Cervical screening , present past crown plaza final copy

Cervical cancer screening Dr. Nisreen Anfinan

Assistant professor ,Obstetric and gynecology

Gynecology Oncology KAAUH

Cervical Cancer: Worldwide Prevalence, Incidence, and Mortality Estimates

Cervical cancer is the 2nd most common cancer among women worldwide

Estimated 530,000 new cases Estimated 274,000 deaths

More than 85% of the global burden occurs in developing countries .

Geneva, Switzerland: World Health Organization; 2003Bosch FX, de Sanjos S. J Natl Cancer Inst Monogr. 2003

Cervical Cancer in Saudi Arabia

Incidence of cervical cancer is low in Saudi Arabia

Rank number 8 between all cancers in female

Every year, 241women are diagnosed with cervical cancer and 84 die from the disease.

Account only 2.4 % of all cases

SCR Report 2012

Infection with oncogenic HPV types is the most significant risk factor in cervical cancer etiology.1

Worldwide , the prevalence of HPV in cervical cancer is 99.7%.

Specific oncogenic HPV types (16, 18, 31, 33, and 45) have been detected in 63%97% of invasive cervical cancer cases worldwide.

Oncogenic HPV & Cervical Cancer

1. Walboomers JM, Jacobs MV, Manos MM, et al. J Pathol. 1999;189:1219. 2. Clifford GM, Smith JS, Plummer M, Muoz N, Franceschi S. Br J Cancer. 2003;88:6373.

PresenterPresentation NotesKey Point

Oncogenic HPV types are a necessary cause of cervical cancer.

BackgroundAn analysis of 932 specimens from women with cervical cancer in 22 countries has indicated that worldwide HPV prevalence in cervical carcinomas is 99.7%.1

Specific oncogenic HPV types have been identified in 63%97% of invasive cervical cancer cases worldwide.2 Among 85 studies measuring HPV prevalence in invasive cervical cancer (N=10,058), HPV 16 was the predominant type in squamous cell carcinoma cases (46%63%), followed by HPV 18 (10%14%), 45 (2%8%), 31 (2%7%), and 33 (3%5%), except in Asia, where HPV 58 and 52 were found in 6% and 4% of cases, respectively. In adenocarcinoma and adenosquamous-carcinoma cases, HPV 18 was predominant (37%41%), followed by Type 16 (26%36%), and Type 45 (5%7%).2

The overall detection of HPV DNA in invasive cervical cancer was similar in different regions worldwide.2

References1. Walboomers JM, Jacobs MV, Manos MM, et al. Human papillomavirus is a necessary cause of invasive cervical cancer worldwide. J Pathol. 1999;189:1219.2. Clifford GM, Smith JS, Plummer M, Muoz N, Franceschi S. Human papillomavirus types in invasive cervical cancer worldwide: A meta-analysis. Br J Cancer. 2003;88:6373.

HPV prevalence

Lancet Infect Dis. 2007;7(7):453,Nature Volume: 488, August 2012

PresenterPresentation NotesA meta-analysis in 157,879 womenThe worldwide prevalence of infection with human papillomavirus (HPV) in women without cervical abnormalities is 11-12% with higher rates in sub-Saharan Africa (24%), Eastern Europe (21%) and Latin America (16%). The two most prevalent types are HPV16 (3.2%) and HPV18 (1.4%). Prevalence increases in women with cervical pathology in proportion to the severity of the lesion reaching around 90% in women with grade 3 cervical intraepithelial neoplasia and invasive cance

HPV prevalence in Saudi Arabia

Author No of patients HPV prevalence

Al mummar 2007 120 38 (31.6% )

Gazzaz 2007 100 5 (5% )

Bondoggi 2013 485 27 (5.6 %)

Alobaid 2014 417 41 (9.8%)

BMC Infect Dis. 2014 Dec Ann Saudi Med. 2007 Jan-Feb;27(1):1-5.Saudi Med J. 2007 Dec;28(12)Ann Saudi Med. 2013 Jan-Feb;33

PresenterPresentation NotesThe prevelance of HPV infection among women and its association with ca cx is scanty in saudi arabia In alimitted study performed on 120 ptsattending routine gyn examination reported the prevelance of 31 infection with 16/18 , 6 had abnormal pap ,follow up 4 years non progress to CIN3

Normal Cervix

HPV Infection

Cervical Dysplasia

Cervical Cancer

Cervical Cancer Prevention

Primary Prevention:

Secondary Prevention:Screening

Primary prevention

Reduced Risk Factors

Vaccination

Normal Cervix

HPV Infection

Cervical Dysplasia

Cervical Cancer

Cervical Cancer Prevention

Primary Prevention:

Secondary Prevention:Screening

Screening test

Should be accurate, practical

Acceptable, highly sensitive (those with disease are most likely to have a positive test)

Highly specific (negative test means there is no disease), and it should have a high

Predictive value (those with a positive test are most likely to have disease)

Options for cervical cancer screening

Visual inspection with acetic acid Visual inspection with Lugols iodine

PAP smearHPV testing hc2

Limitations of Cytology Should be done in the context of an organized screening

program

Quality assurance of cytology needs to be very good

Requires colposcopy and biopsy to confirm dysplasia

The necessity for multiple visits with cytology basedscreening results in significant loss to follow-up

Even with the best quality control ,cytology has low sensitivity

Sensitivity of PAP 53 %

Cuzick et al IGC 2006

PresenterPresentation Notesfalse-positive cytology results were common and an increased understanding of the association between HPV and CC has led to the development of molecular HPV tests with higher sensitivity and slightly lower specificity compared with cytology.

Visual Inspection with Acetic Acid (VIA)

VIA: Visual inspection with acetic acid

VILI: Visual inspection with Lugols iodine

Both Low tech can be done by nurses

May need to utilize colposcopy to triage post positive test to rule out cancer

Country Sensitivity Specificity

Arbyn, 2008 Africa & India 79.2 84.7

Sarian, 2005 Argentina & Brazil 50.0 89.7

Perez-Cruz, 2005 Mexico 14.3 97.3

Al Monte, 2007 Peru 41.2 76.7

Murillo, 2010 Colombia 53.6 93.2Arbyn et al., IJC 2008; Sarian et al., JMedScreen 2005, Perez-Cruz et al., SalpublicaMex 2005, Al Monte, IJC 2007,Murillo et al., IJGO 2010

PresenterPresentation NotesLugols iodine to highlight precancerous lesions so they can be viewed with the naked eye, shifts the identification of precancer from the laboratory to the clinic. Such procedures eliminate the need for laboratories and transport of specimens, require very little equipment and provide women with immediate test results. A range of medical professionals doctors, nurses, or professional midwives can effectively perform the procedure, provided they receive adequate training and supervision. As a screening test, VIA performs equal to or better than cervical cytology in accurately identifying precancerous lesions. This has been demonstrated in various studies where trained physicians and mid-level providers correctly identified between 45% and 79% of women at high risk of developing cervical cancer.

Denny L, Kuhn L, Pollack A, Wright TC Jr. Direct visual inspectionfor cervical cancer screening: an analysis of factors influencing testperformance. Cancer 2002;94(6):1699707.14. Gaffikin L, Lauterbach M, Blumenthal PD. Performance of visualinspection with acetic acid for cervical cancer screening: a qualitativesummary of evidence to date. Obstet Gynecol Surv 2003;58:54350.

HPV TestingADVANTAGES

Very sensitive

It requires laboratory infrastructure

Trained technicians, and storage facilities.

Decreases the number of cytologists needed

Increase screening interval which decreases cost and improves convenience

PresenterPresentation NotesScreening of cervical cancer using HPV testing has been introduce recently since HPV the major cause of ca cervix Its vey sensitive Decreases the number of cytologists neededIncrease screening interval which decreases cost and improves convenience , if test is negative will repeat test after 5 year

Cytology vs HPV testing :variability of cytological diagnosis

Sensitivity for CIN Population No PAP HPV comb Germany 7592 34% 86% 94%UK 10,3358 72% 97% 100%Mexico 6115 57% 94% 98%Costa Rica 6176 80% 86% 92%China 1936 94% 98% 100% Baltimore 1040 60% 100 100%

Qiao etal ,Lancet Oncology, 2008Almonte eta l , nternational Journal of Cancer, 2007Wright et al 2004 obs GnecolJournal of Gynaecology & Obstetrics, 2005

PresenterPresentation NotesThe sensitivity of HPV DNA tests for detecting CIN 23 ranges from 66% to 95%, with most studies reporting values greater than 85% among women aged 30 or older.

HPV Screening for Cervical Cancer in IndiaSankaranarayanan,R:

Total of 131,746 healthy women ages of 30 and 59 years RCT ,4 Arms of screening tool in India HPV test vs. Pap test vs. VIA vs. Observation Cervical cancer as an endpoint 32000 women in each arm Screen positive received colposcopy and treatment Only significant screening method to reduce deaths from

cervical cancer was HPV testing Significant reduction in Ca Cervix in the HPV negative

compared to negative Pap and VIA

NEJM Apr2009 360(14)1385-94

PresenterPresentation NotesScreening by HPV testing alone (without concurrent Pap testing) is not currently recommended in the United States, but may be a reasonable option for screening in geographic areas with limited cytology resources.

CYTOLOGY Lab OrganizerGPTime/travelProgramTotal

Cost 21.7711.2311.766.012.0852.85

HPVLab OrganizerGPTime/travelProgramTotal

Cost 33.8311.2311.766.012.0864.9

BJOG. 2012 May;119(6):699-709. doi: 10.1111/j.1471-0528.2011.03228.x. Epub 2012 Jan 18

PresenterPresentation NotesIncreasing the interval between screening rounds andchanging the primary test from cytology to HPV testing canimprove the effectiveness and decrease the costs of cervical cancerscreening in the Netherlands

http://www.ncbi.nlm.nih.gov/pubmed/22251259

Comparison of Various Methods Available for Detection of HPV

Spitzer, Am J Obstet Gynecol, 1998

Method

Cytology

Dot blot

Filter in situ hybridization

In situ hybridization

Southern blot hybridization

Hybrid capture

Polymerase chain reaction

Sensitivity

Low

Moderate

Low

Moderate

High

High

Very high

Specificity

Low

Moderate

Low

Moderate

High

High

High

Comment

Easy, relatively inexpensive, but subjective, insensitive, and nonspecific

Radioactive, commercially available as ViraPap, ViraType, HPV Profile; labor intensive

Rarely used today

Detects HPV in paraffin-embedded tissue

Gold standard but cumbersome; not feasible for large-scale clinical use

Newly approved for commercial use; nonradioactive, easier to use and less expensive than dot blot

Uses amplification and so is prone to contamination errors (false positive)

Rapid ,affordable and accurate HPV test are being developed

HC 2(existing test )

Care HPV E6 strip test

Test format Batch Rapid-batch Rapid strip

Time 7 hours Less then 2.5 hrs Less then 20 minutes

Detect HPV-DNA HPV-DNA E6 protein

Number ofoncogenic HPV types

13 All 13+type 66

Target price per specimen

More then 20 $ Less then US 5$ Less then US 5$

Lancet Oncology, 2008, 9(10):929936Castro , Program for Appropriate Technology in Health, 2003..

PresenterPresentation NotesEfforts are underway to develop an affordable rapid biochemical HPV test (careHPVtest, Qiagen), with improved sensitivity and almost immediate results that would enable single-visit disease prevention

ortunately, a new, rapid HPV DNA test called careHPV is being developed for the market in low- and middle-income countries.19,22 It will have a lower cost per test than Hybrid Capture 2 and will be simpler to perform. Moreover, it will be portable and will allow for field interpretation of results within 2.5 hours. The sensitivity and specificity of careHPV were evaluated first in Shanxi, China.19 A total of 2,500 rural women aged 3054 were screened, and results from both vaginal and cervical samples were encouraging. The accuracy of the test is substantially better than that of VIA and approaches that of Hybrid Capture 2

Cervical Screening program in Saudi Arabia ??

I f we dont have establish screening program for cervical cancer in low resources setting what you will use ??

Visual inspection of ascitic acid (VIA )

or

HPV testing

Budget for screening efforts is limited Difficult access to health care No follow up surveillance

Screening test must be very sensitive

Screening scheme two visits

Jeddah Cervical Screening programJCSP

www.jcsp.sa.com

Dr. Nisrin AnfinanEarly DetectiveUnit and JCSP Coordinator

Rowaida Al MehyGOU Secretary

Maribi MarquesesGOU Office Assistant

Dr. Faten GazzazDirector ofVirology Laboratory

Eman TaybaJCSP Laboratory Team

Aseel AlsobehiJCSP Laboratory Team

Soheel MelebariJCSP Laboratory Team

Prof. Jim BentleyInternational Advisor

Prof. Khalid SaitDirector of Scientific Chair of Professor Abdullah Hussain Basalamah

Prof. Abdullah Hussain BasalamahGeneral Advisor

Age 30-65 year.

Married for three years.

Saudi & non Saudi.

collecting sampling in our hospital )

Collecting Sample At PHC

Collecting Sample In Our Hospital

Collecting sample at PHC

Collecting sample in our hospital

King Abdulaziz university

PresenterPresentation NotesKAU STAFF CLINIC

Collecting sample at PHC

Collecting sample in our hospital

To start in 40 PHC in Jeddah

King Abdulaziz university

Self sampling

Collecting sample at PHC

Collecting sampling in our hospital

START DATE: January 2012

Our aim to achieve : 10,000 womens

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46

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New Registration for Year 2013

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New Registration for Year 2013 Saudi vs. Non-Saudi

Saudi Non-Saudi

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Jan Feb Mar Apr May Jun Jul Aug Sep Oct Nov Dec

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30 24

0

New Registration for Year 2014 Saudi vs. Non-Saudi

Saudi Non-Saudi

National Cervical

Screening Program

HR-HPV DNA in women 30 + years old

Negative

Negative

Negative

Pap test

Positive

Positive

Colposcopy

Positive

Repeat HR-DNA testing @ 5 year intervals till age

65Repeat HR-

HPV testing at 12 months

Guideline meeting for cervical cancer

screening

Agreed among panel members that HPV testing will be used as primary screening for cervical cancer in SA

www.moh.gov.sa/Ministry/MediaCenter

The future test for cervical cancer screening

Dynamic Spectral Imaging System

DySIS

LuViva Advanced Cervical Scan

PresenterPresentation NotesDySIS A high-resolution digital image of the cervix is displayed on the DySIS touchscreen to allow normal assessment of the cervical area. Image color, brightness, contrast and magnification of the displayed image can be adjusted.a digital video colposcope), particularly in combination with colposcopy, has higher sensitivity than colposcopy alone; a digital video colposcope), particularly in combination with colposcopy, has higher sensitivity than colposcopy alone;

DySIS

It uses Dynamic Spectral Imaging technology to evaluate the aceto- whitening phenomenon andto detect cancerous and precancerous cervical tissue

produces a quantified measurement of the rate, extent, and duration of the aceto-whitening effect that is summarised in a graphical display

Can detect high-grade lesions with 88% sensitivity, compared to the 55% achieved in conventional colposcopy.

(Louwers et al. 2011)

PresenterPresentation NotesDySIS is used according to the standard colposcopic guidelines and process, but additional training is required to ensure that users understand the correct use and interpretation of the DySISmap. DySISmap should be used an adjunct to standard colposcopic indicators.

NICE and the NHSCSP have evaluated the DySIS system and have concluded that the technology is suitable for use in NHS colposcopy clinics. Clinical trials have demonstrated that, when combined with all other usual colposcopic indicators, DySIS colposcopy can detect high-grade lesions with 88% sensitivity, compared to the 55% achieved in conventional colposcopy (Louwers et al. 2011).

LuViva Multimodal Spectroscopy- Identifies both

chemical and physical cell changes

Fluorescence Spectroscopy :The unique chemical components of diseased cells are able to be differentiated from healthy cells by the light they produce.

Reflectance Spectroscopy : Diseased cells absorb and reflect light differently than healthy cells.

Common morphological changes that effect light reflectance are: epithelial thickening, nuclear size and content, and angiogenesis

PresenterPresentation NotesClick on logo to play video

Indications of LuViva

LuViva is intended for use after:

Abnormal cytology

Positive HPV findings

To triage women aged 16+ for additional evaluation prior to colposcopy and biopsy.It may reduce colposcopy by up to 40% thus reducing overall costs

Multimodal hyperspectroscopy as a triage test for cervical neoplasia: Pivotal clinical trial results Original Research Article -Gynecologic OncologyVolume1 Issue1 July 2013, Pages 147151Leo B. Twiggs, Nahida A. Chakhtoura, Daron G. Ferris, Lisa C. Flowers, Marc L. Winter, Daniel R. Sternfeld, Manocher Lashgari, Alexander F. Burnett, Stephen S. Raab, Edward J. Wilkinson

LuViva result screen

Advantage to physician

Physician or nurse operated

Easy to use

Result is immediate

Similar in cost to other GYN devices

Finds disease earlier

Reduces false positives

Self-calibration before each use

PresenterPresentation NotesSpecicityObjective. To prospectively evaluate a new non invasive device that combines uorescence and reectancespectroscopy in a population in women at risk for cervical dysplasia.Methods. A total of 1607 women were evaluated with multimodal hyperspectroscopy (MHS), a painlesstest with extremely high spectral resolution. Subjects who were referred to colposcopy based on abnormalscreening tests or other referral criteria underwent the MHS test and also had a sample taken for additionalcytology and presence of high risk human papilloma virus (HPV) prior to undergoing biopsy.Results. Sensitivity of MHS for cervical intraepithelial neoplasia (CIN) 2+ was 91.3% (252/276). Specicity,or the potential reduction in referrals to colposcopy and biopsy, was 38.9% (222/570) for women withnormal or benign histology and 30.3% (182/601) for women with CIN1 histology. Two year follow-up data,collected for a subgroup of 804 women, revealed 67 interval CIN2+ that originally were diagnosed at enrollmentas normal or CIN1. MHS identied 60 of these (89.6%) as positive for CIN2+ prior to their discoveryduring the two year follow-up period.Conclusions. MHS provides an immediate result at the point of care. Recently, the limitations of cytologyhave become more obvious and as a consequence greater emphasis is being placed on HPV testing for cervicalcancer screening, creating a need for an inexpensive, convenient and accurate test to reduce false positive referralsto colposcopy and increase the yield of CIN2+ at biopsy. MHS appears

Advantage to the patient Procedure is painless and

causes no discomfort

Procedure is fast

Result is immediate, no more waiting and wondering if something is wrong

May avoid having an unnecessary colposcopy examination and or biopsies

Pivotal clinical trial 1,607 women enrolleddata evaluated on 1,330

Subjects 16 to 84 years old Multiple races:

Results : cervical spectroscopy (LuViva) detected 36.4% more

cervical intraepithelial neoplasia (CIN2+) than tests used under current guidelines

It could reduce unnecessary referrals of women with normal pathology by as much as 40%

Multimodal hyperspectroscopy as a triage test for cervical neoplasia: Pivotal clinical trial results Original Research Article -Gynecologic OncologyVolume1 Issue1 July 2013, Pages 147151Leo B. Twiggs, Nahida A. Chakhtoura, Daron G. Ferris, Lisa C. Flowers, Marc L. Winter, Daniel R. Sternfeld, Manocher Lashgari, Alexander F. Burnett, Stephen S. Raab, Edward J. Wilkinson

PresenterPresentation Notes7 sites through out the US

Watch "LuViva Advanced Cervical Scan" on YouTube - LuViva Advanced Cervical Scan:

http://youtu.be/XB-a6URRkY4

http://youtu.be/XB-a6URRkY4

Cervical cancer screening Dr. Nisreen AnfinanCervical Cancer: Worldwide Prevalence, Incidence, and Mortality EstimatesCervical Cancer in Saudi ArabiaOncogenic HPV & Cervical CancerHPV prevalence HPV prevalence in Saudi Arabia Cervical Cancer PreventionPrimary preventionCervical Cancer PreventionScreening test Options for cervical cancer screeningLimitations of CytologyVisual Inspection with Acetic Acid (VIA)VIAHPV TestingCytology vs HPV testing :variability of cytological diagnosis HPV Screening for Cervical Cancer in IndiaCost-effectiveness of cervical cancer screening: cytology versus human papillomavirus DNA testing Comparison of Various Methods Available for Detection of HPVRapid ,affordable and accurate HPV test are being developed Cervical Screening program in Saudi Arabia ??I f we dont have establish screening program for cervical cancer in low resources setting what you will use ??Visual inspection of ascitic acid (VIA )or HPV testing Low- resource settings Slide Number 24JCSP team Women eligibility Slide Number 27Collection of Samples Collection of Samples Collection of Samples Collection of Samples Collection of samples JCSP initial data JCSP Data JCSP Data JCSP Data JCSP Data Cervical Cancer Screening in SA HR-HPV testing and Reflex PapSaudi Center for Evidence Based Health Care (EBHC)www.moh.gov.sa/Ministry/MediaCenterSlide Number 42The future test for cervical cancer screening DySIS LuVivaSlide Number 46Indications of LuViva LuViva result screen Advantage to physicianAdvantage to the patient Slide Number 51Slide Number 52Slide Number 53Slide Number 54Slide Number 55Slide Number 56