Non-Melanoma Skin Cancer Mortality in Spain: A Predictive Model up to 2044

Journal of Clinical Medicine Article Non-Melanoma Skin Cancer Mortality in Spain: A Predictive Model up to 2044 Mercedes Sendín-Martin 1, Juan Carlos Hernández-Rodríguez 1, Antonio-JoséDurán-Romero 1, Juan Ortiz-Álvarez 1, Julian Conejo-Mir 1,2 and José-Juan Pereyra-Rodríguez 1,2,*   Citation: Sendín-Martin, M.; Hernández-Rodríguez, J.C.; Durán-Romero, A.-J.; Ortiz-Álvarez, J.; Conejo-Mir, J.; Pereyra-Rodríguez, J.-J. Non-Melanoma Skin Cancer Mortality in Spain: A Predictive Model up to 2044. J. Clin. Med. 2021, 10, 5750. https://doi.org/10.3390/ jcm10245750 Academic Editors: Simone Garcovich and Elena Pezzolo Received: 31 October 2021 Accepted: 7 December 2021 Published: 8 December 2021 Publisher’s Note: MDPI stays neutral with regard to jurisdictional claims in published maps and institutional affiliations. Copyright: © 2021 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https:// creativecommons.org/licenses/by/ 4.0/). 1Dermatology Departement, Hospital Universitorio Virgen del Rocio, Avda. Manuel Siurot s/n., 41013 Sevilla, Spain; [email protected] (M.S.-M.); [email protected] (J.C.H.-R.); [email protected] (A.-J.D.-R.); [email protected] (J.O.-Á.); [email protected] (J.C.-M.) 2Medicine Department, Universidad de Sevilla, 41004 Sevilla, Spain *Correspondence: jper[email protected]; Tel.: +34-955-013-117 Abstract: Non-melanoma skin cancers (NMSC) are the most common malignancies worldwide and are, worryingly, increasing in incidence. However, data in the literature on NMSC specific mortality are scarce, because these tumors are excluded from most mortality registries. The main objective of this study is to analyze NMSC’s mortality rates and use them to generate a predictive model for the coming years in Spain. Data on mid-year population and death certificates for the period 1979–2019 were obtained from the Spanish National Statistics Institute. The Nordpred program (Cancer Registry of Norway, Oslo, Norway) within statistical program R was used to calculate mortality adjusted rates, as well as the mortality projection with an age-period-cohort model. This is the first study to report a prediction about NMSC mortality in the next years. According to our findings, the number of NMSC deaths in older people will grow in both sexes, especially in those older than >85 years old (y.o.). The age-specific mortality rates of NMSC will tend to stabilize or gradually decrease, with the exception of women between 75–79 y.o., who will present a slight increase at the end of the period. Early prevention and screening of NMSC specifically oriented to this population might change this tendency. Keywords: non-melanoma; skin cancer; epidemiology 1. Introduction Skin cancer has traditionally been divided into melanoma and non-melanoma skin cancers (NMSC). Non-melanoma skin cancers consist of the most common tumors worldwide and their prevalence is higher than the sum of all other cancers combined [ 1 ]. This group of tumors includes common malignancies such as basal cell carcinoma (BCC) and squamous cell carcinoma (SCC), but also rare tumors such as Merkel cell carcinoma or atypical fibroxanthoma. Traditionally, mortality in this NMSC group has been considered low, especially in the case of BCC. However, mortality from SCC has increased significantly in recent years, especially in immunocompromised or elderly patients [2]. Currently, mortality due to SCC appears to be underreported [ 2 ] and it’s considered an increasing worldwide problem. There are recent studies reporting that SCC related mortality in high-incidence areas may be equivalent to mortality associated with other tumors, such as renal or oropharyngeal carcinomas and melanoma [ 3 ]. Nevertheless, data in the literature on SCC-specific mortality are scarce, because this group of tumors is excluded from many mortality registries [ 4 ]. Most national mortality registries include SCC mortality under the heading of NMSC, which also includes other entities mentioned above, such as BCC or Merkel cell carcinomas. However, given the extremely low mortality of BCC (near to none) [ 1 , 2 , 5 ] and the low incidence of other skin tumors, such as Merkel J. Clin. Med. 2021,10, 5750. https://doi.org/10.3390/jcm10245750 https://www.mdpi.com/journal/jcm J. Clin. Med. 2021,10, 5750 2 of 13 cell or adnexal tumors [ 6 – 9 ], the majority of deaths attributed to NMSC would correspond to SCC, as has been previously pointed out in the literature [4,10]. Annual mortality from SCC in the US has been estimated at 2500 and 8000 cases per year in two different studies [ 3 , 10 ]. Concerning Spain, annual incidence of SCC has been calculated at 38.16 per 100,000 person-years [ 4 ], but there are scarce data about mortality. Only one recent study analyzes the mortality associated with NMSC in Spain in the last few years [ 11 ]. To the best of our knowledge, there is no study that predicts mortality trends for NMSC in Spain in the next few years. The main objective of this study is to analyze NMSC mortality rates in Spain and use them to generate a predictive model for the next few years up to 2044. 2. Materials and Methods Data on mid-year population and death certificates for the period 1980–2019 were obtained from the Spanish National Statistics Institute (NSI) (http://www.ine.es, accessed on 26 July 2021). The population data for the 2020–2044 period were obtained from the official population projection figures provided by the NSI. All death records, obtained in microdata files, which included NMSC (International Classification of Diseases (ICD): ICD- 9-CM: 173; ICD-10: C-44) as the cause of the death were included in the study. Age-specific mortality rates by 5-year age groups were computed. The Nordpred program (Cancer Registry of Norway, Oslo, Norway) [ 12 ] within statistical program R [ 13 ] was used to calculate age-specific mortality rates, as well as the mortality projection. The code in R project is provided as Supplementary Material. The European standard population 2013 was used for standardization. We used the R package Nordpred to calculate an age-period-cohort model. Data were compiled in fiveyear blocks. We extrapolated the most recent 10-year linear trend, attenuating the slope by 25% and 50% in the second and third prediction periods, and by 75% in the fourth and fifth periods, as recommended by the authors following empirical validation [ 12 ]. The results of the predictions are presented for the total of observed and expected deaths for each period in Spain. For each period, adjusted mortality rates were calculated based on the age-standardized rates. The annual changes in the number of deaths were calculated for the last projected period (2040–2044) in comparison with the last observed period (2015–2019), where the proportion of this change could be due to changes of risk of death due to NMSC or due to demographic changes (size or structure of population). These two components could be different from zero and present a positive or negative direction. According to our data, the population is not ageing during the study time, so we attribute our results to real changes in mortality trends. Nordpred uses the Power5 and Poisson age-period-cohort models to calculate prediction of mortality from 2020 to 2044 [ 14 ]. Since statistical methods based on age-period-cohort models often overestimated the number of cases due to their exponential growth over time, we decided to use Power5 function to level this off and improve our main predictions (Tables 1and 2and Figure 1). However, a comparison between Poisson and Power5 predictive models is provided at the end of the text. Finally, GraphPad Prism version 6.0 (GraphPad Software, San Diego, CA, USA) was used for graphics of mortality trends. J. Clin. Med. 2021,10, 5750 3 of 13 Table 1. Number of deaths observed (1980–2019) and projected (2020–2044) by periods and age groups by NMSC in Spain. (A) Both sexes; (B) men; (C) women. (A)Both Sexes Observed NMSC Deaths Projected NMSC Deaths Age (Years)1980–1984 1985–1989 1990–1994 1995–1999 2000–2004 2005–2009 2010–2014 2015–2019 2020–2024 2025–2029 2030–2034 2035–2039 2040–2044 0–40 1 0 0 0 0 0 0 0 0 0 0 0 5–91 1 1 0 0 1 0 0 0 0 0 0 0 10–14 1 0 1 0 0 0 0 0 0 0 0 0 0 15–19 3 3 3 0 1 1 0 0 0 0 0 0 0 20–24 2 4 1 2 5 1 1 2 2 2 2 2 2 25–29 5 13 13 13 7 3 7 2 4 4 4 5 4 30–34 11 16 21 21 8 6 8 5 3 2 2 2 2 35–39 16 30 18 18 13 12 10 7 5 4 3 3 3 40–44 24 43 32 29 16 20 29 9 10 7 6 5 5 45–49 55 51 38 38 30 17 37 21 12 12 10 8 7 50–54 113 98 41 56 37 35 49 43 34 20 20 18 15 55–59 163 138 86 60 56 76 76 58 64 53 34 37 33 60–64 162 176 135 114 69 82 100 90 74 86 76 53 58 65–69 200 216 193 156 117 129 140 135 127 113 136 127 93 70–74 265 258 196 201 188 172 182 195 195 186 176 218 207 75–79 333 348 283 264 247 303 333 279 302 321 323 324 397 80–84 330 483 484 375 365 433 498 524 446 508 562 590 608 >85 533 834 990 1128 1134 1146 1540 1914 2049 2057 2312 2724 3006 Total number of deaths 2217 2713 2536 2475 2293 2437 3010 3284 3212 3373 3663 4115 4440 J. Clin. Med. 2021,10, 5750 4 of 13 Table 1. Cont. (B)Men Observed NMSC Deaths Projected NMSC Deaths Age (Years)1980–1984 1985–1989 1990–1994 1995–1999 2000–2004 2005–2009 2010–2014 2015–2019 2020–2024 2025–2029 2030–2034 2035–2039 2040–2044 0–40 0 0 0 0 0 0 0 0 0 0 0 0 5–91 1 1 0 0 0 0 0 0 0 0 0 0 10–14 1 0 1 0 0 0 0 0 0 0 0 0 0 15–19 3 2 2 0 1 1 0 0 0 0 0 0 0 20–24 1 1 0 1 2 0 1 0 1 1 1 1 1 25–29 4 7 11 9 6 1 3 0 1 1 1 2 1 30–34 8 10 19 15 5 5 3 4 3 2 2 2 2 35–39 11 18 14 16 9 8 7 3 4 3 3 3 3 40–44 19 32 25 20 10 13 18 5 4 5 4 4 4 45–49 42 43 28 30 20 11 20 13 8 5 7 6 6 50–54 97 87 32 41 30 26 40 29 25 15 10 14 13 55–59 134 114 70 54 43 60 53 45 46 40 26 19 26 60–64 129 150 107 89 49 61 67 71 58 60 54 39 28 65–69 155 172 146 121 93 101 104 103 101 94 101 96 72 70–74 175 171 132 143 131 122 138 159 152 146 143 158 153 75–79 191 207 174 159 161 213 243 211 232 250 251 259 288 80–84 170 239 254 210 197 272 319 355 321 373 413 432 457 >85 189 294 349 437 456 465 708 910 1049 1090 1247 1473 1620 Total number of deaths 1330 1548 1365 1345 1213 1359 1724 1908 2005 2083 2262 2506 2673 J. Clin. Med. 2021,10, 5750 5 of 13 Table 1. Cont. (C)Women Observed NMSC Deaths Projected NMSC Deaths Age (Years)1980–1984 1985–1989 1990–1994 1995–1999 2000–2004 2005–2009 2010–2014 2015–2019 2020–2024 2025–2029 2030–2034 2035–2039 2040–2044 0–40 1 0 0 0 0 0 0 0 0 0 0 0 5–90 0 0 0 0 1 0 0 0 0 0 0 0 10–14 0 0 0 0 0 0 0 0 0 0 0 0 0 15–19 0 1 1 0 0 0 0 0 0 0 0 0 0 20–24 1 3 1 1 3 1 0 2 1 1 1 1 1 25–29 1 6 2 4 1 2 4 2 3 3 3 3 3 30–34 3 6 2 6 3 1 5 1 1 0 0 0 0 35–39 5 12 4 2 4 4 3 4 1 1 0 0 0 40–44 5 11 7 9 6 7 11 4 8 2 2 1 1 45–49 13 8 10 8 10 6 17 8 4 8 3 2 2 50–54 16 11 9 15 7 9 9 14 10 5 10 4 3 55–59 29 24 16 6 13 16 23 13 18 11 8 17 7 60–64 33 26 28 25 20 21 33 19 18 28 23 15 30 65–69 45 44 47 35 24 28 36 32 29 22 36 33 23 70–74 90 87 64 58 57 50 44 36 46 45 38 63 59 75–79 142 141 109 105 86 90 90 68 75 81 84 78 123 80–84 160 244 230 165 168 161 179 169 127 148 167 182 175 >85 344 540 641 691 678 681 832 1004 933 875 1004 1211 1374 Total number of deaths 887 1165 1171 1130 1080 1078 1286 1376 1272 1231 1378 1611 1802 NMSC: Non-melanoma Skin Cancer J. Clin. Med. 2021,10, 5750 6 of 13 Table 2. Age-specific mortality rates per 100,000 inhabitants (European population 2013) observed (1980–2019) and projected (2020–2044) by periods and age groups by NMSC in Spain. (A) Both sexes; (B) men; (C) women. (A) Both Sexes Age (Years) 1980–1984 1985–1989 1990–1994 1995–1999 2000–2004 2005–2009 2010–2014 2015–2019 2020–2024 2025–2029 2030–2034 2035–2039 2040–2044 0–40 0.01 0 0 0 0 0 0 0 0 0 0 0 5–90.01 0.01 0.01 0 0 0.01 0 0 0 0 0 0 0 10–14 0.01 0 0.01 0 0 0 0 0 0 0 0 0 0 15–19 0.02 0.02 0.02 0 0.01 0.01 0 0 0 0 0 0 0 20–24 0.01 0.02 0.01 0.01 0.03 0.01 0.01 0.02 0.01 0.01 0.01 0.01 0.01 25–29 0.04 0.09 0.08 0.08 0.04 0.02 0.05 0.02 0.03 0.03 0.03 0.03 0.03 30–34 0.09 0.12 0.14 0.13 0.05 0.03 0.04 0.03 0.02 0.02 0.02 0.01 0.01 35–39 0.14 0.24 0.14 0.12 0.08 0.06 0.05 0.04 0.03 0.03 0.02 0.02 0.02 40–44 0.24 0.37 0.26 0.22 0.1 0.11 0.15 0.05 0.05 0.05 0.04 0.04 0.03 45–49 0.48 0.51 0.33 0.31 0.22 0.1 0.2 0.11 0.06 0.06 0.06 0.06 0.05 50–54 0.99 0.88 0.42 0.49 0.3 0.25 0.3 0.24 0.18 0.1 0.11 0.11 0.11 55–59 1.57 1.24 0.79 0.62 0.49 0.6 0.55 0.37 0.37 0.29 0.17 0.2 0.21 60–64 1.9 1.77 1.26 1.08 0.72 0.72 0.81 0.67 0.48 0.5 0.42 0.28 0.32 65–69 2.78 2.72 2.06 1.54 1.15 1.37 1.26 1.13 0.99 0.76 0.82 0.73 0.5 70–74 4.28 4.05 2.74 2.37 2.01 1.8 2.06 1.88 1.73 1.53 1.25 1.39 1.25 75–79 7.49 6.92 5.36 4.38 3.39 3.66 3.91 3.54 3.24 3.14 2.91 2.51 2.77 80–84 13.24 15.54 13.35 9.55 7.94 7.52 7.42 7.44 6.83 6.47 6.49 6.25 5.51 >85 38.18 45.57 41.12 37.05 31.87 26.16 26.55 26.87 25.27 24.46 23.98 24.57 23.87 SMR 2.31 2.5 2.05 1.74 1.43 1.28 1.32 1.25 1.15 1.09 1.04 1.03 0.99 J. Clin. Med. 2021,10, 5750 7 of 13 Table 2. Cont. (B) Men Age (Years)1980–1984 1985–1989 1990–1994 1995–1999 2000–2004 2005–2009 2010–2014 2015–2019 2020–2024 2025–2029 2030–2034 2035–2039 2040–2044 0–40 0 0 0 0 0 0 0 0 0 0 0 0 5–90.01 0.01 0.02 0 0 0 0 0 0 0 0 0 0 10–14 0.01 0 0.01 0 0 0 0 0 0 0 0 0 0 15–19 0.04 0.02 0.02 0 0.02 0.02 0 0 0 0 0 0 0 20–24 0.01 0.01 0 0.01 0.02 0 0.02 0 0.01 0.01 0.01 0.01 0.01 25–29 0.06 0.09 0.14 0.11 0.07 0.01 0.04 0 0.02 0.02 0.02 0.02 0.02 30–34 0.13 0.15 0.26 0.18 0.06 0.05 0.03 0.05 0.04 0.04 0.03 0.03 0.03 35–39 0.19 0.29 0.21 0.21 0.11 0.08 0.07 0.03 0.06 0.05 0.04 0.04 0.04 40–44 0.38 0.55 0.41 0.3 0.13 0.14 0.18 0.05 0.04 0.07 0.06 0.06 0.05 45–49 0.75 0.87 0.49 0.49 0.3 0.13 0.22 0.14 0.08 0.05 0.09 0.08 0.08 50–54 1.73 1.59 0.66 0.73 0.49 0.38 0.49 0.33 0.26 0.15 0.1 0.18 0.18 55–59 2.67 2.11 1.33 1.14 0.77 0.97 0.78 0.58 0.53 0.43 0.27 0.2 0.34 60–64 3.28 3.18 2.1 1.77 1.07 1.1 1.12 1.1 0.77 0.71 0.61 0.41 0.32 65–69 4.96 4.83 3.39 2.57 1.96 2.28 1.97 1.82 1.65 1.32 1.27 1.13 0.8 70–74 6.73 6.45 4.31 3.82 3.13 2.83 3.4 3.32 2.91 2.58 2.17 2.14 1.93 75–79 10.92 10.47 8.46 6.56 5.3 6.06 6.6 6.1 5.62 5.46 5.02 4.42 4.37 80–84 19.08 21.34 19.46 15.04 11.66 12.32 12 12.47 11.97 11.29 11.23 10.65 9.54 >85 43.55 51.74 46.62 46.59 42.59 34.53 37.94 38.19 37.67 37.14 36 36.41 34.9 SMR 3.21 3.41 2.76 2.46 2.03 1.87 1.98 1.92 1.82 1.73 1.64 1.59 1.5 J. Clin. Med. 2021,10, 5750 8 of 13 Table 2. Cont. (C) Women Age (Years)1980–1984 1985–1989 1990–1994 1995–1999 2000–2004 2005–2009 2010–2014 2015–2019 2020–2024 2025–2029 2030–2034 2035–2039 2040–2044 0–40 0.02 0 0 0 0 0 0 0 0 0 0 0 5–90 0 0 0 0 0.02 0 0 0 0 0 0 0 10–14 0 0 0 0 0 0 0 0 0 0 0 0 0 15–19 0 0.01 0.01 0 0 0 0 0 0 0 0 0 0 20–24 0.01 0.04 0.01 0.01 0.04 0.01 0 0.04 0.02 0.02 0.02 0.02 0.02 25–29 0.02 0.08 0.03 0.05 0.01 0.02 0.05 0.03 0.04 0.04 0.04 0.04 0.04 30–34 0.05 0.09 0.03 0.07 0.04 0.01 0.05 0.01 0.01 0 0 0 0 35–39 0.09 0.2 0.06 0.03 0.05 0.04 0.03 0.04 0.01 0.01 0.01 0 0 40–44 0.1 0.19 0.11 0.14 0.08 0.08 0.12 0.04 0.08 0.03 0.02 0.02 0.02 45–49 0.22 0.16 0.17 0.13 0.15 0.07 0.19 0.09 0.04 0.09 0.03 0.03 0.03 50–54 0.27 0.19 0.18 0.26 0.11 0.13 0.11 0.16 0.1 0.05 0.11 0.04 0.04 55–59 0.54 0.42 0.29 0.12 0.22 0.25 0.33 0.16 0.21 0.15 0.08 0.18 0.08 60–64 0.72 0.5 0.5 0.45 0.4 0.36 0.52 0.28 0.22 0.32 0.25 0.16 0.32 65–69 1.11 1 0.93 0.64 0.44 0.56 0.62 0.51 0.43 0.28 0.42 0.36 0.24 70–74 2.51 2.34 1.57 1.23 1.1 0.96 0.92 0.65 0.77 0.69 0.5 0.77 0.67 75–79 5.27 4.62 3.38 2.91 2.02 1.89 1.86 1.54 1.46 1.44 1.38 1.11 1.59 80–84 9.99 12.27 9.92 6.52 5.78 4.53 4.41 4.02 3.31 3.24 3.35 3.37 2.81 >85 35.76 42.79 38.63 32.8 27.26 22.45 21.15 21.18 17.52 15.98 16.26 17.2 17.28 SMR 1.67 1.86 1.57 1.28 1.06 0.89 0.88 0.81 0.69 0.63 0.63 0.65 0.65 SMR: Standardized mortality rate. J. Clin. Med. 2021,10, 5750 9 of 13 Figure 1. Observed (1980–2019) and predicted (2020–2044) age-specific mortality rates for NMSC in Spain. (a) Both sexes; (b) males; (c) females. 3. Results In the period 1980–2019, there were 20,965 deaths from NMSC in Spain. By sex, there were 11,792 NMSC deaths in males and 9173 in females. The predictive model applied predicts that in the period 2020–2044 there will be 18,918 deaths from NMSC in Spain in both sexes, with the age group > 85 years old (y.o.) and males showing the highest number of deaths. The detail of the number of deaths produced in Spain (1980–2019) and its prediction (2020–2044), according to age groups and sex, can be seen in Table 1.