A population-based comparison of organ transplant recipients in whom cutaneous squamous cell develops versus those in whom basal cell carcinoma develops
Authors: Stephanie Menzies, Eamon O'Leary, Grainne Callaghan, Nazish Mansoor, Sandra Deady, Aizuri Murad, Patsy Lenane, Jim O'Neill, Aoife Lally, Diarmuid D. Houlihan, Susan Murray, Donal J. Sexton, P. Aiden McCormick, Jim J. Egan, James Paul O'Neill, Peter J. Conlon, Fergal J. Moloney
Journal: Journal of the American Academy of Dermatology (2021)

To the Editor: Basal cell carcinomas (BCC) occur more frequently than cutaneous squamous cell carcinomas (cSCC) with a general population ratio of 2.5:1.1NCRI Cancer trends.https://www.ncri.ie/sites/ncri/files/pubs/Trends%20report%20skin%20cancer%20final180717.pdfDate accessed: February 23, 2021Google Scholar There is wide variation in this ratio likely due to differences in demographics, latitude, and immunosuppression. The ratio is reversed following solid organ transplantation.2Euvrard S. Kanitakis J. Pouteil-Noble C. et al.Comparative epidemiologic study of premalignant and malignant epithelial cutaneous lesions developing after kidney and heart transplantation.J Am Acad Dermatol. 1995; 33: 222-229Abstract Full Text PDF PubMed Scopus (212) Google Scholar The Irish National Cancer Registry records first cSCC and BCC, providing a robust dataset to explore patient and transplant-related factors unique to the development of cSCC compared to BCC. We matched datasets from national transplant centers with Irish National Cancer Registry data from 1994 to 2014. Eligible participants were divided into 4 groups; "cSCC only," "BCC only," "cSCC and BCC," and "No cSCC or BCC" and compared using multinomial logistic regression analysis (Supplemental Appendix 1). The analysis included 3580 organ transplant recipients over a 21-year follow-up period. The total follow-up time was 28,407 person years with a median follow up of 7.1 years (interquartile range = 9.1; Supplemental Table I). Of these patients, 231 (6%) had "cSCC only," 239 (7%) had "BCC only," 174 (5%) had "cSCC and BCC," and 2936 (82%) had "No cSCC or BCC" (Table I). Female sex was significantly associated with "BCC only" compared with "cSCC only" (P = .001; relative risk ratio = 1.99; 95% CI = 1.31-3.01). There was no significant effect of organ transplant type, age at the time of transplant, year of transplant, and follow-up time on "cSCC only" versus that on "BCC only" risk (P = .487, P = .066, P = .149, and P = .427, respectively; Fig 1).Table IPatient demographic details for each of the 4 outcome groupsTotalcSCC onlyBCC onlycSCC and BCCNo cSCC or BCC3580231 (6%)239 (7%)174 (5%)2936 (82%)Male2256180 (8%)155 (7%)154 (7%)1767 (78%)Female132451 (4%)84 (6%)20 (2%)1169 (88%)Follow up (person years)28,40723362546221821,306Median follow up (years)7.19.410.813.26.2 IQR9.18.18.27.48.4Mean age at the time of transplant (years)44.853.750.555.243.0 Range0.8-77.416.7-76.613.7-77.421.7-76.30.8-75.9Median age at the time of transplant (years)47.255.051.755.945.0 IQR24.515.618.213.925.4Age at the time of transplant (years) <3070210 (1%)11 (2%)4 (1%)677 (96%) 30-3956023 (4%)37 (7%)6 (1%)494 (88%) 40-4971439 (5%)56 (8%)38 (5%)581 (81%) 50-5991678 (9%)74 (8%)62 (7%)702 (77%) >6068881 (12%)61 (9%)64 (9%)482 (70%)Transplant type Renal2446166 (7%)165 (7%)130 (5%)1985 (81%) Heart21618 (8%)23 (11%)21 (10%)154 (71%) Lung19210 (5%)11 (6%)7 (4%)164 (85%) Liver72637 (5%)40 (6%)16 (2%)633 (87%)Year of transplant 1994-199641042 (10%)38 (9%)50 (12%)280 (68%) 1997-199939335 (9%)34 (9%)36 (9%)288 (93%) 2000-200248833 (7%)41 (8%)38 (8%)376 (77%) 2003-200550940 (8%)42 (8%)17 (3%)410 (81%) 2006-200858536 (6%)34 (6%)19 (3%)496 (85%) 2009-201158337 (6%)32 (5%)11 (2%)503 (86%) 2012-20146128 (1%)18 (3%)3 (1%)583 (95%)BCC, Basal cell carcinomas; cSCC, cutaneous squamous cell carcinomas; IQR, interquartile range. Open table in a new tab BCC, Basal cell carcinomas; cSCC, cutaneous squamous cell carcinomas; IQR, interquartile range. Our study showed that the ratio of "BCC only" to "cSCC only" was statistically significantly higher in women than in men. Despite this, men in our study still had overall higher rates of "BCC only" compared to women (7% vs 6%). Similar trends are observed in the non-transplant population.1NCRI Cancer trends.https://www.ncri.ie/sites/ncri/files/pubs/Trends%20report%20skin%20cancer%20final180717.pdfDate accessed: February 23, 2021Google Scholar Heart transplant recipients generally receive a higher level of immunosuppression than renal and liver transplant recipients, which has been associated with higher rates of cSCC, but not BCC, than in the general population.3Fortina A.B. Piaserico S. Caforio A.L. et al.Immunosuppressive level and other risk factors for basal cell carcinoma and squamous cell carcinoma in heart transplant recipients.Arch Dermatol. 2004; 140: 1079-1085Crossref PubMed Scopus (100) Google Scholar However, our study showed no significant effect of organ transplant type on "cSCC only" versus "BCC only" risk. The cumulative incidence of keratinocyte carcinoma increases with time after transplantation4Bavinck J.N. Hardie D.R. Green A. et al.The risk of skin cancer in renal transplant recipients in Queensland, Australia. a follow-up study.Transplantation. 1996; 61: 715-721Crossref PubMed Scopus (443) Google Scholar; however, the year of transplant and follow-up time did not impact "cSCC only" versus "BCC only" risk. The year of transplant can indirectly reflect trends in immunosuppressive protocols and impact on keratinocyte carcinoma risk. The latter supports our recent findings that rates of both cSCC and BCC reduced equally over the last 20 years, maintaining the standardized incidence ratio of cSCC to BCC.5Menzies S. O'Leary E. Callaghan G. et al.Declining incidence of keratinocyte carcinoma in organ transplant recipients.Br J Dermatol. 2019; 181: 983-991Crossref PubMed Scopus (15) Google Scholar The limitations of the study include not adjusting for non-registry variables, which may impact differently on "cSCC only" versus "BCC only" risk, such as immunosuppressive protocols, skin type, and prior UV exposure. Additionally, the outcome groups used in our study are not static, eg, in a patient in the "BCC only" group, a cSCC developed after the study period. Finally, our data relies upon histologically confirmed keratinocyte carcinoma. This study examines keratinocyte cancer risk factors in organ transplant recipients subgroups in which BCC, cSCC, or both developed exclusively. Sex was found to be an independent risk factor, with women at increased risk of "BCC only" relative to "cSCC only" when compared to men. Further studies are required to explore whether different patterns of UV exposure or different responses to immunosuppression in male and female organ transplant recipients might explain our findings. None disclosed.