Welcome to I-TECH HIV/AIDS Clinical Seminar Series

New Tools for Cervical Cancer PreventionJose Jeronimo, MD

June 11, 2009

Condyloma

Neoplastic

Vaginal

≥100 HPV genotypes ~40 mucotropic HPV genotypes ~15 Carcinogenic HPV genotypes

Human Papillomavirus (HPV)Human Papillomavirus (HPV)

FP

V

70

8687

4736

A10

Alpha

OmikronXiGammaPi

NewGenus

Beta

Epsilon

Delta

ZetaLota

NuLambdaMu

ThetaEtaKappa

A11

A9

A8

A13A1

A7

A5

A6

A2

A15A4

A3

Peak Ages: 15-25 25-35 45-50

Natural History of HPV infection

and Cervical Cancer

Schiffman, et al., Lancet, 2007

Primary prevention

Secondary Prevention

Cervical Cancer Incidence1

1. Ferlay J, Bray F, Pisani P, Parkins DM; International Agency for Research on Cancer (IARC). GLOBOCAN 2002: Cancer Incidence, Mortality, and Prevalence Worldwide. Lyon, France: IARCPress; 2004. CancerBase No. 5, version 2.0.

Central and South America

71,862

Europe59,931

North America14,670

Africa78,897

Asia265,884

Current menu of options for screening.

VIA HPV testingPAP smear

Time Pap (CR) Pap (JHU) LBC (US) LBC (CR) Cervigram HCT HPV (PCR) Colpo Histology

0.0 Normal Normal Normal Normal‡ Negative 51;61

13.1 Normal Normal Normal‡ 33

31.4 Reactive Normal Normal‡ 61

44.3 Normal Normal Normal‡ Negative

56.7 Normal Normal Normal‡ Negative

60.4 Normal Normal Normal‡ Negative

84.2 Cancer CIN3 ASCUS Normal‡ 33;35;52;5891.4 Cancer Biopsy = Cancer

Patient 1 (Age = 63; AFS = 18; #Partners = 6)

Case study #1

Time Pap (CR) Pap (JHU) LBC (US) LBC (CR) Cervigram HCT HPV (PCR) Colpo Histology

0.0 ASCUS Reactive ASCUS Normal (Normal)† Positive 162.9 16 Normal13.2 Reactive ASCUS Reactive Normal (Normal)* 1626.4 Normal CIN3 Normal (Normal)* 16

34.4 Biopsy = Cancer

Patient 2 (Age = 49; AFS = 15; #Partners = 3)

Case study #2

Trends in age-standardized incidence rates of cervical cancer in four Nordic countries

Parkin DM. Bray F. Vaccine. 2006 Aug 31;24 Suppl 3:S3/11-25

Limitations of cytology-based programs:

• Deficit of trained cyto-technologists.

• Delay of results.

• Multiple visits: lack of follow-up.

• Cost.

• Sub-optimal sensitivity.

Pap smear sensitivity

100% of Pre-cancer cases

One pap smear identifies about

50% of pre-cancerous cases

Pap smear sensitivity

Pap smear sensitivity

Second pap smear

Unknown CIN 1 cases

Third Pap smear

Pap smear sensitivity

“VIA is a good alternative for settings where conventional cytology is not well implemented.”

–IARC/WHO, 2005

IARC, WHO. IARC Handbooks of Cancer Prevention: Cervical Cancer Screening. Volume 10. IARC Press; 2005.

VIA

Unmagnified view

Combined

HART

Jena

Tuebingen

Hannover

Canada

Seattle

French Private

French Public

0% 10% 30% 50% 70% 90% 100%

HPV sensitivity

CIN 2+

Cuzick et al., IJC, 2006Mayrand et al., NEJM, 2007

HPV DNA testing

0%

5%

10%

15%

20%

25%

0.0 4.5 15.0 27.0 39.0 51.0 63.0 75.0 87.0 99.0 111.0 119.5

Follow-up (months)

Acu

mu

late

In

cid

ence

≥C

IN3

HPV16+HPV18+

HPV+

HPV-

Khan et al., JNCI, 2005; Castle et al., AJOG, 2007

Follow-up according to HPV result

A new HPV-DNA test for low- resource settings

hc2

CareHPV test

Accuracy of CareHPV, hc2, and VIA in China

Sensitivity Specificity PPV NPV

CareHPV cervical samples (0.5 cutoff) 89.7 84.2 14.7 99.6

CareHPV cervical samples (1.0 cutoff) 84.3 87.5 16.9 99.5

CareHPV vaginal samples (0.5 cutoff) 81.4 82.4 11.9 99.3

hc2 97.1 85.7 16.6 99.9

VIA41.2 94.5 17.9 98.2

n=2,382 (Shanxi Province, China)

Reference standard: directed, four-quadrant biopsy and ECC (>CIN 2) externally read.

careHPV

• A new HPV test for low-resource settings.

• Affordable price for public-health programs in low- and middle-income countries.

• First regulatory filing expected in late 2009

• Commercially available in late 2010.

• Currently used in demonstration projects.

START-UP* demonstration projects

*Screening Technologies to Advance Rapid Testing for Cervical Cancer Prevention—Utility and Program Planning (START-UP) project.

Challenges in HIV infected women

• Higher prevalence of HPV infected women.

* Performance of screening tests different than general population:

- Higher positive rates.

* Need for intervention.

* PATH evaluation options in countries with high HIV prevalence.

• There is no screening test 100% effective for detecting cervical pre-cancer.

• There are more affordable options forsecondary prevention in low-resource settings.

• Screening for cervical cancer in HIV infected women seems to be more challenging than HIV negative women.

Conclusions:

Thank you

jjeronimo@path.org

www.path.org

Thank you!Next session: June 18th, 2009

Christina MarraHIV and Neurology

Welcome to I-TECH HIV/AIDS Clinical Seminar Series

Next session: June 18, 2009Listserv:

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