BIOE 301Your CONFIDENTIAL Test ResultsSlide 3Case StudiesBioengineering and Cervical CancerStatistics on cervical cancerGlobal Burden of Cervical CancerRisk factorsHuman papilloma virus (HPV)HPV and cervical cancerSlide 11PathophysiologyHPV vaccineHow Do We Detect Early Cervical Cancer?Pap SmearColposcopy and BiopsyColposcopy and TreatmentDetection and TreatmentScreening Guidelines, ACSSlide 20Slide 22HPV DNA TestSlide 24Liquid Based Pap SmearAutomated Pap Smear ScreeningOptical technologiesCostsSlide 29Slide 30Bioengineering and Prostate CancerStatistics on Prostate CancerGlobal Burden of Prostate CancerSlide 34Slide 35Slide 36Development of Prostate CancerHow Do We Detect Prostate Cancer?Digital Rectal ExaminationSlide 40Prostate biopsyTreatment for Localized Prostate CancerSlide 43New Screening TechnologiesSlide 45Challenge: Should we screen?Cost of screeningSlide 48Efficacy of screeningWhy are RCTs so Important? Lead Time BiasSlide 51Should we screen?Screening guidelinesDo All Countries Screen with PSA?Next TimeBIOE 301Lecture FourteenYour CONFIDENTIAL Test ResultsFirst Chance…Possible Results:Instant freebiesLose 10 points on Exam 2Lose 1 point on Exam 2No effect on Exam 2 scoreYou can open now, or you can wait and learn more…Molecular basis of cancerMutation• Good or bad• Single or multiple• Duration• CausesDNARNAProteinAlterations in cell physiology: (1) Develop self-sufficiency in growth signals (2) Become insensitive to signals of growth inhabitation, (3) Evade programmed cell death, (4) Develop limitless replicative potential(5) Sustain angiogenesis(6) Acquire the ability to invade tissue and metastasize.Central dogma of molecular biologyCase StudiesCervical CancerProstate CancerOvarian CancerAmerican Cancer Society (cancer.org)National Cancer Institute (cancer.gov)Dr. KoopBioengineering and Cervical CancerStatistics on cervical cancerUS data (2007)Incidence: 11,150Mortality: 3,670World data (2004)Incidence: 510,000 (80% developing world)Mortality288,000 deaths per year worldwideGlobal Burden of Cervical CancerHighest incidence in:Central and South America, Southern Afica, AsiaRisk factorsHPV infectionHPV infection is the central causative factor in squamous cell carcinoma of the cervix Sexual behaviors Sex at an early ageMultiple sexual partnersCigarette smokingHuman papilloma virus (HPV)Most common STD>70 subtypesAsymptomatic infections in 5-40% of women of reproductive ageHPV infections are transientHPV and cervical cancerWhat Initiates Transformation?PathophysiologyHPV vaccineVirus-like particles (VLP) made from the L1 protein of HPV 16approved for use in women aged 9 to 26 years in the USnot effective to women already exposed to HPVEffective on 4 HPV isotypesRecombinant technologyAlternative prevention technique to screening?How Do We Detect Early Cervical Cancer?Pap Smear 50,000-300,000 cells/per slideCytotechnologists review slides (<100/day)Se = 62% 3%Sp = 78% $6BColposcopy and Biopsy Se = 95%Sp = 44%ColposcopeBiopsy sectionsColposcopy and TreatmentCIN 1/LGSILCIN 1/LGSILCIN 2/HGSILCIN 2/HGSILCIN 3/HGSILCIN 3/HGSILMicroinvasive CAMicroinvasive CAInvasive CAInvasive CAInvasive CAInvasive CADetection and TreatmentScreening: Pap smearDiagnosis: Colposcopy + biopsyTreatment:Surgery, radiotherapy, chemotherapy5 year survivalLocalized disease: 92% (56% diagnosed at this stage)Screening Guidelines, ACSAll women should begin cervical cancer screening about 3 years after they begin having vaginal intercourse, but no later than when they are 21 years old. Screening should be done every year with the regular Pap test or every 2 years using the newer liquid-based Pap test.Beginning at age 30, women who have had 3 normal Pap test results in a row may get screened every 2 to 3 years with either the conventional (regular) or liquid-based Pap test.Option for women over 30 is to get screened every 3 years with either the conventional or liquid-based Pap test, plus the HPV DNA test.Trends in Screening Cervical CancerChallengeAccess to technologyDeveloped and developing worldCost and infrastructure requirements for screeningNeed for appropriate technologiesNew Detection TechnologiesAims:Reduce the false positive and false negative ratesGive instantaneous resultsReduce the costsHPV DNA TestThe DNA with Pap Test is FDA-approved for routine adjunctive screening with a Pap test for women age 30 and older. Se= 80-90%Sp= 57-89%OOOOOOOOOOOOOOOOOOOOOOOOOOOOOO OOOOOOOOOOOOOOOOOOOOOOOOOOOOOO OOOOOOOOOOOOOOOOOOOOOOOOOOOOOO OOOOOOOOOOOOOOOOOOOOOOOOOOOOOO OOOOOOOOOOOOOOOOOOOOOOOOOOOOOO 1. Release Nucleic Acids Clinical specimens are combined with a base solution which disrupts the virus or bacteria and releases target DNA. No special specimen preparation is necessary. 2. Hybridize RNA Probe with Target DNA Target DNA combines with specific RNA probes creating RNA:DNA hybrids. 3. Capture Hybrids Multiple RNA:DNA hybrids are captured onto a solid phase coated with universal capture antibodies specific for RNA:DNA hybrids. O 4. Label for Detection Captured RNA:DNA hybrids are detected with multiple antibodies conjugated to alkaline phosphatase. Resulting signal can be amplified to at least 3000-fold. 5. Detect, Read and Interpret Results The bound alkaline phosphatase is detected with a chemiluminescent dioxetane substrate. Upon cleavage by alkaline phosphatase, the substrate produces light that is measured on a luminometer in Relative Light Units (RLUs).Liquid Based Pap SmearConventional PapLiquid Based PapAutomated Pap Smear ScreeningTechnology• High-speed video microscope collects images• Algorithms interpret images and classify slidesPerformance• 33% to 44% reduction of false negatives• 16% reduction in false positivesOptical technologiesVisual Inspection with acetic acid (VIA)Digital Image Analysis (DIA)CostsPap Test $10-20Liquid-based Pap$50Automated Pap Smear Screening$20-60HPV DNA test $90HPV vaccine $360Risk factorsDetectionTreatmentChallengesNew technologiesBioengineering and Cervical CancerYour CONFIDENTIAL Test ResultsSecond chancePossible Outcome Cancer DiagnosisFreebiesTrue Positive: You have cancer and the test correctly identified your condition. You will receive treatment.Lose 10 points on Exam 2False Negative: You have cancer, but the test did not
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