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Summary: Background: The worldwide incidence of cutaneous squamous cell carcinoma (cSCC) is increasing. Objectives: To evaluate the tumour burden of in situ and invasive cSCC in Iceland, where the population is exposed to limited ultraviolet radiation. Methods: This whole‐population study used the Icelandic Cancer Registry, which contains records of all in situ and invasive cSCC cases from 1981 to 2017. Incidence of cSCC was evaluated according to age, anatomical location, residence and multiplicity, and trends were assessed using joinpoint analysis. Age‐standardized rates (WSR) and age‐specific incidence rates per 100 000 person‐years were calculated, along with cumulative and lifetime risks. Results: Between 1981 and 2017, in situ cSCC WSR increased from 1·2 to 19·1 for men and from 2·0 to 22·3 for women. Invasive cSCC WSR rose from 4·6 to 14 for men and from 0·3 to 13·2 for women. The average number of in situ cSCC lesions was 1·71 per woman and 1·39 per man. Women developed more in situ cSCCs than invasive cSCCs in almost all anatomical locations, whereas men developed more invasive cSCCs, mostly on the head and neck. The rates of in situ cSCC were higher in Reykjavik compared with rural areas. Furthermore, women more commonly developed multiple in situ lesions. For lip cSCCs, invasive lesions occurred more frequently than in situ lesions among both sexes. Joinpoint analysis showed that in situ cSCC in women exhibited the most rapid incidence increase. Conclusions: cSCC has become an increasingly significant public health problem in Iceland. Tanning bed use and travelling abroad may contribute to skin cancer development. Public health efforts are needed to stem the behaviours leading to this rapid rise in cSCC. What is already known about this topic?Cutaneous squamous cell carcinoma (cSCC) incidence is on the rise worldwide, posing a significant public health threat, especially in light‐skinned populations. What does this study add? Icelandic women were more likely to develop in situ cSCC, and men were more likely to develop invasive cSCC of the head and neck.Women with in situ cSCCs were also at a higher risk of developing more than one cSCC compared with men.cSCC is becoming a significant public health problem in a country with low background ultraviolet radiation. This finding may be due, in part, to increased tanning bed exposure and travel abroad. Linked Comment: Z.C. Venables. Br J Dermatol 2021; 185:477–478. [ABSTRACT FROM AUTHOR]

Summary: Background: An epidemic of basal cell carcinoma (BCC) has led to a significant healthcare burden in white populations. Objectives: To provide an update on incidence rates and tumour burden in an unselected, geographically isolated population that is exposed to a low level of ultraviolet radiation. Methods: This was a whole‐population study using a cancer registry containing records of all cases of BCC in 1981–2017. We assessed BCC incidence according to age, residence and multiplicity and assessed trends using join‐point analysis. Age‐standardized and age‐specific incidence rates were calculated along with cumulative and lifetime risks. Results: During the study period, the age‐standardized incidence rates increased from 25·7 to 59·9 for men, and from 22·2 to 83·1 for women (per 100 000). Compared with the single‐tumour burden, the total tumour burden in the population was 1·72 times higher when accounting for multiplicity. At the beginning of the study period, the world‐standardized rates in men and women were similar, but by the end of the study period the rates were 39% higher in women (83·1 per 100 000, 95% confidence interval 77·9–88·3) than in men (59·9 per 100 000, 95% confidence interval 55·6–64·2). This increase was most prominent in women on sites that are normally not exposed to ultraviolet radiation in Iceland: the trunk and legs. Conclusions: This is the only reported population in which the incidence of BCC is significantly higher in women than in men. The period of notable increase in BCC lesions correlates with the period of an increase in tanning beds and travel popularity. The high multiplicity rates suggest that the total tumour burden worldwide might be higher than previously thought. What is already known about this topic? Basal cell carcinoma (BCC) is becoming an increasing healthcare burden worldwide, especially in white populations.Recent population studies have reported a rapid increase in incidence among younger individuals, especially women. What does this study add? Iceland is the only reported population in which the incidence of BCC is significantly higher in women than in men, and there does not seem to be a clear relationship between latitude and BCC incidence in Europe.Men might be comparatively protected in the northern low‐ultraviolet environment, with tanning beds and travel abroad likely playing important roles in the observed incidence increase, especially in women.The high multiplicity rates suggest that the total tumour burden worldwide might be higher than previously thought. Linked Comment:Pandeya. Br J Dermatol 2020; 183:799–800. What is already known about this topic? Basal cell carcinoma (BCC) is becoming an increasing healthcare burden worldwide, especially in white populations.Recent population studies have reported a rapid increase in incidence among younger individuals, especially women. What does this study add? Iceland is the only reported population in which the incidence of BCC is significantly higher in women than in men, and there does not seem to be a clear relationship between latitude and BCC incidence in Europe.Men might be comparatively protected in the northern low‐ultraviolet environment, with tanning beds and travel abroad likely playing important roles in the observed incidence increase, especially in women.The high multiplicity rates suggest that the total tumour burden worldwide might be higher than previously thought. Linked Comment:Pandeya. Br J Dermatol 2020; 183:799–800. Plain language summary available online [ABSTRACT FROM AUTHOR]

Statins have been associated with an increased risk of keratinocyte carcinoma but data are limited and conflicting. Statins are hypothesized to contribute to KC through immunomodulation. A whole-population case-control study of the Icelandic population was conducted using the Icelandic Cancer Registry and Icelandic Prescription Medicine Register. These are high-quality registers which include all cancer diagnoses, as well as every prescription in the country. Cases included all first-time histologically confirmed diagnoses of (BCC), in situ squamous cell carcinoma (SCCis) and invasive SCC between 2003 and 2017. Each case was paired with 10 age- and sex-matched controls. Multivariate conditional logistic regression analysis was performed. Four thousand seven hundred patients with BCC, 1167 patients with SCCis and 1013 patients with invasive SCC were identified and paired with 47,292, 11,961 and 10,367 controls, respectively. Overall statin use was associated with an increased risk of invasive SCC and SCCis but not BCC (adjusted OR [95% CI]: 1.29 [1.11-1.50]; 1.43 [1.24-1.64]; 1.03 [0.95-1.12], respectively). Subgroup analysis demonstrated that statins were significantly associated with invasive SCC and SCCis in patients over 60, but not in those under 60. Atorvastatin was only associated with an increased risk of SCCis; whereas, simvastatin was associated with an increased risk of both invasive SCC and SCCis. This whole-population study of Iceland demonstrates that statin exposure is associated with increased risk of SCC, but not BCC, in a low UV environment. The reasons are unclear, but our results may suggest that individuals receiving atorvastatin and simvastatin have differing levels of baseline keratinocyte cancer risk or that properties of a statin other than 'statin intensity' affect association with SCC., (© 2021. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Background: Metformin has anticarcinogenic properties and is also known to inhibit the sonic hedgehog pathway, but population-based studies analyzing the potential protective effect for basal cell carcinoma (BCC) and squamous cell carcinoma (SCC) are needed., Objectives: To delineate the association between metformin use and invasive SCC, SCC in situ (SCCis), and BCC., Methods: A population-based case-control study design was employed using all 6880 patients diagnosed in Iceland between 2003-2017 with first-time BCC, SCCis, or invasive SCC, and 69,620 population controls. Multivariate odds ratios (ORs) were calculated using conditional logistic regression., Results: Metformin was associated with a lower risk of developing BCC (OR, 0.71; 95% confidence interval [CI], 0.61-0.83), even at low doses. No increased risk of developing SCC was observed. SCCis risk was mildly elevated in the 501-1500 daily dose unit category (OR, 1.40; 95% CI, 1.00-1.96)., Limitations: This study was retrospective in nature with the inability to adjust for ultraviolet exposure, Fitzpatrick skin type, and comorbidities., Conclusion: Metformin is associated with decreased risk of BCC development, even at low doses. Metformin might have potential as a chemoprotective agent for patients at high risk of BCC, although this will need confirmation in future studies., Competing Interests: Conflicts of interest None disclosed., (Copyright © 2021 American Academy of Dermatology, Inc. Published by Elsevier Inc. All rights reserved.)

Background: Population-based studies analyzing hydrochlorothiazide's (HCTZ's) effect on keratinocyte carcinoma, and particularly invasive squamous cell carcinoma (SCC), are lacking., Objectives: To characterize the association between HCTZ use and invasive SCC, SCC in situ (SCCis), and basal cell carcinoma (BCC)., Methods: This population-based case-control study included all 6880 patients diagnosed with first-time BCC, SCCis, and invasive SCC between 2003 and 2017 in Iceland and 69,620 population controls. Conditional logistic regression analyses were used to calculate multivariate odds ratios (ORs) for keratinocyte carcinoma associated with HCTZ use., Results: A cumulative HCTZ dose above 37,500 mg was associated with increased risk of invasive SCC (OR, 1.69; 95% confidence interval [CI], 1.04-2.74). Users of HCTZ also had an increased risk of SCCis (OR, 1.24; 95% CI, 1.01-1.52) and BCC (OR, 1.14; 95% CI, 1.02-1.29)., Limitations: Limitations include this study's retrospective nature with the resulting inability to adjust for ultraviolet exposure, Fitzpatrick skin type, and comorbidities., Conclusions: High cumulative exposure to HCTZ is associated with the development of keratinocyte carcinoma and, most importantly, invasive SCC. Sun protective behaviors alone may not eliminate the carcinogenic potential of HCTZ., (Copyright © 2020 American Academy of Dermatology, Inc. Published by Elsevier Inc. All rights reserved.)