Cervical Cancer Prevention in CEE and the NIS: The Way Forward - PowerPoint PPT Presentation

Cervical cancer prevention in cee and the nis the way forward
1 / 59

  • Uploaded on
  • Presentation posted in: General

Cervical Cancer Prevention in CEE and the NIS: The Way Forward. John Sellors, MD PATH (Program for Appropriate Technology in Health) Seattle, USA. Overview of Presentation. Global burden of disease Regional statistics and challenges Overview of screening technologies and programmatic issues

I am the owner, or an agent authorized to act on behalf of the owner, of the copyrighted work described.

Download Presentation

Cervical Cancer Prevention in CEE and the NIS: The Way Forward

An Image/Link below is provided (as is) to download presentation

Download Policy: Content on the Website is provided to you AS IS for your information and personal use and may not be sold / licensed / shared on other websites without getting consent from its author.While downloading, if for some reason you are not able to download a presentation, the publisher may have deleted the file from their server.

- - - - - - - - - - - - - - - - - - - - - - - - - - E N D - - - - - - - - - - - - - - - - - - - - - - - - - -

Presentation Transcript

Cervical cancer prevention in cee and the nis the way forward

Cervical Cancer Prevention in CEE and the NIS:The Way Forward

John Sellors, MD

PATH (Program for Appropriate Technology in Health)

Seattle, USA

Overview of presentation

Overview of Presentation

  • Global burden of disease

  • Regional statistics and challenges

  • Overview of screening technologies and programmatic issues

  • Goals and objectives of the Albania Meeting

Cervical cancer a global problem

Cervical Cancer – A Global Problem

  • Over 230,000 women die from cervical cancer worldwide per year.

  • 470,000 new cases per year.

  • 80% are in poor countries.

  • A leading cause of cancer death in poor countries.

Cervical cancer incidence asr

Cervical Cancer Incidence (ASR)

  • Worldwide, cervical cancer is the second most common cancer in women - in many developing countries it remains the most common.

  • Hardest hit regions include

    • Latin America and Caribbean, 33.5 per 100,000

    • sub-Saharan Africa, 31 per 100,000

    • South Central Asia, 26.5 per 100,000

    • Melanesia, 43.8 per 100,000

Cervical cancer incidence

Cervical Cancer Incidence

Age standardized rates per 100,000 (based on world population)

Cervical cancer s impact on women in cee nis

Cervical Cancer’s Impact on Women in CEE/NIS

  • Incidence rates in Eastern Europe tend to range from 15-35 per 100,000 (ASR).

  • Hardest hit countries include

    • Poland, Hungary, Bulgaria (ASRs 20.1 - 30 per 100,000), and

    • Romania, 31.5 per 100,000

  • Remaining countries typically have ASRs between 10-20 per 100,000.

Mortality from cervical cancer in cee nis

Mortality from Cervical Cancer in CEE/NIS

  • Cervical cancer is a leading cause of death from cancer for women in the region (breast cancer is #1).

  • In developed countries, ASR for mortality is approx 4 per 100,000. In developing countries, the rate is more than twice as high, 9.8 per 100,000.

  • Mortality in several CEE/NIS countries exceeds 9.8

South central and west asia

South Central and West Asia

Cervical cancer prevention in cee and the nis the way forward


Northern southern eastern europe

Northern & Southern Eastern Europe

Opportunities for advances in health services in cee nis

Opportunities for Advances in Health Services in CEE/NIS

  • Empower providers, improve clinical training and standards.

  • Implement evidence-based guidelines and practices (effectiveness and efficiency).

  • Implement quality improvement methods.

  • Empower communities to participate.

  • Encourage increased investment in public health services, including health promotion (shift: cure to prevention).

  • Understand country contexts (social, political, economic/CEA, cultural).

Cervical cancer prevention strategies an overview

Cervical Cancer Prevention Strategies:An Overview

Cervical cancer risk factors

Cervical Cancer Risk Factors

  • Human papillomavirus (HPV) is the sexually transmitted cause of precancerous lesions and cervical cancer (Wallboomers et al., ’99).

  • Over a lifetime, 80 percent sexually active women will be infected with a cancer-causing type of HPV(Koutsky, ’97).

  • So…why don’t all women get cancer?

Hpv prevalence in ontario women carcinogenic types

HPV Prevalence in Ontario Women (Carcinogenic Types)

(Sellors et al., CMAJ 2000)

Natural history

Natural History:

  • Cervical cancer develops from an abnormal area - usually present for 15 to 20 years.

  • Precursor lesion does not cause symptoms but can be detected with various tests.

  • Screening = detection of the precancerous lesion in asymptomatic women.

  • Outpatient treatment of precancerous lesions is very effective.

Natural history of cervical cancer

~20% within

10 years





(CIN 1)



(CIN 2/3)





10% in

2 years

Natural History of Cervical Cancer

Screening strategies are intended to identify these abnormalities.

Successful cervical cancer prevention programs it s not just about the test

Successful Cervical Cancer Prevention Programs: It’s not just about the test…

  • The screening test is just one of the key components in an effective cervical cancer prevention program.






Follow up

Methods of prevention vaccines

Methods of Prevention—Vaccines?

  • The most effective prevention would be a protectivevaccine, given at an early age before sexual activity begins.

  • Vaccine programs have a high cost.

  • An HPV vaccine probably will provide excellent protection** but the impact on population health will not seen for 20-30 years.

  • Screening and management would still be necessary, at least until unvaccinated women had grown older.

**Koutsky et al., NEJM, ‘02

Effect of age at vaccination on cc incidence

Effect of age at vaccination on CC Incidence

Barnabas and Garnett, ’02, unpublished

Key considerations for successful programs

Key considerations for successful programs

  • Policy and political will.

  • Infrastructure development.

  • Integration of testing, investigation/treatment, and follow-up care in health services.

  • Evaluation of effectiveness to reduce disease burden.

Screening tests for cervical neoplasia

Screening Tests for Cervical Neoplasia

  • Cytology

    • Conventional

    • Liquid based

    • Automated

  • Non-cytology methods

    • Visual inspection with acetic acid (VIA)

    • Visual inspection with Lugol’s iodine (VILI)

    • HPV-DNA testing





  • Time tested method.

  • Moderately accurate.

  • Unable to achieve concurrently high. sensitivity and specificity in many settings.

  • Resource intensive: laboratory, consumables, personnel, quality assurance.

  • Programmatic issues.

Accuracy of conventional cytology to detect hsil

Study Site

No. Women







Fahey et al.

10 295




U. Harare/ JHPIEGO






21 802




Accuracy of conventional cytology to detect HSIL

Pap test is problematic but

Conventional Pap test is still the only screening test ‘proven’ to reduce incidence and mortality rates of ICC.

CIN is slow growing.

Many low-grade CINs regress.

Abnormalities missed by one screening will probably be detected in next interval.

ICC usually due to lack of screening rather than cytologic errors.

Pap Test Is Problematic But…

Liquid based cytology lbc and computerized reading

ThinPrep (Cytyc)

automated LBC sample prep system

~60,000 selected cells distributed in a thin layer

smaller area than conventional Pap

specimens read optically or digitally

*FDA approved for screening

As of Sept. 2001

AutoPap 300 (Tripath) and Trac Cell 2000 (Accumed International)

automated LBC sample prep

visual intelligence computer technology

sorts by probability of abnormality

*FDA approved only for mandatory rescreening

Liquid-Based Cytology (LBC) and Computerized Reading

Liquid based cytology other considerations


randomly selected cells in thin layer

better quality fixation and less ‘debris’

quicker reading - 3.2 min (double for Pap)

amenable to HPV testing and immunohistochem. for different antigens


costly equipment

more costly than Pap - worse compliance?

retraining needed for smear-takers and pathology lab

morphology changes

Liquid-based Cytology: Other Considerations

Cost effectiveness of conventional pap and lbc

Cost-Effectiveness of Conventional Pap and LBC

  • Base case – Conventional Pap screen every 3 yrs compared with no screening is $4,096/life-year saved

  • If thin-layer cytology can decrease the FNR (by factor of 0.6) and incremental cost/slide is $10, the incremental cost is $22,010/life-year saved, if interval every 3 yrs

  • If computer allows 100% re-reading (decreasing FNR by 0.85) and incremental cost per slide is $10, incremental cost is $45,375/life-year saved, if every 3 yrs

Hpv dna tests


Hpv dna testing

HPV DNA Testing

  • Dependent on proprietary technology:

    HC IITM (Digene, Inc) is the only FDA approved, commercially available test.

  • Higher sensitivity but somewhat lower specificity than Pap.

  • Used in combination with Pap achieves high sensitivity and increases negative predictive value—allows for increase in screening intervals.

Hpv testing

HPV Testing

  • Testing expensive currently

  • Sophisticated testing infrastructure

  • Higher sensitivity, but lower specificity than cytology

  • Range in sensitivity: 80-100%

  • Range in specificity: 61-95%

  • 61.2% sensitivity and 93.8% specificity in Indian studies

  • Currently being evaluated in cross-sectional studies and RCTs

Self sampling vaginal swab

SELF-SAMPLING: Vaginal swab

Cervical cancer prevention in cee and the nis the way forward

Sensitivity and specificity of HC II for the detection of CIN 2/3 infour specimen types

n=200, colposcopy clinic

Sellors et al, 2000

Visual inspection with acetic acid or lugol s iodine

Visual Inspection with Acetic Acid or Lugol’s Iodine

Visual inspection with acetic acid via

Visual Inspection with Acetic Acid (VIA)

  • Promising low technology alternative to Pap smear.

  • Cervix is swabbed with 3-5% acetic acid and examined with a bright light to identify acetowhite lesions.

  • Results are immediate allowing for treatment and management decisions in the same session.

Visual inspection with lugol s iodine vili

Visual Inspection with Lugol’s Iodine (VILI)

  • Normal squamous epithelial cells have substantial stores of glycogen.

  • Glycogen stains mahogany brown with iodine solution.

  • Abnormal areas of squamous epithelium (CIN or inflammation) do not contain glycogen to the same extent and do not stain brown.

Cervical cancer prevention in cee and the nis the way forward



  • VIA-positive: A large acetowhite area

  • (b)VILI-positive: After Lugol’s iodine application, the lesion is iodine negative

Multi centered study of via and vili

Multi-Centered Study of VIA and VILI

  • 11 sites in Africa and India, N=55,000




    *for high grade disease

Sankaranarayanan et al, Int J Cancer 2004

Screening tests summary

Screening Tests: Summary

  • Given an adequate program with all necessary components, conventional cytology works when repeated at intervals.

  • Cytology not feasible in all settings.

  • Increasing evidence-base from a range of settings on cytology, VIA, VILI, and HPV.

  • Incremental life-year gains from newer cytology and HPV technologies are at considerable cost.

Programmatic considerations

Programmatic Considerations

Key components for quality assurance in cee nis

Key Components for Quality Assurance in CEE/NIS

  • Assess quality and effectiveness of current strategies

    • Identify common deficits & modify strategies as needed:

      • inadequate information systems

      • faulty transport mechanisms

      • poorly trained providers/laboratory specialists

      • poor quality of care

      • low participation rates

Key components for involving women in cee nis

Key Components for Involving Women in CEE/NIS

  • Increase awareness of cervical cancer and preventive health seeking behavior among women ages 30-50.

  • Emphasize the need for screening in this age group.

  • Increase coverage first and add rescreening later.

  • Resources are always scarce – use CEA.

Key components of screening strategies for cee nis

Key Components of Screening Strategies for CEE/NIS

  • Screen all women aged 30-50 at least once before expanding services to other age groups or decreasing the interval between screenings.

  • Refer screen-positive women for colposcopy.

  • Treat women with high-grade precancers, refer those with invasive disease, provide palliative care for women with advanced cancer.

Key components for monitoring impact

Key Components for Monitoring Impact

  • Collect service delivery and quality control data that will facilitate ongoing monitoring and evaluation of program activities and outputs.

The durres albania conference on cervical cancer prevention in cee and the nis march 11 13 2004

The Durres, Albania Conference on Cervical Cancer Prevention in CEE and the NISMarch 11-13, 2004

Objective of the conference

Objective of the Conference

  • Unique opportunity to bring together the most interested and involved professionals and key Ministry of Health staff to:

    • Share experiences of implementing cervical cancer programs in CEE/NIS countries.

    • Provide technical update about cervical cancer prevention practices.

    • Facilitate exchange of information about key recommendations and potential policy change at the national level.

Anticipated success

Anticipated Success:

  • Important step in strengthening cervical cancer prevention efforts in the region.

  • Raising profile of cervical cancer prevention in CEE/NIS via unified messages.

  • Accelerating progress through sharing materials, experience, lessons learned.

  • Using evidence base to inform cervical cancer prevention work.

Thank you

Thank you

Cervical cancer prevention in cee and the nis the way forward


Screening management strategies

Screening & Management Strategies

  • Test in primary care and refer women screened positive for treatment

  • Test, investigate, and treat in the same session

  • Test and treat in the same session

Longitudinal studies of pap sensitivity

Longitudinal Studies of Pap Sensitivity

  • Ranges between 60-90% IARC (WHO, 1986)

  • Organized program: smear @ 30 and 45 yrs of age, with 80% coverage and public education can reduce mortality rate by 50% Ponten et al (Int J Cancer, 1995)

  • Incidence of stage > II disease is decreased by screening

  • Mortality also a good indicator since IA disease only contributes to incidence

Is an hpv test detecting the same thing as pap

Is an HPV Test Detecting the Same Thing as Pap?

  • Hypothesis: CIN 3 lesions detected by new tests may be different (less likely to progress) than the lesions detected by Pap…and CIN 3 lesions missed are more likely to progress

Treatment options

Treatment Options

Funding and support

Funding and Support

  • Funding has been a remarkable catalyst to interest, research, and program efforts in cervical cancer prevention around the world, particularly in countries where the need is greatest and resources most limited.

Health services in cee nis

Health Services in CEE/NIS

  • Countries in Central and Eastern Europe and the former Soviet Union inherited centralized Soviet models of health care.

  • Since the 1990s health reforms have been introduced including health financing, coordinated services, quality of care, community participation, and public health reforms.

Health services continued

Health Services (continued)

  • Health expenditures have increased in all countries, although remain lower than countries in Western Europe.

  • More reforms are needed!

Cervical cancer prevention in cee and the nis the way forward

Proportion of HC II positive specimens with viral levels above a cutoff (RLU > 15.0)

n=200, colposcopy clinic

Via sensitivity and specificity

VIA Sensitivity and Specificity

  • VIA has equal or greater sensitivity but lower specificity than conventional cytology.

Important changes in terminology

CIN System

CIN 3 includes CIS

‘Condyloma/HPV effect’ separated from CIN 1 (together had been ‘Mild Dysplasia’)

Bethesda System

HSIL contains CIN 2 & 3

LSIL includes HPV

ASCUS distinct from atypia due to repair, reaction, infection

Important Changes in Terminology

  • Login