In India“Your cooperation is needed”

Down staging of cervical cancer

Dr. Sharda JainDirector: Global Institute of Gynaecoloy at Pushpanjali Crosslay HospitalSecretary general: DelhiGynaecologist Forum

Early Carcinoma Advanced Carcinoma

Global Burden of Cervical Cancer

• Worldwide,

• 500,000 women diagnosed per year1

• 270,000 deaths per year1

• >1 million new cases of cervical cancer each year, 20502

One Death every 2 minutes

Cancer Cervix World - No. - 2 New - 5 Lack

Deaths - 2.75

India Number One New – 1.32 lack

Deaths - o.74 lack

One death every 7th minutes in India

Cancer Cervix Life Time Risk

India = 20 – 35 / lack (35 – 64 yrs)

Developed countries = 1-8/ lack

It is expected by 2050 = double

If no action is taken

Most effective program of down staging of cervical Cancer is

paps smear screening

PATH (prog. Of appro. tech in Health)

MASS PAPS SMEAR SCREENING {IARC - Int. agency of research on cancer }

35 – 64 yrs = 93% reduction if Screening 1-3 years = 84 % Reduction 5 years = 64% reduction 10years

India No Govt. Effort

for public Screening

(non availability of Tech/ doctors to read paps smear )

Alternative methods for down staging of the cervical cancer

1. VISUAL INSPECTION OF CERVIX WITH ACETIC ACID. (VIA)

2. Use of MAGNASCOPE instead of colposcope

3. SINGLE VISIT APPROACH i.e.Treatment with cryosurgery for VIA +ve women

4. SELF COLLECTED SAMPLE for cytology or HPV – DNA testing

5. Education and counseling

6. Increase coverage by camp

approach

7. Low cost HPV test

8. HPV Vaccines.

Alternative methods for

down staging of the cervical cancer

VIA AFTER APPLYING 3 % ACETIC ACID TO

CERVIX “WHITE PATCHES” APPEARS DUE TO COAGULATION OF CELLULAR PROTEINS AND INDICATE THE ABNORMAL EPITHELIUM WHICH IS THICK AND DOES NOT ALLOW THE LIGHT REACTION TO PASS THROUGH.

CERVICAL BIOPSIES - LSIL/HSIL

Women were examined visually by simple speculum and colposcopically after application of 3 % acetic acid to cervix.

Equal detection rates of cervical

abnormalities by both techniques.

Ottaviano and la torre 1982,

VILI WHEN LUGOL’S IODINE IS APPLIED

TO THE CERVIX, THE NORMAL CELLS CONTAINING GLYCOGEN STAIN DARK BROWN. THE ABNORMAL CELLS ARE RAPIDLY DIVIDING AND ARE DEFICIENT IN GLYCOGEN HENCE, REMAIN UNSTAINED WHICH ARE FURTHER EVALUATED BY COLPOSCOPY & BIOPSY.

IARC studies in India and Africa

• proved that VIA performed by trained paramedics has sensitivity of 64 to 90% and specificity of 73 to 91% which is comparable to conventional cytology.

• specificity of VIA was increased by adding adjunctive test like VILI.

• Advantages of visual technique are immediate results, making cost effective and has more than 99% negative predictive value.

muwonge R (2007)

Sensitivity and specificity are often used to summarise the performance of a diagnostic test.

Sensitivity is the probability of testing positive if the disease is truly present.

Specificity is the probability of testing negative if the disease is truly absent.

Who Needs colposcopy ± Biopsy

Ten to fifteen percent VIA+ve women require referral for colposcopy & colposcopic guided biopsies.

LSIL / LGSIL

Conservative treatment and follow up subsequently 6 monthly .

HSIL / Cancer

Specialized Treatment

In single visit approach cryo therapy is offered to all those women who are VIA +ve and cannot visit more than once for treatment.

What Is Single Visit approach?

Tamil Nadu Study

Single Visit approach - follow up

after 7 years showed• 25% reduction in cervical cancer incidence

• 35% reduction in cervical cancer mortality

• 27.5% reduction in the incidence of stage II or advanced cancer compared to control group.

What should be Indian Govt. Approach

Cervical cancer Should be taken seriously

for ↓ number & reduction in mortality .

• Camp approach

• Single visit approach

Both can help to down stage the disease in resource poor settings like India.

Self sampling in rural areas/ slumsPap Smear/ HPV

HPVInfection

100% of cervical cancers are

caused by HPV

93.5% of all cancer caused by HPV is Cervical Cancer

In India over 90% of Cervical Cancers are Caused by 5 HPV Types:

HPV 16, 18, 45, 31 and 332

100 HPV Types Have Been Identified1

30 HPV Types are Transmitted by Genital skin to skin Contact

15 HPV Types are Oncogenic

Human Papillomavirus (HPV)

In India, HPV 16, 18, 31, 33 & 45 account for

>92% Squamous Cell

Carcinoma

>95% Cervical

Adenocarcinoma

• Adenocarcinoma is difficult to detect with routine screening methods1

– The cervical smear brush cannot access the endocervical canal as easily as the outer surface of the cervix1

Adenocarcinoma is difficult to detect

Adenocarcinoma: may beinaccessible to the cervical

smear brush

Squamous cell carcinoma:

usually accessible to the cervical smear brush

Cervical smear brush

Cervix

Adenocarcinoma of the cervix- An Emerging concern

• Incidence increasing (20–25% of all cervical cancers), not prevented with traditional pap screening

• More aggressive and occurs in younger women

• > 90% of adenocarcinomas result from HPV 16, 18, 45, 33 and 311

• HPV 18 confers the highest risk

Every woman is at risk of Cervical Cancer

• HPV infections are very common

• The risk starts from sexual debut1 and continues throughout life2

• Up to 80% of women will acquire an HPV infection in their lifetime5–7

• HPV infections continue to occur in women over 25 years of age

Low-grade squamous intraepithelial lesion (ASCUS/LSIL)

High-grade squamous intraepithelial lesion (HSIL)

Invasivecarcinoma

Time YearsMonths

Normal epithelium

HPV infectionkoilocytosis

CIN1 CIN2 CIN3

Regression

Progression*

Progression of Cervical Disease

The need for Vaccination against

Cervical Cancer

HPV-containing double stranded DNA

‘Empty’ non-infectious virus-like particle (VLP) mimics the

virus

Virus-like particles (VLPs) as HPV vaccine antigens mimic the virus structure

Stanley M, et al. Vaccine 2006; 24(suppl 3):S3/106–113.

Why vaccination is needed ??

• No protection through natural infection as HPV evades the immune system

• Vaccines are highly immunogenic

• Higher the serum antibodies, more is local neutralising antibody & longer the protection

HPV types and cervical cancer

1. Bosch FX et al. Vaccine 2008; 26S: K1–16. 2. Bhatla N et al. Vaccine 2008; 26(23):2811-2817.

Five most frequent and aggressive HPV types that cause cervical cancer worldwide

+ + +

HPV 16 HPV 18 HPV 45 HPV 31 HPV 33

+

These 5 HPV types are responsible for up to 92% of Cervical Cancer in India2

2 Vaccines

•Gardasil

•Cerverix

HPV Type % Efficacy (96.1% CI) **

HPV 16/18* 98.4% 1 (90.4-100) 1

HPV 31* 100% 2 (78.3-100) 2

HPV 33* 72.3% 2 (19.1-92.5) 2

HPV 45* 100% 2 (-19.5-100) 2

HPV 31, 33, 35, 39, 45, 51, 52, 56, 58, 59*

68.4% 2 (45.7-82.4) 2

* The total vaccinated naive cohort (TVC-naive) included women who were given at least one vaccine dose, were evaluable for efficacy, and at baseline had normal cytology, were DNA negative for all 14 oncogenic HPV types investigated, and were seronegative for HPV-16 and HPV-18 (n=11641).** Median follow-up of 39.5 months (post dose1)***CIN2+ was defined histologically as CIN2, CIN3, adenocarcinoma in situ, or invasive carcinoma

References:1.Paavonen J et al. Final Phase III Efficacy Analysis Of Cervarix™ In Young Women Abstract presented at the 25th International Papillomavirus conference, Malmo, Sweden, 8-14 May 20092.Skinner R et al. Cross-protective efficacy of Cervarix against oncogenic HPV types beyond HPV-16/18: final analysis of cross-protection-PATRICIA study. Abstract presented at the 25th International Papillomavirus conference, Malmo, Sweden, 8-14 May 2009

Cervarix™ efficacy: Summary

HPV vaccines: Safety and approval

• WHO’s Global Advisory Committee on Vaccine Safety (GACVS) concluded that the HPV vaccines had good safety profiles1

• U.S. Food and Drug Administration (FDA) approved both vaccines.

Potential impact of HPV Vaccination

• HPV vaccination is the primary prevention strategy against cervical cancer

• HPV vaccination is predicted to have a major impact on the burden of cervical cancer, especially in settings without optimal screening programs

FOGSI Recommendations

• Cervical cancer causes significant morbidity/

mortality

• HPV vaccine to be offered to all appropriate

females who can afford the vaccine

• Vaccine should be given prior to sexual

debut

www.fogsi.org/hpv vaccine

• When is the best time to vaccinate?

• Upto what age can the

Vaccine be given

FOGSI Recommendations – Vaccine Schedule

• Age for initiation of vaccination is 10- 12 years. – Catch up vaccination is permitted up to 45 yrs

• Three doses at 0, 2 and 6 months with quadrivalent

vaccine

(Gardasil)

• Three doses 0, 1 and 6 months with bivalent vaccine

(Cerverix)

Intra muscular – Deltoid reason

FOGSI RecommendationsNeed for Booster

• At present there is no data to support use of boosters

www.fogsi.org/hpv vaccine

• Not recommended for use in pregnancy

• If patient becomes pregnant - Delay remaining doses till delivery

• If vaccinated during pregnancy - No intervention (MTP) needed

• Lactating women can receive the HPV vaccine and still continue breastfeeding as it is a vaccine without live viral DNA

FOGSI Recommendations:Pregnancy & Lactation

www.fogsi.org/hpv vaccine

Do we need to Screen before Vaccination?

• No!• The results of screening will not influence to

decision to vaccinate because:– Sexually active women continue to be at risk of

new infections – Hence, vaccination will protect women from future

infections regardless of an on going infection– NOTE: Vaccination will have NO effect on the on-

going infection or lesion.