- Email: [email protected]
Incidence ratio of basal cell carcinoma to squamous cell carcinoma equalizes with age
J AM ACAD DERMATOL
Research Letters 353
VOLUME 76, NUMBER 2
2.
3.
4.
5.
establishing basal cell carcinoma subtype: analysis of 500 cases. J Eur Acad Dermatol Venereol. 2013;27(8):985-989. Kamyab-Hesari K, Seirafi H, Naraghi ZS, et al. Diagnostic accuracy of punch biopsy in subtyping basal cell carcinoma. J Eur Acad Dermatol Venereol. 2014;28(2):250-253. Roozeboom MH, van Kleef L, Arits AH, et al. Tumor thickness and adnexal extension of superficial basal cell carcinoma (sBCC) as determinants of treatment failure for methylaminolevulinate (MAL)-photodynamic therapy (PDT), imiquimod, and 5-fluorouracil (FU). J Am Acad Dermatol. 2015;73(1):93-98. McKay KM, Sambrano BL, Fox PS, Bassett RL, Chon S, Prieto VG. Thickness of superficial basal cell carcinoma (sBCC) predicts imiquimod efficacy: a proposal for a thickness-based definition of sBCC. Br J Dermatol. 2013;169(3):549-554. Hoogedoorn L, Hendriks JC, Knuiman GJ, et al. Treatment failure in superficial basal cell carcinoma following treatment with photodynamic therapy: is this a result of underdiagnosis? J Eur Acad Dermatol Venereol. 2016. Epub 2016/06/04. http://dx.doi.org/10.1016/j.jaad.2016.09.028
Incidence ratio of basal cell carcinoma to squamous cell carcinoma equalizes with age To the Editor: In the United States, the incidence ratio of basal cell carcinomas (BCCs) to cutaneous squamous cell carcinomas (SCCs) is traditionally taught as 4:1.1,2 However, the origin of this ratio is unclear, as earlier US-based studies ( published before 1989) report an incidence ratio ranging from 1.4:1 to 9:1.3 Recently, Rogers and colleagues4 reported a 1:1 incidence ratio of BCC:SCC using procedural data from the predominantly Caucasian, elderly Medicare fee-for-service population. To evaluate this incidence ratio across all age groups, we performed a retrospective review of BCC and SCC incidence in a northern Californian population. Furthermore, to corroborate our findings, we assessed the lifetime prevalence of BCC and SCC in a larger independent cohort. This study was approved by the institutional review board of Stanford University. To calculate incidences, we analyzed all 8032 diagnostic BCC and SCC dermatopathology reports collected at Stanford Healthcare from 2005 to 2015 (set 1). Patients of all ethnicities were included and 86% were Caucasian. To calculate lifetime prevalence, we used self-reported BCC and SCC cases from 23andMe (set 2), totaling 12,945 patients with BCC, 6579 patients with SCC, and over 250,000 control subjects, all of whom were Caucasian. Accuracy of self-reported answers was previously validated via comparison with medical records in a subset of patients.5 Analysis of set 1 demonstrates an overall BCC:SCC incidence ratio of 1.4:1 (Table I). In the younger age groups, BCCs heavily outnumber SCCs; however, the
Table I. Basal and squamous cell carcinoma biopsy counts stratified by age group, 2005 to 2015 Age, y
#30
31-45
46-60
[60
BCC 57 378 1248 2984 SCC 29 76 552 2708 BCC:SCC 2.0:1* 5.0:1 2.3:1 1.1:1
Combined
4667 3365 1.4:1
BCC, Basal cell carcinoma; SCC, squamous cell carcinoma. Data source: Dermatopathology reports for patients seen and biopsied at Stanford Hospital and Clinics, from June 2005 to June 2015. Among patients with BCC, roughly 58% were male and 90% were Caucasian; for SCC cases, these values are 62% and 85%, respectively. Cases defined as recurrences were excluded. For more information about this cohort, please contact the corresponding author ([email protected]). *Small sample size limits accuracy.
ratio equalizes as age increases, reaching 1.1:1 in the age group older than 60 years. Set 2 reveals a lifetime prevalence of 11% and 6% for BCC and SCC, respectively, in Caucasians older than 60 years (Table II), consistent with prior studies.6 As expected for low-mortality diseases, the lifetime prevalence of these cancers increases steadily with age. The overall BCC:SCC incidence ratio of 1.4:1 in this predominantly Caucasian population is significantly lower than 4:1 and corroborates the recent finding of a 1:1 ratio among Medicare beneficiaries.4 Because these cancers have low mortality and can occur multiple times per individual, the overall lifetime prevalence ratio is expected to approximate the overall incidence ratio yet also demonstrate a slight skew away from the cancer with the greater net increase in incidence across age groups (SCC in this case). Hence, our finding of a 2.0:1 overall lifetime prevalence ratio in an independent cohort substantiates our incidence results. Notably, we included both invasive SCC and SCC in situ under the term ‘‘SCC.’’ If we exclude SCC in situ from set 1, then the BCC:SCC ratio in the group older than 60 years increases to 1.8:1, which is greater than the corresponding value of 1.2:1 found in the Medicare study.4 This difference is unsurprising considering that SCC in situ is often treated nonsurgically (and is consequently underreported in Medicare claims data). In addition, the high average ultraviolet index in California likely influenced rates of SCC and SCC in situ in our study. Strengths of this study include large sample size for lifetime prevalence estimates and incidences based on dermatopathology reports. Overall, we demonstrate that the BCC:SCC incidence ratio is much closer to 1:1 than 4:1ethus, clinicians should increase their index of suspicion for SCC, particularly when evaluating older patients.
J AM ACAD DERMATOL
354 Research Letters
FEBRUARY 2017
Table II. Lifetime prevalence of basal cell carcinoma and squamous cell carcinoma in Caucasians, stratified by age group Age, y
BCC SCC BCC:SCC
#30
31-45
46-60
[60
Combined
0.1% (42) 0.0% (12) 3.5:1
0.8% (650) 0.2% (199) 3.3:1
4.1% (3194) 1.6% (1263) 2.5:1
10.6% (9059) 6.0% (5105) 1.8:1
4.5% (12,945) 2.3% (6579) 2.0:1
Lifetime prevalence values are reported as percentages, with number of self-reported cases in parentheses. To calculate each percentage, the number of cases in an age group was divided by the total number of subjects (cases plus controls) within that age group. Data source: 23andMe (Mountain View, CA) research participants with at least 97% European ancestry. BCC cases, SCC cases, and both sets of controls had 52%, 53%, and 54% males, respectively. Participants provided informed consent to take part in this research, in accord with 23andMe human subjects protocol (reviewed and approved by Ethical and Independent Review Services, an Association for the Accreditation of Human Research Protection Programs, Inceaccredited institutional review board). For more information about this cohort, please contact the corresponding author ([email protected]) or see: a. Pickrell JK, Berisa T, Liu JZ, et al. Detection and interpretation of shared genetic influences on 42 human traits. Nat. Genet. 2016. http://dx. doi.org/10.1038/ng.3570. b. Chahal HS, Lin Y, Ransohoff K, et al. Genome-wide association study identifies novel susceptibility loci for cutaneous squamous cell carcinoma. Nature Commun. 2016;7(12048):1-8. http://dx.doi.org/10.1038/ncomms12048. c. Chahal HS, Wu W, Ransohoff K, et al. Genome-wide association study identifies 14 novel risk alleles associated with basal cell carcinoma. Nature Commun. 2016;7(12510):1-10. http://dx.doi.org/10.1038/ncomms12510. BCC, Basal cell carcinoma; SCC, squamous cell carcinoma.
Harvind S. Chahal, BA, Kerri E. Rieger, MD, PhD, and Kavita Y. Sarin, MD, PhD Department of Dermatology, Stanford University School of Medicine, California Funding sources: Dermatology Foundation (Dr Sarin) and Stanford Medical Scholars Research Program (Mr Chahal). Conflicts of interest: None declared. Correspondence to: Kavita Y. Sarin, MD, PhD, Department of Dermatology, Stanford University Medical Center, 450 Broadway St, Pavilion C, 2nd Floor, Redwood City, CA 94063 E-mail: [email protected] REFERENCES 1. Lever WF, Elder DE, eds. Lever’s histopathology of the skin. 10th ed. Philadelphia (PA): Wolters Kluwer, Lippincott Williams and Wilkins; 2009. 2. Miller DL, Weinstock MA. Nonmelanoma skin cancer in the United States: incidence. J Am Acad Dermatol. 1994;30(5 Pt 1): 774-778. 3. Yiannias JA, Goldberg LH, Carter-Campbell S, Reddick M, Chamberlain RM. The ratio of basal cell carcinoma to squamous cell carcinoma in Houston, Texas. J Dermatol Surg Oncol. 1988;14(8):886-889. 4. Rogers HW, Weinstock MA, Feldman SR, Coldiron BM. Incidence estimate of nonmelanoma skin cancer (keratinocyte carcinomas) in the US population, 2012. JAMA Dermatol. 2015; 151:1081-1086. 5. Chahal HS, Lin Y, Ransohoff KJ, et al. Genome-wide association study identifies novel susceptibility loci for cutaneous squamous cell carcinoma. Nat Commun. 2016;7:12048. 6. Stern RS. Prevalence of a history of skin cancer in 2007: results of an incidence-based model. Arch Dermatol. 2010;146(3):279-282. http://dx.doi.org/10.1016/j.jaad.2016.08.019
The detection of human papillomaviruse16 in squamous cell carcinoma of the nail unit: A case series To the Editor: The correlation between human papillomavirus (HPV) and squamous cell carcinoma (SCC) of the skin and adnexa is still controversial.1 The detection of the virus has been described in several case series of nail unit SCC.2,3 This study aimed to evaluate the presence of HPV in a series of 41 cases of nail unit SCC referred to our dermatology skin cancer unit between January 2006 and December 2014. The study was carried out on residual biopsy sections after diagnostic analysis in the course of institutional diagnostic services and was exempted from institutional review board review. The INNO-LiPA HPV Genotyping Extra assay (Fujirebio, Pomezia, Italia Srl) was used to detect 28 mucosal HPV, including 18 high-risk and probable high-risk HPV (16, 18, 26, 31, 33, 35, 39, 45, 51, 52, 53, 56, 58, 59, 66, 68, 73, 82), 7 low-risk HPV (6, 11, 40, 43, 44, 54, 70), and 3 undetermined-risk HPV (69, 71, 74). All samples were amplified in real-time polymerase chain reaction (PCR) with a primer pair specific for the E6 region of HPV-16 to avoid false negatives because of the loss of the L1 region, resulting from viral integration in cancer cells. Finally, a nested PCR (FAP nested PCR) was used for the detection of a broad spectrum of cutaneous -HPV; a consensus outer primer pair FAP 59/6415 and a consensus inner primer pair FAP 6085/6319 were used for end point PCR amplification. Table I shows patients’ demographic data, and clinical and histopathologic characteristics of the
Research Letters 353
VOLUME 76, NUMBER 2
2.
3.
4.
5.
establishing basal cell carcinoma subtype: analysis of 500 cases. J Eur Acad Dermatol Venereol. 2013;27(8):985-989. Kamyab-Hesari K, Seirafi H, Naraghi ZS, et al. Diagnostic accuracy of punch biopsy in subtyping basal cell carcinoma. J Eur Acad Dermatol Venereol. 2014;28(2):250-253. Roozeboom MH, van Kleef L, Arits AH, et al. Tumor thickness and adnexal extension of superficial basal cell carcinoma (sBCC) as determinants of treatment failure for methylaminolevulinate (MAL)-photodynamic therapy (PDT), imiquimod, and 5-fluorouracil (FU). J Am Acad Dermatol. 2015;73(1):93-98. McKay KM, Sambrano BL, Fox PS, Bassett RL, Chon S, Prieto VG. Thickness of superficial basal cell carcinoma (sBCC) predicts imiquimod efficacy: a proposal for a thickness-based definition of sBCC. Br J Dermatol. 2013;169(3):549-554. Hoogedoorn L, Hendriks JC, Knuiman GJ, et al. Treatment failure in superficial basal cell carcinoma following treatment with photodynamic therapy: is this a result of underdiagnosis? J Eur Acad Dermatol Venereol. 2016. Epub 2016/06/04. http://dx.doi.org/10.1016/j.jaad.2016.09.028
Incidence ratio of basal cell carcinoma to squamous cell carcinoma equalizes with age To the Editor: In the United States, the incidence ratio of basal cell carcinomas (BCCs) to cutaneous squamous cell carcinomas (SCCs) is traditionally taught as 4:1.1,2 However, the origin of this ratio is unclear, as earlier US-based studies ( published before 1989) report an incidence ratio ranging from 1.4:1 to 9:1.3 Recently, Rogers and colleagues4 reported a 1:1 incidence ratio of BCC:SCC using procedural data from the predominantly Caucasian, elderly Medicare fee-for-service population. To evaluate this incidence ratio across all age groups, we performed a retrospective review of BCC and SCC incidence in a northern Californian population. Furthermore, to corroborate our findings, we assessed the lifetime prevalence of BCC and SCC in a larger independent cohort. This study was approved by the institutional review board of Stanford University. To calculate incidences, we analyzed all 8032 diagnostic BCC and SCC dermatopathology reports collected at Stanford Healthcare from 2005 to 2015 (set 1). Patients of all ethnicities were included and 86% were Caucasian. To calculate lifetime prevalence, we used self-reported BCC and SCC cases from 23andMe (set 2), totaling 12,945 patients with BCC, 6579 patients with SCC, and over 250,000 control subjects, all of whom were Caucasian. Accuracy of self-reported answers was previously validated via comparison with medical records in a subset of patients.5 Analysis of set 1 demonstrates an overall BCC:SCC incidence ratio of 1.4:1 (Table I). In the younger age groups, BCCs heavily outnumber SCCs; however, the
Table I. Basal and squamous cell carcinoma biopsy counts stratified by age group, 2005 to 2015 Age, y
#30
31-45
46-60
[60
BCC 57 378 1248 2984 SCC 29 76 552 2708 BCC:SCC 2.0:1* 5.0:1 2.3:1 1.1:1
Combined
4667 3365 1.4:1
BCC, Basal cell carcinoma; SCC, squamous cell carcinoma. Data source: Dermatopathology reports for patients seen and biopsied at Stanford Hospital and Clinics, from June 2005 to June 2015. Among patients with BCC, roughly 58% were male and 90% were Caucasian; for SCC cases, these values are 62% and 85%, respectively. Cases defined as recurrences were excluded. For more information about this cohort, please contact the corresponding author ([email protected]). *Small sample size limits accuracy.
ratio equalizes as age increases, reaching 1.1:1 in the age group older than 60 years. Set 2 reveals a lifetime prevalence of 11% and 6% for BCC and SCC, respectively, in Caucasians older than 60 years (Table II), consistent with prior studies.6 As expected for low-mortality diseases, the lifetime prevalence of these cancers increases steadily with age. The overall BCC:SCC incidence ratio of 1.4:1 in this predominantly Caucasian population is significantly lower than 4:1 and corroborates the recent finding of a 1:1 ratio among Medicare beneficiaries.4 Because these cancers have low mortality and can occur multiple times per individual, the overall lifetime prevalence ratio is expected to approximate the overall incidence ratio yet also demonstrate a slight skew away from the cancer with the greater net increase in incidence across age groups (SCC in this case). Hence, our finding of a 2.0:1 overall lifetime prevalence ratio in an independent cohort substantiates our incidence results. Notably, we included both invasive SCC and SCC in situ under the term ‘‘SCC.’’ If we exclude SCC in situ from set 1, then the BCC:SCC ratio in the group older than 60 years increases to 1.8:1, which is greater than the corresponding value of 1.2:1 found in the Medicare study.4 This difference is unsurprising considering that SCC in situ is often treated nonsurgically (and is consequently underreported in Medicare claims data). In addition, the high average ultraviolet index in California likely influenced rates of SCC and SCC in situ in our study. Strengths of this study include large sample size for lifetime prevalence estimates and incidences based on dermatopathology reports. Overall, we demonstrate that the BCC:SCC incidence ratio is much closer to 1:1 than 4:1ethus, clinicians should increase their index of suspicion for SCC, particularly when evaluating older patients.
J AM ACAD DERMATOL
354 Research Letters
FEBRUARY 2017
Table II. Lifetime prevalence of basal cell carcinoma and squamous cell carcinoma in Caucasians, stratified by age group Age, y
BCC SCC BCC:SCC
#30
31-45
46-60
[60
Combined
0.1% (42) 0.0% (12) 3.5:1
0.8% (650) 0.2% (199) 3.3:1
4.1% (3194) 1.6% (1263) 2.5:1
10.6% (9059) 6.0% (5105) 1.8:1
4.5% (12,945) 2.3% (6579) 2.0:1
Lifetime prevalence values are reported as percentages, with number of self-reported cases in parentheses. To calculate each percentage, the number of cases in an age group was divided by the total number of subjects (cases plus controls) within that age group. Data source: 23andMe (Mountain View, CA) research participants with at least 97% European ancestry. BCC cases, SCC cases, and both sets of controls had 52%, 53%, and 54% males, respectively. Participants provided informed consent to take part in this research, in accord with 23andMe human subjects protocol (reviewed and approved by Ethical and Independent Review Services, an Association for the Accreditation of Human Research Protection Programs, Inceaccredited institutional review board). For more information about this cohort, please contact the corresponding author ([email protected]) or see: a. Pickrell JK, Berisa T, Liu JZ, et al. Detection and interpretation of shared genetic influences on 42 human traits. Nat. Genet. 2016. http://dx. doi.org/10.1038/ng.3570. b. Chahal HS, Lin Y, Ransohoff K, et al. Genome-wide association study identifies novel susceptibility loci for cutaneous squamous cell carcinoma. Nature Commun. 2016;7(12048):1-8. http://dx.doi.org/10.1038/ncomms12048. c. Chahal HS, Wu W, Ransohoff K, et al. Genome-wide association study identifies 14 novel risk alleles associated with basal cell carcinoma. Nature Commun. 2016;7(12510):1-10. http://dx.doi.org/10.1038/ncomms12510. BCC, Basal cell carcinoma; SCC, squamous cell carcinoma.
Harvind S. Chahal, BA, Kerri E. Rieger, MD, PhD, and Kavita Y. Sarin, MD, PhD Department of Dermatology, Stanford University School of Medicine, California Funding sources: Dermatology Foundation (Dr Sarin) and Stanford Medical Scholars Research Program (Mr Chahal). Conflicts of interest: None declared. Correspondence to: Kavita Y. Sarin, MD, PhD, Department of Dermatology, Stanford University Medical Center, 450 Broadway St, Pavilion C, 2nd Floor, Redwood City, CA 94063 E-mail: [email protected] REFERENCES 1. Lever WF, Elder DE, eds. Lever’s histopathology of the skin. 10th ed. Philadelphia (PA): Wolters Kluwer, Lippincott Williams and Wilkins; 2009. 2. Miller DL, Weinstock MA. Nonmelanoma skin cancer in the United States: incidence. J Am Acad Dermatol. 1994;30(5 Pt 1): 774-778. 3. Yiannias JA, Goldberg LH, Carter-Campbell S, Reddick M, Chamberlain RM. The ratio of basal cell carcinoma to squamous cell carcinoma in Houston, Texas. J Dermatol Surg Oncol. 1988;14(8):886-889. 4. Rogers HW, Weinstock MA, Feldman SR, Coldiron BM. Incidence estimate of nonmelanoma skin cancer (keratinocyte carcinomas) in the US population, 2012. JAMA Dermatol. 2015; 151:1081-1086. 5. Chahal HS, Lin Y, Ransohoff KJ, et al. Genome-wide association study identifies novel susceptibility loci for cutaneous squamous cell carcinoma. Nat Commun. 2016;7:12048. 6. Stern RS. Prevalence of a history of skin cancer in 2007: results of an incidence-based model. Arch Dermatol. 2010;146(3):279-282. http://dx.doi.org/10.1016/j.jaad.2016.08.019
The detection of human papillomaviruse16 in squamous cell carcinoma of the nail unit: A case series To the Editor: The correlation between human papillomavirus (HPV) and squamous cell carcinoma (SCC) of the skin and adnexa is still controversial.1 The detection of the virus has been described in several case series of nail unit SCC.2,3 This study aimed to evaluate the presence of HPV in a series of 41 cases of nail unit SCC referred to our dermatology skin cancer unit between January 2006 and December 2014. The study was carried out on residual biopsy sections after diagnostic analysis in the course of institutional diagnostic services and was exempted from institutional review board review. The INNO-LiPA HPV Genotyping Extra assay (Fujirebio, Pomezia, Italia Srl) was used to detect 28 mucosal HPV, including 18 high-risk and probable high-risk HPV (16, 18, 26, 31, 33, 35, 39, 45, 51, 52, 53, 56, 58, 59, 66, 68, 73, 82), 7 low-risk HPV (6, 11, 40, 43, 44, 54, 70), and 3 undetermined-risk HPV (69, 71, 74). All samples were amplified in real-time polymerase chain reaction (PCR) with a primer pair specific for the E6 region of HPV-16 to avoid false negatives because of the loss of the L1 region, resulting from viral integration in cancer cells. Finally, a nested PCR (FAP nested PCR) was used for the detection of a broad spectrum of cutaneous -HPV; a consensus outer primer pair FAP 59/6415 and a consensus inner primer pair FAP 6085/6319 were used for end point PCR amplification. Table I shows patients’ demographic data, and clinical and histopathologic characteristics of the