WEBVTT 1 00:00:00.540 --> 00:00:01.560 Hi all. 2 00:00:01.560 --> 00:00:02.730 In this lecture we'll be discussing 3 00:00:02.730 --> 00:00:05.460 the epidemiology of penile cancer. 4 00:00:05.460 --> 00:00:08.160 Our goals for this lecture are to describe the global burden 5 00:00:08.160 --> 00:00:09.600 of penile cancer 6 00:00:09.600 --> 00:00:12.210 and the global distribution of penile cancer. 7 00:00:12.210 --> 00:00:15.240 We also will look at the pathogenesis, risk factors, 8 00:00:15.240 --> 00:00:17.733 and prevention and control of this cancer. 9 00:00:19.470 --> 00:00:21.600 So carcinoma of the penis is an uncommon 10 00:00:21.600 --> 00:00:23.250 and potentially mutilating disease 11 00:00:23.250 --> 00:00:25.500 with a heterogeneous etiology. 12 00:00:25.500 --> 00:00:27.480 The malignancy is predominantly found in men 13 00:00:27.480 --> 00:00:29.700 who are not circumcised shortly after birth 14 00:00:29.700 --> 00:00:31.005 and is rarely found in populations 15 00:00:31.005 --> 00:00:34.080 where neonatal circumcision is routine. 16 00:00:34.080 --> 00:00:36.300 Sexually transmitted infectious agents 17 00:00:36.300 --> 00:00:38.220 like Oncogenic Human Papilloma virus 18 00:00:38.220 --> 00:00:40.983 may cause disease even in circumcised men. 19 00:00:42.510 --> 00:00:44.610 There are approximately 26,000 new cases 20 00:00:44.610 --> 00:00:48.420 of penile cancer diagnosed every year among males globally. 21 00:00:48.420 --> 00:00:49.950 Carcinomas with the penis are rare 22 00:00:49.950 --> 00:00:52.650 among men living in developed or high income countries 23 00:00:52.650 --> 00:00:55.110 but are relatively common among the male populations 24 00:00:55.110 --> 00:00:57.690 of some low and middle income countries. 25 00:00:57.690 --> 00:01:01.200 Low annual incidents rates ranging from 0.3 to 1 26 00:01:01.200 --> 00:01:03.810 per 100,000 are observed in high income countries 27 00:01:03.810 --> 00:01:06.720 like the US, Canada, Great Britain, Australia, New Zealand, 28 00:01:06.720 --> 00:01:10.200 and Western Europe and Scandinavian nations. 29 00:01:10.200 --> 00:01:12.840 Rates are very low among Israeli Jewish men, 30 00:01:12.840 --> 00:01:16.110 0.1 per 100,000 who are circumcised shortly after birth 31 00:01:16.110 --> 00:01:19.470 and among Muslim men or 0.2 per 100,000 32 00:01:19.470 --> 00:01:21.320 who are circumcised during childhood. 33 00:01:22.200 --> 00:01:24.900 In contrast, rates are much higher, 34 00:01:24.900 --> 00:01:27.900 3 to 10 per 100,000 among men living 35 00:01:27.900 --> 00:01:30.960 in certain parts of the world where circumcision is rare. 36 00:01:30.960 --> 00:01:33.090 Several high risk populations have been identified 37 00:01:33.090 --> 00:01:35.010 in regions of Uganda, India, Thailand, 38 00:01:35.010 --> 00:01:37.320 Puerto Rico, Paraguay, Brazil, and elsewhere 39 00:01:37.320 --> 00:01:40.350 in which penile cancer accounts for 10 to 22% 40 00:01:40.350 --> 00:01:42.870 of all malignancies in men. 41 00:01:42.870 --> 00:01:45.570 Penile cancer is diagnosed predominantly in elderly men 42 00:01:45.570 --> 00:01:48.570 although onset in young adult males does occur. 43 00:01:48.570 --> 00:01:50.580 The median age of diagnosis of penile cancer 44 00:01:50.580 --> 00:01:52.320 is about 68 years of age 45 00:01:52.320 --> 00:01:53.970 and the incidence increases steadily 46 00:01:53.970 --> 00:01:55.410 throughout life and rates are highest 47 00:01:55.410 --> 00:01:58.650 for elderly men aged 70 years or older. 48 00:01:58.650 --> 00:02:01.680 In 2020, there was an age standardized incidence of 0.8 49 00:02:01.680 --> 00:02:06.183 per 100,000 men and a mortality of 0.29 per 100,000 men. 50 00:02:07.560 --> 00:02:11.010 The vast majority, or over 95% of penile malignancies 51 00:02:11.010 --> 00:02:12.270 are squamous cell carcinomas 52 00:02:12.270 --> 00:02:15.330 that arise from the epithelium covering the organ. 53 00:02:15.330 --> 00:02:18.630 Other rare forms include basal cell carcinoma, melanoma, 54 00:02:18.630 --> 00:02:20.103 lymphoma, and sarcoma. 55 00:02:21.300 --> 00:02:23.160 Squamous cell carcinomas of the penis 56 00:02:23.160 --> 00:02:24.990 evolved through a stepwise process. 57 00:02:24.990 --> 00:02:26.430 Over a period of several years, 58 00:02:26.430 --> 00:02:28.620 early dysplastic lesions develop in procrast 59 00:02:28.620 --> 00:02:30.480 to carcinomas and in situ. 60 00:02:30.480 --> 00:02:33.300 Penile carcinoma in situ is called Bowen's disease, 61 00:02:33.300 --> 00:02:38.050 Bowenoid papulosis, and Erythroplasia of Queyrat. 62 00:02:39.420 --> 00:02:41.370 Cancer cells can breach the basement membrane 63 00:02:41.370 --> 00:02:42.750 leading to invasive carcinoma, 64 00:02:42.750 --> 00:02:45.600 which has the capability of disseminating to lymph nodes 65 00:02:45.600 --> 00:02:46.503 and other tissues. 66 00:02:48.690 --> 00:02:51.240 There's several key forms of penile cancer. 67 00:02:51.240 --> 00:02:56.240 The first or rather forms or precursors to penile cancer. 68 00:02:56.280 --> 00:02:58.500 The first, Lichen sclerosis is characterized 69 00:02:58.500 --> 00:03:01.050 by white atrophic plaques on the glands 70 00:03:01.050 --> 00:03:05.070 and pupus or the foreskin of the penis. 71 00:03:05.070 --> 00:03:06.840 These plaques may enlarge and coalesce 72 00:03:06.840 --> 00:03:08.940 to form sclerotic masses. 73 00:03:08.940 --> 00:03:11.130 Uncircumcised men with Lichen sclerosis 74 00:03:11.130 --> 00:03:12.570 are at markedly elevated risk 75 00:03:12.570 --> 00:03:15.360 for the development of carcinoma of the penis. 76 00:03:15.360 --> 00:03:17.820 Leukoplakia refers to the solitary or multiple 77 00:03:17.820 --> 00:03:21.960 white scaly plaques often involving the glands or mitis. 78 00:03:21.960 --> 00:03:24.450 Such lesions arise due to chronic irritation 79 00:03:24.450 --> 00:03:25.950 and inflammation and are often found 80 00:03:25.950 --> 00:03:29.430 in close proximity to squamous cell carcinomas. 81 00:03:29.430 --> 00:03:32.520 Focal areas of dysplasia which can progress to cancer 82 00:03:32.520 --> 00:03:35.913 are present in up to 20% of cases of penial leukoplakia. 83 00:03:38.130 --> 00:03:43.130 Finally, Condyloma acuminata or genital warts 84 00:03:43.140 --> 00:03:46.380 can arise on the penis as well as other intergenital sites 85 00:03:46.380 --> 00:03:48.060 of both men and women. 86 00:03:48.060 --> 00:03:49.950 These are usually benign 87 00:03:49.950 --> 00:03:51.570 but malignant transformation has been observed 88 00:03:51.570 --> 00:03:55.110 in association with oncogenic subtypes of HPV infection, 89 00:03:55.110 --> 00:03:57.693 particularly HPV 16 and 18. 90 00:03:59.220 --> 00:04:02.902 Poor genital hygiene, smegma retention, and phimosis 91 00:04:02.902 --> 00:04:05.220 or unretractable foreskin are key risk factors 92 00:04:05.220 --> 00:04:06.930 for penile cancer. 93 00:04:06.930 --> 00:04:09.150 Infection of the genitalia by oncogenic strains 94 00:04:09.150 --> 00:04:11.430 of human papilloma virus has been confirmed 95 00:04:11.430 --> 00:04:14.910 to play an etiologic role in a subset of cases. 96 00:04:14.910 --> 00:04:17.250 Penile rash, abrasion, urethral stricture, 97 00:04:17.250 --> 00:04:20.700 and inflammation have also been found to increase the risk. 98 00:04:20.700 --> 00:04:23.280 Chronic inflammation is a key component of tumor development 99 00:04:23.280 --> 00:04:26.670 and progression, and most penile cancers arise at sites 100 00:04:26.670 --> 00:04:29.760 of chronic infection, chronic irritation, or injury. 101 00:04:29.760 --> 00:04:31.050 Multiple studies have found 102 00:04:31.050 --> 00:04:33.750 that neonatal circumcision reduces the risk of carcinoma 103 00:04:33.750 --> 00:04:36.450 in the penis by 60 to 70%. 104 00:04:36.450 --> 00:04:39.060 Finally, although circumcision is controversial 105 00:04:39.060 --> 00:04:41.340 a recent report from the American Academy of Pediatrics 106 00:04:41.340 --> 00:04:43.950 concluded the health benefits of infant circumcision 107 00:04:43.950 --> 00:04:45.393 outweigh the risks. 108 00:04:48.300 --> 00:04:50.550 This figure shows the global prevalence of circumcision 109 00:04:50.550 --> 00:04:51.720 by country. 110 00:04:51.720 --> 00:04:54.510 Overall, about one third of all men have been circumcised. 111 00:04:54.510 --> 00:04:56.850 Prevalence rates of circumcision are highest among Jewish 112 00:04:56.850 --> 00:05:00.480 and Muslim men and men living in industrialized nations. 113 00:05:00.480 --> 00:05:02.460 The incidence and mortality rates of penile cancer 114 00:05:02.460 --> 00:05:03.840 tend to be lower in those countries 115 00:05:03.840 --> 00:05:06.840 with higher prevalence rates of circumcision. 116 00:05:06.840 --> 00:05:10.800 Phimosis refers to circumferential fibrosis 117 00:05:10.800 --> 00:05:14.490 of preputial tissues or the foreskin in uncircumcised men 118 00:05:14.490 --> 00:05:16.950 that leads to narrowing and inability to retract 119 00:05:16.950 --> 00:05:19.710 the penile foreskin over the gland's penis. 120 00:05:19.710 --> 00:05:21.900 This condition leads to the accumulation of smegma 121 00:05:21.900 --> 00:05:23.520 beneath the foreskin and predisposes 122 00:05:23.520 --> 00:05:26.010 to chronic inflammation and infection. 123 00:05:26.010 --> 00:05:28.740 Fibrosis is found in about 1% of uncircumcised men 124 00:05:28.740 --> 00:05:31.152 but rarely in circumcised men. 125 00:05:31.152 --> 00:05:33.060 In a study of uncircumcised school boys 126 00:05:33.060 --> 00:05:35.280 conducted in Denmark, the incidence of phimosis 127 00:05:35.280 --> 00:05:40.280 among 3,355 adolescent boys aged 14 to 17 years was 1.1%. 128 00:05:41.340 --> 00:05:43.290 Several studies have found that phimosis 129 00:05:43.290 --> 00:05:45.270 among uncircumcised men is associated with 130 00:05:45.270 --> 00:05:48.510 an approximate tenfold higher risk of penile cancer, 131 00:05:48.510 --> 00:05:51.090 whereas uncircumcised men with no history of phimosis 132 00:05:51.090 --> 00:05:53.043 are not at elevated risk. 133 00:05:55.200 --> 00:05:56.850 Cancer of the scrotum was the first 134 00:05:56.850 --> 00:06:00.510 documented malignancy arising from an occupational exposure. 135 00:06:00.510 --> 00:06:02.850 In 1775, Percival Pott described 136 00:06:02.850 --> 00:06:04.830 that the development of cancer of the scrotum 137 00:06:04.830 --> 00:06:07.020 among chimney sweeps in England. 138 00:06:07.020 --> 00:06:09.900 He called this tumor the "chimney sweeper's cancer" 139 00:06:09.900 --> 00:06:12.960 and attributed the condition to a lodgement of scoot 140 00:06:12.960 --> 00:06:14.553 in the reggae of the scrotum. 141 00:06:16.440 --> 00:06:19.830 Finally, to discuss prevention and control of cancer 142 00:06:19.830 --> 00:06:21.600 from the male genitalia. 143 00:06:21.600 --> 00:06:23.940 Prevention strategies should target the major risk factors 144 00:06:23.940 --> 00:06:26.160 for penile carcinoma, including phimosis 145 00:06:26.160 --> 00:06:28.860 in uncircumcised men, promiscuous sexual activity, 146 00:06:28.860 --> 00:06:31.530 infection with HPV 16, or other oncogenic strains 147 00:06:31.530 --> 00:06:33.270 and cigarette smoking. 148 00:06:33.270 --> 00:06:36.030 The WHO includes circumcision as a key component 149 00:06:36.030 --> 00:06:37.950 of a comprehensive program for HIV control 150 00:06:37.950 --> 00:06:39.480 in sub-Saharan Africa and other areas 151 00:06:39.480 --> 00:06:41.790 with high endemic rates of HIV. 152 00:06:41.790 --> 00:06:43.590 And other options include vaccination 153 00:06:43.590 --> 00:06:46.230 against oncogenic HPV strains, condom use 154 00:06:46.230 --> 00:06:47.550 to prevent virus transmission, 155 00:06:47.550 --> 00:06:50.340 and health education to prevent smoking, 156 00:06:50.340 --> 00:06:53.583 promote smoking cessation, and to improve genital hygiene.