New Global Approaches to Cervical Cancer Prevention

1
New Global Approaches to Cervical Cancer
Prevention

• Dr Martha Jacob FRCOG, MPH
• EngenderHealth
• March 2004

Funded by Bill Melinda Gates Foundation
2
Barriers to Cervical Cancer Prevention

• Early Detections Services Unavailable,
  Unreliable
• Treatment of Precancer
• Inaccessible
• Inappropriate
• Inadequate follow up of women needing treatment
• Lack of monitoring evaluation, corrective
  action improve program performance
• Failure to reach target age group
• Limited awareness of cervical cancer as a health
  problem, lack of a policy, lack of political will

3

• Womens perspectives
• Medical profile
• Sociocultural and gender influences
• Community outreach
• Education

WOMEN
TECHNOLOGY
SERVICE

• Policies, program structure, management
• Availability and accessibility
• Quality of services
• Health Information Systems
• Referrals
• Qualified providers

• Efficacy
• Safety
• Procedures supplies
• Labs (including quality control)
• Costs
• Acceptability

Adapted from Simmons et al. The Strategic
Approach to Contraceptive Introduction. Studies
in Family Planning 2879-94. 1997
4
SCREENING TESTS FOR CERVICAL NEOPLASIA

• Cytology- Conventional method
• Time tested method
• Organized programs, periodic re-screening
• Unable to achieve consistently high sensitivity
  and specificity in many settings
• Resource intensive laboratory, consumables,
  personnel, quality assurance
• Programmatic issues

5
Alternate Screening Tests
Immediate results Minimal
requirements

• Visual inspection with acetic acid (VIA)
• 3-5 Acetic Acid (Vinegar)
• Abnormal epithelium transiently turns white
• ACETO- WHITE

• Visual inspection with Lugols iodine (VILI)
• Normal epithelium take up iodine stain and
  appears mahogany brown
• Abnormal epithelium not stained and appears
  yellow.

Subjective - Needs standardized definitions
- Regular quality assurance
6
VIA images
Source EngenderHealth, Wright TC, 1996
7
Alternate Screening Tests - contd

• HPV testing
• Detect High Risk HPV types
• Sample from cervix- similar to PAP
• Special transport medium
• Processed in the lab
• Rapid turn around of results

Objective tests Expensive
8
Alternate Screening Tests
For detecting HSIL. Source Personal
Communication IARC 2004
Long term impact yet to be evaluated
9
(No Transcript)
10
Traditional ApproachScreen, Diagnosis Treat
11
Colposcopy Biopsy

• Diagnosis Cytology, Colposcopy and Histology
  are complementary
• Sensitivity 87 to 99 Specificity 23-87
  (Mitchell 98)
• High sensitivity for high grade lesions,
• Less accurate for differentiating metaplasia
  versus low grade lesions.
• Intensive training and sophisticated
• equipment required.

12
Methods of treatment for Pre Cancer

• Ablative Methods
• Cryosurgery.
• Diathermy
• Cold Coagulation.
• Laser ablation

• Excision Methods
• Loop Electrosurgical Excision Procedure (LEEP).
• Laser Cone.
• Cold Knife Cone

• Decision on treatment modality
• Exclusion of invasive lesion
• Training and experience of the provider
• Availability of resources
• Clinical value of method for the patient
• Preference of the patient

13
Cochrane 2002 Conclusions

• No overwhelmingly superior technique to treat
  cervical intraepithelial neoplasia (CIN)
• Cryotherapy viable alternative in limited
  resource settings
• easy to use,
• relatively cheap,
• associated with lowest morbidity.

14
Treatment Options
Low lt 500 Moderate 500-1500 High gt
1500 1 Loop electrosurgical excision procedure 2
Requires use of operating room lighting and
equipment
JHPIEGO 2003
15
Cryotherapy
Freezing abnormal tissue CO2 or N2O Single
Freeze or Double Freeze

• Strengths
• Cure rate 85-95
• Lowest morbidity

• Limitations
• Low cure rate (70 to 90) related to lesion size,
  possibly grade and location
• Confirming the exact nature of lesion not
  possible
• Difficult to determine the amount of tissue
  destroyed

Source for Cure rates ACCP review Cochrane 02
16
LEEP
Excise with thin wire loop Cauterize base

• Strengths
• Cure rate 91-98 (Cochrane 02)
• Reliable histology specimen with least
  morbidity.

• Limitations
• Pathologic margins often involved and more
  difficult to interpret
• Requires intensive training
• More sophisticated equipment

17

• Cold Knife Cone
• Replaced by less invasive excisional or ablative
  out- patient procedures
• Excision of wide and deep cervical cones using a
  surgical knife
• Cure rate 90-94
• (Cochrane 02)

• Hysterectomy
• Unacceptable as primary treatment

18
Traditional Approach Screen, Diagnosis Treat

19
Alternate Approach SCREEN TREAT
20
Alternate Approach Screen Treat

• Reduce the number of steps
• VIA gt Cryotherapy
• HPV testgt Cryotherapy
• VILIgt Cryotherapy
• Reduce the lost to FU Treatment
• Single Visit Approach
• Multiple (2) Visit Approach
• Increase Availability, Accessibility
  Utilization
• Primary Care mid level providers
• Static Mobile (Outreach)
• Integrated Vertical

• Over treatment
• Safety Critical concern
• Under treatment
• Miss disease
• Treatment procedure fails
• Feasibility
• Acceptability

21
Screen Treat

• Midlevel providers trained to level of competence
• Counsel
• Screen
• Select
• Cryotherapy Double Freeze
• Post Treatment Follow Up

22
Safety Screen Treat

• Screen Treat performed by Mid level providers
• Major Complications 2 cases ( 6000 procedures)
• Minor Complications 2-4

Safety of cryotherapy for HIV-seroconversion
needs further evaluation.
23
Effectiveness Screen Treat

• Three arm RCT (South Africa) comparing the safety
  and efficacy of screening (using VIA or HPV test)
  followed by cryotherapy by mid level providers
  in reducing the burden of high-grade cervical
  cancer precursors.
• ACCP strict selection criteria for cryotherapy
• Not suspicious of cancer
• All edges are fully visible with no extension
  into endocervix beyond cryoprobe.
• Cryotherapy can be used to treat large
  proportion of women with positive screening
  tests.

24
Feasibility Screen Treat

• Primary care facilities
• Static
• Clinical Outreach (Mobile)

Integrated or Vertical
25
Feasibility Screen Treat

• Number of visits
• Single visit- Avoids attrition due to lost to FU
• Multiple visit- Requires well organized tracking
  system

26
Feasibility Screen Treat

• Reliable supply of refrigerant is crucial
• Identify and rely on local suppliers
• Machines break
• Repair Maintenance (RAM) Services by creating
  local capacity for common repairs

27
Acceptability Screen Treat

• Satisfied would recommend to others (95- 99)
  
• Testing Treating experience equal to or better
  than expected (95)
• At 3 months 97 had recommended to others.
• Source RTCOG JHPIEGO 2003

28
Cost-Effectiveness of Screening Strategies
Source Goldie, et al. Policy Analysis of
Cervical Cancer Screening Strategies in
Low-Resource Settings. Journal of the American
Medical Association 20012853107-3115.
29
Future in Cervical Cancer Prevention

• VACCINES
• Prophylactic Vaccines
• Therapeutic Vaccines
• Combination of screening
• Immunization

30
Conclusions-1

• In countries where infrastructure and quality
  assurance requirements are consistently met,
  cytology-based programs can be implemented
  effectively.
• Screen-and-treat approach
• Safe Effective Feasible Acceptable
• Range of trained and competent health providers
  including non physicians can perform screening
  tests and cryotherapy.
• Screening tests and cryotherapy can be provided
  at all levels of facilities including primary
  care settings and integrated with general
  reproductive care services.

31
Conclusions-2

• HPV testing
• HPV test characteristics better than visual tests
  and cytology
• Technical and infrastructure requirements can
  make it difficult to implement
• VIA
• The sensitivity of VIA is equivalent to or better
  than cytology its specificity is lower
• Can be implemented in a range of settings
• Special attention to regular and consistent
  quality assurance is required due to its
  subjective nature
• VILI
• VILI test characteristics may be better than VIA
  
• Demands further research

32
Thank you
33

• Sensitivity the proportion of individuals
  correctly identified by the test as having
  disease. The higher the sensitivity, the fewer
  infections that will be missed (false negatives).
• Specificity the proportion of individuals
  correctly identified by the test as NOT having
  disease. The higher the specificity, the fewer
  false positives there will be. The lower the
  specificity, the more over treatment there will
  be
• Positive Predictive Value refers to the
  probability of having a disease given a test is
  positive.
• Negative Predictive Value refers to the
  probability of NOT having a disease given a test
  is negative.

34

• Liquid based cytology
• Merits of LBC debated
• Compared to conventional cytology
• No statistically significant differences in all
  diagnostic categories (WNL to HSIL)
• Sensitivity Specificity similar
• Specimen adequacy superior
• More expensive
• Impact on cancer incidence and mortality and cost
  effectiveness yet to be established