Women-specific Illness

Vivien Tsu, PhD MPH

Determinants of Women’s Health

Biological:

• pregnancy/delivery

• unwanted pregnancy

• conditions aggravated by pregnancy

• infections

• reproductive cancers

Social:

• poverty

• lower status

• less education

• seclusion rules

• gender roles

Deciding on Action

• Magnitude and seriousness of problem, i.e. disease burden

• Affected groups

• Causes

• Feasible interventions

Burden of disease in women aged 15-44 in developing countries, 1993

Source: Tinker, IJGO 70:149-58, 2000. (based on World Bank DALYs, 1993)

Maternal causes 18%

STDs & AIDS 16%

Tuberculosis 7%

Other commun. Disease 9%

Depression/psychiatric 12%

Malnutrition 6%

Other non-commun. dis.

14%

Cardiovascular disease 6%

Injuries 12%

Leading causes of disease burden (DALYs) for women aged 15–44 years, high-income countries,

and low- and middle-income countries, 2004

WHO, Global Burden of Disease

Cancer: not just a disease of the rich

• More than 3.3 million deaths among women globally

• Despite younger populations, 63% are in poorer countries

• Women-specific cancers are substantial portion everywhere

Breast

Cervix

Uterus

OvaryAll

other

Cancer deaths in more developed countries, 2008

Breast

Cervix

Uterus

Ovary

All other

Cancer deaths in less de-veloped countries, 2008

Survival difference is dramatic

Breast cancer Cervical cancer0.00

0.10

0.20

0.30

0.40

0.50

0.60

0.70

Mortality ratio, 2008

USAfrica

Rat

io o

f d

eath

s to

cas

es

Cervical Cancer

Cervical Cancer Incidence, 2008

Numbers indicate cases per 100,000 population

Central and South America

63,487

North America12,491

Europe54,517

Africa80,419

Asia312,990

Source: Ferlay J, Shin HR, Bray F, Forman D, Mathers C and Parkin DM. GLOBOCAN 2008, Cancer Incidence and Mortality Worldwide: IARC CancerBase No. 10 [Internet]. Lyon, France: International Agency for Research on Cancer; 2010. Available from: http://globocan.iarc.fr

Another way to look at it

www.worldmapper.org (2002)

Why is the burden so high in low-resource countries?

• ~490,000 cases; ~270,000 deaths each year• >80% in developing countries• Expected to increase to >775,000 new cases by 2030, with >99% of

deaths in developing countries• No organized screening programs, despite many efforts• “Competing” health problems• Prevalence of high-risk HPV infection higher• Limited awareness of cost-effective approaches to prevention• Until recently, no vaccine available to prevent infection

HPV Infection & Cervical Cancer

• HPV is a necessary but insufficient cause of cervical cancer

• 99.7% of cervix cancer cases associated with HPV

• Human papillomavirus (HPV) is a very common STI (more than 50% of adults get it)

• Most HPV+ women do not develop cervical cancer• Two HPV types—16 and 18—account for 70 percent of

cervical cancer cases (though regional variations exist)• Progression from HPV infection to cancer usually takes

20–30 years

Source: Wright, TC and Schiffman, M. Adding a Test for Human Papillomavirus DNA to Cervical-Cancer Screening. The New England Journal of Medicine 2003;348:489-490.

How cervical cancer develops

Long latent period allows screening to detect precancer

Opportunities for screening

• Visible pre-cancerous lesion

• Long development of pre-cancer stage (10-15 years)

• Despite different rates, age pattern is consistent - peak in pre-cancer in 30s and 40s

Why hasn’t cytologic screening (Pap testing) worked for low-income areas?

• Low sensitivity and limited reproducibility

• Requires frequent visits and high coverage

• Requires quality controls and regular training

• Global costs of programs are very high

IARC MONOGRAPH: SCREENING FOR CERVICAL CANCER 2005

Potential cervical cancer screening methods in low-resource settings

careHPV (QIAGEN)

Conventional pap Hybrid Capture® 2 (hc2, QIAGEN)

Visual inspection with acetic acid (VIA)

Visual inspection with Lugol’s iodine (VILI)

Visual Inspection with Acetic Acid (VIA)

• Cervix washed with vinegar (3-5% acetic acid) and inspected with naked eye 1 minute later

• HPV-infected cells contain more proteins, which vinegar coagulates and causes to appear more opaque (acetowhite) than nearby normal tissues

• 5-day curriculum for nurses and midwives

• Equipment and supplies: speculum, cotton swabs, vinegar, lamp or torch

• Immediate results

• ~31,000 women screened with VIA, ~30,000 in control group

• Incidence of cervical cancer ~25% lower, and mortality ~35% lower

• 38% reduction in incidence and 66% lower mortality among women 30-39

(Lancet, 2007)

VIA and low-resource settings• VIA is better than Pap smear for identifying

high-grade CIN - especially if testing is only once in a lifetime

• VIA is simple to perform and provides an immediate result without expensive equipment

• Possible to link confirmation/treatment to screening visit

• Healthcare provider can be trained in one week

A new HPV DNA test for low-resource settings

hc2

ThecareHPVTM

test

START project:

-Developed the new test.

-Validated it with specimens from China and India.

QIAGEN:

-Set up production in

China.

-Seeking regulatory approval in China.

Cryotherapy: Simple treatment

• Metal probe applied to the cervix to freeze (-50o C) the abnormal area for total of 6 minutes• Does not require electricity; uses low-cost CO2 or NO2

gas• 80-90% effective in ablating even high-grade

precancerous lesions (CIN 2 or 3)• Ideal for nurses to perform at district hospitals and

maybe even in health centers• Appropriate for most lesions, except very large ones and

those involving the canal

Promising prevention option

• 2 new vaccines: Merck Gardasil; GSK Cervarix

• HPV vaccines are prepared from virus-like particles (VLPs) using recombinant technology

• They are non-infectious

• Current HPV vaccines are designed to protect against HPV 16 and 18; one also protects against low-risk types 6 and 11

• The vaccines are highly effective and safe

• They provide protection for at least 6 years, likely much longer

Current HPV VLP vaccines

Gardasil (Merck) Cervarix (GSK)

Vaccine Type HPV 6/11/16/18 HPV 16/18

Licensure status Licensed in > 120 countries Licensed in > 80 countries

Target groups

Girls/Women age 9–26

(age varies by country)

Boys 9–15 (Europe, Australia, Mexico, others)

Girls/Women age 10–55

Clinical trials ~21,000 ~27,000

Schedule 0-, 2-, 6-months 0-, 1-, 6-months

India

Peru

Vietnam

Uganda

Getting ready in 4 countries

Room for cautious optimism?

Acceptance high in all 4 countries (75-95%)

Positive support from parents, communities, and leaders

No serious adverse events

High completion of 2nd and 3rd doses

Peru has now joined 32 other countries

Challenges for the vaccine

• Financing• GAVI recently approved funding, but doesn’t help middle-

income countries• Price has already dropped from $120/dose in US and

Europe to <$15-25 in Asia and Latin America• Countries need to pay delivery costs while also introducing

other new vaccines

• New platforms for delivery (schools, community outreach)

• Evaluating impact (time lag, technical difficulties)

Breast cancer – on the rise

• 269,000 deaths in developing countries

• Women living longer

• Changing reproductive patterns

• Increasing obesity and smoking

• Again, inadequate services for detection and treatment; fear and stigma

• Breast Health Global Initiative, developed resource-specific guidelines http://www.fhcrc.org/science/phs/bhgi/

Indoor air pollution

Chimney woodstove in Guatemala (Smith-Sivertsen et al, Am J Epid 2009)

• New stove vs. open fire among rural Mayan women (n=504)

• After 18 months, significantly fewer respiratory symptoms (RR=0.42) and 61.6% less carbon monoxide exposure

Anemia

Iron supplements and deworming in Vietnam (Phuc et al, BMC Public Health, 2009)

• Women 15-45 received weekly iron-folic acid supplements and periodic deworming

• Delivered by village health workers as part of regular care, achieved 85% coverage (full or partial compliance)

• After 12 months, anemia dropped from 37.5% → 19.3%, hookworm infection dropped from 76.2% → 23.0%

Emergency Contraceptive Pills (ECPs)

• ~85 million women experience unintended pregnancy annually (Singh, Stud Fam Pl, 2010)

• 8 to 30 million women experience contraceptive failure annually

• 21.6 million unsafe abortions occur annually –21.3 million in developing countries (Ahman, IJGO, 2011)

ECPs: Health Need

What is Emergency Contraception?• Emergency Contraceptive Pills (ECPs)

• Often referred to as “the morning-after pill”

• Birth control pill hormones taken in high dose within 3 days (72 hours) of unprotected sex

• IUD Insertion• Within 5 days (120 hours) of unprotected sex

• Can also be a long-term contraceptive method

• Safe for women and for fetuses

ECP Mechanism of Action

• Clinical studies have shown that ECPs can inhibit or delay ovulation

• Evidence regarding endometrial alterations equivocal

­ Not clear that changes observed would inhibit implantation

• Biologic plausibility regarding inhibition of fertilization

­ Thickening of cervical mucous­ Alterations in tubal transport of sperm or egg

Sources: Swahn et al., 1996, Ling et al., 1979, Rowlands et al., 1983, Ling et al., 1983, Kubba et al., 1986, Taskin et al., 1994

Common EC Misperceptions

• ECPs are abortion pills

• Widespread ECP availability will

• encourage irresponsible behavior

• encourage adolescent sexual activity

• reduce men’s willingness to use condoms

• reduce reliance on other methods

Not true

Not true

Not true

Not true

Not true

Women’s Health Websites

• www.rho.org (for info on cervical cancer)

• www.path.org/cervicalcancer

• http://www.path.org/publications/detail.php?i=828 (for EC

toolkit)

• www.who.int/reproductive-health/

• www.reproline.jhu.edu/index.htm

• www.guttmacher.org

• www.who.int/gender/women_health_report/en/

Vivien Tsu, PhD, MPHAssociate Director, Reproductive Health

vtsu@path.org