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screening for cancer cervix
1.
SCREENING FOR CERVICAL CANCER Prof. Aboubakr Elnashar Benha university, Egypt Aboubakr Elnashar CONTENTS 1. MAGNITUDE OF THE PROBLEM 2. PREMALIGNANT STAGES 3. RISK FACTORS 4. SCREENING STRATEGY 5. METHODS OF SCREENING Aboubakr Elnashar
2.
1. MAGNITUDE OF THE PROBLEM ▪World wide: 3 rd most common female cancer ▪ Developing countries: 80 % of all cases ▪ Egypt: 2 nd most common female cancer ▪ Developed countries: decrease since mid 1980 s Aboubakr Elnashar ❑Incidence of Gynecologic Cancers in Egyptian Women 0 5 10 15 20 25 Breast Cancer Cervical Cancer Ovarian Cancer Uterine Cancer Percent Source: GLOBOCAN 2000. Aboubakr Elnashar
3.
CIN (%) N o Study University Year Author 1.07 4458 Hospital Cairo 1987 Hammad et al 3.1 5453 Community Suez canal 2007 Abd El All et al 3.1 25522 Hospital Ain Shams 2004- 2010 Shalakany (2012) 5.8 3600 Hospital Minia 2014 Sanad et al 1.3 6173 Alexandria 2015 Abdelhady et al 3.2 1600 Community Assuit 2017 Elmoselhy et al 3.00 46806 Total ❑ Incidence ▪ CIN in Egypt (Elnashar, 2019) Aboubakr Elnashar ❑ Cx ca in Egypt: ▪ 0.04% (AbdelAll et al, 2007) ▪ 0.06% populations [Feraly et al, 2010) ▪ 8th among the most common females' cancers (National Cancer Institute registry for the years 2002- 2004) ▪ increasing incidence from 2002 to 2004 [Elattar, 2004) ▪ increase by 34.0% from 2013 to 2050 [Ebrahim et al, 2014) Aboubakr Elnashar
4.
Incidence rates, crude rates, females, Egypt 2008–2011 National Population-Based Registry Program of Egypt. (2014) Crude rate % Breast 35.8 32 Ovary 4.6 4.1 Uterus unspecific 2.5 2.3 Cervix uteri 1.3 1.2 Corpus uteri 0.7 0.6 Vagina 0.2 0.14 Vulva 0.1 0.09 Other female genital 0.1 0.05 Aboubakr Elnashar Cervical Cancer in Egypt (Ibrahim AS et al. 2014) 0 5 10 15 20 25 30 35 < 45 years 45 - 59 years ≥ 60 years ASR Incidence/100,000 W Aboubakr Elnashar
5.
2. PREMALIGNANT STAGE ❑ Cervical intraepithelial neoplasia (CIN): includes ▪ Dysplasia & CIS ▪ CIN 1 = Mild D. CIN 2= Moderate D. CIN 3= Severe D or CIS. Aboubakr Elnashar CIN I CIN II CINIII Aboubakr Elnashar
6.
❑Squamous intraepithelial lesion (SIL): includes ▪ HPV & CIN. ▪ Low grade SIL= CIN 1 or HPV. High grade SIL= CIN 2 or 3 Aboubakr Elnashar 3. RISK FACTORS I. Medical risk factors ▪Cervical high-risk HPV infection: ▪99% of cervical cancer & high grade CIN are associated with HPV ▪Types 16 and 18: responsible for 70% of all cervical cancers. ▪Parity: ▪Multiparity ▪4 live births ▪Early age of 1 st birth ▪Immunosuppression Aboubakr Elnashar
7.
II. Demographic risk factors ▪Ethnicity (Latin American countries, U.S. minorities) ▪Low socioeconomic status ▪Age III. Behavioral risk factors ▪Infrequent or absent cancer screening Pap tests ▪Early coitarche ▪Multiple sexual partners ▪Male partner who has had multiple sexual partners ▪Tobacco smoking ▪Dietary deficiencies: folic ac, vit A Aboubakr Elnashar HPV types Oncogenic potential HPV TYPES LOW 6, 11,14,43,44 INTERMEDIATE 31,33,35,51,52, HIGH 16,18, 45, 56 Aboubakr Elnashar
8.
❑13 high-risk HPV ▪ 16, 18, ▪ 31, 33, 35, 39 ▪ 45, ▪ 51, 52, 56, 58, 59, ▪ 68. Aboubakr Elnashar ❖Cervical cancer is a preventable disease 1. Has a characteristic natural course with a slow progression through a premalignant stage 2. A premalignant stage can be detected by noninvasive means: Pap smear, VIA 3. An effective tt for the premalignant lesions Aboubakr Elnashar
9.
4. SCREENING STRATEGY ❑Methods of Prevention ▪ Primary: ▪ Avoidance of the precipitating & risk factors ▪ Counseling ▪ Vaccination ▪ Secondary: ▪ Screening ▪ Early detection ▪ Tertiary: ▪ Treatment or mitigation of damage Aboubakr Elnashar ▪ Screening: ▪ Definition ▪ Systematic application of a test in ▪ asymptomatic person ▪ to identify pre clinical lesions. ▪ Types : ▪ Selective: Screening high risk groups ▪ Mass: Screening all population Aboubakr Elnashar
10.
▪ In developing countries (lower and middle-income countries (LMICs) 1. Poor financial, human & technical resources 2. Higher incidence: 80% of cases 3. Higher mortality: 90% 4. Different risk factors 5. NO screening guidelines . 6. Decreased access to treatment 7. Inadequate follow up ▪ Screening used in the developed world is inappropriate in developing countries Aboubakr Elnashar ▪ In Higher -income counteries ▪ have guidelines for screening women ▪ These guidelines define not only the target population for screening, but also ▪ screening methods, intervals, and ▪ appropriate interventions depending on test results ▪ The incidence of cervical cancer has decreased by approximately 80% Aboubakr Elnashar
11.
Choosing an appropriate screening modality ▪ The three main modalities of screening in use ▪ HPV testing ▪ Cytology ▪ VIA ▪ Selection of method depends on existing resources rather than differences in efficacy ▪ In good resource settings: ▪ Validated primary HPV screening: The most effective method ▪ In centers with an established cytology program with good quality control may continue with cytology. ▪ In limited resource settings one may screen with VIA. Aboubakr Elnashar ▪ Pap-only testing ▪ performed every 3 y ▪ Pap-HPV cotesting ▪ Performed every 5 y in women older than 30 with past normal screening. ▪ Until 2018, all 3 organizations recommended cotesting as the preferred screening algorithm for women ages 30 to 65. ▪ Patients with a history of abnormal test results require more frequent testing as recommended by the ASCCP, 2012 Aboubakr Elnashar
12.
ASCCP, ACOG Aboubakr Elnashar ▪ In L&MIC: WHO Aboubakr Elnashar
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▪ In HIC: Preventive Services Task Force, 2018 ▪ For average-risk women ▪ Age:21–29: cervical cytology alone every 3 years. ▪ 30–65 years, screening options include 1. Cytology alone every 3 years 2. High-risk HPV testing alone every 5 years, or 3. Cotesting every 5 years. ▪ Do not screen for cervical cancer. 1. Women younger than 21 y 2. women older than 65 years with adequate prior screening 3. women who have had a total hysterectomy Aboubakr Elnashar ▪ Risk Assessment ▪ All women aged 21 to 65 years are at risk for cervical cancer because of potential exposure to high-risk HPV types through sexual intercourse and should be screened. ▪ Certain risk factors further increase risk for cervical cancer 1. HIV infection 2. Compromised immune system 3. In utero exposure to diethylstilbestrol 4. Previous treatment of a high-grade precancerous lesion or cervical cancer. ▪ Women with these risk factors should receive individualized follow-up. Aboubakr Elnashar
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5. METHODS OF CERVICAL CANCER SCREENING A. Cytological 1. Conventional Pap. Smear 2. Liquid-based monolayers: LBC 3. Automated cytological screening B. HPV testing Aboubakr Elnashar C. Visual 1. Visual inspection of the cervix a. Unaided b. Visual inspection with acetic acid (VIA) c. Visual inspection with acetic acid and magnification (VIAM) d. Visual inspection with Lugol’s Iodine (VILI) Aboubakr Elnashar
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A. CYTOLOGY 1. Conventional Pap test ▪ used for ≥50 y all across the globe. ▪ widely used for in most developed countries ▪Meets all the requirements for mass screening:. ▪ Fairly tolerated by patients ▪Easy to administer ▪ Reasonable sensitivity & specificity. ▪Detection of endocervical lesions. Aboubakr Elnashar ❑Precautions: No ▪ Sexual intercourse ▪ Vaginal douche ▪ Medication ▪ Lubrication ▪ Powder ▪ Pelvic examination ▪ Acetic acid Aboubakr Elnashar
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▪ Instruments & materials: ▪ Speculum ▪ Spatula: ▪ Cytobrush ▪ cotton tipped swab for the endocervical canal ▪ Ayre s spatula for the ectocervix ▪ Fixative ▪ Jar ▪ Slide Aboubakr Elnashar ❑Steps: 1. Taking the sample: ▪from the ectocervix and endocervix ▪with a spatula or brush 2. Smearing: circular motion 3. Fixation: ▪Ethyl alcohol ▪Coating spray 4. Staining: 5. Examination under a microscope by specially trained technologists and doctors. Aboubakr Elnashar
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❑Limitations ▪Requires: ▪Complex infrastructure: Complex laboratory test ▪Trained cytologist ▪Multiple visits ▪Continuous monitoring to maintain high-quality results ▪Results: ▪Moderate to low sensitivity:High rate of false-negative test results 20-40%: Women must be screened frequently ▪Rater dependent ▪Not immediately available ▪Less accurate among post-menopausal women ▪Impossible to locate the lesion. ▪Available: only in large cities in many countries Aboubakr Elnashar 2. Liquid-based monolayers (ThinPrep, CytoRich) ❑Steps: 1. Cells are collected using a brush instead of a spatula. 2. Head of the brush is vigorously shaken or broken off into a small pot of liquid containing preservative solution. 3. The sample is filtered or centrifuged to remove excess blood and debris. 4. The cells are then transferred to the slide in a “mono” layer. 5. Staining. Aboubakr Elnashar
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▪ LBC Vs Conventional Pap ▪ More expensive ▪ Repeat smear rates: 1 to 2% Vs 9% ▪ Less false negative rate ▪ No difference in the relative sensitivity. ▪ No difference in the relative specificity, when H and L- GSIL were considered as cutoff. ▪ Better in predicting CIN ▪ It is the preferred tool for cervical cytology screening Aboubakr Elnashar Aboubakr Elnashar
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3. Automated Pap smears ▪ To reduce errors by using computerized analysis to evaluate Pap smear slides. 1. Autocyte ▪ Composed of an algorithmic & neural network scanner ▪ Scans the slides & records images of 128 of the most abnormal fields found on the slide, with the most significant abnormality found in the center. ▪ It reduces costs & shortens screening time. ▪ Detects 97.2% of the abnormal tests (Koss et al,1994). Aboubakr Elnashar Aboubakr Elnashar
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2. AutoPap. ▪The material on the slide is reviewed and scored based on an algorithm, as to the likelihood of an abnormality being present. ▪Typically, it does not show the cytotechnologist which of the cells are likely to be abnormal. ▪Variety of visual characteristics, such as shape and optical density of the cells, are included in the algorithm. •It reviews all normal & satisfactory smears •As a primary screener, it removes 30 % of slides from the workload •97% sensitivity (Lee et al, 1997) Aboubakr Elnashar B. HPV TESTING ▪ Role of HPV as a causative agent of cervical cancer has been well established. ▪ However, most HPV infections in young women ▪ Regress rapidly, without causing clinically significant disease. ▪ infection is a marker of sexual activity than of cervical cancer risk. Aboubakr Elnashar
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▪ The most sensitive modality, suitable for screening in all resource settings. ▪ Even a single round of HPV testing was shown to significantly reduce the incidence of cervical cancer ▪ However, it is expensive and not widely available. ▪ It is recommended for women aged over 30 years using validated tests. Aboubakr Elnashar ▪ Validated tests ▪ are those that have demonstrated efficacy in RCT or have shown test accuracy comparable to a validated test. ▪ Reported as ▪ Detected/not detected for a pool of 13 or 14 high-risk HPV genotypes ▪ Some report individual genotypes for the most oncogenic types (HPV 16/18). ▪ Examples: Hybrid Capture 2, careHPV, Cobas, Xpert, Cervista, APTIMA etc. Aboubakr Elnashar
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▪ The high-risk HPV-only test ▪ utilizes real-time PCR to detect ▪ HPV 16, ▪ HPV 18, and ▪ 12 other HPV genotypes. ▪ Only 2 tests are approved by the FDA as stand-alone cervical cancer screening tests ▪ Roche Cobas HPV test approved in 2014 ▪ Becton Dickinson Onclarity HPV assay approved in 2018. ▪ Other HPV tests that are used in a cotesting strategy ▪ should not be used for high-risk HPV-only testing ▪ because their performance characteristics may differ. Aboubakr Elnashar Aboubakr Elnashar
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C. Visual inspection with acetic acid (VIA) ▪ Sensitivity comparable to cytology ▪ Poor specificity: larger number of women will require further triage by colposcopy ▪ Can be used in all resource settings by all levels of healthcare providers. ▪ Currently it is the only test that can be used in low resource settings with considerable accuracy and safety but in future, the availability of affordable HPV testing may change this paradigm. Aboubakr Elnashar ❑ Effects of acetic acid: ▪Coagulates the proteins of the nucleus & cytoplasm: protein opaque & white. ▪Dehydrates the cells: cytoplasmic volume is reduced & the reflection is increased. ❑Duration: ▪ appears after 20 seconds ▪ disappears after 2 minutes. Aboubakr Elnashar
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Category Clinical Findings Negative No acetowhite lesions or faint acetowhite lesions; polyp, cervicitis, inflammation, Nabothian cysts. Positive Sharp, distinct, well-defined, dense (opaque/dull or oyster white) acetowhite with or without raised margins touching SCJ; leukoplakia and warts. Suspicious for cancer ulcerative, cauliflower-like growth or ulcer; oozing and/or bleeding on touch. Visual inspection with acetic acid (VIA) Aboubakr Elnashar Normal NAAT Positive Suspicious for cancer Aboubakr Elnashar
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▪Visual inspection after application of Lugol’s iodine Test performance: (Sankaranarayanan et al., 2008). Specificity Sensitivity 85.5 76.8 VIA 85.4 91.7 VILI Aboubakr Elnashar ❑Categories for VILI test results: Category Clinical Findings Negative ▪Squamous epithelium turns brown ▪Columnar epithelium does not change color; or ▪Irregular, partial or non-iodine uptake areas. Positive ▪Well-defined, bright yellow iodine non- uptake areas touching SCJ or close to the os if SCJ is not seen. Suspicious for cancer ▪Ulcerative, cauliflower- like growth or ▪Ulcer; oozing and/or bleeding on touch. Aboubakr Elnashar
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• VILI: test-positive • Well-defined • bright yellow iodine non-uptake areas • touching the SCJ Aboubakr Elnashar
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