WEBVTT 1 00:00:00.330 --> 00:00:01.200 Hi everyone. 2 00:00:01.200 --> 00:00:03.330 In this lecture, we'll be discussing epidemiology 3 00:00:03.330 --> 00:00:05.850 of cancers of the oral cavity. 4 00:00:05.850 --> 00:00:07.230 Our goals for this lecture 5 00:00:07.230 --> 00:00:10.500 are to review the anatomy and function of the oral cavity, 6 00:00:10.500 --> 00:00:12.150 to summarize the global pattern 7 00:00:12.150 --> 00:00:15.420 of deaths from oral cavity cancer, 8 00:00:15.420 --> 00:00:17.340 as well as the incidence. 9 00:00:17.340 --> 00:00:19.320 We'll describe high-risk populations 10 00:00:19.320 --> 00:00:21.660 and review key studies of tobacco, alcohol, 11 00:00:21.660 --> 00:00:23.610 and oral cavity cancer. 12 00:00:23.610 --> 00:00:26.520 We'll also describe tobacco and alcohol carcinogenesis 13 00:00:26.520 --> 00:00:29.880 and review studies of HPV and oral cavity cancer. 14 00:00:29.880 --> 00:00:31.290 Finally, we're going to describe 15 00:00:31.290 --> 00:00:33.753 other risk factors for oral cavity cancer. 16 00:00:34.890 --> 00:00:37.170 So first, to give a brief overview 17 00:00:37.170 --> 00:00:39.270 of the anatomy of the oral cavity, 18 00:00:39.270 --> 00:00:40.440 it's also known as the mouth. 19 00:00:40.440 --> 00:00:43.350 It's the initial portion of the alimentary canal. 20 00:00:43.350 --> 00:00:45.450 The digestive process begins when food enters 21 00:00:45.450 --> 00:00:48.030 the oral cavity and is mechanically masticated 22 00:00:48.030 --> 00:00:51.360 or mechanically digested by chewing. 23 00:00:51.360 --> 00:00:53.670 It is moistened by saliva and undergoes reactions 24 00:00:53.670 --> 00:00:57.390 with salivary enzymes to initiate chemical digestion. 25 00:00:57.390 --> 00:01:00.120 Anatomic structures of the oral cavity include the lips, 26 00:01:00.120 --> 00:01:02.340 teeth, hard and soft palate, 27 00:01:02.340 --> 00:01:06.060 upper and lower gingiva or gums, 28 00:01:06.060 --> 00:01:09.300 the tongue, the uvula, tonsils, and pharynx. 29 00:01:09.300 --> 00:01:12.060 The pharynx is a channel situated behind the oral cavity 30 00:01:12.060 --> 00:01:13.320 and beneath the nasal cavity 31 00:01:13.320 --> 00:01:16.320 that extends to the level of the larynx. 32 00:01:16.320 --> 00:01:18.330 The oropharynx is continuous, 33 00:01:18.330 --> 00:01:19.770 with the back of the oral cavity 34 00:01:19.770 --> 00:01:23.220 extending from the soft palette to the epiglottis. 35 00:01:23.220 --> 00:01:26.070 A closely related structure is the nasopharynx, 36 00:01:26.070 --> 00:01:28.110 which is a channel that connects the nasal cavity 37 00:01:28.110 --> 00:01:29.400 and paranasal sinuses 38 00:01:29.400 --> 00:01:32.100 to the upper portion of the oropharynx. 39 00:01:32.100 --> 00:01:34.350 The laryngopharynx is the portion of the pharynx 40 00:01:34.350 --> 00:01:37.590 between the oropharynx and larynx. 41 00:01:37.590 --> 00:01:40.290 Finally, the oral cavity and pharynx are lined 42 00:01:40.290 --> 00:01:42.780 by stratified squamous epithelium, 43 00:01:42.780 --> 00:01:44.820 which is important when we discuss 44 00:01:44.820 --> 00:01:46.080 the various types of cancers 45 00:01:46.080 --> 00:01:48.723 that can occur in the oral cavity. 46 00:01:49.890 --> 00:01:52.350 So we see that there's a number of benign 47 00:01:52.350 --> 00:01:57.300 or non-cancerous tumors of the oral cavity and oropharynx. 48 00:01:57.300 --> 00:02:01.560 Most tumors of the oral cavity are benign, 49 00:02:01.560 --> 00:02:03.870 but some are pre-malignant. 50 00:02:03.870 --> 00:02:05.700 For example, leukoplakia 51 00:02:05.700 --> 00:02:08.400 and erythroplakia are pre-malignant lesions 52 00:02:08.400 --> 00:02:09.900 and should be removed. 53 00:02:09.900 --> 00:02:12.600 Without treatment, these two kinds of tumors 54 00:02:12.600 --> 00:02:15.090 may transform into invasive squamous cell 55 00:02:15.090 --> 00:02:17.340 carcinoma of the oral mucosa, 56 00:02:17.340 --> 00:02:19.110 though this transformation is estimated 57 00:02:19.110 --> 00:02:20.763 to take 5 to 10 years. 58 00:02:21.780 --> 00:02:24.390 When we think about the histology of oral cavity cancer, 59 00:02:24.390 --> 00:02:27.210 more than 90% of malignant tumors of the oral cavity 60 00:02:27.210 --> 00:02:30.000 and related structures are squamous cell carcinomas, 61 00:02:30.000 --> 00:02:33.540 which arise from the mucosal lining of the oral cavity. 62 00:02:33.540 --> 00:02:35.470 5% are a dental carcinomas 63 00:02:36.480 --> 00:02:39.390 arising from the salivary glands within the mouth. 64 00:02:39.390 --> 00:02:41.730 Late-stage diagnosis is common, 65 00:02:41.730 --> 00:02:43.170 and survival rate for oral cancer 66 00:02:43.170 --> 00:02:46.470 has not changed over the past three decades. 67 00:02:46.470 --> 00:02:49.620 When we turn to look at the incidence rates 68 00:02:49.620 --> 00:02:52.020 for cancer of the lip and oral cavity, 69 00:02:52.020 --> 00:02:54.120 we see the malignancies of the oral cavity and lip 70 00:02:54.120 --> 00:02:58.260 caused 145,328 deaths in 2012. 71 00:02:59.220 --> 00:03:01.350 And there were significantly more deaths 72 00:03:01.350 --> 00:03:04.050 in men than in women. 73 00:03:04.050 --> 00:03:06.469 In the same year, in 2012, 74 00:03:06.469 --> 00:03:09.150 300,373 new cases of oral cavity 75 00:03:09.150 --> 00:03:10.840 and lip cancer were diagnosed 76 00:03:11.700 --> 00:03:14.790 with approximately 200,000 being diagnosed in men 77 00:03:14.790 --> 00:03:18.060 and approximately 100,000 being diagnosed in women. 78 00:03:18.060 --> 00:03:22.500 This represents an overall increase of 14.1% 79 00:03:22.500 --> 00:03:24.423 from 2008 to 2012. 80 00:03:25.590 --> 00:03:27.660 Cancers of the lip and oral cavity 81 00:03:27.660 --> 00:03:31.680 constitute approximately 2.1% of all malignant neoplasms 82 00:03:31.680 --> 00:03:34.290 and account for about 1.8% of cancer deaths 83 00:03:34.290 --> 00:03:36.330 in the human population. 84 00:03:36.330 --> 00:03:38.310 Rates of oral cavity cancer are highest 85 00:03:38.310 --> 00:03:41.640 in populations with high rates of tobacco and alcohol use. 86 00:03:41.640 --> 00:03:43.350 So rates are very high in populations 87 00:03:43.350 --> 00:03:45.650 where individuals commonly chew, (indistinct), 88 00:03:46.530 --> 00:03:49.140 or practice reverse smoking. 89 00:03:49.140 --> 00:03:51.330 And rates of lip cancer are high 90 00:03:51.330 --> 00:03:52.680 in Australia and New Zealand 91 00:03:52.680 --> 00:03:55.983 due to the high levels of solar radiation there. 92 00:03:57.630 --> 00:03:59.970 When we turn to look at mortality, 93 00:03:59.970 --> 00:04:04.970 we see mortality rates 94 00:04:05.010 --> 00:04:07.800 that track closely with incidence rates. 95 00:04:07.800 --> 00:04:12.800 So a high mortality rates in areas exposed 96 00:04:14.070 --> 00:04:17.913 or in communities exposed to risk factors for oral cancer. 97 00:04:18.990 --> 00:04:22.530 When we look at 2020 data in the United States, 98 00:04:22.530 --> 00:04:24.060 we see that the overall incidence 99 00:04:24.060 --> 00:04:26.730 was 4.1 per 100,000 people, 100 00:04:26.730 --> 00:04:31.730 with a rate in men almost three times that of women. 101 00:04:32.160 --> 00:04:33.570 When we look at mortality, 102 00:04:33.570 --> 00:04:38.310 overall, there was 1.9 deaths per 100,000 people, 103 00:04:38.310 --> 00:04:41.490 and 2.8 deaths per 100,000 men, 104 00:04:41.490 --> 00:04:44.253 while only 1 death per 100,000 women. 105 00:04:45.240 --> 00:04:46.947 In the US, cancers of the oral cavity 106 00:04:46.947 --> 00:04:49.500 and oropharynx represent approximately 3% 107 00:04:49.500 --> 00:04:51.150 of all malignancies in men 108 00:04:51.150 --> 00:04:53.193 and 2% of all malignancies in women. 109 00:04:56.010 --> 00:04:59.190 When we look at some of the risk factors 110 00:04:59.190 --> 00:05:02.460 for oral cavity cancer, we see that tobacco use 111 00:05:02.460 --> 00:05:04.680 is responsible for more than 90% of tumors 112 00:05:04.680 --> 00:05:09.150 of the oral cavity among men and 60% among women. 113 00:05:09.150 --> 00:05:11.220 Tobacco use is responsible for 90% 114 00:05:11.220 --> 00:05:13.590 of oral cancer deaths in males. 115 00:05:13.590 --> 00:05:16.650 All forms of tobacco, cigarettes, pipes, cigars, 116 00:05:16.650 --> 00:05:18.030 and snuff have been implicated 117 00:05:18.030 --> 00:05:20.160 in the development of oral cancers, 118 00:05:20.160 --> 00:05:23.340 and while tobacco confers the highest rate of cancer 119 00:05:23.340 --> 00:05:25.560 of the floor of the mouth, it's associated 120 00:05:25.560 --> 00:05:28.593 with an increased risk for all sites of oral cancer. 121 00:05:29.670 --> 00:05:31.050 We also see that alcohol use 122 00:05:31.050 --> 00:05:32.820 is an independent major risk factor 123 00:05:32.820 --> 00:05:34.770 for the development of oral cancer, 124 00:05:34.770 --> 00:05:37.980 and there's a suggestion that beer and hard liquor 125 00:05:37.980 --> 00:05:39.993 confer a greater risk than wine. 126 00:05:40.980 --> 00:05:44.850 We also see that the risk of oral cancer increases 127 00:05:44.850 --> 00:05:46.890 with the number of cigarettes smoked per day, 128 00:05:46.890 --> 00:05:49.530 as well as the number of alcoholic drinks consumed per day 129 00:05:49.530 --> 00:05:51.600 in a dose-dependent fashion. 130 00:05:51.600 --> 00:05:53.340 The combined use of alcohol and tobacco 131 00:05:53.340 --> 00:05:55.320 increases the risk for oral cancer 132 00:05:55.320 --> 00:05:58.710 far greater than either independently, 133 00:05:58.710 --> 00:06:00.603 as we can tell from this figure. 134 00:06:01.620 --> 00:06:03.300 We also see that tobacco and alcohol use 135 00:06:03.300 --> 00:06:05.752 have been associated with the development of leukoplakia 136 00:06:05.752 --> 00:06:08.823 or erythroplakia which can progress to cancer. 137 00:06:10.380 --> 00:06:13.290 When we look at the etiology and biology of oral cancer, 138 00:06:13.290 --> 00:06:16.860 we see that there's a number of risk factors. 139 00:06:16.860 --> 00:06:18.090 There appears to be an association 140 00:06:18.090 --> 00:06:22.023 between human papillomavirus or HPV and oral cancer, 141 00:06:23.670 --> 00:06:26.580 and in particular, HPV type 16. 142 00:06:26.580 --> 00:06:30.180 Multiple case control studies have shown this association. 143 00:06:30.180 --> 00:06:32.850 Independently, the Association of HPV infection 144 00:06:32.850 --> 00:06:37.020 with oral cancer is much lower than tobacco or alcohol, 145 00:06:37.020 --> 00:06:39.933 although it can modify the effect of these two substances. 146 00:06:40.980 --> 00:06:43.260 We also see that there's relationships 147 00:06:43.260 --> 00:06:46.680 between other viral infections and oral cancer in humans, 148 00:06:46.680 --> 00:06:50.730 and those would be human immunodeficiency virus, or HIV, 149 00:06:50.730 --> 00:06:54.180 and Epstein-Barr Virus, or EBV. 150 00:06:54.180 --> 00:06:57.180 Oral cancer is also known to exhibit field cancerization, 151 00:06:57.180 --> 00:06:59.733 resulting in development of second primary tumors. 152 00:07:01.067 --> 00:07:02.490 Studies utilizing a variety 153 00:07:02.490 --> 00:07:04.050 of chemo preventive interventions 154 00:07:04.050 --> 00:07:05.730 have demonstrated promising results 155 00:07:05.730 --> 00:07:09.210 for induction of apoptosis in oral malignant 156 00:07:09.210 --> 00:07:10.533 and pre-malignant cells. 157 00:07:12.450 --> 00:07:14.520 In HPV-16 related disease, 158 00:07:14.520 --> 00:07:17.763 chronic exposure to tobacco and alcohol may be absent. 159 00:07:18.600 --> 00:07:22.470 The age of diagnosis is much earlier, 20 to 50 years. 160 00:07:22.470 --> 00:07:25.290 The male to female ratio is closest to one to one 161 00:07:25.290 --> 00:07:28.740 and tumors develop on the tonsils and base of the tongue. 162 00:07:28.740 --> 00:07:32.010 HPV-16 and 18 are the same viruses responsible 163 00:07:32.010 --> 00:07:34.710 for the vast majority of cervical cancers, 164 00:07:34.710 --> 00:07:37.800 and HPV is the most common sexually transmitted infection 165 00:07:37.800 --> 00:07:39.900 in the US and elsewhere. 166 00:07:39.900 --> 00:07:41.280 Though, as we've discussed before, 167 00:07:41.280 --> 00:07:43.680 infection by these high-risk HPV strains 168 00:07:43.680 --> 00:07:45.693 is preventable by vaccination. 169 00:07:46.530 --> 00:07:48.720 The Plummer-Vinson Syndrome, 170 00:07:48.720 --> 00:07:52.170 which is characterized by iron deficiency, dysphagia, 171 00:07:52.170 --> 00:07:54.780 and atrophy of the oral cavity mucosa 172 00:07:54.780 --> 00:07:58.530 is associated with predisposition to oral cavity cancer. 173 00:07:58.530 --> 00:08:00.480 Other conditions, which associated 174 00:08:00.480 --> 00:08:03.741 with oral cavity neoplasms include sprue, 175 00:08:03.741 --> 00:08:06.210 which is the malabsorption of wheat germ, 176 00:08:06.210 --> 00:08:08.793 and scurvy, or deficiency in vitamin C. 177 00:08:09.750 --> 00:08:11.610 Pipe smoking and cigar smoking, 178 00:08:11.610 --> 00:08:13.710 sunburn, and other excessive exposures 179 00:08:13.710 --> 00:08:15.960 to UV radiation are noted risk factors 180 00:08:15.960 --> 00:08:18.813 for development of squamous cell carcinomas of the lip. 181 00:08:19.830 --> 00:08:21.557 We also see that rare malignant neoplasms 182 00:08:21.557 --> 00:08:24.720 of the oral cavity include cancers of the salivary glands, 183 00:08:24.720 --> 00:08:28.710 including the parotid glands and submandibular glands. 184 00:08:28.710 --> 00:08:30.840 These are typically glandular carcinomas 185 00:08:30.840 --> 00:08:32.763 with mixed histologic features. 186 00:08:33.900 --> 00:08:36.270 The risk of salivary gland cancer is increased 187 00:08:36.270 --> 00:08:40.350 by ionizing radiation like that which occurs 188 00:08:40.350 --> 00:08:43.203 in atomic bomb survivors and after radiotherapy. 189 00:08:44.190 --> 00:08:46.350 We also see that malignant melanomas 190 00:08:46.350 --> 00:08:48.750 can present initially in the oral cavity. 191 00:08:48.750 --> 00:08:50.700 Certain genetic syndromes predisposed 192 00:08:50.700 --> 00:08:53.190 to oral cavity malignant melanomas 193 00:08:53.190 --> 00:08:56.430 including Peutz-Jeghers syndrome and Addison's disease, 194 00:08:56.430 --> 00:08:58.650 both of which lead to melanotic pigmentation 195 00:08:58.650 --> 00:09:00.183 of the oral cavity mucosa. 196 00:09:01.500 --> 00:09:04.170 Finally, to briefly discuss the etiology 197 00:09:04.170 --> 00:09:06.360 and biology of oral cancer, 198 00:09:06.360 --> 00:09:08.220 we see that the cessation of cigarette smoking 199 00:09:08.220 --> 00:09:10.170 is associated with a 50% reduction 200 00:09:10.170 --> 00:09:11.760 of risk of developing oral cancer 201 00:09:11.760 --> 00:09:14.880 within three to five years, and a return to normal level 202 00:09:14.880 --> 00:09:18.424 of risk for development of oral cancer within 10 years. 203 00:09:18.424 --> 00:09:20.130 Because of this, dentists 204 00:09:20.130 --> 00:09:22.320 and other health professionals can play an integral role 205 00:09:22.320 --> 00:09:25.260 in smoking cessation advice and encouragement. 206 00:09:25.260 --> 00:09:26.610 Dentists can also participate 207 00:09:26.610 --> 00:09:29.550 in the full scope of pharmacological 208 00:09:29.550 --> 00:09:32.100 and behavioral interventions for smoking cessation. 209 00:09:33.090 --> 00:09:35.490 However, only 25% of tobacco users 210 00:09:35.490 --> 00:09:37.620 report receiving advice to quit tobacco use 211 00:09:37.620 --> 00:09:40.290 from their dentist, a proportion that is less 212 00:09:40.290 --> 00:09:43.050 than that is received from their physician. 213 00:09:43.050 --> 00:09:45.150 Because alcohol is associated with oral cancer 214 00:09:45.150 --> 00:09:46.740 in a dose-dependent fashion, 215 00:09:46.740 --> 00:09:48.420 cessation or avoidance of alcohol 216 00:09:48.420 --> 00:09:51.570 would result in lower incidence of oral cancer. 217 00:09:51.570 --> 00:09:54.840 The evidence is inadequate, however, of reduced oral cancer 218 00:09:54.840 --> 00:09:57.240 among people who have stopped consuming alcohol. 219 00:09:58.380 --> 00:10:00.900 Several studies also have shown an inverse association 220 00:10:00.900 --> 00:10:03.120 of fruit intake and the development of oral cancer, 221 00:10:03.120 --> 00:10:05.730 particularly in those who use tobacco. 222 00:10:05.730 --> 00:10:07.890 Fiber in the form of vegetable intake 223 00:10:07.890 --> 00:10:09.780 has similarly been shown to be associated 224 00:10:09.780 --> 00:10:13.050 with a decreased risk of oral cancer. 225 00:10:13.050 --> 00:10:14.670 It's estimated that intake of fruits 226 00:10:14.670 --> 00:10:16.350 and vegetables may lower the development 227 00:10:16.350 --> 00:10:19.590 of oral cancer by 30% to 50%. 228 00:10:19.590 --> 00:10:22.560 The evidence is inadequate, however, of reduced oral cancer 229 00:10:22.560 --> 00:10:25.083 among people who have made changes in their diet. 230 00:10:26.430 --> 00:10:30.930 Considering all of these various preventive measures 231 00:10:30.930 --> 00:10:35.930 and risk factors, it's clear that both doctors 232 00:10:36.090 --> 00:10:40.530 and dentists and nutritionists can all play important roles 233 00:10:40.530 --> 00:10:44.013 in oral and lip cancer prevention campaigns.