Anatomical Distributions of Basal Cell Carcinoma and Squamous Cell Carcinoma in a Population-Based Study in Queensland, Australia

Key Points

Question  How great are the differences in anatomical distributions of basal cell carcinoma (BCC) and squamous cell carcinoma (SCC)?

Findings  In this population-based study, the anatomical distribution of 3398 keratinocyte cancers arising during 2 years of follow-up of 37 103 Australians consisted of BCCs primarily on the head and neck and trunk and SCCs predominantly on the upper limbs and head and neck. Sites with the greatest discrepancy in relative tumor densities between BCC and SCC were the hand and back and buttocks.

Meaning  Basal cell carcinoma and SCC have high relative tumor densities on the head, consistent with sun exposure as the primary etiologic factor; however, for BCC, the low relative tumor densities on the hand and high relative tumor densities on less sun-exposed sites suggest a complex association with sun exposure.

Importance  Keratinocyte cancers (KCs), including basal cell carcinoma (BCC) and squamous cell carcinoma (SCC), are the most common cancers among fair-skinned populations worldwide. Although studies have indicated that the anatomical distribution of BCC and SCC differ, few have compared them directly in well-defined population samples.

Objectives  To describe and compare the anatomical distribution of BCC and SCC in a population-based sample in Queensland, Australia.

Design, Setting, and Participants  This study was nested within the population-based QSkin Sun and Health Study in Queensland, Australia. Of 37 103 study participants linked to national medical insurance records, 3398 diagnosed with KCs from September 1, 2010, to September 30, 2012, were identified, and information about their KCs was extracted from pathology reports. Data were analyzed from January 1, 2013, to March 30, 2016.

Main Outcomes and Measures  The relative tumor densities (RTDs) on defined body sites, calculated by dividing the proportion of tumors occurring at a specified site by the proportion of skin area of that site.

Results  A total of 5150 KCs with complete data were identified in 2374 study participants (1339 men [56.4%] and 1035 women [43.6%]; mean [SD] age, 59.7 [7.4] years). Of these, 3846 KCs (74.7%) were BCCs. Most BCCs were on the head and/or neck (1547 [40.2%]) and the trunk (1305 [33.9%]); most SCCs were on the head and/or neck (435 [33.4%]) and upper limbs (455 [34.9%]). The greatest differences in RTDs between BCC and SCC were on the hand (BCC:SCC ratio, 1:14) and the back and/or buttocks (BCC:SCC ratio, 8:1). Relative tumor densities of KCs were higher on the scalp and ear in men compared with women, and on the upper arm in women compared with men. The pattern of RTDs did not differ with age for BCC. Compared with younger adults (40-54 years), the RTDs in older adults (55-69 years) were 2-fold higher for SCC on the scalp (0.38 [95% CI, 0.00-0.81] vs 1.07 [95% CI, 0.75-1.38]) and the back and/or buttocks (0.05 [95% CI, 0.00-0.12] vs 0.12 [95% CI, 0.07-0.16]).

Conclusions and Relevance  The high RTDs on sun-exposed body sites for BCC and SCC are in keeping with sun exposure as the primary etiologic factor for both tumors. However, for BCC, the low RTD on the hand and high RTDs on less sun-exposed sites suggest a complex association between sun exposure and occurrence of BCC. Knowledge about the anatomical distribution of BCC and SCC may provide insight into their diagnoses and causes.

Basal cell carcinoma (BCC) and squamous cell carcinoma (SCC), collectively termed keratinocyte cancers (KCs), are the most common cancers among fair-skinned populations worldwide. Australia has the highest incidence,¹ with approximately 434 000 people (or nearly 2% of the population) estimated to have been diagnosed with KCs in the calendar year 2008.² The cost of managing KCs in Australia was projected to reach A$703 million (US $536 million) in 2015.³

Although UV radiation is the major risk factor for BCC and SCC, their anatomical distributions differ. Squamous cell carcinoma occurs primarily on sites habitually exposed to sunlight, such as the face and exposed parts of the upper and lower limbs, whereas BCC occurs on these sites and those less frequently exposed to sunlight, such as the trunk.^4-15

Most studies report the proportion of tumors on specified body sites without taking into account the proportion of surface area of the defined body site, which prevents direct comparison of tumor burden across different anatomical sites. A few studies have reported the relative tumor density (RTD),^5,6,16-19 calculated as the ratio of the proportion of tumors at a specific anatomical site to the proportion of skin surface area at that site, or have reported surface area–adjusted incidence rates.^5-7 These studies^5,6,17,18 showed that the highest RTDs occurred on the face for both cancers, but analysis of facial subsites has been limited.

Some studies suggest that the body site distribution of BCC and SCC varies with age and sex,^5,17,18 although few studies have compared both tumor types from 1 population sample. Given the relatively small number of studies reported to date, the aim of our study was to compare the anatomical distribution of BCC and SCC arising in participants from a large, population-based cohort in Queensland, Australia, and to investigate differences according to age and sex.

This study is nested within the QSkin Sun and Health Study, which consists of 43 794 residents of Queensland, Australia. Participants aged 40 to 69 years were randomly selected from the Australian electoral roll (enrollment to vote is compulsory) and recruited in 2010. They completed a survey that included questions about ancestry, lifestyle, skin phenotype, past treatment of skin lesions, and sun exposure history. Details of the survey have been published previously.²⁰ This study was approved by the human ethics committees of the QIMR Berghofer Medical Research Institute and Queensland University of Technology, Brisbane, Queensland. All participants provided written informed consent for linkage of records with the Medicare Australia database.

Through record linkage to Medicare Australia, Australia’s national health insurance scheme, we identified participants in the QSkin cohort who had been treated for skin cancer from September 1, 2010, to September 30, 2012. Medicare Australia subsidizes health care for all Australians and records information about medical services to Australian residents, except for some services delivered in public hospitals. The data held by Medicare Australia records medical billing events for KCs and the type of procedure undertaken, but no details about histologic type or specific anatomical site are recorded. We therefore obtained the corresponding pathology reports for each treatment event by linking our QSkin data set to pathology service providers for those participants identified from the Medicare Australia data as having had KC treatments.

The diagnosis, treatment procedures, and anatomical site of each tumor were manually abstracted from the pathology reports. We included only primary BCCs and SCCs; recurrent lesions, defined as the regrowth of a previously treated malignant neoplasm, were excluded. Thus, we cross-checked all biopsies, excisions, and reexcisions of apparently multiple BCC or SCC lesions diagnosed within a 6-month period on the same anatomical site in the same person in Medicare Australia records and pathology reports and omitted verified recurrent lesions from our analysis.

Data were analyzed from January 31, 2013, to March 30, 2016. We were able to match 65% of individual Medicare Australia claims for KC treatment (72.1% of people) with pathology reports. The median follow-up duration of the participants was 12.6 (range, 4.0-19.8) months. Almost all lesions for which we had pathology reports (99.5%) had complete information on body site and histologic findings and were included in the analysis. To allow for differences in the skin surface area at different body sites, the RTD for each body site was calculated by dividing the proportion of tumors at a defined anatomical site by the mean proportion of the skin surface area of that site.¹⁶ An RTD of 1 corresponds to the density of tumors on the whole body.

The proportion of the surface area of skin attributed to each body site was based on the estimated proportion of surface area described by Lund and Browder.²¹ We classified body sites into 4 broad areas—head and/or neck, trunk (including shoulders), upper limbs, and lower limbs—that constituted 9.0%, 32.0%, 19.0%, and 40.0% of the skin surface, respectively. These 4 body sites were further subdivided into subsites as shown in Table 1. The classification of facial subsites according to their sun exposure was adapted and modified from previous studies^5,6 as follows: most exposed included the ears, nose, cheeks, and lips; less exposed, the forehead, eyebrows, chin, jaw, temple, and preauricular area; and least exposed, under the eyebrow, upper and lower eyelids, medial and lateral canthus, and nasolabial fold.

We calculated the RTDs and 95% CIs for BCC and SCC overall and within the strata of sex and age groups (40-54 and 55-69 years). We calculated the ratio of RTDs for BCC to SCC for each anatomical site and 95% CIs of these ratios, overall and within strata of age and sex.²² Statistical analysis was conducted using SAS (version 9.4; SAS Institute, Inc) and Excel (Microsoft) software.

Of the 43 794 QSkin participants, 39 033 consented to linkage with Medicare and 37 103 were linked to the Medicare Australia database (Figure 1). Of these, we identified 3398 participants who were treated for KCs during the study period. Histopathology reports for at least 1 KC lesion were retrieved and matched for 2387 of these participants (70.2%) (1346 men [56.4%] and 1041 women [43.6%]; mean [SD] age, 59.7 [7.4] years). Participants with available histopathologic data were similar with respect to age and sex to those without available data.

Most participants reported having white European ancestry (2327 [97.5%]) and 1473 (68.3%) had lived longest as a child or youth in the north and central regions (10°S-30° S parallels) of Australia. For skin characteristics, 1820 participants (76.3%) had fair skin, 2265 (94.9%) reported that their skin burned after exposure to 30 minutes of midday sun, and 2079 (87.1%) reported that they tanned after long-term sun exposure.

From the pathology reports, we identified 5189 primary KC lesions in 2387 participants. We excluded 39 BCCs and SCCs from 13 participants with missing site information. Of the 5150 KCs from 2374 participants included in the final analysis, 3846 (74.7%) were BCCs. Of these, 3233 lesions (62.8%) were treated in men and 2891 (57.3%) were treated in people aged 60 to 69 years. Among the participants with a histologically confirmed BCC or SCC, 806 (42.6%) had multiple BCCs (range, 2-40 lesions), and 223 (28.1%) had multiple SCCs (range 2-8 lesions). Three hundred eight participants (12.9% of those with KC) had both BCC and SCC. Of those with BCC, 16.3% also had SCC, and of those with SCC, 38.7% also had BCC.

The most commonly diagnosed sites of the 3846 identified BCCs were on the head and/or neck (40.2%) and trunk (33.9%). The 1304 SCCs occurred with similar frequency on the upper limbs (34.9%) and head and/or neck (33.4%) (Table 1 and Figure 2). Although the differences in the proportion of lesions on the most commonly affected sites were small, we found marked differences in the RTDs once we accounted for the surface area of these sites (Table 1, Figure 2, and Figure 3). For BCCs, highest RTDs were observed on the head and/or neck (RTD, 4.47; 95% CI, 4.30-4.64), which was 4 times higher than on the trunk, the second most commonly affected site (RTD, 1.06; 95% CI, 1.01-1.11). Similarly, SCCs occurred at highest density on the head and/or neck region (RTD, 3.71; 95% CI, 3.42-3.99), which was twice as high as that on the upper limbs (RTD, 1.84; 95% CI, 1.70-1.97).

Subsites with the highest RTDs for BCC were the most (14.24; 95% CI, 13.30-15.18) and least (11.18; 95% CI, 9.28-13.08) sun-exposed face. The lowest RTDs for BCC were observed on the foot (0.08; 95% CI, 0.05-0.12), thigh (0.09; 95% CI, 0.07-0.11), and hand (0.19; 95% CI, 0.13-0.25). Sites with the highest RTDs for SCC were the most sun-exposed face (12.56; 95% CI, 11.02-14.11) and ears (8.28; 95% CI, 6.12-10.45). The lowest RTDs of SCC were observed on the back and/or buttocks (0.10; 95% CI, 0.07-0.14), thigh (0.12; 95% CI, 0.08-0.16), and foot (0.19; 95% CI, 0.10-0.27).

The greatest disparity in RTD was seen on the hand, for which the RTD for SCC was 14 times higher than that for BCC (2.70 [95% CI, 2.33-3.07] vs 0.19 [95% CI, 0.13-0.25]). At the other extreme, BCCs occurred on the back and/or buttocks at a more than 8-fold higher RTD (0.90; 95% CI, 0.84-0.96) than SCCs (0.10; 95% CI, 0.07-0.14) (Table 1). Overall, RTDs for SCC on the upper and lower limbs were almost twice those of BCC, whereas BCCs were twice as dense as SCCs on the neck and chest and/or abdomen. For participants with multiple lesions, the RTDs on the body sites followed a similar pattern of distribution to the overall distribution of lesions (eTable 1 in the Supplement).

For BCC, we found little difference between men and women in the RTDs overall, except that the relative density of BCCs on the ears and scalp were 3.7-fold (2.68 [95% CI, 1.51-3.84] vs 10.03 [95% CI, 8.27-11.80]) and 1.6-fold (0.45 [95% CI, 0.28-0.63] vs 0.74 [95% CI, 0.56-0.91]), respectively, higher in men than in women. In contrast, BCCs occurred 80% more frequently (in relative terms) on the upper arms of women than men (RTDs, 1.05 [95% CI, 0.87-1.22] vs 0.58 [95% CI, 0.47-0.69]). The occurrence of BCC on the face was marginally higher in women than men (13.61 [95% CI, 12.14-14.49] vs 10.60 [95% CI, 9.68-11.33]); this was most marked on the least exposed areas of the face (13.83 [95% CI, 10.46-17.20]vs 9.50 [95% CI, 7.25-11.74]; 1.5-fold higher) (eTable 2 in the Supplement).

In contrast, the site distribution of SCC differed markedly between men and women, with RTDs in men 10 times higher on the scalp (1.35 [95% CI, 0.96-1.74] vs 0.13 [95% CI, 0.00-0.30]) and 5 times higher on the ears (11.12 [95% CI, 8.10-14.15] vs 2.36 [95% CI, 0.30-4.42]) compared with women. With the exception of the forearm, the RTDs of SCC on the trunk (0.23 [95% CI, 0.18-0.28] vs 0.33 [95% CI, 0.23-0.42]) and upper (1.74 [95% CI, 1.57-1.90] vs 2.04 [95% CI, 1.80-2.28]) and lower (0.52 [95% CI, 0.45-0.59] vs 0.72 [95% CI, 0.61-0.83]) limbs was higher in women than in men.

The distributions of BCC were similar among younger and older participants (Table 2) at all anatomical sites. For SCC, higher RTDs were seen on the scalp (0.38 [95% CI, 0.00-0.81] vs 1.07 [95% CI, 0.75-1.38]), ears (5.63 [95% CI, 1.19-10.08] vs 8.80 [95% CI, 6.37-11.23]), and back and/or buttocks (0.05 [95% CI, 0.00-0.12] vs 0.12 [95% CI, 0.07-0.16]) in the older compared with the younger participants. Although numbers were small, some evidence suggested that the RTD of SCCs on the face was higher among younger than older people, especially on the least sun-exposed facial sites.

Among younger participants, the RTD of BCC on the scalp was higher than the RTD of SCC on the scalp (0.84 [95% CI, 0.56-1.13] vs 0.38 [95% CI, 0.00-0.81]), whereas the opposite was observed among older participants (0.54 [95% CI, 0.40-0.68] vs 1.07 [95% CI, 0.75-1.38]). On the back and buttocks, the RTD of BCC compared with SCC was 18-fold higher among younger participants (0.91 [95% CI, 0.79-1.03] vs 0.05 [95% CI, 0.00-0.12]), but just more than 7-fold higher among older participants (0.90 [95% CI, 0.82-0.97] vs 0.12 [95% CI, 0.07-0.16]).

In this study, we analyzed the anatomical site distributions of BCC and SCC and compared them within strata of age and sex. This study is, to our knowledge, one of the largest population-based studies to compare the site distribution of BCC and SCC within the same sample of participants.

Compared with the whole body, the head and/or neck region (face, ears, and neck) had a higher RTD of BCC than the mean. Although the RTD of BCC was highest on sites of frequent sun exposure, a large number of lesions also occurred on body sites less frequently exposed to sunlight, particularly the trunk. For SCC, RTDs higher than the mean were seen on the frequently sun-exposed parts of the body, with the head and/or neck region (face, ears, and neck), upper limbs (forearm and hands), and lower legs all exhibiting high RTDs. The highest RTDs were present on the most sun-exposed facial sites, followed by the ears.

The pattern of distribution^5,6,18 and the absolute tumor densities¹⁷ of BCC and SCC were consistent with other Australian studies. However, studies from other countries have found a much higher proportion of both cancer types on the head and/or neck region, with as many as 80% of BCCs and SCCs occurring on this site.^7-15,23,24 A number of possible reasons may explain this frequency. First, these studies differed in age range of the participants and methodologic approach. Second, variability in medical care, such as differences in opportunistic screening practice, may have led to fewer lesions being diagnosed on less habitually sun-exposed sites than in Australia. This variability is particularly likely to influence the body site distribution of BCC.²⁵ Finally, the relatively higher proportion of lesions on sites other than the head and/or neck in Australia is likely owing to lifestyle and sun exposure practices. For example, the climate in Australia is conducive to outdoor recreational pursuits that are commonly enjoyed with minimal clothing, which would contribute to higher exposure on the trunk and limbs compared with other populations.

The anatomical distribution of SCC corresponds closely to the pattern of intensity of sun exposure, with the highest density of lesions occurring on body sites frequently exposed to sunlight. Basal cell carcinoma was less clearly aligned with sun exposure patterns, with a relatively high RTD on less frequently exposed body sites. The infrequent exposure of these sites results in less melanin protection, increasing the risk for sunburn. Basal cell carcinoma on less exposed body sites may thus arise as a result of infrequent or intermittent high doses of UV radiation.²⁶ Alternatively, the potential cells of origin of BCC on the trunk and buttocks may require a lower total dose of sun exposure to become neoplastic. The relatively high RDT of BCC in the periorbital region, which receives the least amount of sunlight among the facial subsites, also supports the theory that lower doses of UV radiation give rise to BCCs compared with SCCs.

The RTD of SCC on the hand was 14 times higher than the RTD of BCC (2.70 [95% CI, 2.33-3.07] vs 0.19 [95% CI, 0.13-0.25]). The relative paucity of BCC on the hands, which are chronically exposed to intense sunlight, has been reported in clinical and epidemiologic studies previously.^16,27 We calculated the BCC:SCC ratio in previous studies as 1:9¹⁸ and 1:20.¹⁶ The difference in RTDs between BCC and SCC on the hands cannot be explained simply by sun-exposure patterns. The significantly greater thickness of the epidermis on the dorsum of the hand compared with the forearm²⁸ may explain the relative lack of BCC on the hands but fails to explain the relative abundance of SCC. Basal cell carcinoma is postulated to arise from basal cells that are situated deeper in the epidermis of the skin, in contrast to the more superficially placed squamous cells, thought to be the origin of SCC. Thus, one plausible explanation for the marked differences in the occurrence of BCC and SCC on the dorsum of the hand is that the depth of epidermis protects the deeply situated basal cells from the UV rays compared with the exposure received by the more superficial squamous cells. Studies have also suggested that BCC may arise from follicular stem cells,²⁹ so an alternate explanation for the lower RTD of BCC could be the relative lack of hair on the back of the hands compared with the forearm.

A limited number of studies have shown that the association between the anatomical distributions of KC varies according to sex. We found that the RTDs of BCC and SCC on the scalp and ears were higher in men than in women, a pattern that has been reported previously.^6,7,18 This difference is likely owing to sex differences in hair cover. Higher densities of KCs occurring on the upper arm of women compared with men may be attributed to clothing choice, with more women than men choosing to wear short-sleeved or sleeveless shirts.

Our findings did not show significant differences between the younger and the older groups for BCC. Higher RTDs for SCCs seen on less exposed sites, such as the back and/or buttocks region, in older compared with younger participants could be attributed to higher cumulative sun exposure with increasing age. Differential treatment according to age (eg, older people having more regular full-body screening) may partly explain the age differences in SCC RTDs but is unlikely to be entirely responsible because the same differences are not observed for BCC.

This study has a number of strengths and weaknesses. We recruited a large community-based sample from the compulsory voting register. Moreover, because we identified patients with KCs through linkage with the national insurance scheme and confirmed the diagnoses with pathology reports, the information regarding diagnosis and anatomical distribution is likely to be accurate. Although we did not capture services delivered in public hospitals, the 2002 National Skin Cancer Survey reported that fewer than 2% of the survey participants underwent skin cancer treatment in a hospital setting, indicating near-complete capture of skin cancer events.³⁰ A potential weakness in this analysis is the lack of histologic confirmation of all KCs identified in the Medicare records. We obtained pathology records from the 2 largest and 2 smaller pathology service providers for the state of Queensland, but we were unable to obtain pathology reports from all laboratories in the state. However, we interrogated the Medicare data by item numbers that broadly identify the site of the lesion, which showed that the overall patterns of site distribution did not differ between participants with and without pathology reports. Therefore, the RTD estimates are likely to be representative of the fair-skinned population of Queensland, and by inference to other populations residing in low latitudes, although they may not be applicable to other population groups.

The results from this large cohort study emphasized differences in the anatomical distributions of BCC and SCC. High densities of BCCs and SCCs observed on sun-exposed body sites confirm sun exposure as the primary etiologic factor for both tumors; the differences in RTDs of SCCs by age and sex underscore the association with cumulative sun exposure. In contrast, the observations that BCCs occur relatively infrequently on the hand but relatively frequently on body sites that are only intermittently exposed to UV radiation point to more complex associations with sun exposure. Understanding the etiology and pathogenesis of BCC may lead to new avenues for prevention and treatment.

Corresponding Author: Padmini Subramaniam, MBBS, MSc, MClinSc, Department of Population Health, QIMR Berghofer Medical Research Institute, Locked Bag 2000, Royal Brisbane Hospital, Brisbane, QLD 4029, Australia (padmini.subramaniam@qimrberghofer.edu.au).

Accepted for Publication: September 2, 2016.

Published Online: November 23, 2016. doi:10.1001/jamadermatol.2016.4070

Author Contributions: Drs Subramaniam and Whiteman had full access to all the data in the study and take responsibility for the integrity of the data and the accuracy of the data analysis.

Study concept and design: Subramaniam, Whiteman, Neale.

Acquisition, analysis, or interpretation of data: All authors.

Drafting of the manuscript: Subramaniam, Neale.

Critical revision of the manuscript for important intellectual content: All authors.

Statistical analysis: Subramaniam, Thompson.

Administrative, technical, or material support: Subramaniam, Olsen, Whiteman.

Study supervision: Whiteman, Neale.

Conflict of Interest Disclosures: None reported.

Funding/Support: This study was supported by program grants APP552429, and APP1073898 from the National Health and Medical Research Council (NHMRC); by research fellowships from the NHMRC (Drs Neale and Whiteman), and Australian Postgraduate Award, the Queensland University of Tehnology Vice Chancellor’s Top-Up scholarship, and NHMRC Centre for Research Excellence in Sun and Health (Dr Subramaniam).

Role of the Funder/Sponsor: The funding sources had no role in the design and conduct of the study; collection, management, analysis, and interpretation of the data; preparation, review, or approval of the manuscript; and decision to submit the manuscript for publication.

Group Members: Participating investigators in the QSkin Sun and Health Study included the following: David C. Whiteman, MBBS, PhD, Catherine M. Olsen, PhD, MPH, and Adèle C. Green, MBBS, PhD, Department of Population Health, QIMR Berghofer Medical Research Institute, Royal Brisbane Hospital, Queensland, Australia (chief investigators); Rachel E. Neale, BVSc, PhD, and Penelope M. Webb, MA, DPhil, Department of Population Health, QIMR Berghofer Medical Research Institute, Royal Brisbane Hospital (associate investigators); Rebekah A. Cicero, BA, Lea M. Jackman, DipBA, Suzanne M. O’Brien, BN, Barbara A. Ranieri, and Bridie S. Thompson, PhD, Department of Population Health, QIMR Berghofer Medical Research Institute, Royal Brisbane Hospital (study team); Conrad J. Morze, MBBS, and H. Peter Soyer, MD, Dermatology Research Centre, University of Queensland, Queensland, Australia (clinical collaborators); and Dallas English, PhD, University of Melbourne, Melbourne, Australia, and Allison Venn, PhD, Menzies Research Institute, Hobart, Australia (scientific advisory board).

Previous Presentation: This study was presented as an abstract at the 21st Australasian Epidemiological Association Annual Scientific Meeting; October 10, 2014; Auckland, New Zealand.