{"id":32,"date":"2023-05-23T17:44:04","date_gmt":"2023-05-23T21:44:04","guid":{"rendered":"https:\/\/pressbooks.bccampus.ca\/pathophysiology\/?post_type=chapter&p=32"},"modified":"2024-09-30T20:26:02","modified_gmt":"2024-10-01T00:26:02","slug":"section-2-cellular-responses-to-stress-injury-and-aging","status":"web-only","type":"chapter","link":"https:\/\/pressbooks.bccampus.ca\/pathophysiology\/chapter\/section-2-cellular-responses-to-stress-injury-and-aging\/","title":{"raw":"Cellular Responses to Stress, Injury, and Aging","rendered":"Cellular Responses to Stress, Injury, and Aging"},"content":{"raw":"

Testing, Testing, Testing: Diagnostic Tests<\/h1>\r\n

The Range and Importance of Diagnostic Tests - Which one to use? And is it sensitive enough? Is it specific enough?<\/strong><\/h2>\r\nThere are so many health care tests<\/strong> that provide clues as to the diagnosis.\r\n\r\nThere are chemistry tests<\/strong> to assess: components of blood (e.g. lipids, pH and oxygen levels) and components of urine (e.g. urinalysis).\u00a0 There are volume tests<\/strong> for measuring: blood pressure and functional lung volumes.\u00a0 There are palpation tests<\/strong> to assess: heart and pulse rates for example.\u00a0 \u00a0There are microscopy tests<\/strong> to analyze:\u00a0 cellular features within biopsies as well as the presence of possible pathogens (e.g. throat or vaginal swabs, fecal analysis, sputum tests).\u00a0 There are listening tests<\/strong> (e.g. auscultation of breath, heart and bowel sounds, etc.).\u00a0 There are flow cytometry tests<\/strong> that can be used to count the numbers of WBCs and RBCs per mL in blood,.\u00a0 These tests and more are used in health care research.\r\n\r\nLet's look at an example in which different tests (in this case weight, BMI, and genetic) may signal there is a risk of, or even the presence of a disease.\r\n\r\nExample:\u00a0 Research has found that there are several risk factors for developing Type 2 Diabetes:\u00a0 high birth weight, high BMI (body mass index) at age 10, high BMI as an adult, being biological male (XY) and at times, there may be some genetic components.\r\n\r\n[caption id=\"attachment_381\" align=\"alignnone\" width=\"1024\"]\"\" Figure: Body Mass Index and Birth Weight Improve Polygenic Risk Score (PRS) for Type 2 Diabetes. PRS is the combining of several clinical metrics, which was found to increase the power of disease prediction in particular from early life. Risk factors for the development of Type 2 Diabetes includes: birth weight, BMI at age 10, BMI as adult, genetic variants, and biological sex. Currently, T2D has a higher prevalence in biological males.[\/caption]\r\n\r\n \r\n\r\nIn the previous pages, we discussed the importance of determining whether a person's test results fall into the range of normal<\/strong> (and presumably healthy), or perhaps indicate disease<\/strong> and disruption in homeostasis.\u00a0 <\/strong>Also we should clarify - even though the terms normal and abnormal are used at times in test results, it is likely obvious to you that normal (test results) is not always the same as healthy, and abnormal (test results) does not always mean the presence of a disease or disorder.<\/em>\r\n\r\n[caption id=\"attachment_374\" align=\"alignnone\" width=\"578\"]\"\" Figure:\u00a0 Distribution plot of heart rate of 57 college men. The mean pulse rate was found to be 70.4211 beats per minute (bpm) with a standard deviation of 9.9480 bpm.[\/caption]\r\n\r\nIn the above figure, a typical bell curve<\/strong> indicates the range of test results that can be expected in a set population.\u00a0 In this case, resting heart rate data<\/strong> has been graphed for 57 college males.\u00a0 Even though the low and high ends of the graph have been coloured red, all of the resting heart rates in this particular population ( which are from ~60-80bpm) are in the expected normal range.\u00a0 Typically, if a resting heart rate is below 60bpm or above 100bpm, it would be considered abnormal, and indicative of a disruption in homeostasis.\u00a0 If a disease is suspected, and results fall outside of what is considered normal, usually follow-up and complementary tests are performed in order to gain enough information to make an accurate diagnosis.\r\n
<\/div>\r\nIt should be noted that test results that are high or low, don't necessarily indicate disease.\u00a0 If there isn't<\/span> a disease despite abnormal test results we would use the term False Positive<\/strong>.\u00a0 Additionally individuals with<\/span> disease can have test results that are normal.\u00a0 In this situation we would use the term\u00a0False Negative<\/strong>.\r\n\r\nLet's examine this further including the terms: True Positives<\/strong>, True Negatives<\/strong>.,\r\n\r\nQuick Reminder:\u00a0 In the last section we defined <\/span>different terms such as: atrophy,<\/span>\u00a0hypertrophy, dysplasia, anaplasia, neoplasia.<\/span> We noted that dysplasia is considered<\/span> pre-cancerous, and dysplastic<\/span>\u00a0cells<\/span>\u00a0are no longer completely differentiated.<\/span>\u00a0They are slightly<\/span>\u00a0undifferentiated and they might<\/span>\u00a0be having<\/span>\u00a0a little bit more mitosis than normal.<\/span>\u00a0If that continues, might well develop<\/span>\u00a0a neoplasia or an actual growth or tumour<\/span>.<\/span> \u00a0If the tumour stays within the basement membrane,<\/span>\u00a0we know it's a benign neoplasia<\/span>\u00a0and if it starts spreading,<\/span>\u00a0it breaches the basement membrane,<\/span>\u00a0we know that it's become malignant (or cancerous).<\/span>\r\n\r\nIn this table, let's examine the possible results of a <\/span>Pap smear in which<\/span> cervical cells are scraped and are examined<\/span>\u00a0to<\/span>\u00a0see whether the cells have reverted to an undifferentiated state.<\/span> \u00a0Luckily, cervical cancer is<\/span>\u00a0a very slow cancer,<\/span>\u00a0so routine screening once every 2-3yrs (as per recommended by a physician, depending on patient's risk level) means you're more<\/span>\u00a0likely to catch it in a dysplastic<\/span>\u00a0state well before <\/span>a malignant state.<\/span>\u00a0 This is important in ensuring that it can be treated with a good degree of success.\r\n\r\n\r\n\r\n\r\n\r\n\r\n\r\n
<\/td>\r\n\r\n

Normal Test Results<\/strong><\/span><\/h3>\r\n<\/td>\r\n

\r\n

Abnormal Test Results<\/strong><\/span><\/h3>\r\n<\/td>\r\n<\/tr>\r\n

\r\n

Healthy - this person does not<\/span> have disease\u00a0 \u00a0(e.g. cervical cancer)<\/strong><\/span><\/h3>\r\n<\/td>\r\n

\r\n
True Negative - a healthy person's test results are normal<\/span><\/strong><\/span><\/h5>\r\n<\/td>\r\n
\r\n
False Positive - a healthy person's test results are abnormal<\/span><\/strong><\/span><\/h5>\r\n<\/td>\r\n<\/tr>\r\n
Example<\/strong> - Pap Test to detect signs of cervical cell dysplasia or anaplasia. Healthy person does not have cervical pre-cancer or cancer.<\/span><\/em><\/td>\r\nCervical cells examined under microscope have normal cell morphology = True Negative<\/strong><\/span><\/td>\r\nCervical cells examined under microscope have abnormal cell morphology - which may indicate pre-cancer or cancer.\u00a0 Perhaps cells are affected by minor infection or other temporary non-cancerous issues\u00a0 = False Positive<\/strong><\/span><\/td>\r\n<\/tr>\r\n
\r\n

Sick - this person does have the disease\u00a0 \u00a0 \u00a0 \u00a0 (e.g. cervical cancer)<\/strong><\/span><\/h3>\r\n<\/td>\r\n

\r\n
False Negative - a sick person's test results are normal<\/span><\/strong><\/span><\/h5>\r\n<\/td>\r\n
\r\n
True Positive - a sick person's test results are abnormal<\/span><\/strong><\/span><\/h5>\r\n<\/td>\r\n<\/tr>\r\n
Example<\/strong> - Pap Test to detect signs of cervical cell dysplasia or anaplasia. This person does have cervical pre-cancer or cancer.<\/span><\/em><\/td>\r\nCervical cells examined under microscope have normal cell morphology.\u00a0 Missed scrapping cells that are affected by pre-cancer or cancer = False Negative<\/strong><\/span><\/td>\r\nCervical cells examined under microscope have abnormal cell morphology - which in this case accurately reflect pre-cancer or cancer\u00a0 = True Positive<\/strong><\/span><\/td>\r\n<\/tr>\r\n<\/tbody>\r\n<\/table>\r\n \r\n\r\nNow as we can see in the above test, it is virtually impossible to design a diagnostic test that is 100% accurate all of the time.\u00a0 Most often complementary and follow-up tests are done in order to become more confident in diagnoses.\r\n\r\nSo, the goal of tests is to be either specific<\/strong> or sensitive<\/strong> (or both).\u00a0 What does that mean?\r\n\r\nSensitivity <\/strong>- Can a test accurately detect True Positives? <\/strong>- which is important!\u00a0<\/span> Sensitivity,<\/strong> is a test's ability to be <\/span>positive<\/strong> in the <\/span>presence<\/strong> of the disease.\u00a0 If a test can correctly identify 99 out of 100 sick people that do<\/span><\/span> have the disease, the test is 99% sensitive, which is an extremely impressive ability for a test.<\/span>\r\n\r\nSpecificity - Can a test accurately detect True Negatives? <\/strong>- which is important!\u00a0 Specificity,<\/strong> is a test's ability to be negative<\/strong> in the absence<\/strong> of the disease.\u00a0 If a test can correctly identify 99 out of 100 healthy people that do not<\/span> have the disease, the test is 99% specific, which is an extremely impressive ability for a test.\r\n\r\n \r\n\r\n[caption id=\"attachment_407\" align=\"alignnone\" width=\"1024\"]\"\" Figure: Management algorithm in primary HPV screening. Abnormal cytology refers to a borderline or more severe cytological result. This figure was adapted from Chrysostomou et al. (2018) [15]. This algorithm was developed based on \u201cThe supplements of the second edition of the European Guidelines for Quality Assurance in Cervical Cancer Screening of 2015\u201d[\/caption] \r\n\r\nIn the above figure, a new added step to the protocol for cervical testing is being developed and implemented in some countries.\u00a0 \u00a0The newly added step is the first one, in which a Primary HPV<\/strong> (Human Papilloma Virus) test, a highly sensitive<\/strong> test is used that screens for the DNA presence of the HPV strains that are considered high risk for cancer development.\u00a0 The cytology test<\/strong> involves the Pap smear<\/strong> with microscopic analysis of cervical cellular morphology.\u00a0 Traditionally, the cytology (Pap smear) test is used as the initial test, and is also considered highly sensitive<\/strong> with an even greater degree of specificity<\/strong> than the HPV test.\u00a0 The third test in the above figure, the colposcopy<\/strong> test is considered a highly specific<\/strong> test.\r\n\r\nWhat is a colpscopy?\u00a0 Colpscopy is a specificity test performed when abnormal cells are detected in a Pap smear.\u00a0 It involves using a colpscope, a thin flexible tube with lighted, magnifying camera that can examine the cervix, vagina, and vulva for lesions and signs of cancer.\r\n\r\n[caption id=\"attachment_426\" align=\"alignnone\" width=\"1024\"]\"\" Figure:\u00a0 Pocket Colposcope (2018)[\/caption]\r\n\r\n
<\/div>\r\n\r\n[caption id=\"attachment_427\" align=\"alignnone\" width=\"1024\"]\"\" Figure: Anatomical view of cervix (a), cross-sectional view of cervix (b).[\/caption]\r\n\r\n[caption id=\"attachment_432\" align=\"alignnone\" width=\"1024\"]\"\" Figure: Colposcopy[\/caption]\r\n\r\nThe above figures show the strategy most often used in diagnostic testing, in which the first test used is a highly Sensitive<\/strong> test, which is very good at identifying illness, and makes sure that you can alert as many people as possible that may have the illness.\u00a0 \u00a0The Specificity<\/strong> test typically follows the Sensitivity test, and is used to identify false positives (e.g. make sure those that are healthy are correctly identified, and then alerted that they don't have the disease,\u00a0 and are not treated for a disease that they don't have).\u00a0 a more specific test next.\r\n\r\n \r\n

Ethics of Diagnostic Tests - Design of and Use of?<\/h1>\r\nIf we pause to think about the design and use of diagnostic tests, we can start to imagine that there are a lot of ethical questions that are encountered.\r\n\r\na) For example how do you decide which tests to try to develop? <\/span>\r\n\r\nb) How much funding should be given to each test development research?\u00a0 <\/span>\r\n\r\nc) Once developed, how much should each test cost (to the patient and to the taxpayer)?\u00a0 <\/span>\r\n\r\nd) When and how often should each test be recommended?<\/span>\r\n\r\n[h5p id=\"50\"]\r\n\r\nPause and Reflect:\u00a0 Most often tests are developed and used with the following priorities involved:<\/span>\r\n
    \r\n \t
  1. a significant percentage of<\/span>\u00a0<\/span>the population is at risk<\/span><\/li>\r\n \t
  2. the development of a test is feasible,<\/li>\r\n \t
  3. the test will be reliable (valid, repeatable),<\/li>\r\n \t
  4. the test will be sensitive and\/or specific,<\/li>\r\n \t
  5. the test produced will be inexpensive\/affordable,<\/li>\r\n \t
  6. the test will be easy to store\/deliver,<\/li>\r\n \t
  7. the test will be user-friendly and not prone to human-error,<\/li>\r\n \t
  8. ideally, the test is non-invasive (which also helps to make it less expensive and less time consuming).<\/li>\r\n<\/ol>\r\nPause and Reflect:\u00a0 What is an example of a Non-invasive test?\r\n\r\nNon-invasive tests include: blood test, urinalysis, sputum and stool sample analysis, x-rays (e.g. mammograms), physical exams.\r\n\r\nLet's brainstorm - what type of tests are you familiar with?<\/span>\r\n
      \r\n \t
    1. Blood tests have many uses including:<\/span>\r\n
        \r\n \t
      • checking red blood cell (RBC) and white blood cell (WBC) numbers - RBC and WBC counts would give an indication of the status of <\/span>red blood cell (erythrocyte) and <\/span>white blood cell production and survival rates.<\/span>\u00a0<\/span><\/li>\r\n \t
      • monitoring plasma protein levels cand be a good way to check liver function, as the liver manufactures a lot<\/span>\u00a0<\/span>of the blood proteins.<\/span><\/li>\r\n \t
      • the presence of abnormal proteins\u00a0 can be used to detect some types of cancer and organ damage or dysfunction.<\/span><\/li>\r\n \t
      • the presence of certain antibodies or pathogens can indicate disease.<\/span><\/li>\r\n<\/ul>\r\n<\/li>\r\n \t
      • Heart and lung function tests and in those units, we will discuss:<\/span>\r\n
          \r\n \t
        • Spirometry measurements of lung volumes\u00a0<\/span><\/li>\r\n<\/ul>\r\n<\/li>\r\n \t
        • Imaging test can be helpful in viewing internal problems:<\/span>\r\n
            \r\n \t
          • X-rays are used to evaluate radio-dense materials in the body (e.g. bones and detection of bone fractures)<\/span><\/li>\r\n \t
          • CT (Computed Tomography, or CAT) scans a 3-dimensional (3D) x-ray provides more resolution than the traditional 2D X-ray<\/span><\/li>\r\n \t
          • MRI (Magnetic Resonance Imaging) scans are used to examine soft-tissues of the body<\/span><\/li>\r\n \t
          • Ultrasound<\/span> can be used to\u00a0<\/span>take a close look at<\/span> heart valves or heart wall movement in addition to<\/span>\u00a0<\/span>fetal development <\/span><\/li>\r\n \t
          • ECG<\/span>\u00a0<\/span>(EKG, electrocardiogram) examining cardiac conduction (the<\/span>\u00a0electrical<\/span>\u00a0<\/span>waves) within the heart<\/span><\/li>\r\n \t
          • EEG<\/span> (<\/span>electroencephalogram)<\/span>\u00a0measures<\/span>\u00a0<\/span>the electrical currents in the brain.<\/span>\u00a0<\/span><\/li>\r\n \t
          • EMG (electromyography) m<\/span>easuring skeletal m<\/span>uscle function (specifically the ability of a muscle to contract when electrically stimulated)<\/span><\/li>\r\n \t
          • Conduction tests are used to assess motor <\/span>nerve function <\/span><\/li>\r\n \t
          • Endoscopy utilizes a camera on a flexible tube that can be inserted into the body to take a closer look at suspected areas of damage. <\/span><\/li>\r\n \t
          • Biopsy followed by Histology (with a microscope) to monitor changes in cellular morphology<\/span><\/li>\r\n \t
          • Microscopy to examine sputum, urine, feces for signs of pathogens or other abnormalities (e.g. crystals or protein casts in urine).<\/span><\/li>\r\n<\/ul>\r\n<\/li>\r\n<\/ol>\r\n \r\n

            Degenerative Diseases and Microscopic Cellular Accumulations<\/strong><\/h3>\r\nAging is a risk factor for several degenerative diseases, particularly those that affect the nervous system (e.g. Alzheimer's, ALS, Parkinson's) or a result of a lifetime of wear and tear (e.g. Osteoarthritis).\u00a0 <\/span>\r\n\r\nSome cells in the body have very have long life spans.\u00a0 For example, neurons and most heart and skeletal muscle cells are as old as you are.\u00a0 It may not be surprising that over time, these cells can accumulate different materials that become detrimental to their function.\u00a0 <\/span>Cells can accumulate endogenous compounds such as lipids,<\/span>\u00a0<\/span>proteins, carbohydrates, pigments, metabolic toxins.<\/span>\u00a0 Endogenous means it's accumulating<\/span>\u00a0a substance that's part of you,<\/span>\u00a0it's a normal part of you.\u00a0 <\/span>Cells can also accumulate exogenous compounds from the environment such as lead or mercury.\u00a0\u00a0<\/span>\r\n\r\nSo it might not be surprising<\/span>\u00a0<\/span>that as your brain gets older,<\/span>\u00a0<\/span>accumulating potentially some of<\/span>\u00a0<\/span>these things, it becomes more susceptible to different forms of dementia,<\/span> all of <\/span>which are considered <\/span>degenerative diseases<\/span>.<\/span>\u00a0<\/span>\r\n\r\n\u00a0<\/span>\r\n\r\n[caption id=\"attachment_445\" align=\"alignnone\" width=\"1024\"]\"\" Figure: Simplified cartoons of (left) healthy liver with normal hepatocytes flanked by a quiescent hepatic stellate cell (HSC) with large lipid droplets (LDs), and (right) injured liver with lipid-filled hepatocytes flanked by activated HSCs devoid of large LDs.[\/caption]\r\n\r\n \r\n\r\n[caption id=\"attachment_448\" align=\"alignnone\" width=\"1024\"]\"\" Figure: Proposed aggregation cascade of the expanded polyglutamine (polyQ) proteins and potential therapeutic targets for polyQ accumulation\/aggregation diseases.[\/caption]\r\n\r\n[caption id=\"attachment_450\" align=\"alignnone\" width=\"1024\"]\"\" Figure: Schematic diagram of the events that lead to Lysosomal Storage Disorders (LSDs). Orange spheres: accumulation of undegraded substrates. LSDs are rare inherited metabolic disorders characterized by lysosomes that are impaired by having mutations in lytic enzymes. The inability of the lysosomes (the recycling centers) to breakdown either lipids or glycoproteins leading to the accumulation of large lipid or saccharide molecules that lead to cell death.[\/caption]\r\n\r\n \r\n\r\n ","rendered":"

            Testing, Testing, Testing: Diagnostic Tests<\/h1>\n

            The Range and Importance of Diagnostic Tests – Which one to use? And is it sensitive enough? Is it specific enough?<\/strong><\/h2>\n

            There are so many health care tests<\/strong> that provide clues as to the diagnosis.<\/p>\n

            There are chemistry tests<\/strong> to assess: components of blood (e.g. lipids, pH and oxygen levels) and components of urine (e.g. urinalysis).\u00a0 There are volume tests<\/strong> for measuring: blood pressure and functional lung volumes.\u00a0 There are palpation tests<\/strong> to assess: heart and pulse rates for example.\u00a0 \u00a0There are microscopy tests<\/strong> to analyze:\u00a0 cellular features within biopsies as well as the presence of possible pathogens (e.g. throat or vaginal swabs, fecal analysis, sputum tests).\u00a0 There are listening tests<\/strong> (e.g. auscultation of breath, heart and bowel sounds, etc.).\u00a0 There are flow cytometry tests<\/strong> that can be used to count the numbers of WBCs and RBCs per mL in blood,.\u00a0 These tests and more are used in health care research.<\/p>\n

            Let’s look at an example in which different tests (in this case weight, BMI, and genetic) may signal there is a risk of, or even the presence of a disease.<\/p>\n

            Example:\u00a0 Research has found that there are several risk factors for developing Type 2 Diabetes:\u00a0 high birth weight, high BMI (body mass index) at age 10, high BMI as an adult, being biological male (XY) and at times, there may be some genetic components.<\/p>\n

            \"\"
            Figure: Body Mass Index and Birth Weight Improve Polygenic Risk Score (PRS) for Type 2 Diabetes. PRS is the combining of several clinical metrics, which was found to increase the power of disease prediction in particular from early life. Risk factors for the development of Type 2 Diabetes includes: birth weight, BMI at age 10, BMI as adult, genetic variants, and biological sex. Currently, T2D has a higher prevalence in biological males.<\/figcaption><\/figure>\n

             <\/p>\n

            In the previous pages, we discussed the importance of determining whether a person’s test results fall into the range of normal<\/strong> (and presumably healthy), or perhaps indicate disease<\/strong> and disruption in homeostasis.\u00a0 <\/strong>Also we should clarify – even though the terms normal and abnormal are used at times in test results, it is likely obvious to you that normal (test results) is not always the same as healthy, and abnormal (test results) does not always mean the presence of a disease or disorder.<\/em><\/p>\n

            \"\"
            Figure:\u00a0 Distribution plot of heart rate of 57 college men. The mean pulse rate was found to be 70.4211 beats per minute (bpm) with a standard deviation of 9.9480 bpm.<\/figcaption><\/figure>\n

            In the above figure, a typical bell curve<\/strong> indicates the range of test results that can be expected in a set population.\u00a0 In this case, resting heart rate data<\/strong> has been graphed for 57 college males.\u00a0 Even though the low and high ends of the graph have been coloured red, all of the resting heart rates in this particular population ( which are from ~60-80bpm) are in the expected normal range.\u00a0 Typically, if a resting heart rate is below 60bpm or above 100bpm, it would be considered abnormal, and indicative of a disruption in homeostasis.\u00a0 If a disease is suspected, and results fall outside of what is considered normal, usually follow-up and complementary tests are performed in order to gain enough information to make an accurate diagnosis.<\/p>\n

            <\/div>\n

            It should be noted that test results that are high or low, don’t necessarily indicate disease.\u00a0 If there isn’t<\/span> a disease despite abnormal test results we would use the term False Positive<\/strong>.\u00a0 Additionally individuals with<\/span> disease can have test results that are normal.\u00a0 In this situation we would use the term\u00a0False Negative<\/strong>.<\/p>\n

            Let’s examine this further including the terms: True Positives<\/strong>, True Negatives<\/strong>.,<\/p>\n

            Quick Reminder:\u00a0 In the last section we defined <\/span>different terms such as: atrophy,<\/span>\u00a0hypertrophy, dysplasia, anaplasia, neoplasia.<\/span> We noted that dysplasia is considered<\/span> pre-cancerous, and dysplastic<\/span>\u00a0cells<\/span>\u00a0are no longer completely differentiated.<\/span>\u00a0They are slightly<\/span>\u00a0undifferentiated and they might<\/span>\u00a0be having<\/span>\u00a0a little bit more mitosis than normal.<\/span>\u00a0If that continues, might well develop<\/span>\u00a0a neoplasia or an actual growth or tumour<\/span>.<\/span> \u00a0If the tumour stays within the basement membrane,<\/span>\u00a0we know it’s a benign neoplasia<\/span>\u00a0and if it starts spreading,<\/span>\u00a0it breaches the basement membrane,<\/span>\u00a0we know that it’s become malignant (or cancerous).<\/span><\/p>\n

            In this table, let’s examine the possible results of a <\/span>Pap smear in which<\/span> cervical cells are scraped and are examined<\/span>\u00a0to<\/span>\u00a0see whether the cells have reverted to an undifferentiated state.<\/span> \u00a0Luckily, cervical cancer is<\/span>\u00a0a very slow cancer,<\/span>\u00a0so routine screening once every 2-3yrs (as per recommended by a physician, depending on patient’s risk level) means you’re more<\/span>\u00a0likely to catch it in a dysplastic<\/span>\u00a0state well before <\/span>a malignant state.<\/span>\u00a0 This is important in ensuring that it can be treated with a good degree of success.<\/p>\n\n\n\n\n\n\n\n
            <\/td>\n\n

            Normal Test Results<\/strong><\/span><\/h3>\n<\/td>\n

            		\n

            Abnormal Test Results<\/strong><\/span><\/h3>\n<\/td>\n<\/tr>\n

            \n

            Healthy – this person does not<\/span> have disease\u00a0 \u00a0(e.g. cervical cancer)<\/strong><\/span><\/h3>\n<\/td>\n

            		\n
            True Negative – a healthy person’s test results are normal<\/span><\/strong><\/span><\/h5>\n<\/td>\n
            		\n
            False Positive – a healthy person’s test results are abnormal<\/span><\/strong><\/span><\/h5>\n<\/td>\n<\/tr>\n
            Example<\/strong> – Pap Test to detect signs of cervical cell dysplasia or anaplasia. Healthy person does not have cervical pre-cancer or cancer.<\/span><\/em><\/td>\nCervical cells examined under microscope have normal cell morphology = True Negative<\/strong><\/span><\/td>\nCervical cells examined under microscope have abnormal cell morphology – which may indicate pre-cancer or cancer.\u00a0 Perhaps cells are affected by minor infection or other temporary non-cancerous issues\u00a0 = False Positive<\/strong><\/span><\/td>\n<\/tr>\n
            \n

            Sick – this person does have the disease\u00a0 \u00a0 \u00a0 \u00a0 (e.g. cervical cancer)<\/strong><\/span><\/h3>\n<\/td>\n

            		\n
            False Negative – a sick person’s test results are normal<\/span><\/strong><\/span><\/h5>\n<\/td>\n
            		\n
            True Positive – a sick person’s test results are abnormal<\/span><\/strong><\/span><\/h5>\n<\/td>\n<\/tr>\n
            Example<\/strong> – Pap Test to detect signs of cervical cell dysplasia or anaplasia. This person does have cervical pre-cancer or cancer.<\/span><\/em><\/td>\nCervical cells examined under microscope have normal cell morphology.\u00a0 Missed scrapping cells that are affected by pre-cancer or cancer = False Negative<\/strong><\/span><\/td>\nCervical cells examined under microscope have abnormal cell morphology – which in this case accurately reflect pre-cancer or cancer\u00a0 = True Positive<\/strong><\/span><\/td>\n<\/tr>\n<\/tbody>\n<\/table>\n

             <\/p>\n

            Now as we can see in the above test, it is virtually impossible to design a diagnostic test that is 100% accurate all of the time.\u00a0 Most often complementary and follow-up tests are done in order to become more confident in diagnoses.<\/p>\n

            So, the goal of tests is to be either specific<\/strong> or sensitive<\/strong> (or both).\u00a0 What does that mean?<\/p>\n

            Sensitivity <\/strong>– Can a test accurately detect True Positives? <\/strong>– which is important!\u00a0<\/span> Sensitivity,<\/strong> is a test’s ability to be <\/span>positive<\/strong> in the <\/span>presence<\/strong> of the disease.\u00a0 If a test can correctly identify 99 out of 100 sick people that do<\/span><\/span> have the disease, the test is 99% sensitive, which is an extremely impressive ability for a test.<\/span><\/p>\n

            Specificity – Can a test accurately detect True Negatives? <\/strong>– which is important!\u00a0 Specificity,<\/strong> is a test’s ability to be negative<\/strong> in the absence<\/strong> of the disease.\u00a0 If a test can correctly identify 99 out of 100 healthy people that do not<\/span> have the disease, the test is 99% specific, which is an extremely impressive ability for a test.<\/p>\n

             <\/p>\n

            \"\"
            Figure: Management algorithm in primary HPV screening. Abnormal cytology refers to a borderline or more severe cytological result. This figure was adapted from Chrysostomou et al. (2018) [15]. This algorithm was developed based on \u201cThe supplements of the second edition of the European Guidelines for Quality Assurance in Cervical Cancer Screening of 2015\u201d<\/figcaption><\/figure>\n

             <\/p>\n

            In the above figure, a new added step to the protocol for cervical testing is being developed and implemented in some countries.\u00a0 \u00a0The newly added step is the first one, in which a Primary HPV<\/strong> (Human Papilloma Virus) test, a highly sensitive<\/strong> test is used that screens for the DNA presence of the HPV strains that are considered high risk for cancer development.\u00a0 The cytology test<\/strong> involves the Pap smear<\/strong> with microscopic analysis of cervical cellular morphology.\u00a0 Traditionally, the cytology (Pap smear) test is used as the initial test, and is also considered highly sensitive<\/strong> with an even greater degree of specificity<\/strong> than the HPV test.\u00a0 The third test in the above figure, the colposcopy<\/strong> test is considered a highly specific<\/strong> test.<\/p>\n

            What is a colpscopy?\u00a0 Colpscopy is a specificity test performed when abnormal cells are detected in a Pap smear.\u00a0 It involves using a colpscope, a thin flexible tube with lighted, magnifying camera that can examine the cervix, vagina, and vulva for lesions and signs of cancer.<\/p>\n

            \"\"
            Figure:\u00a0 Pocket Colposcope (2018)<\/figcaption><\/figure>\n
            <\/div>\n
            \"\"
            Figure: Anatomical view of cervix (a), cross-sectional view of cervix (b).<\/figcaption><\/figure>\n
            \"\"
            Figure: Colposcopy<\/figcaption><\/figure>\n

            The above figures show the strategy most often used in diagnostic testing, in which the first test used is a highly Sensitive<\/strong> test, which is very good at identifying illness, and makes sure that you can alert as many people as possible that may have the illness.\u00a0 \u00a0The Specificity<\/strong> test typically follows the Sensitivity test, and is used to identify false positives (e.g. make sure those that are healthy are correctly identified, and then alerted that they don’t have the disease,\u00a0 and are not treated for a disease that they don’t have).\u00a0 a more specific test next.<\/p>\n

             <\/p>\n

            Ethics of Diagnostic Tests – Design of and Use of?<\/h1>\n

            If we pause to think about the design and use of diagnostic tests, we can start to imagine that there are a lot of ethical questions that are encountered.<\/p>\n

            a) For example how do you decide which tests to try to develop? <\/span><\/p>\n

            b) How much funding should be given to each test development research?\u00a0 <\/span><\/p>\n

            c) Once developed, how much should each test cost (to the patient and to the taxpayer)?\u00a0 <\/span><\/p>\n

            d) When and how often should each test be recommended?<\/span><\/p>\n

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