Cervical Cancer Prevention in Low Resource Settings: Notes from the Field Paul D' Blumenthal, MD, MP

1
Cervical Cancer Prevention in Low Resource
SettingsNotes from the FieldPaul D.
Blumenthal, MD, MPHJHPIEGOJohns Hopkins
University
2
Cervical Cancer Magnitude of the Problem

• 400,000 new cases identified each year
• 80 of the new cases occur in developing
  countries
• At least 250,000 women die of cervical cancer
  each year
• 1/5 of global burden of disease in India
• In 2003, 12,200 cases of invasive cervical cancer
  will be diagnosed in the US 4,100 women will die
  1
• Cervical cancer is the third most common cancer
  worldwide

3
Natural History of Cervical Cancer
Normal Cervix
About 60 regress within 2-3 yrs
HPV Infection
HPV-related Changes
Low-Grade SIL (Atypia, CIN I)
Cofactors High-Risk HPV Types (16, 18, 33, etc.)
About 15 progress within 3-4 yrs
High-Grade SIL (CIN II, III/CIS)
30-70 progress within 10 yrs
Invasive Cancer
Source Sherris 1998 Bishop et al 1995.
4
Secondary Prevention Why a New Approach Is Needed

• Primary prevention takes a long time to
  successfully implement
• Available and accepted screening methods are not
  practical or accessible to the majority of women
  living in many countries

Source Blumenthal 1994 Gaffikin 1997.
5
Good Prevention Programs Must be Able to

• Reach a significant proportion of at-risk women
• Effectively test these women.
• Treat/Manage women who test positive and ensure
  effective follow up.
• Monitor and evaluate program impact.

6
Limitations of Cervical Cytology

• Complex laboratory test
• (sampling instruments, slides, fixatives,
  reagents, cover slips, processing equipment,
  microscopes,)
• Requires trained cytotechnician for reading and
  pathologist for review
• Continuous monitoring needed to maintain
  high-quality results
• Reports often take months to obtain
• Follow-up of women is difficult
• Usually available only in large cities in many
  countries

7
Programmatic Constraints in Low Resource Settings

• Clinical expertise
• Very limited capacity for confirmatory or
  diagnostic testing
• Poor Infrastructure
• Limited reporting, monitoring
• Difficult to contact patients
• Have to See your opportunity and take it

8
Premises /Guiding Principles

• Research aims to identify generalizable
  conclusions
• It is a means implementation/incorporation is
  the end
• Public health approaches are about population
  interventions rather than the individuals
  diagnosis
• Policy makers can be motivated to use data to
  make decisions
• The Good is not the Enemy of the Best
• If you cant be with the one you love, love the
  one youre with.

9
Effectiveness of cancer prevention programs
influenced by
Linking Screening and Treatment
Effectiveness of treatment
Screening Coverage
10
Positive or Negative?
Positive
Negative
11
Visual Inspection Methods

• VIA - visual inspection with acetic acid naked
  eye
• VIAM - visual inspection with acetic acid low
  magnification
• VILI - visual inspection with Lugols Iodine

12
TEST CHARACTERISTICS OF VISUAL METHODS VIA

• BASED ON gt65,000 WOMEN
• SCREENED IN 8 COUNTRIES
• Average sensitivity 77 (range 56-90)
• Average specificity 84 (range 64-93
• PPV range 5-10
• NPV gt99

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TEST CHARACTERISTICS OF VISUAL METHODS VIAM

• BASED ON gt 20,000 WOMEN
• SCREENED IN 2 COUNTRIES
• Average sensitivity 68 (range 61-74)
• Average specificity 84 (range 79-89)
• PPV range 5-10
• NPV gt99.5

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TEST CHARACTERISTICS OF VISUAL METHODS VILI

• BASED ON gt 50,000 WOMEN
• SCREENED IN 6 COUNTRIES
• Average sensitivity 92 (range 76-97)
• Average specificity 85 (range 73-91)
• PPV range 6-11
• NPV gt99.5

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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

16
TATI (Screening and Immediate Treatment)
ProgramSan Martin, Peru

• Goal Demonstrate safety, acceptability, and
  accuracy of a single visit approach (VIA,
  followed by VIAM plus necessary treatment) under
  usual conditions in a low-resource setting.
• screen 80 of women between 25 and 49 years of
  age in 3 years (81,000 women)
• achieve complete follow up of women with abnormal
  screening results
• Collaborators PAHO, PATH, Regional Department
  of Health (MOH of San Martin), Peruvian Cancer
  Foundation, ICRF

17
JHPIEGO/Thailand Cervical Cancer Prevention
(CECAP) Program Roi-et Province, Thailand

• SAFE goal demonstrate safety, acceptability,
  feasibility and program effort using a
  single-visit approach in a low-resource setting
  (5559 women tested by 2001)
• ACE goal demonstrate sustainable strategy for
  access and coverage expansion
• QAANT- Quality Assurance Approaches for New
  Technologies
• Collaborators Royal Thai College of Ob/Gyns
  Depts. of Ob/Gyn, Khon Kaen University
  Chulalongkorn University, Thailand MOPH

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ACOG/SOGC/RCOG Statement

• ACOG Statement of Policy
• As issued by the ACOG Executive Board
• A joint policy statement from the American
  College of Obstetricians and Gynecologists, the
  Society of Obstetricians and Gynaecologists of
  Canada, the Central American Federation of
  Associations and Societies of Obstetrics and
  Gynecology, the Gynaecologic Oncologists of
  Canada, the Society of Canadian Colposcopists,
  the Society of Gynecologic Oncologists, and the
  Royal College of Obstetricians and
  Gynaecologists.
• This policy
• Establishes the need for practical and
  affordable interventions
• Recognizes obstacles associated with
  implementing cytology-based screening
• Validates the single-visit approach, which
  links a detection method with an immediate
  management option, as a safe, acceptable and
  cost-effective approach to cervical cancer
  prevention
• Calls for obstetric-gynecologic organizations
  worldwide to play a greater role in advocating
  for sustainable cervical cancer prevention
  programs
• Challenges funding agencies to underwrite
  cost-effective, resource-appropriate
  interventions
• Published in the Green Journal, March 2004

19
Co-Assessment Data Training
JHPIEGO, 2002, unpublished
20
SAFE Project ThailandSelected
Results
Lancet. 2003 Mar 8361(9360)814-20.
21
CryotherapyOne Year Followup-Visibility of SCJ
92
80
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Key Findings One year Follow up

• Among 609 VIA-negative women, colposcopy was
  abnormal in 27.3 (166)
• Two cases of HGSIL confirmed (0.3) by
  endocervical biopsy (negative colposcopy)
• No cancers missed
• Among the VIA-positive women, colposcopy was
  abnormal 82 (31/38) of the time
• Two HGSILs confirmed (5)
• One adenocarcinoma confirmed

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Summary One year Follow up

• One year after cryotherapy
• The SCJ appears to be visible in the large
  majority of cases, thus the cervix is evaluable
  by VIA
• High correlation between nurses and colposcopists
  on test-positives
• VIA picked up the majority of positives
  identified on colposcopy
• Triage for biopsy would have been similar if
  based on VIA versus colposcopy

24
ACE Phase

• ACE Access and Coverage Expansion
• Rationale for ACE
• Effectiveness of treatment established
• Effectiveness of linking testing with treatment
  using a SVA established
• Needed to establish how to optimize coverage
  using SVA

25
Percentage VIA Coverage Roi Et Province, August
2003
Data on File, JHPIEGO
26
Percentage VIA CoverageNong Khai Province,
November 2003
Data on file, JHPIEGO
27
Mean Health Expenditures by Income
Public Sector Health Expenditure
GDP per capita
(US) Lowest 1.4 3.19 (GNP per
capitaltUS 300) Low 1.7 9.58 (GNP
per capita US 300-765) Middle 3.2 71.99
(GNP per capita gtUS 765) All Africa 1.6
11.22
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Cost-Effectiveness of Prevention Strategies
Source Goldie, et al. Policy Analysis of
Cervical Cancer Screening Strategies in
Low-Resource Settings. Journal of the American
Medical Association 20012853107-3115.
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Cost-Effectiveness of Prevention Strategies
Mortality
Cost (US )
Life-Exp (Yrs)
CE Ratio (/YLS)
Strategy
Reduction
-----
-----
No screening
2
27.024
VIA Referral
7
27.0418
290
12.3
VIA Treatment
11
27.0565
263
34.9
Pap
25
27.0393
1,459
13.5
HPV
78
27.0457
3,477
22.0
VIA HPV
83
27.0453
3,805
28.5
Pap HPV
95
27.0456
4,309
26.2
Mandelblatt et al JNCI, 2002
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HPV vaccines

• Premise
• Preventing the acquisition of high-risk type HPV
  strains (prophylactic vaccine)
• or
• Arresting the progression of cervical lesions
  and/or cancer (therapeutic vaccine)
• will reduce cervical cancer incidence and
  mortality

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HPV-16 L1 VLP vaccine RCT results

• Incidence of persistent
• HPV-16 infection
• (HPV detected at gt 2 visits)
• HPV-16 vaccine (n 768) 0 per 100 woman
  yrs
• Placebo (n 765) 3.8 per 100 woman yrs
• 9 cases HPV-related CIN occurred among placebo
  recipients
• 100 efficacy, 95 CI, Plt0.0001
• Koutsky, LA et al. NEJM 347(21) 2645-1651

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A vaccine and a vaccination program are two
different things.

• School/Pediatrician based Program?
• Vaccine may not necessarily be available in
  communities most affected by cervical cancer 2
• Unvaccinated women will continue to need
  screening and management
• Need for Re-vaccination?
• Vaccination among already-exposed women?

33
The challenge enabling impact of vaccine
Vaccine Provided
Testing needed
30
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Global Conclusions

• An ounce of prevention is worth a pound of cure.
• Public health (prevention) approaches are about
  population interventions rather than the
  individuals diagnosis
• The Good is not the Enemy of the Best
• If you cant be with the one you love (e.g. Pap,
  HPV),
• love the one you can be with.

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Pearls

• A death every 2 minutes were mad as hell and
  were not going to take it anymore
• Pap is passé
• HPV Health Promotion through Vinegar