and a meta-analysis. , 2012, International journal of epidemiology.

[17]  D. Whiteman,et al.  Good test-retest reproducibility for an instrument to capture self-reported melanoma risk factors. , 2012, Journal of clinical epidemiology.

[18]  J. Leonardi-Bee,et al.  Smoking and the risk of nonmelanoma skin cancer: systematic review and meta-analysis. , 2012, Archives of dermatology.

[19]  C. Proby,et al.  Known and potential new risk factors for skin cancer in European populations: a multicentre case–control study , 2012, The British journal of dermatology.

[20]  D. Whiteman,et al.  Cohort profile: the QSkin Sun and Health Study. , 2012, International journal of epidemiology.

[21]  A. Hauschild,et al.  Improved survival with vemurafenib in melanoma with BRAF V600E mutation. , 2011, The New England journal of medicine.

[22]  L. Goldberg,et al.  Keratoacanthomas: overview and comparison between Houston and minneapolis experiences. , 2010, Journal of drugs in dermatology : JDD.

[23]  D. S. Santa Cruz,et al.  Keratoacanthoma: hyperplasia, benign neoplasm, or a type of squamous cell carcinoma? , 2009, Seminars in diagnostic pathology.

[24]  P. Cuevas,et al.  Keratoacanthoma , 2009, BMJ Case Reports.

[25]  Theo Stijnen,et al.  Using the outcome for imputation of missing predictor values was preferred. , 2006, Journal of clinical epidemiology.

[26]  H. Miot,et al.  Association between solitary keratoacanthoma and cigarette smoking: a case-control study. , 2006, Dermatology online journal.

[27]  S. Nonaka,et al.  Incidence of xeroderma pigmentosum in Larkana, Pakistan: a 7‐year study , 2005, The British journal of dermatology.

[28]  V. Tron,et al.  Multiple Keratoacanthomas Arising Post-UVB Therapy , 2004, Journal of cutaneous medicine and surgery.

[29]  Hans Clevers,et al.  Notch1 functions as a tumor suppressor in mouse skin , 2003, Nature Genetics.

[30]  N. Silvis,et al.  Keratoacanthoma developing in sites of previous trauma: a report of two cases and review of the literature. , 2003, Journal of the American Academy of Dermatology.

[31]  M. Sopori,et al.  Effects of cigarette smoke on the immune system , 2002, Nature Reviews Immunology.

[32]  L. Requena,et al.  Solitary Keratoacanthoma: A Self-Healing Proliferation That Frequently Becomes Malignant , 2000, The American Journal of dermatopathology.

[33]  J. Sullivan Keratoacanthoma: The Australian experience , 1997, The Australasian journal of dermatology.

[34]  R. Dufresne,et al.  Seasonal presentation of keratoacanthomas in Rhode Island , 1997, The British journal of dermatology.

[35]  J. L. Stone,et al.  KERATOACANTHOMA IN JAPANESE HAWAIIANS IN KAUAI, HAWAII , 1995, International journal of dermatology.

[36]  J. L. Stone,et al.  Basal cell carcinoma and keratoacanthoma in Hawaiians: an incidence report. , 1993, Journal of the American Academy of Dermatology.

[37]  Robert E. Jones,et al.  Solitary keratoacanthoma is a squamous-cell carcinoma: three examples with metastases. , 1993, The American Journal of dermatopathology.

[38]  J. L. Stone,et al.  Keratoacanthoma in Kauai, Hawaii. The first documented incidence in a defined population. , 1993, Archives of dermatology.

[39]  Matthew D. Schultz,et al.  PUVA and skin cancer. A historical cohort study on 492 patients. , 1992, Journal of the American Academy of Dermatology.

[40]  D. Rubin Multiple imputation for nonresponse in surveys , 1989 .

[41]  M. Cristofolini,et al.  A gigantic, metastasizing keratoacanthoma: Report of a case and discussion on classification , 1984, The American Journal of dermatopathology.

[42]  G. Colditz,et al.  KERATOACANTHOMA IN A SUBTROPICAL CLIMATE * , 1979 .

[43]  Whiting Da Skin tumours in White South Africans. Part I. Patients, methods and incidence. , 1978 .

[44]  I. Caro,et al.  KERATOACANTHOMA IN A BANTU CHILD , 1976, International journal of dermatology.

[45]  M. R. Robertson,et al.  Skin cancer and immunosuppression. , 1971, Lancet.

[46]  F. N. Ghadially,et al.  The etiology of keratoacanthoma , 1963 .

[47]  D. Elder,et al.  WHO classification of skin tumours , 2018 .

[48]  D. Whiting Skin tumours in White South Africans. Part I. Patients, methods and incidence. , 1978, South African medical journal = Suid-Afrikaanse tydskrif vir geneeskunde.