2Screening GenerallyIs to seek about certain problem in certain high risk group.
3Validity of Screening Test Validity of test determined by ability to correctly categories subjects to test-positive or test-negative
4Validity of Screening Test cont... Sensitivity = ability of test to give a positive result when disease is present= a / a+cSpecificity= ability of test to give a negative result when disease is absent= d / b+d
5Validity of Screening Test Predictive value is determined by sensitivity & specificity and also by the prevalence of preclinical diseasPositive predictive value= probability that a person with a positive test actually has the disease = a / a+bNegative predictive value= probability that a person with a negative test is truly disease-free = d / c+d
6When to Suspect Gynecologic Cancer Woman with:Ovarian mass/cystGrowth or ulcer of cervix, vagina or vulvaAbdominal mass, increased abdominal girthPostcoital bleedingNew onset of hematuria or renal failureNew onset of bowel obstruction
7When to Suspect Gynecologic Cancer cont…. Premenopausal woman with:Irregular mensesWomen older than 35 or with long history of irregular mensesPostmenopausal woman with:Vaginal bleedingAbnormal vaginal discharge
8Concept Prevention is better than cure. Cancer cervix Screening programs are in adulthoodBut ovarian cancer programs are still in relative infancy, why?
9Phases of Tumorgenesis Normal cellsDysplasiaInvasiveasymptomaticAs cancer ovaryCancer cx.End. C.Invasivesymptomatic
10Most Cancers Develop In The Unscreened And The Underscreened.
11CRITERIA FOR SCREENING Disease:Must be serious enoughMust be widespread enoughMust be fairly reliably diagnosableMust be treatableMust be affordableHopefully legally defensible
12Criteria for Screening Test 1. Simple & quick2. Capable of being performed by paramedics3. Inexpensive4. Acceptable to population5. Accurate6. Repeatable7. Sensitive8. Specific
13Incidence of Gynecologic Cancers in Taiwanese Women 70605040Incidenceper 100,000302010Breast CancerCervical CancerOvarian CancerUterine CancerSource: Department of Health 2007.
14Epidemiology of Cervical Cancer Magnitude of the Problem: -500,000 new cases identified each year (1725 new cases in Taiwan,2008)80% of the new cases occur in developing countriesAt least 200,000 women die of cervical cancer each year (657 women in Taiwan, 2008)Cervical cancer is the second/third most common cancer worldwide
15Epidemiology of Cervical Cancer cont…. Most common female cancer in developing countries:leading cause of cancer death in women.10-15% cases seen at late incurable stages.
16Epidemiology of Cervical Cancer cont…. High risk patients:High parity?!!Multiple partnerGenital infectionsHPV & HSV IISmokingSexual behavior of women’s partnerCervix:
17Pathogenesis of CIN Normal Cervix HPV Infection HPV-related ChangesNormal CervixLow-Grade SIL (Atypia, CIN I)High-Grade SIL (CIN II, III/CIS)Invasive CancerHPV InfectionCofactorsHigh-Risk HPV(Types 16, 18, etc.)About 60% regress within2-3 yrsAbout 15% progress within 3-4 yrs30% - 70% progress within 10 yrs
19Prevention of Cervical Cancer Cervical cancer is a preventable diseasePrimary prevention:Education to reduce high risk sexual behaviourMeasures to reduce/avoid exposure to HPV and other STIsSecondary prevention:Treatment of precancerous lesions before they progress to cervical cancer (implies practical screening test)Now : HPV vaccines.
20Secondary Prevention of Ca.Cx. Key Point is to detect precancerous lesions –BYA good screening methodPAP smear test is considered to be the gold standard – Has limitations ?Alternatives to Pap Smear – What are they?
21Why screening for cervical cancer? 1. Is relatively common in unscreened women.2. Has a relatively good prognosis if found early stage in its natural course of disease.3.Has a characteristic natural course that is a slow progression through a premalignant stage.
22Why screening for cervical cancer? 4. A premalignant stage can be detected by noninvasive means (the Pap smear, colposcope).5. There are effective treatment modalities to eradicate premalignant lesions and early invasive cervical cancer.
23Screening by Pap. Cx. Smear a. Importance:unscreened female have ten fold risk > screened female- Every sexually active female (3y after sex)- Specially, high risk group.- Annually up to the age of 70y- No need to extend screening > 70y if smear is N.- At each pregnancy- If new risk factors appear after 70y.b. To whom :c. When:d. Abnormal smear colposcopy
24Limitations of Pap Smear Complex laboratory testRequires trained cytotechnician for reading and pathologist for reviewContinuous monitoring needed to maintain high-quality resultsReports often take minimum 1-2 weeks to obtainFollow-up of women is difficultUsually available only in large cities in many countries
25Alternatives to Pap smear Visual inspection with acetic acid (VIA).Liquid-based cytology (ThinPrep test).Automated pap smear (Computer reading).HPV DNA test in conjunction with pap smear.Colposcopy.
39Introduction Originally developed by Hans Hinselmann in the 1920s. By the 1930s, colposcopy was widely used in Europe.1970s, the colposcopy was accepted procedure for the verification of abnormal cytologic findings in the United States.
41Supplies for colposcopy Acetic acid (3% to 5%)(vagina and cervix: 30 to 60 seconds; should be reapplied, as needed, after three to five minutes. ) (vulva: 3 to 5 minutes for the solution to permeate the cells and for the lesion to appear white. )Lugol’s solution
42Figure 1. A representative parous adolescent cervix showing the outer boundaries of several important areas of exocervical epithelium that correspond to the histological representations in Figure 2. External os (os), new squamocolumnar junction (nscj), area of cervical ectopy (ect) between nscj and external os, cervical transformation zone (ctz) between the original squamocolumnar junction (oscj) and nscj that includes an area of immature metaplasia (im), which is lightened by the application of 5% acetic acid. Adapted from.
43Abnormal Transformation Zone Features suggestive of an ATZ：LeukoplakiaAcetowhite epitheliumErosion/UlcerationInternal marginsAbnormal/atypical vessels
51MEANING OF Acetowhite Not all acetowhite patches are cancer: Any of these epithelial changes can also become acetowhite:Healing or regenerating epitheliumCongenital transformation zoneInflammationImmature squamous metaplasia
53EFFICACY For HSIL or cancer: sensitivity: 85%, specificity: 69% For any CIN: sensitivity: 96%, specificity: 48%It is important to note that the experience and training of the colposcopist are important factors in assuring reliable diagnostic results.
55Endometrial Cancer Risk Identification Several risk factors:1. Nulliparous women 2-3 times the risk of parous women2. Infertility history, irregular mense, anovulatory cycles3. Late menopause (> 52 y/o): 2.4 times for those < 49%4. Obesity: overweight pounds: 3 timesoverweight > 50 pounds: 10 times(peripheral conversion of adrenally derivedandrostenedione by aromatization in fat to estrone)5. PCOD -- Functioning ovarian tumors6. HRT (E without P): 4-8 times7. Tamoxifen for breast cancer: 2-3 times8. DM: times
56PRE-INVASIVE LESIONS OF END. Malig. PotentialPathologyLittle or noneReplacement of usual gland cell by cells having cilia, sq. cellsMetaplasia1-3% over 15yIrregular glands, minor budding or out pouchingSimle hyperplasia3-4% over 13yBack to back glands, budding, papillary process, minor stratificationComplex hyperplasia23% over 10yAtypism + back to back + buddingAtypical hyperplasia
57Endometrial Cancer Screening Screening of unproven benefitPap smear: inadequateTransvaginal sonography (TVS) examinationsHelpful in evaluating vaginal bleedingEndometrial samplingRisks include discomfort, bleeding, infection, uterine perforation (rare)
58Endometrial Cancer Screening - TVS Endometrial Stripe ThicknessDiagnosis<5mm6-10mm11-15mm>15mmAtrophy93%7%Hyperplasia58%42%Polyp53%47%Cancer18%41%Grigoriou: Maturitus 23:9-14,1996
59Endometrial Cancer Screening - TVS Normal endometrial stripe
60Endometrial Cancer Screening - TVS Thickened Endometrial Stripe:A case of endometrial cancer
61Endometrial Cancer Screening - TVS Thickened Endometrial Stripe:A case of endometrial cancer
62Endometrial Cancer Screening – EM sampling Endometrial Suction Curette
66Ovarian Cancer Screening Risk identification:IncreaseDecreaseAgeOCPsFamily historyPregnancyInfertility/low parityTubal ligationPersonal cancer historyBreast-feeding
67Ovarian Cancer Screening Benefit to screening is unprovenAnnual bimanual gynecologic examinationTransvaginal ultrasoundCA 125 serum levelsScreening may result in more unnecessary surgeries than new ovarian cancers
68Screening For Early Diagnosis Ovarian Malignancy Multiple modalities:1- Clinical.2- Cul-de-sac evaluation (PV).3- Imaging techniques (TVS).4- Tumour markers (CA125).5- Multimodels.
69Ovarian Cancer: Ultrasound Screening Studies Screening of 5,000 women65 exploratory surgeries for every case of ovarian cancerScreening of 1,600 women with a family history12 exploratory surgeries for every case of ovarian cancerSurvival benefit unproven
70Ovarian Cancer: CA125 Testing Is elevated in greater than 80% of advanced EOCsIs elevated in 25-50% of Stage I cancersHas poor specificity, especially in premenopausal womenNOT a screening test for the general population
71Screening For Early Diagnosis Ovarian Malignancy Recommendations:1- Comprehensive family history on all patients.2- None or 1 family memberAnnual rectovaginal pelvic exam.3- 2 or more family membersGenetic counseling (BRCA I, II mutation)Annual rectovaginal pelvic exam, CA125, transvaginal ultrasound.4- Consider clinical trial participation.