Sunburn and Cutaneous Squamous Cell Carcinoma: A Meta-Analysis

Isaac Weber; Kaiping Liao; Tran Dang; Malay Shah; Mackenzie R Wehner

doi:10.1001/jamadermatol.2025.3473

. 2025 Sep 24;161(11):1148–1156. doi: 10.1001/jamadermatol.2025.3473

Sunburn and Cutaneous Squamous Cell Carcinoma

A Meta-Analysis

Isaac Weber ¹, Kaiping Liao ¹, Tran Dang ², Malay Shah ³, Mackenzie R Wehner ^1,^4,^✉

PMCID: PMC12461597 PMID: 40991277

Key Points

Question

Is sunburn history associated with the risk of developing cutaneous squamous cell carcinoma (cSCC)?

Findings

In this meta-analysis that included 17 studies with a combined 321 473 participants, medium to high frequencies of painful, blistering, and/or severe sunburns over an individual’s lifetime, as well as high frequencies of such sunburns during childhood, were significantly associated with increased odds of cSCC. Furthermore, any painful, blistering, and/or severe sunburn across the lifetime significantly elevated the odds of cSCC.

Meaning

This study supports evidence for an association between painful, blistering, and/or severe sunburns and cSCC.

This meta-analysis reviews studies assessing the association between sunburn history and risk for developing cutaneous squamous cell carcinoma.

Abstract

Importance

While UV radiation is a known carcinogen associated with cutaneous squamous cell carcinoma (cSCC), sunburn’s specific role remains less clear.

Objective

To quantitatively assess the association between sunburn history and the risk of developing cSCC.

Data Sources

A comprehensive search of Embase, PubMed, and Cochrane Library (CENTRAL) was conducted from inception up to May 6, 2025, with no language or date restrictions. Search terms included Non melanoma skin cancer or nonmelanoma skin cancer or NMSC or squamous cell carcinoma or SCC or cSCC or Bowen disease and Sunburn or sun exposure or sunlight or sun damage or ultraviolet radiation or ultraviolet light or ultraviolet rays.

Study Selection

The study included analytical investigations of the general population that assessed the association between cSCC and any type of sunburn history at any age. The initial screening of 9310 titles and abstracts by 3 masked independent reviewers resulted in 279 articles for full-text review, with 43 ultimately meeting eligibility criteria.

Data Extraction and Synthesis

This study follows the Meta-analysis of Observational Studies in Epidemiology (MOOSE) reporting guideline. Two reviewers worked independently to extract relevant data. The random effects DerSimonian-Laird method was used to pool data.

Main Outcome and Measures

The main outcome was the risk of developing cSCC. Main measures included sunburn frequency (both undefined and painful, blistering, and/or severe) in any life period, categorized into ordinal variables: none, low, medium, and high. The primary analysis was the most adjusted measure of association, standardized to odds ratio (OR). This incorporated adjusted measures of association when available and unadjusted measures when adjusted measures were absent.

Results

Seventeen studies with a combined 321 473 participants were included in the meta-analysis. Pooled analyses of the most adjusted results revealed significantly increased odds of developing cSCC with medium (OR, 1.51; 95% CI, 1.26-1.81) and high (OR, 1.69; 95% CI, 1.39-2.06) lifetime painful, blistering, and/or severe sunburn frequencies. Similarly, high frequencies of painful, blistering, and/or severe sunburns in childhood were significantly associated with increased cSCC odds (OR, 3.11; 95% CI, 1.26-7.66). A history of any painful, blistering, and/or severe sunburn was also significantly associated with increased odds of cSCC (OR, 1.38; 95% CI, 1.06-1.79).

Conclusions and Relevance

This meta-analysis supports an association between painful, blistering, and/or severe sunburns and cSCC.

Introduction

Cutaneous squamous cell carcinoma (cSCC) is among the most common cancers, with over 2.2 million global cases reported in 2021.¹ Although typically associated with a favorable prognosis, metastasis occurs in approximately 1.2% to 5% of cases, leading to a reported age-standardized cSCC mortality rate of 0.81 per 100 000 in high-income North America.^1,2 Recent cSCC incidence and mortality estimates show significant increases over the past 3 decades, postulated to be due to lifestyle changes associated with increased UV exposure.³

Sunburn is an indication of skin damage that is caused by large doses of UV radiation penetrating melanocytes at the epidermal base.^4,5 In sporadic cSCC more than 50% of the DNA mutations are UV signature, with both the US Department of Health & Human Services and the International Agency for Research on Cancer classifying UV radiation as carcinogenic.^6,7,8 In addition, the association with UV radiation is supported by animal studies, migrant studies, ecological studies correlating incidence to latitude, and case-control studies.^9,10

Some studies show that only chronic UV exposure is associated with increased cSCC risk, with no increased risk for sunburn history; however, other studies contradict these results.^11,12 Given the rising incidence and costs associated with cSCC, understanding the association between sunburn and cSCC is essential. While the role of UV exposure in cSCC is well-established, the specific effect of sunburns remains less certain, likely due to inherent measurement limitations and the potential for past sunburns to influence future sun-protective behaviors and subsequent sunburn frequencies.^6,13 This study aims to quantitatively assess the association between sunburn history and the risk of cSCC through a systematic review and meta-analysis.

Methods

This study follows and conforms to the Meta-analysis of Observational Studies in Epidemiology (MOOSE) reporting guideline. This study is registered with Prospero (CRD42024607339). This research involves a meta-analysis of existing, deidentified, publicly available data from previously conducted studies and is exempt from institutional review board approval as determined by the US Department of Health and Human Services under the Common Rule.

Outcome and Exposure Definitions

The outcome of this meta-analysis was histologically confirmed cSCC. The exposure definition was any type of sunburn measure, regardless of UV source, as defined by study authors (any undefined sunburn; any painful, blistering, and/or severe sunburn; frequency of undefined sunburns; frequency of painful, blistering, and/or severe sunburns; age of first sunburn).

Data Sources and Search Strategy

Our literature search, including the development of search terms, was conducted in collaboration with an academic librarian. We searched Embase, PubMed, and Cochrane Library (CENTRAL). No restrictions on date or language were placed, and English translations of all non-English language articles were pursued. The search terms comprised the following: Non melanoma skin cancer or nonmelanoma skin cancer or NMSC or squamous cell carcinoma or SCC or cSCC or Bowen disease and Sunburn or sun exposure or sunlight or sun damage or ultraviolet radiation or ultraviolet light or ultraviolet rays. The final search was conducted on May 6, 2025. References were imported to a systematic review platform (Covidence) for organization, deletion of duplicates, and relevance screening. After title and abstract screening by 3 independent reviewers (I.W., T.D., M.S.), any potentially relevant articles were reviewed independently as full text for relevant inclusion or exclusion criteria by 2 reviewers (I.W. and M.S.), with any disagreements mediated by a third reviewer (M.R.W.).

Studies were included if they assessed the association between cSCC incidence and any type of sunburn history at any age in the general population (Figure). Case-control, cohort, and cross-sectional studies were included and analyzed together. Related reviews and meta-analyses were searched for relevant articles but were not included in the analysis. We excluded skin propensity to sunburn and skin reaction to sun exposure, as this is a reflection of skin phenotype and not direct sunburn history. Studies focusing solely on disease-specific populations or high-risk groups, such as HIV-positive, xeroderma pigmentosum, or solid organ transplant recipients, were excluded, as were mucosal SCC (eg, head and neck) and special site SCCs, such as lip, conjunctival, anogenital, and SCC arising in chronic wounds. cSCC in situ and keratoacanthomas were excluded. Animal studies, case reports, case series, reviews, conference abstracts, and studies with fewer than 5 participants were excluded. Studies evaluating cSCC incidence in the context of photosensitive or immunosuppressive drug use were excluded. Reference lists of obtained articles were searched for additional studies meeting inclusion. In studies that assessed sunburn and cSCC but did not report statistical measures of association, or reported findings of nonmelanoma skin cancer without differentiating cSCC, corresponding authors were contacted.

Extraction and Unification of Data

Two reviewers worked independently to review the full-text articles (I.W., T.D.) and extract the relevant data with a third reviewer mediating disagreements, assuring agreement, and identifying discrepancies (M.R.W.). Data collection was performed utilizing standardized Covidence forms. Information recorded included study design, methods, population, country of study, years of study, outcome description, exposure measurement variables, case and control counts, measures of association, and adjustment variables. Extracted data was placed into spreadsheets, verified, and then subsequently analyzed. Certainty of evidence was assessed for studies in each subgroup using GRADE assessment.¹⁴ Risk of bias was assessed using the Newcastle-Ottawa Quality Assessment Scale (NOS) for both case-control and cohort studies (eTable 1 in Supplement 1). Concerns about NOS reliability and validity exist, however, recent evidence for NOS shows similar reliability to other risk of bias assessment tools.¹⁵

Data Analysis

To pool measures of association, we required at least 3 articles to report specific exposure measurements. Sunburn was analyzed in subgroups by age category of exposure (childhood [younger than 15 years], adulthood [older than 15 years or older], or lifetime) and by type of sunburn measure (any undefined sunburn; any painful, blistering, and/or severe sunburn; frequency of undefined sunburns; frequency of painful, blistering, and/or severe sunburns; age of first sunburn). Adolescent and adult categories were combined due to overlapping age categories of studies looking at these time periods (eg, ages 15 to 25 years). If studies included both an adolescent category in the range of ages 15 to 25 years and an adult category of greater than ages 20 to 25 years, the adult category was selected. Studies investigating sunburn frequency were mapped onto ordinal variables for analysis (none, low, medium, high) due to the varying scales used across studies to record sunburn frequency (eg, numerical scoring scales, sunburn frequency ranges, or descriptive sunburn frequency) (eTables 2-5 in Supplement 1).

Multiple studies used the same population cohort; therefore, to prevent the pooling of duplicate data, we organized studies into separate numerical cohorts that represented a single population used across multiple studies (eTable 6 in Supplement 1). As a result, data for different life periods within a single cohort may have been sourced from multiple articles. Within each defined life period for sunburn occurrence, we prioritized data with the most detailed reporting of sunburn frequency. When multiple publications in the same population cohort presented identical sunburn categories, we selected the data adjusted for the most comprehensive set of potential confounders; when adjustments were uniform, we selected based on the number of study participants.

Measures of association were pooled together and included odds ratio (OR) and relative risk (RR). When studies included only count data on cSCC and sunburn without including measures of association, an unadjusted OR was manually calculated. We reported pooled unadjusted, adjusted-only, and most adjusted measures of association, standardized to OR across studies. The adjusted-only analysis included only studies providing adjusted effect estimates. The most adjusted analysis aimed to maximize the number of included studies by incorporating adjusted measures of association when available and unadjusted measures of association when adjusted measures were absent for a given study. For all analyses, the reference group was the frequency that included zero sunburns in the associated category. The random effects DerSimonian-Laird method was used to estimate between-study variance.³⁰ To examine heterogeneity across study populations, we calculated the I² statistic. We assessed for the presence of publication bias using Egger test. All statistical analysis was completed using STATA software version 18.0 (StataCorp).

Results

Our search resulted in 9310 articles, which were screened by titles and abstracts; 279 studies were reviewed in full-text screening (Figure). Overall, 43 studies met inclusion criteria and were included in the systematic review (eTable 6 in Supplement 1).^{11,12,13,16,17,18,19,20,21,22,23,24,25,26,27,28,29,31,32,33,34,35,36,37,38,39,40,41,42,43,44,45,46,47,48,49,50,51,52,53,54,55,56} Multiple studies utilized the same cohort, which resulted in the identification of 22 distinct population cohorts. Twenty-six studies were not included due to a lack of standardizable data, a lack of a sufficient number of studies to perform subgroup analysis and/or overlapping population cohorts. Quality assessment and risk of bias in individual studies are reported in eTable 1 in Supplement 1.

We pooled 17 studies in 1 or more analyses (Table 1). Four studies reported lifetime sunburn frequency (2 case-control, 1 cross-sectional, 1 cohort) (eTable 2 in Supplement 1).^24,25,28,29 Sunburns specified as painful, blistering, and/or severe sunburn were pooled separately. Six studies reported a lifetime history of any (yes/no) painful, blistering, and/or severe sunburns (5 case-control, 1 cohort) (eTable 3 in Supplement 1).^{16,17,19,20,21,26} Six studies reported lifetime painful, blistering, and/or severe sunburn frequency (3 case-control, 3 cohort) (eTable 4 in Supplement 1).^{11,12,13,18,22,27} Three studies reported childhood painful, blistering, and/or severe sunburn frequency (2 case-control, 1 cohort) (eTable 5 in Supplement 1).^11,19,23 Funnel plots of each pooled category of unadjusted, adjusted only, and most adjusted ORs are included in the supplemental material (eFigures 1-27 in Supplement 1).

Table 1. Studies of cSCC and Sunburn Included in Pooled Analysis.

Source	Source of case patients or controls	Sample size	Sunburn types reported	Population cohort	Country	Years of study period	Sex	Numerical cohort^a
Case-control
Asgari et al,¹⁶ 2011	Hospital or clinic-based	415 Case patients, 415 controls	>2 Severe sunburns (yes/no)	Kaiser Permanente Northern California	US	2004	Mixed	11
Cheng et al,¹⁷ 2015	Population-based	254 Case patients, 432 controls	Frequency of lifetime painful sunburns	New Hampshire cohort	US	2001-2002	Mixed	16
English et al,¹⁸ 1998	Community-based	132 Case patients, 1031 controls	Frequency of painful sunburns, frequency of blistering sunburns	Geraldton Skin Cancer Prevention Survey	Australia	1987-1994	Mixed	6
Gallagher et al,¹⁹ 1995	Population-based	180 Case patients, 406 controls	Frequency of sunburns age 5-15 y, frequency of painful sunburn age 5-15 y, lifetime painful sunburn (yes/no), last decade painful sunburn (yes/no)	Alberta Cancer registry	Canada	1983-1984	Male	2
Han et al,¹² 2006	Nested	275 Case patients, 804 controls	Frequency of lifetime painful sunburns	NHS	US	1989-1998	Female	17
Hogan et al,²⁰ 1990	Population-based	178 Case patients, 284 controls	History of severe sunburn (yes/no)	Saskatchewan Cancer Foundation	Canada	1982-1983	Mixed	22
Iannacone et al,²¹ 2012	Clinic-based	169 Case patients, 316 controls	Age at first blistering sunburn, history of blistering sunburn (yes/no)	USF and Moffitt Cancer Center clinics	US	2006-2008	Mixed	26
Robinson et al,²² 2013	Population-based	1599 Case patients, 1906 controls	Frequency of lifetime painful sunburns	New Hampshire cohort	US	1993-1995, 1997-2000, 2001-2002, 2007-2009	Mixed	16
Savoye et al,²³ 2018	Nested	165 Case patients, 3647 controls	Frequency of sunburn at age <15 y, frequency of sunburn at age 15-25 y, frequency of sunburn at age >25 y,	E3N (Etude Epidémiologique auprès de femmes de l’Education Nationale)	France	1989-2008	Female	4
Zanetti et al,²⁴ 1996	Multicenter	228 Case patients, 1795 controls	Age at first sunburn (age >15 y or never, <15 y), frequency of lifetime sunburn	Helios cohort	Italy, Sicily, France, Spain	1989-1993	Mixed	9
Zanetti et al,²⁵ 2006	Multicenter	139 Case patients, 349 controls	Frequency of lifetime sunburn, sunburns in childhood (yes/no), frequency of severe sunburns in childhood	Helios II (different regions and institutions from Helios cohort studies)	Italy, France, Germany, Denmark, Spain, Argentina, Portugal	2001-2002	Male	10
Cohort
Foote et al,²⁶ 2001	Population-based	129 Case patients, 918 total cohort	History of >1 severe sunburn that blistered (yes/no)	Healthy adults living in Arizona (vitamin A cohort)	US	1985-1989	Mixed	8
Green et al,²⁷ 1996	Population-based	94 Case patients, 2095 total cohort	Frequency of lifetime painful sunburns	Nambour Queensland cohort	Australia	1985-1992	Mixed	15
Lergenmuller et al,¹³ 2022	Population-based	946 Case patients, 168 533 total cohort	Frequency of painful or blistering lifetime sunburn trajectory at ages <40 y, <50 y, and <60 y	Norwegian Women and Cancer cohort	Norway	1991-2007	Female	19
Liu et al,²⁸ 2021	Occupation-based	137 SCC case patients, 27 772 total cohort	Frequency of sunburns age >20 y, frequency of lifetime sunburns	Norwegian Offshore Petroleum Workers cohort	Norway	1999-2017	Mixed	18
Veierød et al,¹¹ 2014	Population-based	141 Case patients, 106 548 total cohort	Frequency of painful or blistering sunburn at ages <10 y, 10-19 y, 20-29 y, 30-39 y, 40-49 y; combined (ages 10-39 y), summarized (ages 10-39 y, 10-49 y)	Norwegian-Swedish Women’s Lifestyle and Health Cohort	Norway, Sweden	1991-2009	Female	20
Cross-sectional
Uotila et al,²⁹ 2024	Hospital-based	38 Case patients, 488 total cohort	Frequency of lifetime sunburns	Kuopio University Hospital	Finland	2017-2020	Mixed	12

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Abbreviations: cSCC, cutaneous squamous cell carcinoma; KA, keratoacanthoma; NHS, Nurses’ Health Study; USF, University of South Florida; SCC, squamous cell carcinoma.

^{^a}

Overlapping population cohorts were designated a number to prevent pooling of duplicate data.

Categories including any sunburn (yes/no) in childhood, adulthood, and lifetime, frequency of sunburns in childhood and adulthood, any painful, blistering, and/or severe sunburn (yes/no) in childhood and adulthood, and frequency of painful, blistering, and/or severe in adulthood all contained fewer than 3 independent studies assessing association with cSCC and thus were unable to be pooled. Studies assessing age of first sunburn included data too heterogeneous for pooling (eg, a different age specified in each).

Pooled unadjusted, adjusted-only, and most adjusted OR were calculated as data permitted. Five studies did not report any adjusted values.^{13,16,17,22,28} Twelve studies reported adjusted values.^{11,12,18,19,20,21,23,24,25,26,27,29} Age was uniformly adjusted for, with sex adjusted for in every mixed-sex study but one.²⁶ Skin phenotypic characteristics, including skin color, skin sensitivity to sun exposure, and/or phototype, were adjusted for by 2 studies (50%) in the lifetime pooled analysis on sunburn frequency (eTable 2 in Supplement 1). These characteristics were adjusted for in 3 of 6 studies (50%) pooled in history of ever having a painful, blistering, and/or severe sunburn; 2 of 6 studies (33%) of lifetime painful, blistering, and/or severe sunburn frequency; and 3 studies (100%) of childhood painful, blistering, and/or severe sunburn frequency categories, respectively (eTables 3-5 in Supplement 1). Adjustment for geographic region or country of residence was performed in 2 of 4 studies (50%) in the lifetime pooled analysis on sunburn frequency (eTable 2 in Supplement 1). These factors were adjusted for in no studies pooled in history of ever having a painful, blistering, and/or severe sunburn; 2 of 6 studies (33%) pooled in lifetime painful, blistering, and/or severe sunburn frequency; and 1 of 3 studies (30%) in the pooling childhood severe, painful, and/or blistering sunburn frequency categories (eTables 3-5 in Supplement 1).

Sunburn Frequency

Table 2 shows the pooled unadjusted, adjusted, and most adjusted OR of sunburn frequency throughout the lifetime. Within this category, 3 studies reported ordinal categories of sunburn frequency, and 1 reported a numerical category (eTable 2 in Supplement 1).^24,25,28,29 No association was found between a low (OR, 1.43; 95% CI, 0.75-2.76) or high (OR, 0.98; 95% CI, 0.55-1.72) frequency of sunburns throughout the lifetime and cSCC. The certainty of evidence for this association was very low. Funnel plots and the Egger test showed inconclusive evidence of publication bias in the studies included in this subgroup (eTable 7 in Supplement 1).

Table 2. Association of cSCC and Sunburns Over Individuals’ Lifetime.

Sunburn	Unadjusted		Adjusted		Most adjusted
Sunburn	No. of studies	OR (95% CI)^a	No. of studies	OR (95% CI)^a	No. of studies	Certainty of evidence^c	OR (95% CI)^a	I², %
None	4^24,25,28,29	[Reference]	3^24,25,29	[Reference]	4^24,25,28,29	NA	[Reference]	NA
Low	4^24,25,28,29	1.06 (0.83-1.36)	3^24,25,29	1.54 (0.64-3.74)	4^24,25,28,29	Very low	1.43 (0.75-2.76)	70.78
Medium	2^24,28	NR^b	1²⁴	NR^b	2^24,28	NA	NR^b	NA
High	4^24,25,28,29	1.10 (0.81-1.50)	3^24,25,29	0.91 (0.38-2.19)	4^24,25,28,29	Very low	0.98 (0.55-1.72)	51.27

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Abbreviations: cSCC, cutaneous squamous cell carcinoma; NA, not applicable; NR, not reportable; OR, odds ratio.

^{^a}

Relative risks were pooled with OR, treating them as comparable effect measures.

^{^b}

Too few studies to pool.

^{^c}

Summary certainty of evidence for studies in most adjusted estimates.

Painful, Blistering, and/or Severe Sunburns

Table 3 shows the pooled unadjusted, adjusted, and most adjusted OR of painful, blistering, and/or severe sunburn frequency throughout childhood and the lifetime as well as the pooled unadjusted, adjusted, and most adjusted OR for any painful, blistering, and/or severe sunburn.^11,17,25 Within the painful, blistering, and/or severe sunburn frequency throughout the lifetime subgroup, 2 studies reported ordinal categories of sunburn frequency, and 4 reported numerical categories (eTable 4 in Supplement 1).^{11,12,13,18,22,27} Within the painful, blistering, and/or severe sunburn frequency throughout childhood subgroup, 1 study reported ordinal categories of sunburn frequency, and 2 reported numerical categories (eTable 5 in Supplement 1).^11,19,23 All studies in the childhood category reported adjusted measures of effect; therefore, the adjusted and most adjusted ORs are the same.

Table 3. cSCC and Painful, Blistering, and/or Severe Sunburns.

Age category	Sunburn	Unadjusted		Adjusted		Most adjusted
Age category	Sunburn	No. of studies	OR (95% CI)^a	No. of studies	OR (95% CI)^a	No. of studies	Certainty of evidence^c	OR (95% CI)^a	I², %
Childhood	None	2^19,23	[Reference]	3^11,19,23	[Reference]	3^11,19,23	NA	[Reference]	NA
	Low	2^19,23	NR^b	3^11,19,23	1.31 (0.87-1.97)	3^11,19,23	Very low	1.31 (0.87-1.97)	0
	Medium	1²³	NR^b	1²³	NR^b	1²³	NA	NR^b	NA
	High	2^19,23	NR^b	3^11,19,23	3.11 (1.26-7.66)	3^11,19,23	Very low	3.11 (1.26-7.66)	62.65
Lifetime	None	4^12,13,18,22	[Reference]	4^11,12,18,27	[Reference]	6^{11,12,13,18,22,27}	NA	[Reference]	NA
	Low	4^12,13,18,22	1.22 (0.89-1.68)	4^11,12,18,27	1.37 (1.02-1.84)	6^{11,12,13,18,22,27}	Low	1.21 (0.99-1.48)	40.80
	Medium	4^12,13,18,22	1.63 (1.33-2.00)	4^11,12,18,27	1.72 (1.07-2.74)	6^{11,12,13,18,22,27}	Low	1.51 (1.26-1.81)	36.41
	High	4^12,13,18,22	1.82 (1.47-2.26)	4^11,12,18,27	1.56 (1.03-2.34)	6^{11,12,13,18,22,27}	Low	1.69 (1.39-2.06)	55.79
Lifetime	No	6^{16,17,19,20,21,26}	[Reference]	4^19,20,21,26	[Reference]	6^{16,17,19,20,21,26}	NA	[Reference]	NA
Lifetime	Yes	6^{16,17,19,20,21,26}	1.45 (1.06-1.99)	4^19,20,21,26	1.21 (0.93-1.57)	6^{16,17,19,20,21,26}	Very low	1.38 (1.06-1.79)	79.74

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Abbreviations: cSCC, cutaneous squamous cell carcinoma; NA, not applicable; NR, not reportable; OR, odds ratio.

^{^a}

Relative risks were pooled with OR, treating them as comparable effect measures.

^{^b}

Too few studies to pool.

^{^c}

Summary certainty of evidence for most adjusted estimates.

A medium and high frequency of painful, blistering, and/or severe sunburns throughout lifetime was associated with a significantly increased odds of developing cSCC when compared with those with no painful, blistering, and/or severe sunburns throughout the lifetime in most adjusted analyses (medium: OR, 1.51; 95% CI, 1.26-1.81; high: OR, 1.69; 95% CI, 1.39-2.06). Even a single history of any painful, blistering, and/or severe sunburn throughout the lifetime was significantly associated with an elevated cSCC risk (OR, 1.38; 95% CI, 1.06-1.79). The Egger test showed no evidence of publication bias in either group (eTable 8 in Supplement 1). A significant association was also found between a high frequency of painful, blistering, and/or severe sunburns in childhood and cSCC (OR, 3.11; 95% CI, 1.26-7.66). For the association between cSCC and childhood frequency of painful, blistering, and/or severe sunburns, and lifetime history of any painful, blistering, and/or severe sunburn and cSCC the certainty of evidence was very low. The certainty of evidence was low for lifetime frequency of painful, blistering, and/or severe sunburns and association with cSCC. Funnel plots and the Egger test showed inclusive evidence of publication bias in the childhood subgroup (eTable 8 in Supplement 1).

Discussion

This systematic review and meta-analysis provides a novel pooled analysis of the association between the frequency of sunburns throughout different life periods and cSCC. Our pooled analyses on sunburn frequency show increased odds of developing cSCC when exposed to increased frequencies of painful, blistering, and/or severe sunburns throughout childhood and the lifetime. We also found that a history of any painful, blistering, and/or severe sunburn was associated with increased odds of developing cSCC. We found no significant association between the frequency of undefined sunburns throughout the lifetime and cSCC.

Meta-analyses examining other skin cancers and sunburn have shown similar results regarding sunburns in childhood and throughout the lifetime: a 2023 meta-analysis on basal cell carcinoma (BCC) demonstrated an increased risk associated with ever experiencing a painful or blistering sunburn across the lifetime, and a dose-response relationship with sunburn frequency per decade.⁵⁷ Similarly, multiple meta-analyses on melanoma risk and sunburn history indicate that melanoma risk rises with increasing numbers of severe sunburns across all life periods, and that the risk associated with being sunburned is highest in childhood.^5,58 However, these meta-analyses also found a significantly increased risk of BCC and melanoma with a history of undefined sunburns across the lifetime.^57,58 We found no significant increase in cSCC risk in the lifetime frequency of undefined sunburns, potentially reflecting the differences in the underlying etiology of cSCC compared with BCC and melanoma. These results highlight the potentially widespread association of severe sunburns in childhood and throughout the lifetime on skin cancer development, including BCC, melanoma, and cSCC. Conventionally, increased cSCC risk has been linked to chronic UV exposure, whereas BCC was thought to be more associated with acute UV exposure.⁵¹ However, the findings of this meta-analysis highlight the potentially significant role of acute UV exposure in the development of cSCC.

Disentangling chronic UV exposure from sunburn is challenging due to their potential overlap—individuals with more sunburns may also have greater chronic exposure. In addition, geographic location with high ambient UV radiation and skin phenotype significantly influence both sunburn frequency and cSCC risk.⁵⁹ These characteristics may all play a role in influencing cSCC risk and were adjusted for by many of the included studies; however, they may act as mediators rather than true confounders. Within our analysis, age was uniformly adjusted for across studies, and sex was adjusted for in nearly all mixed-sex studies, indicating a consistent effort to account for these fundamental demographic factors. Furthermore, skin phenotypic characteristics, such as skin color, sun sensitivity, and phototype, were commonly adjusted for across subcategories, in contrast to adjustments for geographic region, which was more varied. While these widespread adjustments demonstrate an awareness of potential confounding factors, the potential for mediation by these characteristics warrants further consideration when interpreting the direct association between sunburns and cSCC risk.

Strengths and Limitations

The strengths of this meta-analysis lie in its methodology, including a comprehensive search without language or date restrictions. Our detailed classification of sunburns by age period and type enabled a more accurate synthesis of heterogeneous data. The lack of evidence for publication bias across most subgroup analyses supports the robustness of our conclusions.

This study has limitations. The inconsistent adjustment for phenotypic and geographic factors across included studies, coupled with many studies providing only unadjusted data on case patients and non–case patients or controls, constrained our ability to perform universal adjustment, leading to adjusted-only analysis not reflecting the totality of the literature. In addition, our pooled analysis included a variety of study designs (eg, case-control, cohort) that are subject to varying sources of bias and error, and when combined, may move effect estimates in unpredictable directions. The high risk of bias inherent in many of the included studies likely overstates the association between sunburns and cSCC and the certainty of evidence for all subgroups was also rated either low or very low. Our findings, therefore, should be interpreted as the potential upper threshold of this association. The measurement of sunburn presented a methodological challenge due to different in recording and coding practices across studies. This may play a role in the significant statistical heterogeneity that exists across studies and within subcategories, potentially reflecting the broad definition of sunburn and the diverse populations included. In addition, the absence of standardized definitions for sunburn severity necessitated the creation of 2 broad severity groups for analysis: sunburns (undefined) and painful, severe, and/or blistering sunburns. While the retrospective design of many included studies presents a limitation due to potential reporting and recall bias, resulting in differential misclassification, the literature indicates moderate reliability for recalled sunburn history, with reported reliability coefficients for recalling both childhood and adulthood sunburns, ranging from 0.49 to 0.77, varying by recall period and sunburn type.^60,61,62,63

Conclusions

Synthesizing evidence from 17 studies, our results show that painful, blistering, and/or severe sunburns are associated with cSCC, whereas undefined sunburn frequency throughout an individual’s lifetime did not show an association. These findings align with existing literature and suggest a connection between severe sunburns and cSCC, similar to the established association with BCC. Future research could focus on developing standardized, quantifiable sunburn metrics and consistently adjusting for key confounding variables such as skin color and UV index or geographic region. This study further emphasizes the importance of effective sunburn prevention strategies, especially against painful, blistering, and/or severe burns.

Supplement 1.

eTable 1. Risk of Bias Assessment: Newcastle-Ottawa Quality Assessment Scale

eTable 2. Lifetime Sunburn Frequency Subgroup

eTable 3. Lifetime History (Yes/No) of Painful, Blistering or Severe Sunburn Subgroup

eTable 4. Lifetime Painful, Blistering or Severe Sunburn Frequency Subgroup

eTable 5. Childhood Painful, Blistering or Severe Sunburn Frequency Subgroup

eTable 6. Studies of cSCC and Sunburn

eTable 7. cSCC and Sunburns With Egger Test and I² Statistic

eTable 8. cSCC and Painful, Blistering or Severe Sunburns With Egger test and I² Statistic

eFigure 1. Low Sunburn Frequency in Lifetime Forest Plot (Unadjusted Odds Ratio)

eFigure 2. Medium Sunburn Frequency in Lifetime Forest Plot (Unadjusted Odds Ratio)

eFigure 3. High Sunburn Frequency in Lifetime Forest Plot (Unadjusted Odds Ratio)

eFigure 4. Low Sunburn Frequency in Lifetime Forest Plot (Adjusted Odds Ratio)

eFigure 5. Medium Sunburn Frequency in Lifetime Forest Plot (Adjusted Odds Ratio)

eFigure 6. High Sunburn Frequency in Lifetime Forest Plot (Adjusted Odds Ratio)

eFigure 7. Low Sunburn Frequency in Lifetime Forest Plot (Most Adjusted Odds Ratio)

eFigure 8. Medium Sunburn Frequency in Lifetime Forest Plot (Most Adjusted Odds Ratio)

eFigure 9. High Sunburn Frequency in Lifetime Forest Plot (Most Adjusted Odds Ratio)

eFigure 10. Yes/No Painful, Blistering or Severe Sunburn in Lifetime Forest Plot (Unadjusted Odds Ratio)

eFigure 11. Yes/No Painful, Blistering or Severe Sunburn in Lifetime Forest Plot (Adjusted Odds Ratio)

eFigure 12. Yes/No Painful, Blistering or Severe Sunburn in Lifetime Forest Plot (Most Adjusted Odds Ratio)

eFigure 13. Low Painful, Blistering or Severe Sunburn Frequency in Lifetime Forest Plot (Unadjusted Odds Ratio)

eFigure 14. Medium Painful, Blistering or Severe Sunburn Frequency in Lifetime Forest Plot (Unadjusted Odds Ratio)

eFigure 15. High Painful, Blistering or Severe Sunburn Frequency in Lifetime Forest Plot (Unadjusted Odds Ratio)

eFigure 16. Low Painful, Blistering or Severe Sunburn Frequency in Lifetime Forest Plot (Adjusted Odds Ratio)

eFigure 17. Medium Painful, Blistering or Severe Sunburn Frequency in Lifetime Forest Plot (Adjusted Odds Ratio)

eFigure 18. High Painful, Blistering or Severe Sunburn Frequency in Lifetime Forest Plot (Adjusted Odds Ratio)

eFigure 19. Low Painful, Blistering or Severe Sunburn Frequency in Lifetime Forest Plot (Most Adjusted Odds Ratio)

eFigure 20. Medium Painful, Blistering or Severe Sunburn Frequency in Lifetime Forest Plot (Most Adjusted Odds Ratio)

eFigure 21. High Painful, Blistering or Severe Sunburn Frequency in Lifetime Forest Plot (Most Adjusted Odds Ratio)

eFigure 22. Low Painful, Blistering or Severe Sunburn Frequency in Childhood Forest Plot (Unadjusted Odds Ratio)

eFigure 23. Medium Painful, Blistering or Severe Sunburn Frequency in Childhood Forest Plot (Unadjusted Odds Ratio)

eFigure 24. High Painful, Blistering or Severe Sunburn Frequency in Childhood Forest Plot (Unadjusted Odds Ratio)

eFigure 25. Low Painful, Blistering or Severe Sunburn Frequency in Childhood Forest Plot (Adjusted/Most Adjusted Odds Ratio)

eFigure 26. Medium Painful, Blistering or Severe Sunburn Frequency in Childhood Forest Plot (Adjusted/Most Adjusted Odds Ratio)

eFigure 27. High Painful, Blistering or Severe Sunburn Frequency in Childhood Forest Plot (Adjusted/Most Adjusted Odds Ratio)

eReferences.

jamadermatol-e253473-s001.pdf^{(2MB, pdf)}

Supplement 2.

Data Sharing Statement

jamadermatol-e253473-s002.pdf^{(16KB, pdf)}

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