SCREENING WITH SCREENING WITH ALTERNATIVE ALTERNATIVE MODALITIESMODALITIES

Towards Comprehensive Cervical Cancer Towards Comprehensive Cervical Cancer Prevention and ControlPrevention and Control

CARLOS SANTOS, MDCARLOS SANTOS, MDIntituto Nacional de Enfermedades NeoplIntituto Nacional de Enfermedades Neopláásicassicas

LimaLima--PerPerúú

MMééxico 2008xico 2008

The Most Frequent Female Cancer Sites 1994-1997

The Most Frequent Female Cancer Sites 1994-1997

Female breastFemale breastCervix uteriCervix uteriStomachStomachOther skinOther skinLungLungOvary Ovary Non-Hodg.lymp.Non-Hodg.lymp.PSUPSUColon Colon Thyroid Thyroid Brain Brain Leukaemia Leukaemia GallbladderGallbladder

n = 21 051n = 21 051 n = 11 071n = 11 071

Incidence MortalityIncidence Mortality

Registro de Cáncer Lima MetropolitanaRegistro de Cáncer Lima Metropolitana

638643684703727774

853890938

1177

523480

393123

428630

474450

75393

14621247

14783738

19552751

32.3

23.5

17.6

7.5

7.5

8.7

10.6

7.0

6.6

5.6

5.6

5.2

5.1 4.9

3.8

3.3

3.9

5.7

4.2

4.1

7.0

13.1

10.9

13.2

Female Cancer IncidenceFemale Cancer Incidence

9.4

12.9

25.5

30

52.4

0 10 20 30 40 50 60

Cervix uteri

Breast

Stomach

Galbladder

NonHodgkinLimphoma

9.4

12.9

25.5

30

52.4

0 10 20 30 40 50 60

Cervix uteri

Breast

Stomach

Galbladder

NonHodgkinLimphoma

Age. - standarized rate 100,000

Registro de Cáncer de Trujillo 1991 - 95

Age. - standarized rate 100,000

Registro de Cáncer de Trujillo 1991 - 95

Female Cancer MortalityFemale Cancer Mortality

0 5 10 15 20

Cervix uteri

Stomach

Gallbladder

Breast

Hematopoye

Age. - standarized rate 100,000

Registro de Cáncer de Trujillo 1988 - 90

Age. - standarized rate 100,000

Registro de Cáncer de Trujillo 1988 - 90

18.2

17.1

7.7

7.4

7.4

CERVICAL CANCER IN LATIN AMERICA

Worldwide Highest Incidence Rates

CERVICAL CANCER IN LATIN AMERICA

Worldwide Highest Incidence Rates

47.1

53.5

64.3

67.2

83.2

87.3

0 20 40 60 80 100

PernambucoPernambuco

HarareHarare

BelénBelénTrujilloTrujilloAsunciónAsunción

Rate / 100,000Rate / 100,000

CIFC, IARC, 1982 - 87, 92, 97Globocan 2002CIFC, IARC, 1982 - 87, 92, 97Globocan 2002

HaitiHaiti

CIN MANAGEMENT INCIN MANAGEMENT INDEVELOPING COUNTRIESDEVELOPING COUNTRIES

Screening ProgramsScreening Programs

nn Classic cytology Classic cytology –– based: based: Developed worldDeveloped world

nn Non successful in developingNon successful in developingworldworld

Leopold Koss

CIN MANAGEMENT INCIN MANAGEMENT INDEVELOPING COUNTRIESDEVELOPING COUNTRIES

nn Established laboratoryEstablished laboratory

nn Highly trained personnel Highly trained personnel

nn At least 3 visitsAt least 3 visits

Cytologic ScreeningCytologic Screening

CIN MANAGEMENT INDEVELOPING COUNTRIES

CIN MANAGEMENT INCIN MANAGEMENT INDEVELOPING COUNTRIESDEVELOPING COUNTRIES

n PAP result = two weeks

n Colposcopy = up to 2 months

nn PAP result = two weeksPAP result = two weeks

nn Colposcopy = up to 2 monthsColposcopy = up to 2 months

Denny, 2002Denny, 2002

Controlled StudiesControlled Studies

CERVICAL CANCERCERVICAL CANCERCERVICAL CANCER

SCREENINGSteps of a Classic Program

Sampling ReportFixation Sending report backTransport ColposcopyProcessing ResultsReading Treatment

SCREENINGSCREENINGSteps of a Classic ProgramSteps of a Classic Program

Sampling ReportSampling ReportFixation Fixation Sending report backSending report backTransport ColposcopyTransport ColposcopyProcessing ResultsProcessing ResultsReadingReading TreatmentTreatment

CENTRALCENTRALCYTOLOGY

LAB

TREATMENT

SCREENING PARADOXSCREENING PARADOX

Alternative Screening TestAlternative Screening Test

nn High technologyHigh technology

nn Low technologyLow technology

Meeting 2007Meeting 2007

ACCURACY OF SCREENING TESTS: ACCURACY OF SCREENING TESTS: ACCURACY OF SCREENING TESTS:

How accurate is cytology in developing countries in detecting CIN 2 and 3 lesions? How accurate is cytology in developing countries in How accurate is cytology in developing countries in detecting CIN 2 and 3 lesions? detecting CIN 2 and 3 lesions?

Author, year and country of study

Number of participants

Sensitivity % Specificity %

U. Zimbabwe/JHPIEGO, 1999 Zimbabwe

2092 44 91

Cronje et al., 2003, South Africa

1093 48 96

Denny et al., 2002, South Africa

2754 57 96

Salmeron et al., 2003 7868 59 98

Sankaranarayanan et al., 2004, India

22 663 61 95

Denny et al., 2000, South Africa

2885 78 95

Denny et al., Cancer 2000; 89: 826-33; Denny et al., Cancer 2002; 94:1699-707; Lancet 1999; 353: 869-73;Cronje et al., Am J Obstet Gynecol 2003; 188: 395-400; Salmeron et al., Cancer Causes Control 2003; 14: 505-12; Sankaranarayanan et al., J Med Screening 2004; 110: 907-13.

Denny et al., Cancer 2000; 89: 826-33; Denny et al., Cancer 2002; 94:1699-707; Lancet 1999; 353: 869-73;Cronje et al., Am J Obstet Gynecol 2003; 188: 395-400; Salmeron et al., Cancer Causes Control 2003; 14: 505-12; Sankaranarayanan et al., J Med Screening 2004; 110: 907-13.

Meeting 2007Meeting 2007

ACCURACY OF VIA (for CIN 2 + Diseases)ACCURACY OF VIA (for CIN 2 + Diseases)ACCURACY OF VIA (for CIN 2 + Diseases)

Denny et al., Cancer 2000; 89: 826-33; Denny et al., Cancer 2002; 94:1699-707; Belinson et al., Obstet Gynecol 2001;98: 441-44; Lancet 1999; 353: 869-73; Cronje et al., Am J Obstet Gynecol 2003; 188: 395-400; Sankaranarayanan et al., Int J Cancer 2004;110:907-13.

Denny et al., Cancer 2000; 89: 826-33; Denny et al., Cancer 2002; 94:1699-707; Belinson et al., Obstet Gynecol 2001;98: 441-44; Lancet 1999; 353: 869-73; Cronje et al., Am J Obstet Gynecol 2003; 188: 395-400; Sankaranarayanan et al., Int J Cancer 2004;110:907-13.

Author, year and country of study Number of participants

Sensitivity % Specificity %

Denny et al, 2000, South Africa 2885 67 84

Denny et al., 2000, South Africa 2754 70 79

Belinson et al., 2001, China 1997 71 74

U. Zimbabwe/JHPIEGO, 1999 Zimbabwe

2148 77 64

Cronje et al., 2003, South Africa 1093 79 49

Sankaranarayanan et al., 2004 India & Africa

54 981 79 86

Santos et al Gyn Onc 61: 11(April 1996)Santos et al Gyn Onc 61: 11(April 1996)

29%

2%

69%

29%

2%

69%

N= 639N= 639

One Session CIN Management in Developing Countries

One Session CIN Management in Developing Countries

Adequacy of Day Management Adequacy of Day Management

Adequately ManagedAdequately Managed

UndermanagedUndermanaged

OvermanagedOvermanaged

Cervical Cancer ControlCervical Cancer ControlCervical Cancer Control

ALTERNATIVE APPROACH

Two concepts

♦ Diagnosis : VIAA - VIAAM

♦ Treatment : “See and Treat”

ALTERNATIVE APPROACH

Two concepts

♦ Diagnosis : VIAA - VIAAM

♦ Treatment : “See and Treat”

CCÁÁNCER DE CNCER DE CÉÉRVIXRVIX

IVA vs. IVAMIVA vs. IVAM(3 Observadores)(3 Observadores)

n = 218n = 218

Ojo Ojo Lupa pLupa p

44 Sensibilidad Sensibilidad 66.666.6 84.9 84.9 s.s.

44 Especificidad Especificidad 6868 52.8 s.52.8 s.

Santos. Tesis, 2005

CCÁÁNCER DE CNCER DE CÉÉRVIXRVIXIVA vs. IVAMIVA vs. IVAM

(3 Observadores)(3 Observadores)n = 218n = 218

RENDIMIENTO POR OBSERVADORRENDIMIENTO POR OBSERVADOR

MagnificaciMagnificacióónn ObservadorObservador SensibilidadSensibilidad EspecificidadEspecificidad

NONO112233

767681815555

606064648888

SSÍÍ112233

949485859090

464658585151

Santos. Tesis, 2005

TATI PROJECT

• GOALS

n Effectiveness VIA-screening VIAM-triage

n Effectiveness CO2 cryotherapy

n Cost and feasibility ofincorporating VIA,VIAM and cryotherapy in rutine delivery of women’s health services

• GOALS

n Effectiveness VIA-screening VIAM-triage

n Effectiveness CO2 cryotherapy

n Cost and feasibility ofincorporating VIA,VIAM and cryotherapy in rutine delivery of women’s health services

Magnified Visual InspectionMagnified Visual Inspection

AviscopeAviscope

§§ Device with Device with monocular lens, monocular lens, green and white green and white light, 4 x power.light, 4 x power.

§§ Portable (batteries) Portable (batteries)

Screening Screening –– Treatment Fluxogram Treatment Fluxogram

TATI PROJECTTATI PROJECT

Women25 - 49

VIA PAP

+ - - +VIAM

HSIL LSIL

+ -Bp

Cryo Follow up

3 years

+

RepeatPAP

6 monthsColpo

SECONDARY PREVENTION SECONDARY PREVENTION CERVICAL CANCERCERVICAL CANCER

Previous SituationPrevious Situation

TATI PROJECTTATI PROJECT

• Opportunistic

• Only 25% of positives completed diag/treat

• Opportunistic

• Only 25% of positives completed diag/treat

Intervention Team Intervention Team

TATI PROJECTTATI PROJECT

• 1 – 4 midwives

1 primary care physician

• 12 teams

• 30 base health centers

• 1 – 4 midwives

1 primary care physician

• 12 teams

• 30 base health centers

H.R. Saposoa

C.S. La Merced

H.R. Picota

H.R. Lamas

C.S. LlulluycuchaC.S. Nva. Rioja

C.S. Nva.Cajamarca

C.S. JuanGuerra

C.M.P Tarapoto

P.S. San Pablo

P.S. Naranjillo

H.R. San Josede Sisa

C.S. Morales

C.S. Pongo delCaynarachiI

C.S. SAN ANTONIO

C.S.9 de Abril

P.S. La Huarpia

P.S. Collpa

H.A. Bda. De Shilcayo

C.S. Chazuta

C.S. Cuñumbuque

C.S. Consuelo

P.S. Shatoja

C.S. Leoncio Prado

P.S.Tres Unidos

C.S. Huimbayoc

INTERVENTION TEAMS. TATI SAN MARTIN REGION

INTERVENTION TEAMS. TATI SAN MARTIN REGION

MIDWIFE

PHYSICIAN

48 Midwives VIAA

35 Physicians VIAAM – CRYO

4 Gynecologists COLPO – TTO

3 Cytotechnicians

3 Training courses

48 Midwives VIAA

35 Physicians VIAAM – CRYO

4 Gynecologists COLPO – TTO

3 Cytotechnicians

3 Training courses

REFERRAL CENTERS

REGION SAN MARTIN

REFERRAL CENTERS

REGION SAN MARTIN

InformationEducation

Community

Screening Treatment

VIAVIAM

Cryotherapy

Primary level

Especialized treatment

ColposcopyLEEP, Cone, Histerectomy

Secondary level

Follow-up

IdentificationEducation

Community

TATI PROJECT

Training of Providers Training of Providers

TATI PROJECTTATI PROJECT

• 48 midwives

35 primary care physicians

• 3 training courses

• 48 midwives

35 primary care physicians

• 3 training courses

Health Promotion

Client’s satisfaction

Education Community support

Research Subcomponent Research Subcomponent Cancer Research Fund UKCancer Research Fund UK

TATI PROJECTTATI PROJECT

n = 5,460

• HPV DNA: HC II

• Liquid – based cytology

n = 5,460

• HPV DNA: HC II

• Liquid – based cytology

RESULTSRESULTS

TATI PROJECTTATI PROJECT

TATI PROJECTTATI PROJECT

• Coverage: 35%

• First time: 19%

• 35 – 49 years: 45%

• Coverage: 35%

• First time: 19%

• 35 – 49 years: 45%

COVERAGECOVERAGE

Table 3: What most influenced women to participate in the TATI pTable 3: What most influenced women to participate in the TATI project San roject San Martin, Peru November 2000 Martin, Peru November 2000 –– October 2003October 2003

Number of women

Proportion (%)

Education session or awareness raising meeting in women’s organizations 8,636 23.6

Individual contact with a health professional 8,437 23.0

Education session or awareness raising in health centers 5,352 14.6

Contact with the TATI project team 4,412 12.0

Relative/neighbor who had been screened 2,667 7.3

Mass media: Tv/radio/magazine 1,045 2.9

Other 1,013 2.7

Table 5: Women Served in the TATI ProjectTable 5: Women Served in the TATI ProjectSan Martin, Peru November 2000 San Martin, Peru November 2000 –– October 2003October 2003

Activity Number of women Proportion

(%)

Nª women screened 36,759 100

Nº women VIA positive 6,473 17.6

Nº women VIAM positive 2,732 7.4

Nº women eligible for treatment 1,491 4.0

Nº women eligible treated1,398 3.8

VIA vs. VIAM by physician VIA vs. VIAM by physician

TATI PROJECTTATI PROJECT

• Aviscope had no discernable

advantage over VIA

• Triage can be done by physician

with naked eye

• Aviscope had no discernable

advantage over VIA

• Triage can be done by physician

with naked eye

TATI PROJECTTATI PROJECT

• Most women felt satisfied (90%)

• Cryotherapy is an acceptable procedure

• Most women felt satisfied (90%)

• Cryotherapy is an acceptable procedure

Women’s satisfaction with cryotherapyJuly - October 2001

TATI PROJECT: lost to follow-up

VIAVIA

Treatment Cryotherapy

Colposcopy

8%lost

Treatment

44% lost

9%lost

9%lost9%lost

VIAMVIAM

Cost of ScreeningMethods

Cost of ScreeningMethods

Procedures CostUS$

VIA 1.60VIAA 2.80PAP 3.47LBC 3.92

Procedures CostUS$

VIA 1.60VIAA 2.80PAP 3.47LBC 3.92

CostCost--Effectiveness for age groupEffectiveness for age group

Cost for CIN treatment proceduresCost for CIN treatment procedures

Procedure

Cryotherapy

Cold conizationLEEP

Cost

TATI PROJECTSan Martín - PerúTATI PROJECTTATI PROJECTSan MartSan Martíín n -- PerPerúú

HPV positivity

12.6 %

HPV positivityHPV positivity

12.6 %12.6 %

Almonte M., et alInt J. Cancer (2007)

TATI PROJECTTATI PROJECT

0

2

4

6

8

10

12

14

16

25 30 35 40 45

HPV positivity by ageHPV positivity by age

Almonte et al, 2007age

HPV

+ %

Yielding of screening tests Yielding of screening tests -- TATITATISan MartSan Martíín, Pern, Perúú

CIN 2 +CIN 2 +

MethodMethod Senstivity (%) Senstivity (%) Especificity (%) Especificity (%)

VIAVIA 54.954.9 76.776.7

VIAMVIAM 42.742.7 90.990.9

PAPPAP 26.226.2 98.698.6

LBCLBC 69.669.6 83.783.7

HPVHPV 77.377.3 89.389.3

Almonte M, Ferreccio C, Winkler JL, Cuzick J, Tsu V, Robles S, Takahashi R, Sasieni P. Cervical screening by visual inspection, HPV testing, liquid-based and conventional cytology in Amazonian Peru. In press

Effectiveness of CryotherapyEffectiveness of Cryotherapy

TATI PROJECTTATI PROJECT

CIN 418/472 88%

CIN 3 49/70 70%

CIN 418/472 88%

CIN 3 49/70 70%

Luciani S., et al

5

4.5

4

3.5

3

2.5

2

1.5

1

0.5

0

0 2 4 6 8 10 12 14 16 18

Required Depth Of NecrosisRequired Depth Of Necrosis

Dep

th o

f n

ecr

osi

s (m

m)

Dep

th o

f n

ecr

osi

s (m

m)

IndividualIndividual

3 minute5 minute

DEPTH OF NECROSIS IN CO2 CRYOTHERAPY OF THE CERVIXDEPTH OF NECROSIS IN CO2 CRYOTHERAPY OF THE CERVIX

Santos y col, Int. J. Gynaec. Ca.,2004Santos y col, Int. J. Gynaec. Ca.,2004

Figure 1. Profundidad de necrosis del labio anterior y posterior del cérvix con crioterapia N2O y CO2. Se calculo las diferencias para significancia estadística (p<005) usando ANOVA. El cuadro inferior muestra un resumen descriptivo de la profundidad de necrosis

Dep

th o

f Nec

rosi

s (m

m)

0

1

2

3

4

5

6

7

8

9

10

N20Upper Lip

N20Lower Lip

CO2

Upper LipCO2

Lower Lip

P < 0.001

P < 0.001

Dep

th o

f Nec

rosi

s (m

m)

0

1

2

3

4

5

6

7

8

9

10

N20Upper Lip

N20Lower Lip

CO2

Upper LipCO2

Lower Lip

P < 0.001

P < 0.001

Prof

undi

dad

de N

ecro

sis (

mm

)

Labio anterior Labio posterior Labio anterior Labio posterior

N N 2020 2020 2020 1919

Media Media 5.35.3 5.05.0 3.43.4 3.13.1

MMíínimonimo 3.53.5 3.03.0 1.51.5 1.51.5

MMááximo ximo 7.07.0 7.07.0 6.06.0 5.05.0

% % ≥≥4.8mm4.8mm 75%75% 60%60% 15%15% 5%5%

Mariategui,Santos,Jerónimo 2007

SUMMARY SUMMARY SUMMARY

v Visual tests have similar sensitivity as that of good quality cytology, but lower specificity.

v Visual screening is feasible in low resource settings, but require adequate inputs in training of test providers, close monitoring of test positivity, CIN detection and treatment rates on a continuing basis.

v Visual tests have similar sensitivity as that of good quality cytology, but lower specificity.

v Visual screening is feasible in low resource settings, but require adequate inputs in training of test providers, close monitoring of test positivity, CIN detection and treatment rates on a continuing basis.

LESSONS LEARNED LESSONS LEARNED

TATI PROJECTTATI PROJECT

• Achieve higher coverage

• Discard magnification

• Improve fast treatment availability

• Improve training and quality assurance

• Engaging communities

• Achieve higher coverage

• Discard magnification

• Improve fast treatment availability

• Improve training and quality assurance

• Engaging communities

CONCLUSIONS CONCLUSIONS

TATI PROJECTTATI PROJECT

• It is safe to incorporate VIA – Cryo inhealth services

• Feasible• Affordable

• It would be feasible to replicate this program in low resources settings

• It is safe to incorporate VIA – Cryo inhealth services

• Feasible• Affordable

• It would be feasible to replicate this program in low resources settings

ESCUELA LATINOAMERICANA DE

CÁNCER DE CÉRVIX

INEN - IARC

INCTR

Regional Training Center

ESCUELA LATINOAMERICANA DE ESCUELA LATINOAMERICANA DE

CCÁÁNCER DE CNCER DE CÉÉRVIX RVIX

INEN INEN -- IARCIARC

INCTR INCTR

Regional Training Center Regional Training Center