Cervical Cancer Disease Burden

Cervical CancerThe disease and its burden in India

Cervical cancer Epidemiology: India

Population prospects for women >15 years

1. FX Bosch, X Castellsague´. S de Sanjose´. British Journal of Cancer (2008) 98(1), 15 – 21

Incidence (Women: all ages) - Cervical Cancer

1. X. Castellsagué, S. de Sanjose, T. Aguado, K. S. Louie, L. Bruni, J.Muñoz, M. Diaz, K. Irwin, M. Gacic, O. Beauvais, G. Albero, E. Ferrer, S. Byrne, F. X. Bosch. HPV and Cervical Cancer in the World. 2007 Report. WHO/ICO Information Centre on HPV and Cervical Cancer (HPV Information Centre). Available at: www.who.int/hpvcentre


Mortality (Women: all ages) - Cervical Cancer

Age Specific Incidence vs Mortality

2. WHO/ICO Information Centre on HPV and Cervical Cancer (HPV Information Centre). Summary report on HPV and cervical cancer statistics in India. 2007. [Accessed on 18th March 2008. Available at www. who. int/ hpvcentre c WHO/ICO Information Centre on HPV and Cervical Cancer

HPV Type Distribution - Invasive cervical cancer


HPV 16+18=76.7%

0 5 10 15 20 25 30

Cervical Breast (Female) Ovarian

Years of Life Lost to Cervical Cancer*

*In women in the United States (2003), 1. Ries LAG, Harkins D, Krapcho M, et al. (eds). SEER Cancer Statistics Review, 1975–2003, National Cancer Institute. Bethesda, MD; 2006.

26

19

18

Largest single cause of years of life lost to cancer in the developing world

Cervical Cancer - Disease Burden

New cervical cancer cases diagnosed annually

India : 1,32,082, World : 4,93,243

India accounts for ~27% of new Cervical Cancer cases in world

Deaths due to cervical cancer annually

India : 74,118, World : 2,73,505

India - 27%

Rest of World - 73%

India accounts for 27% of deaths due to Cervical Cancer in world

Rest of World - 73%

India - 27%India - 27%


> 200 women die every day

Every 7 minutes a women dies

8 women die every hourCervical Cancer :

India

This ‘Cause’ need to be taken up by multiple stake holders.

Cervical Cancer in India

*Ray K et al, Indian J Med Res 2006; 124: 559-568

18%

6%

11% 10.5%

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1214161820

1990-93 1994-97 1998-01 2002-04

Study Period

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Genital Warts – Disease Burden: India*

Increasing trend of Genital warts in India

HPV & Cervical cancer

HPV 16

HPV 18

HPV 6

HPV 11

Cancer causing Types1,2,4 Non-cancer causing types1,2

• >75% of Cervical Cancer5,6

• ~50% of Vaginal & Vulvar Cancer590% of Anogenital warts5

HPV is a necessary cause of cervical cancer - 99.7%4

HPV

1.Schiffman M, Castle PE. Arch Pathol Lab Med. 2003;127:930–934. 2. Wiley DJ, Douglas J, Beutner K, et al. Clin Infect Dis. 2002;35(suppl 2):S210–S224. 3. Muñoz N, Bosch FX, Castellsagué X, et al. Int J Cancer. 2004;111:278–285. Reprinted from J Virol. 1994;68:4503–4505 with permission from the American Society for Microbiology Journals Department. 4. Walboomers JM, Jacobs MV, Manos MM, et al. J Pathol. 1999;189:12–19. 5. X. Castellsagué, S. de Sanjose, T. Aguado, K. S. Louie, L. Bruni, J.Muñoz, M. Diaz, K. Irwin, M. Gacic, O. Beauvais, G. Albero, E. Ferrer, S. Byrne,F. X. Bosch. HPV and Cervical Cancer in the World. 2007 Report. WHO/ICO Information Centre on HPV and Cervical Cancer (HPV Information Centre). Available at: www.who.int/hpvcentre6. Bhatla N et al.Vaccine (2008;26; 2811-17

Human Papillomavirus (HPV)

Human Papilloma Virus (HPV)

http://www.who.int/hpvcentre6

Human Papilloma Virus (HPV) Non enveloped double stranded DNA virus: over 100 types

15–20 oncogenic 30–40 anogenital

L1: major viral capsid protein – immunogenic L2: minor viral capsid protein – immunogenic

Capsid proteins:Capsid proteins:L1L1L2L2

Viral DNAViral DNA

Viral exterior Viral interior

1. Baker TS, et al. Biophys J. 1991;60:1445–1456. 2. Chen XS, et al. Mol Cell. 2000;5:557–567.

Changes in Cervical Epithelium by HPV Infection

Normal Normal CervixCervix

HPV Infection / CIN* 1HPV Infection / CIN* 1 CIN 2 / CIN 3 /CIN 2 / CIN 3 /Cervical CancerCervical Cancer

*CIN = cervical intraepithelial neoplasiaAdapted from Goodman A, Wilbur DC. N Engl J Med. 2003;349:1555–1564. Copyright © 2003 Massachusetts Medical Society. All rights reserved.

HPV Infection

Low Grade

Lesions

High Grade

Lesions

Invasive Cancer

0–1 Year 0–5 Years 1–20 Years

HPV Infection may clear

Adapted from Pinto AP et al. Clin Obstet Gynecol. 2000;43:352–362.

Facts about HPV Infection

Facts about HPV Infection

Neutralizing Antibodies and HPV Infection

Chen XS, et al. Molecular Cell. 2000;5:557–567.

Neutralizing Neutralizing antibodies prevent antibodies prevent

HPV infectionHPV infection

Nonneutralizing Nonneutralizing antibodies do not antibodies do not prevent infectionprevent infection

No antibodies— No antibodies— viral infectionviral infection

Cell surface Cell surface receptorsreceptors

Antibody color legend:Blue = Neutralizing antibodiesYellow = Nonneutralizing antibodies

Antibodies The minimum protective antibody level against HPV is not known.

USFDA and WHO: Reduction in incidence of CIN 2/3 or AIS caused

by vaccine HPV types should be criteria for licensure.

No International standards for assays have been developed as yet.

Different assay use different units so their results can not be compared

The major basis of protection against infection is neutralizing antibody

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Can

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ate

(×10

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* Two different cohorts (cross-sectional study) followed during the same time span to measure the rate of high-risk HPV infection in one and the rate of cervical cancer in the other.1. Adapted from Bosch FX, Lorincz A, Muñoz N, Meijer CJLM, Shah KV. J Clin Pathol. 2002;55:244–265, with permission from the BMJ Publishing Group.

0

5

10

15

20

25

20–24 25–29 30–34 35–39 40–44 45–49 50–54 55–59 60–64

Age Group (Years)

HPV infectionCervical Cancer

25

20

15

10

5

0

(n=3752)

Peak of HPV infection

Peak of cervical cancer

Age-Specific Rates of HPV Infection & Cancer*

Age for vaccination: 9 – 26 yrs

Age for Screening > 35yrs

Summary HPV is a necessary cause of cervical cancer – 99.7%

Induction of neutralising antibodies by vaccination is critical for protection

HPV 16 & 18 cause ~75%* of cervical cancer cases while HPV 6 & 11 cause ~90% genital warts

27% of the world burden of Cervical Cancer is seen in India.

Every 7 minutes a woman dies in India due to cervical cancer

Cervical Cancer is usually diagnosed in late stages in India.

Cervical cancer screening is recommended in women >30yrs

Vaccination between 9-26yrs can be an effective strategy to help reduce this huge disease burden.

* India

Health & Medicine

Cervical Cancer Disease Burden