Overdiagnosis and Thyroid cancer incidence
If you read about thyroid cancer, everyone agrees that its incidence is on the rise. In recent months, there has been lots of press coverage as how this increased thyroid incidence is due to overdiagnosis. To illustrate the overdiagnosis with an example, we need to take a look at South Korea. There was a huge increase in the incidence of thyroid cancer in South Korea which was blamed on overdiagnosis. But a recent review article on this topic cautions; not so fast.
Thyroid cancers form about 2.1% of total cancer diagnoses worldwide, with women disproportionately affected, accounting for about 77% of the cases. The phenomenon of more women patients than men is unique to thyroid pathology and is also seen in Hashimoto's thyroiditis and Graves' disease. Majority of thyroid cancers are termed differentiated with two main subtypes, papillary thyroid cancers (PTC) and follicular thyroid cancers (FTC). The increased incidence of the thyroid cancer is mainly attributed to increase in PTC cases. However, FTC cases are also on the rise especially in USA. Starting from 1980s, advances in diagnostics such as imaging (ultrasound, CT, MRI scans) and biopsy (fine needle aspirations) are thought to be mainly responsible for early detection of thyroid nodules. This led to the increased incidence of small, localized and subclinical nodules. Again to understand the numbers, this meant a 15 fold increase in incidence in South Korea between 1993 and 2011. A subclinical nodule means that the nodule may not be classified yet as thyroid cancer and may or may not develop into full blown cancer. This phenomenon of subclinical disease is not limited to thyroid and thyroid cancer. For instance, a study in Norway while back came to the conclusion that majority of the breast cancer lumps spontaneously regress. This shows that there is a lot of subclinical pathology which resolves on its own, probably due to our immune system. Coming back to thyroid, Okayasu and Rose discovered a large incidence of focal thyroiditis in US, British and Japanese population. All the thyroids were from organ donors at the time of death. This demonstrates that a subclinical disease pathology might be present in majority of population at any given time. However, special circumstances/risk factors allow these subclinical or focal pathologies to fully manifest as disease (autoimmune inflammation or cancer).
The scientific community agrees that indeed there has been some over-zealousness in describing and treating thyroid cancers. This year, American Thyroid Association (ATA) came up with new guidelines regarding treatment of thyroid cancer cases. This involved grading the nodules according to the size which will then be treated accordingly. For example, very small nodules are not supposed to be touched and left alone and monitored. Also there are new guidelines regarding surgery, instead of total thyroidectomy to thyroid lobectomy. All the new guidelines are designed with doing less harm than intended. In future hopefully these guidelines will be revisited when more data starts coming from labs across the world in dealing with small nodules. A big part of this year's ATA meeting has been on management of this new clinical entity.
The article argues how increased diagnoses wouldn't account for increased incidence. For instance, if all the increased thyroid cancer was due to non-pathogenic tumor nodules, in long term this would lead to fall in thyroid cancer mortality, which is obviously not the case. Another point refuting the overdiagnosis is that if we classify the thyroid nodules according to size, only small nodules would be increasing. Again this is not the case, with increase in incidence in all types of thyroid nodules, irrespective of the size.
Now the next question would be to identify the risk factors for thyroid cancer. Many of these are the usual suspects including age, sex, race/ethnicity and family history. There is a research group at The Ohio state university which is involved in identifying familial risk associated with thyroid cancer and thereby identify new genes involved. Apart from the above, the other modifying factors are exposure to ionizing radiation. Obesity in recent years has also been termed as a risk factor for thyroid cancer. However, there are conflicting reports and therefore more research needs to be done to further understand obesity as a risk factor. Interestingly, smoking is also a known risk factor for thyroid cancer. Smoking reduces the incidence of Hashimoto's thyroiditis and also known to reduce the risk for thyroid cancer.
We hardly know all the risk factors that are contributing to increased incidence of thyroid cancers. Deviating a little bit from Humans, many species of fish are known to spontaneously develop cancers including thyroid cancers. EPA uses many local species of fishes to understand the pollution of water. This was shown in many instances, one such being pollution of Black river, Ohio which led to increased incidence of cancer in bullhead fishes. EPA then imposed additional restrictions which then led to decrease in incidence of cancers in fishes. We need to do more epidemiological studies to understand the risk factors involved in thyroid cancers. Similarly basic research scientists can make use of animal models which spontaneously develop thyroid cancers to understand the risk factors. One such model might involve using swordtail fishes or amazon mollies.
Hopefully in near future, new research on thyroid cancer would lead to better understanding of risk factors, diagnostics and better therapeutics.
Thyroid cancers form about 2.1% of total cancer diagnoses worldwide, with women disproportionately affected, accounting for about 77% of the cases. The phenomenon of more women patients than men is unique to thyroid pathology and is also seen in Hashimoto's thyroiditis and Graves' disease. Majority of thyroid cancers are termed differentiated with two main subtypes, papillary thyroid cancers (PTC) and follicular thyroid cancers (FTC). The increased incidence of the thyroid cancer is mainly attributed to increase in PTC cases. However, FTC cases are also on the rise especially in USA. Starting from 1980s, advances in diagnostics such as imaging (ultrasound, CT, MRI scans) and biopsy (fine needle aspirations) are thought to be mainly responsible for early detection of thyroid nodules. This led to the increased incidence of small, localized and subclinical nodules. Again to understand the numbers, this meant a 15 fold increase in incidence in South Korea between 1993 and 2011. A subclinical nodule means that the nodule may not be classified yet as thyroid cancer and may or may not develop into full blown cancer. This phenomenon of subclinical disease is not limited to thyroid and thyroid cancer. For instance, a study in Norway while back came to the conclusion that majority of the breast cancer lumps spontaneously regress. This shows that there is a lot of subclinical pathology which resolves on its own, probably due to our immune system. Coming back to thyroid, Okayasu and Rose discovered a large incidence of focal thyroiditis in US, British and Japanese population. All the thyroids were from organ donors at the time of death. This demonstrates that a subclinical disease pathology might be present in majority of population at any given time. However, special circumstances/risk factors allow these subclinical or focal pathologies to fully manifest as disease (autoimmune inflammation or cancer).
The scientific community agrees that indeed there has been some over-zealousness in describing and treating thyroid cancers. This year, American Thyroid Association (ATA) came up with new guidelines regarding treatment of thyroid cancer cases. This involved grading the nodules according to the size which will then be treated accordingly. For example, very small nodules are not supposed to be touched and left alone and monitored. Also there are new guidelines regarding surgery, instead of total thyroidectomy to thyroid lobectomy. All the new guidelines are designed with doing less harm than intended. In future hopefully these guidelines will be revisited when more data starts coming from labs across the world in dealing with small nodules. A big part of this year's ATA meeting has been on management of this new clinical entity.
The article argues how increased diagnoses wouldn't account for increased incidence. For instance, if all the increased thyroid cancer was due to non-pathogenic tumor nodules, in long term this would lead to fall in thyroid cancer mortality, which is obviously not the case. Another point refuting the overdiagnosis is that if we classify the thyroid nodules according to size, only small nodules would be increasing. Again this is not the case, with increase in incidence in all types of thyroid nodules, irrespective of the size.
Now the next question would be to identify the risk factors for thyroid cancer. Many of these are the usual suspects including age, sex, race/ethnicity and family history. There is a research group at The Ohio state university which is involved in identifying familial risk associated with thyroid cancer and thereby identify new genes involved. Apart from the above, the other modifying factors are exposure to ionizing radiation. Obesity in recent years has also been termed as a risk factor for thyroid cancer. However, there are conflicting reports and therefore more research needs to be done to further understand obesity as a risk factor. Interestingly, smoking is also a known risk factor for thyroid cancer. Smoking reduces the incidence of Hashimoto's thyroiditis and also known to reduce the risk for thyroid cancer.
We hardly know all the risk factors that are contributing to increased incidence of thyroid cancers. Deviating a little bit from Humans, many species of fish are known to spontaneously develop cancers including thyroid cancers. EPA uses many local species of fishes to understand the pollution of water. This was shown in many instances, one such being pollution of Black river, Ohio which led to increased incidence of cancer in bullhead fishes. EPA then imposed additional restrictions which then led to decrease in incidence of cancers in fishes. We need to do more epidemiological studies to understand the risk factors involved in thyroid cancers. Similarly basic research scientists can make use of animal models which spontaneously develop thyroid cancers to understand the risk factors. One such model might involve using swordtail fishes or amazon mollies.
Hopefully in near future, new research on thyroid cancer would lead to better understanding of risk factors, diagnostics and better therapeutics.
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