WEBVTT 1 00:00:00.570 --> 00:00:01.740 Hi everyone. 2 00:00:01.740 --> 00:00:04.470 In today's lecture, we'll be discussing the epidemiology 3 00:00:04.470 --> 00:00:06.467 of non-melanoma skin cancer. 4 00:00:08.660 --> 00:00:10.920 In this lecture, our goals are to review 5 00:00:10.920 --> 00:00:13.290 the anatomy and function of human skin, 6 00:00:13.290 --> 00:00:16.080 and discuss cell types of non-melanoma skin cancer, 7 00:00:16.080 --> 00:00:17.850 and differentiate between basal cell 8 00:00:17.850 --> 00:00:20.100 and squamous cell carcinomas. 9 00:00:20.100 --> 00:00:22.470 We'll also look at the global burden of skin cancer 10 00:00:22.470 --> 00:00:25.230 and trends in skin cancer rates. 11 00:00:25.230 --> 00:00:28.260 Next, we'll look at risk factors, the ozone hole, 12 00:00:28.260 --> 00:00:30.360 and conclude with a discussion of prevention 13 00:00:30.360 --> 00:00:32.583 and therapy strategies for skin cancer. 14 00:00:33.660 --> 00:00:38.660 So to begin with, the skin consists of three layers: 15 00:00:39.450 --> 00:00:42.930 the epidermis, the dermis, and the subcutaneous. 16 00:00:42.930 --> 00:00:45.240 The outer layer of skin is called the epidermis 17 00:00:45.240 --> 00:00:48.210 which consists of layers of cells called keratinocytes 18 00:00:48.210 --> 00:00:49.953 that produce the protein keratin. 19 00:00:49.953 --> 00:00:52.920 Keratin is a durable but flexible protein 20 00:00:52.920 --> 00:00:55.409 that provides strength and elasticity to the skin. 21 00:00:55.409 --> 00:00:59.190 Basal cells and squamous cells of the epidermis 22 00:00:59.190 --> 00:01:01.067 are collectively called keratinocytes, 23 00:01:01.067 --> 00:01:03.843 since both cell types produce keratin. 24 00:01:04.950 --> 00:01:07.200 The epidermis also contains melanocytes 25 00:01:07.200 --> 00:01:08.700 which produce melanin, a pigment 26 00:01:08.700 --> 00:01:10.740 which absorbs radiant energy from the sun 27 00:01:10.740 --> 00:01:12.690 and protects the skin from the harmful effects 28 00:01:12.690 --> 00:01:14.443 of UV radiation. 29 00:01:14.443 --> 00:01:17.068 Immune cells, called Langerhans cells, 30 00:01:17.068 --> 00:01:20.671 circulate in the epidermis and play an important role 31 00:01:20.671 --> 00:01:24.319 in immunosurveillance and defense against infection. 32 00:01:24.319 --> 00:01:27.111 The epidermis also contains neurosensory cells, 33 00:01:27.111 --> 00:01:30.030 called Merkel cells, that connect with nerve endings 34 00:01:30.030 --> 00:01:33.843 to transmit electrical impulses in response to touch. 35 00:01:36.810 --> 00:01:40.320 There are two principle forms of nonmelanoma skin cancer: 36 00:01:40.320 --> 00:01:43.143 basal cell carcinoma, and squamous cell carcinoma. 37 00:01:43.980 --> 00:01:46.143 These two cell types make up over 99% 38 00:01:46.143 --> 00:01:48.984 of all nonmelanoma skin cancers. 39 00:01:48.984 --> 00:01:53.299 And in one study, 82% of nonmelanoma skin cancers 40 00:01:53.299 --> 00:01:56.218 were basal cell carcinomas while 17% 41 00:01:56.218 --> 00:02:00.000 were squamous cell carcinomas. 42 00:02:00.000 --> 00:02:03.063 Less than 1% were other histological forms. 43 00:02:04.380 --> 00:02:06.630 Basal cell carcinoma is the most common form 44 00:02:06.630 --> 00:02:09.030 of human cancer, and these tumors arise 45 00:02:09.030 --> 00:02:13.500 from the keratinized basal cells of the epidermis, 46 00:02:13.500 --> 00:02:15.900 which are in contact with the basement membrane. 47 00:02:16.830 --> 00:02:19.560 Basal cell carcinomas most often develop from the skin 48 00:02:19.560 --> 00:02:22.050 of the face, neck, or upper trunk that has been damaged 49 00:02:22.050 --> 00:02:23.760 by intermittent blistering sunburns 50 00:02:23.760 --> 00:02:25.881 during childhood or adolescence. 51 00:02:25.881 --> 00:02:29.250 While basal cell carcinomas rarely metastasize 52 00:02:29.250 --> 00:02:30.180 to distant organs, 53 00:02:30.180 --> 00:02:32.937 they can invade and damage contiguous tissues. 54 00:02:32.937 --> 00:02:35.970 Squamous cell carcinoma, or SCC, 55 00:02:35.970 --> 00:02:38.619 is the second most common human cancer. 56 00:02:38.619 --> 00:02:41.570 SCC arises from keratinized squamous cells 57 00:02:41.570 --> 00:02:44.520 in the uppermost cell layers of the epidermis. 58 00:02:44.520 --> 00:02:47.250 Squamous cell carcinomas of the skin occasionally develop 59 00:02:47.250 --> 00:02:51.120 as a consequence of continuous sun exposure throughout life. 60 00:02:51.120 --> 00:02:54.023 SCC almost always develops due to malignant transformation 61 00:02:54.023 --> 00:02:56.800 of sun induced pre-cancerous skin lesions, 62 00:02:56.800 --> 00:02:59.637 known as the actinic keratoses. 63 00:03:00.870 --> 00:03:03.510 Exposed skin of the face, neck, and backs of the hands 64 00:03:03.510 --> 00:03:05.910 are the most common sites of cumulative sun damage 65 00:03:05.910 --> 00:03:08.220 leading to tumor development. 66 00:03:08.220 --> 00:03:12.750 In contrast to basal cell carcinoma, SCC can metastasize 67 00:03:12.750 --> 00:03:15.354 to other organs through the lymph and blood. 68 00:03:15.354 --> 00:03:18.660 While basal cell and squamous cell carcinomas 69 00:03:18.660 --> 00:03:21.258 are the two principle forms of non-melanoma skin cancer, 70 00:03:21.258 --> 00:03:25.500 Merkel cell carcinomas are a rare malignancy of the skin 71 00:03:25.500 --> 00:03:29.343 and make up less than 1% of cancers of this type. 72 00:03:30.930 --> 00:03:33.720 Age-specific incidence rates of the two major forms 73 00:03:33.720 --> 00:03:36.030 of non-melanoma skin cancer, basal cell 74 00:03:36.030 --> 00:03:38.520 and squamous cell carcinoma were estimated, 75 00:03:38.520 --> 00:03:40.320 based upon national survey data 76 00:03:40.320 --> 00:03:42.903 collected in Australia during 2002. 77 00:03:43.830 --> 00:03:45.870 The Australian population has the highest rates 78 00:03:45.870 --> 00:03:47.670 of non-melanoma skin cancer in the world, 79 00:03:47.670 --> 00:03:51.450 and it's indeed striking that the 2002 Australian rates 80 00:03:51.450 --> 00:03:54.270 are 10 to 20 times higher than the corresponding 81 00:03:54.270 --> 00:03:56.643 age-specific rates for the US population. 82 00:03:58.260 --> 00:04:00.874 The age-specific incidence rates of figure 24.3 83 00:04:00.874 --> 00:04:03.900 reflect a clear difference in the pathogenesis 84 00:04:03.900 --> 00:04:07.563 of basal cell versus squamous cell carcinoma. 85 00:04:07.563 --> 00:04:10.290 Note that the risk ratio of basal cell 86 00:04:10.290 --> 00:04:12.240 to squamous cell carcinoma for individuals 87 00:04:12.240 --> 00:04:17.240 under 40 years of age is 29.0, whereas after age seven, 88 00:04:17.910 --> 00:04:20.040 or whereas after age 40, rather, 89 00:04:20.040 --> 00:04:23.130 the rate ratios progressively declined from 2.9 90 00:04:23.130 --> 00:04:26.940 for individuals aged 40 to 49 years to 1.8. 91 00:04:26.940 --> 00:04:30.240 for individuals over 70 years of age. 92 00:04:30.240 --> 00:04:33.030 The sharper increase in the risk of squamous cell carcinoma 93 00:04:33.030 --> 00:04:36.060 compared to basal cell carcinoma with aging 94 00:04:36.060 --> 00:04:37.890 is a possible consequence of the effects 95 00:04:37.890 --> 00:04:40.267 of cumulative sun damage. 96 00:04:40.267 --> 00:04:42.900 When we look at the incidence and mortality rates 97 00:04:42.900 --> 00:04:45.188 of non-melanoma skin cancer in 2020, 98 00:04:45.188 --> 00:04:49.170 we see that overall rates of incidents are 11 per 100,000 99 00:04:49.170 --> 00:04:53.940 with nearly double the rate in men as for women. 100 00:04:53.940 --> 00:04:58.050 Similarly, we see rates of 0.6 deaths 101 00:04:58.050 --> 00:05:00.073 per 100,000 people globally, 102 00:05:00.073 --> 00:05:03.360 but mortality rates nearly twice as high 103 00:05:03.360 --> 00:05:04.983 in men than as in women. 104 00:05:06.167 --> 00:05:08.670 The incidence of non-melanoma skin cancer 105 00:05:08.670 --> 00:05:11.610 is highly correlated with the level of solar radiation 106 00:05:11.610 --> 00:05:15.030 and various inversely with the degree of skin pigmentation 107 00:05:15.030 --> 00:05:17.130 amongst populations. 108 00:05:17.130 --> 00:05:19.230 Amongst Caucasians in the United States, 109 00:05:19.230 --> 00:05:22.317 non-melanoma skin cancer constitutes 20 to 30% 110 00:05:22.317 --> 00:05:25.410 of all neoplasms, whereas among African Americans, 111 00:05:25.410 --> 00:05:26.850 such lesions are infrequent 112 00:05:26.850 --> 00:05:29.343 and makes up less than 1% of all neoplasms. 113 00:05:31.530 --> 00:05:33.420 Australia has the highest reported incidence 114 00:05:33.420 --> 00:05:35.490 of non-melanoma skin cancer in the world, 115 00:05:35.490 --> 00:05:38.190 and a national survey of the Australian population conducted 116 00:05:38.190 --> 00:05:40.636 in 2002, found an age-adjusted rate 117 00:05:40.636 --> 00:05:45.478 of 1,170 cases per 100,000. 118 00:05:45.478 --> 00:05:48.180 The incidence of non-melanoma skin cancer in men 119 00:05:48.180 --> 00:05:53.180 was 39% higher than in women and based on these data, 120 00:05:53.970 --> 00:05:57.233 69% of Australian men and 58% of Australian women 121 00:05:57.233 --> 00:05:59.610 develop non-melanoma skin cancer 122 00:05:59.610 --> 00:06:01.571 by 70 years of age. 123 00:06:01.571 --> 00:06:04.537 The major predisposing factors in the Australian population 124 00:06:04.537 --> 00:06:06.473 are light skin pigmentation, 125 00:06:06.473 --> 00:06:08.850 high ambient levels of ultraviolet light, 126 00:06:08.850 --> 00:06:10.770 due to the south polar ozone hole, 127 00:06:10.770 --> 00:06:13.140 and cultural emphasis on outdoor activities 128 00:06:13.140 --> 00:06:15.168 and sun exposure throughout life. 129 00:06:15.168 --> 00:06:18.840 Longitudinal investigations of multiple cohorts 130 00:06:18.840 --> 00:06:20.190 provide evidence that the incidence 131 00:06:20.190 --> 00:06:21.734 of non-melanoma skin cancer, 132 00:06:21.734 --> 00:06:23.964 basal cell and squamous cell carcinoma 133 00:06:23.964 --> 00:06:26.284 has increased among Caucasian populations 134 00:06:26.284 --> 00:06:28.202 of several different regions. 135 00:06:28.202 --> 00:06:30.990 Four national surveys were conducted 136 00:06:30.990 --> 00:06:34.650 in the Australian population during 1985 to 2002 137 00:06:34.650 --> 00:06:36.240 to determine trends in the incidence 138 00:06:36.240 --> 00:06:38.670 of non-melanoma skin cancer. 139 00:06:38.670 --> 00:06:40.688 Results reflect an overall increase of 35% 140 00:06:40.688 --> 00:06:42.621 for basal cell carcinoma, 141 00:06:42.621 --> 00:06:47.000 and 233% for squamous cell carcinoma. 142 00:06:47.000 --> 00:06:49.680 The increases were similar for men and women 143 00:06:49.680 --> 00:06:52.925 and tended to occur primarily among older individuals. 144 00:06:52.925 --> 00:06:56.307 Investigators in the US examined trends 145 00:06:56.307 --> 00:06:58.950 in the annual incidence of basal cell carcinoma 146 00:06:58.950 --> 00:07:02.153 in two large prospective cohorts of older adults. 147 00:07:02.153 --> 00:07:05.850 95,743 women of the Nurses' Health Study 148 00:07:05.850 --> 00:07:10.230 from 1986 to 2006 and nearly 45,000 men 149 00:07:10.230 --> 00:07:12.000 of the Health Professionals' Follow-up Study 150 00:07:12.000 --> 00:07:15.240 from 1988 to 2006. 151 00:07:15.240 --> 00:07:17.700 Age-adjusted incidents rates increased markedly 152 00:07:17.700 --> 00:07:22.700 in women from 519 to 1019 per 100,000 153 00:07:22.972 --> 00:07:27.972 and in men from 606 to 1,488 per 100,000. 154 00:07:29.640 --> 00:07:31.860 The investigator suggested that several factors 155 00:07:31.860 --> 00:07:33.450 may have contributed to these trends 156 00:07:33.450 --> 00:07:36.810 including increasing susceptibility with greater longevity 157 00:07:36.810 --> 00:07:38.924 and heightened exposure to solar radiation 158 00:07:38.924 --> 00:07:42.603 and/or artificial ultraviolet radiation in tanning beds. 159 00:07:44.018 --> 00:07:47.400 The largest and most comprehensive comparative study 160 00:07:47.400 --> 00:07:50.280 of effects of solar radiation in the development 161 00:07:50.280 --> 00:07:52.860 of basal cell and squamous cell carcinoma of the skin, 162 00:07:52.860 --> 00:07:55.920 is the European study, Helios, that was conducted 163 00:07:55.920 --> 00:07:57.780 in Southern Europe. 164 00:07:57.780 --> 00:08:01.149 Between 1989 and 1993, investigators in seven regions 165 00:08:01.149 --> 00:08:02.580 of Southern Europe interviewed 166 00:08:02.580 --> 00:08:07.580 1,549 incident cases of basal cell carcinoma, 167 00:08:07.860 --> 00:08:10.350 228 cases of squamous cell carcinoma, 168 00:08:10.350 --> 00:08:15.350 and 1,795 disease-free controls, matched to the cases 169 00:08:16.320 --> 00:08:19.032 by age, gender, and location of residents. 170 00:08:19.032 --> 00:08:22.320 Results of the study revealed that both forms 171 00:08:22.320 --> 00:08:24.390 of non-melanoma skin cancer developed primarily 172 00:08:24.390 --> 00:08:27.240 in sun exposed areas of skin on the face, head, 173 00:08:27.240 --> 00:08:30.300 arms, legs and trunk, and pigmentary traits, 174 00:08:30.300 --> 00:08:31.920 like red hair and pale eye color, 175 00:08:31.920 --> 00:08:33.951 as well as tendency to sunburn were strong 176 00:08:33.951 --> 00:08:36.240 and independent indicators of risk 177 00:08:36.240 --> 00:08:39.303 for both basal cell carcinoma and squamous cell carcinoma. 178 00:08:41.010 --> 00:08:43.470 The investigators concluded that basal cell carcinoma 179 00:08:43.470 --> 00:08:45.420 and squamous cell carcinoma are influenced 180 00:08:45.420 --> 00:08:48.900 by different patterns of exposure to solar radiation. 181 00:08:48.900 --> 00:08:51.390 Basal cell carcinoma risk is increased by periods 182 00:08:51.390 --> 00:08:54.270 of intense exposure, cumulative episodes of sunburn, 183 00:08:54.270 --> 00:08:57.840 and poor ability to tan, where squamous cell carcinoma risk 184 00:08:57.840 --> 00:09:00.483 is associated with prolonged exposure over time. 185 00:09:01.410 --> 00:09:03.180 These data revealed a sharp increase 186 00:09:03.180 --> 00:09:05.220 in the risk of developing squamous cell carcinoma, 187 00:09:05.220 --> 00:09:06.390 beginning at a threshold level 188 00:09:06.390 --> 00:09:09.540 of 70,000 hours of cumulative sun exposure 189 00:09:09.540 --> 00:09:13.173 and maximizing it over 100,000 hours of exposure. 190 00:09:15.240 --> 00:09:17.040 Sources of radiation other than the sun 191 00:09:17.040 --> 00:09:18.535 also increase the risk of developing 192 00:09:18.535 --> 00:09:21.480 squamous cell carcinoma of the skin. 193 00:09:21.480 --> 00:09:23.670 Artificial devices that emit UV radiation, 194 00:09:23.670 --> 00:09:26.130 like tanning beds, have been found to increase the risk 195 00:09:26.130 --> 00:09:29.080 of both squamous cell and basal cell carcinoma of the skin. 196 00:09:30.844 --> 00:09:35.580 Psoralen and ultraviolet A, or PUVA, is sometimes used 197 00:09:35.580 --> 00:09:38.380 for the treatment of psoriasis and other skin disorders. 198 00:09:39.390 --> 00:09:41.400 In a long-term follow-up study 199 00:09:41.400 --> 00:09:44.427 of nearly 5,000 Swedish patients who had received PUVA 200 00:09:44.427 --> 00:09:46.075 for the treatment of skin disorders, 201 00:09:46.075 --> 00:09:49.080 significant risk increases were noted 202 00:09:49.080 --> 00:09:50.430 for both men and women, 203 00:09:50.430 --> 00:09:53.360 compared to the general Swedish population. 204 00:09:53.360 --> 00:09:56.070 Next, exposure to arsenic in drinking water 205 00:09:56.070 --> 00:09:58.470 and combustion products has been found to increase the risk 206 00:09:58.470 --> 00:10:01.413 of both basal cell carcinoma and squamous cell carcinoma. 207 00:10:02.768 --> 00:10:05.430 There's also several genetic factors that play a role 208 00:10:05.430 --> 00:10:07.920 in basal cell carcinoma of the skin. 209 00:10:07.920 --> 00:10:10.666 The primary one is the Hedgehog signaling pathway 210 00:10:10.666 --> 00:10:13.920 that regulates spatial orientation and bilateral development 211 00:10:13.920 --> 00:10:16.950 of certain structures and organs during embryogenesis 212 00:10:16.950 --> 00:10:18.588 in all vertebrates, including humans. 213 00:10:18.588 --> 00:10:23.280 It's called Hedgehog because mutated genes of the pathway 214 00:10:23.280 --> 00:10:25.920 cause the development of aberrant larvae and drosophila, 215 00:10:25.920 --> 00:10:29.133 or fruit flies, that resemble miniature hedgehogs. 216 00:10:30.210 --> 00:10:32.400 Molecular studies have revealed that mutations 217 00:10:32.400 --> 00:10:34.860 and tumor suppressor genes that encode important proteins 218 00:10:34.860 --> 00:10:36.870 of the Hedgehog pathway are present 219 00:10:36.870 --> 00:10:39.660 in about 90% of sporadic or non-heritable 220 00:10:39.660 --> 00:10:41.193 basal cell carcinomas. 221 00:10:42.300 --> 00:10:44.670 Hedgehog mutations, which are presumably the result 222 00:10:44.670 --> 00:10:48.050 of UV radiation, enhance carcinogenesis of basal cells 223 00:10:48.050 --> 00:10:50.250 in the epidermis by distributing the regulation 224 00:10:50.250 --> 00:10:53.433 of cell division, transcription, and protein synthesis. 225 00:10:55.440 --> 00:10:58.203 Other genetic syndromes that influence risk 226 00:10:58.203 --> 00:11:00.480 for basal cell carcinoma of the skin 227 00:11:00.480 --> 00:11:01.863 are listed on the slide. 228 00:11:03.930 --> 00:11:05.460 Squamous cell carcinoma of the skin 229 00:11:05.460 --> 00:11:06.570 characteristically develops 230 00:11:06.570 --> 00:11:09.480 by a multi-step model of carcinogenesis. 231 00:11:09.480 --> 00:11:11.693 The vast majority, 97%, of sporadic cases 232 00:11:11.693 --> 00:11:15.421 involve transformation of the precursor lesion, 233 00:11:15.421 --> 00:11:18.603 actinic keratosis to squamous cell carcinoma. 234 00:11:19.770 --> 00:11:21.210 A key factor in the development 235 00:11:21.210 --> 00:11:23.280 of actinic keratosis is the loss of function 236 00:11:23.280 --> 00:11:26.119 of the p53 tumor suppressor gene on chromosome 17, 237 00:11:26.119 --> 00:11:30.093 that's essential for regulation of the cell cycle. 238 00:11:31.710 --> 00:11:34.500 Xerodermic pigmentosum is a rare genetic syndrome 239 00:11:34.500 --> 00:11:36.660 which is caused by germline mutations 240 00:11:36.660 --> 00:11:39.000 that regulate DNA repair. 241 00:11:39.000 --> 00:11:42.150 The prevalence of this syndrome is one per million, 242 00:11:42.150 --> 00:11:43.950 and individuals with this condition are prone 243 00:11:43.950 --> 00:11:46.497 to the development of multiple cutaneous malignancies, 244 00:11:46.497 --> 00:11:48.870 particularly squamous cell carcinoma, 245 00:11:48.870 --> 00:11:51.513 but also melanomas and basal cell carcinomas. 246 00:11:53.520 --> 00:11:56.220 There are also other rare genetic syndromes that predispose 247 00:11:56.220 --> 00:11:58.440 to the development of SCC of the skin, 248 00:11:58.440 --> 00:12:01.860 like Ferguson Smith Syndrome, various forms of albinism, 249 00:12:01.860 --> 00:12:05.400 Rothman-Thomsom Syndrome, Fanconi Anemia, 250 00:12:05.400 --> 00:12:08.400 Zinsser-Cole Engman Syndrome, Bloom syndrome, 251 00:12:08.400 --> 00:12:10.233 and Werner syndrome. 252 00:12:12.960 --> 00:12:15.270 Immunosuppression also contributes to the development 253 00:12:15.270 --> 00:12:17.072 of non-melanoma skin cancers. 254 00:12:17.072 --> 00:12:19.590 Among solid organ transplant recipients, 255 00:12:19.590 --> 00:12:21.150 the incidence of squamous cell carcinoma 256 00:12:21.150 --> 00:12:23.446 is 65 to 250 times higher, and the incidence 257 00:12:23.446 --> 00:12:26.760 of basal cell carcinoma is 10 times higher 258 00:12:26.760 --> 00:12:28.983 than is observed in the general population. 259 00:12:30.540 --> 00:12:32.130 Skin infections by certain strains 260 00:12:32.130 --> 00:12:35.220 of human papilloma virus, or HPV, have also been linked 261 00:12:35.220 --> 00:12:38.580 to the development of nonmelanoma skin cancer. 262 00:12:38.580 --> 00:12:40.433 A review of the literature identified 17 studies 263 00:12:40.433 --> 00:12:44.730 in which HPV positivity was determined in specimens 264 00:12:44.730 --> 00:12:47.793 of squamous cell carcinoma compared to normal skin. 265 00:12:49.205 --> 00:12:52.320 Chronic inflammation induced by solar UV radiation 266 00:12:52.320 --> 00:12:54.690 and/or environmental exposures undoubtedly 267 00:12:54.690 --> 00:12:57.290 plays a critical role in the genesis of skin cancer. 268 00:12:58.260 --> 00:13:00.935 Molecular studies of basal cell and squamous cell carcinoma 269 00:13:00.935 --> 00:13:03.540 have identified a variety of inflammatory factors 270 00:13:03.540 --> 00:13:05.403 that stimulate carcinogenesis. 271 00:13:07.220 --> 00:13:11.593 Finally, the third key kind of non-melanoma skin cancer, 272 00:13:11.593 --> 00:13:15.030 or Merkel cell carcinoma, is a rare 273 00:13:15.030 --> 00:13:17.070 and highly aggressive form of skin cancer that develops 274 00:13:17.070 --> 00:13:19.620 from specialized cells of the epidermis. 275 00:13:19.620 --> 00:13:21.930 As mentioned previously, Merkel cells are located 276 00:13:21.930 --> 00:13:24.300 at terminal nerve endings in the epidermis, 277 00:13:24.300 --> 00:13:26.820 where they regulate the sensation of touch. 278 00:13:26.820 --> 00:13:29.250 This carcinoma occurs primarily in elderly adults 279 00:13:29.250 --> 00:13:30.982 who are 60 to 80 years of age, 280 00:13:30.982 --> 00:13:33.840 and malignant transformation occurs 281 00:13:33.840 --> 00:13:36.330 in viral infected Merkel cells of older adults 282 00:13:36.330 --> 00:13:38.370 with skin damage due to solar radiation 283 00:13:38.370 --> 00:13:40.413 and/or immunosuppressive conditions. 284 00:13:42.480 --> 00:13:44.850 The primary line of defense against harmful rays 285 00:13:44.850 --> 00:13:48.900 from the sun in the ozone layer is the ozone layer 286 00:13:48.900 --> 00:13:50.340 in the stratosphere. 287 00:13:50.340 --> 00:13:53.341 That's 10 to 50 kilometers above the surface of the earth, 288 00:13:53.341 --> 00:13:58.341 and these ozone molecules effectively absorb UV radiation 289 00:13:59.280 --> 00:14:02.880 for up to a 310 nanometer wavelength, 290 00:14:02.880 --> 00:14:06.840 and the ozone layer blocks all UVC and most UVB radiation 291 00:14:06.840 --> 00:14:09.870 emitted by the sun, therefore protecting life on earth 292 00:14:09.870 --> 00:14:11.793 from these dangerous rays. 293 00:14:14.790 --> 00:14:17.820 Finally, the key to effective primary preventive skin cancer 294 00:14:17.820 --> 00:14:21.063 is a protection of the skin from damaging solar radiation. 295 00:14:22.230 --> 00:14:24.960 Key strategies for this are to wear protective clothing 296 00:14:24.960 --> 00:14:27.600 and use sunscreen products with a sun protective factor 297 00:14:27.600 --> 00:14:30.959 or SPF of 30 or higher. 298 00:14:30.959 --> 00:14:35.010 It's also important to avoid UV radiation 299 00:14:35.010 --> 00:14:37.140 from tanning devices, skin irritants, 300 00:14:37.140 --> 00:14:39.693 arsenic containing compounds, and tobacco smoking. 301 00:14:41.839 --> 00:14:45.390 The call to action to prevent skin cancer was published 302 00:14:45.390 --> 00:14:47.330 by a former US Surgeon General, 303 00:14:47.330 --> 00:14:49.530 and this is a comprehensive plea 304 00:14:49.530 --> 00:14:51.840 for increased awareness policies and research, 305 00:14:51.840 --> 00:14:54.453 with a goal of supporting skin cancer prevention.