HUMAN PAPILLOMA-

VIRUS VACCINE (DO WE

NEED IT IN EGYPT)

Moustapha Ramadan

2010

Epidemiology of cancer cervix

WorldWide

2nd most frequent cancer among women

490 000 women diagnosed annually with invasive cervical

cancer

3rd leading cause of death among cancer ( after cancer

breast and cancer lung) with 270 000 annually death

Worldwide incidence of cervical

cancer per 100000 females (2005)

Cervical cancer mortality per

100000 females (2008)

Human papilloma-virus

characteristics

1. Double stranded, enveloped DNA virus

2. Over 100 characterized serotypes

3. Grouped into three categories

4. At least 40 serotypes infect human mucosa

5. At least 14 serotypes are considered high risk‟ for

malignancy

HPV serotypes

Epidemiology of HPV

1.Most common sexually transmitted disease in the United

States

2. Estimated 6.2 million people infected annually

3. 80% of women are infected during their lifetime

4. More than 50% of women are infected within first three

years of sexual debut

5. In women HPV has a bimodal distribution

a. Peaks in early 20s (20 to 24)

b. Progressively declines

c. Increases sharply in late 40s and early 50s (45 to 55)

6. HPV is responsible of about 70% of cervical cancer

worldwide

Pathophysilogy

HPV enters epithelial tissues through microabrasions in host mucosa

Viral reproduction in bloodless epithelial cells allows HPV to efficiently evade the host immune system

Cervical intraepithelial neoplasia (CIN) is cell dysplasia caused by HPV infection

CIN is categorized by level of severity; CIN 2 and 3 are widely accepted surrogate markers for cancer

HPV vaccine

Administration

3 doses (Now,1,6) intramuscularly (IM)

Contraindicated in anyone with a history of an immediate

hypersensitivity to yeast

Can be administered at same visit as other vaccines

Quadrivalent Vaccine (Gardasil) contains HPV serotypes 6,

11, 16, 18

Bivalent Vaccine (Cervarix) contains HPV serotypes 16 and

18

Vaccination in females 9 to 26 years of age (before first

intercourse)

Adverse effects:

94% non-serious: dizziness, syncope, nausea, rash pain,

erythema, swelling at injection site, headache, fatigue,

myalgia.

6% serious: Guillain-Barre, venous thromboembolism,

death. Do no appear to be causally linked to

vaccine.

Countries using HPV vaccines (June

2010)

STUDIES

Paavonen J, Naud P, Salmeron J, et al. Efficacy of

human papillomavirus (HPV)-16/18 ASO4 –adjuvanted

vaccine against cervical infection and precancer caused

by oncogenic HPV types (PATRICIA): final analysis of a

double-blind, randomized study in young women. Lancet,

2009. 25;374(9686):301-14

Methodolgy

Multi-center, randomized, double-blind, placebo-controlled trial

18,644 women aged 15 to 25 years (92% had the full dose

schedule)

Between May2004, and June 2005, at 135 centres in 14

countries in Asia Pacific, Europe, Latin America, and North

America

Inclusion criteria: not pregnant at time of enrollment, < 6 lifetime

sexual partners, no previous colposcopy, no autoimmune

disease or immunodeficiency

Subjects received HPV 16/18 vaccine at 0, 1, and 6 months and were asked to use effective birth control during vaccination period

Cervical biopsy samples taken every 6 months for HPV DNA typing of 14 oncogenic HPV strains

Blood samples gathered at months 0, 7, and 24 for HPV 16/18 antibodies

Two study cohorts:

Total vaccinated- naive cohort (TVC-N): women receiving all doses of vaccine who had no virologic evidence of infection with HPV 16/18 through 1 month after third dose of vaccine (represent girls before sexual debut)

Total vaccinated cohort (TVC): all women including those who had evidence of HPV 16 or 18 infection (represent the general population of young women)

Follow-up visits every 12 months for Papanicolaou smear

(and colposcopy if necessary) based on a standardized

treatment algorithm

CIN grade 2 or 3, adenocarcinoma in situ, or invasive

cancer associated with HPV 16/18

CIN associated with other oncogenic HPV types

Results

Mean follow-up time was 34.9 months after third dose

Seroconversion at 36 months: HPV-16 100%, HPV-18 100%

Vaccine efficacy in preventing CIN 2+ lesions caused by HPV 16/18:

TVC-naïve cohort: 98.1% (CI, 88.4 to 100%)

TVC cohort: 30%: (CI, 21.5 to 38%)

Significant cross-protection against HPV 31, 33, 45, 52 and 58

Vaccine efficacy in preventing CIN 2+ lesions caused by any HPV type TVC-N: 68.2% (CI, 54 to 80.9%)

Conclusion

Bivalent HPV vaccine significantly lowers incidence of

high-grade CIN related to HPV 16/18 in women without

previous HPV 16/18 infection

Vaccine does not appear to alter the course of HPV 16/18

infection or lesions already present

Vaccine provides cross protection against HPV 31, 33, 45,

52, 58

Helen Saxenian, International AIDS vaccine initiative,

PATH. HPV vaccine adoption in developing countries:

Cost and Financing issues. December 2007

Disease and burden

Distribution of New cervical cancer cases by

country income grouping (2002)

About 6.6 million 11-year-old girls are in

industrialized countries in 2010 and about 52

million girls in developing countries.

The cost of quadrivalent vaccine is 120 USD/

dose.

Additional cost should be considered, wastage,

cold chain etc…

Developing Countries found that the population-

weighted mean cost per fully immunized child in

27 developing countries was about 17 USD,

with a range from 3 USD to 31 USD

Costs varied considerably by region, given

variation in labor costs and in delivery strategies

Cost-effectiveness models have been used to

compare the net cost of HPV vaccination with

the potential benefits, expressed as years of life

saved (YLS) or quality-adjusted life years

(QALYs)

At a cost of ID 50, the cost-effectiveness ratio

was about ID 300 per YLS with a reduction of

about 43% in the lifetime risk of cancer

Combined vaccination and screening at costs of

ID 75, 100, and 450 per vaccinated girl resulted

in cost-effectiveness ratios of about ID 1,100,

1,700, and 9,600 per YLS compared to

screening alone.

GDP per capita, estimated in current

international dollars, was 9,500 for that year

SITUATION IN EGYPT

Egypt has a population of 25.76 millions women

ages 15 years and older who are at risk of

developing cervical cancer.

Current estimates indicate that every year 514

women are diagnosed with cervical cancer and

299 die from the disease.

Cervical cancer ranks as the 14th most frequent

cancer among women in Egypt, and the 12th

most frequent cancer among women between

15 and 44 years of age.

About 10.3% of women in the general population

are estimated to harbor cervical HPV infection at

a given time.

Incidence of cervical cancer compared to other cancers in

women in all ages in Egypt

Age-specific cervical cancer incidence compared to age-

specific incidence of other cancers among women 15-44

years of age in Egypt

Age-specific incidence rates of cervical cancer in Egypt

compared to estimates in Northern Africa and the World

Cervical cancer mortality compared to other cancers in

women of all ages in Egypt

Age-specific mortality rates of cervical cancer in Egypt

compared to estimates in Northern Africa and the World

Human papilloma virus situation in

Egypt

HPV prevalence with normal cytology 10.3%

HPV type distribution among women with normal

cytology, precancerous cervical lesions and

cervical cancer ------

HPV prevalence among men -----

Human papilloma virus vaccine in

Egypt

Licensure status of current HPV vaccines in Egypt

2009

Country recommendations on the inclusion of HPV

vaccines in national immunization program -----

National decision-making process for new vaccine

introduction

Policy issues: Public health priority

Disease burden

Economic burden Vaccine cost-effectiveness Vaccine quality, efficacy and safety Vaccine cost, financing options, sustainability

Operational issues: Vaccine presentation, vial size, cold chain

requirements Reliable vaccine supply Adequate program capacity

Constrains against introduction of HPV

vaccine

Social factors

1- Rumors about new vaccine

2- Beliefs and traditions

Economic factors

1- High cost of the vaccine which may increase the rumors

2- Absence of surveillance for HPV incidence among

females, males and its relations in developing cancer

3- Absence of effective cancer cervix screening program

Overcoming the constraints

1- Launching cancer cervix screening program

2- Launching surveillance program for Human papilloma

virus

3- Health insurance system could cover part of vaccine

cost

4- Cost-effectivness studies as regards induction of Human

papilloma virus vaccine to prevent Cancer cervix and not

human papilloma infection.