Cancer Screening

Developed by Dr. Alanna FitzgeraldHusek and Dr. Hamidah Meghani

Objectives
To provide an introduction to basic concepts in cancer screening To understand the criteria for cancer screening programs (WHO) To understand the role of screening in prevention and control of cancer Through the example of cervical cancer, to provide students with an overview of effective cancer screening programs

Readings
Denny L, Quinn M, Sankaranarayanan R. 2006. Chapter 8: Screening for cervical cancer in developing countries. Vaccine 24S3: S3/71-S3/77. World Health Organization. 2007. Early detection. Cancer control: Knowledge into action, WHO guide for effective programmes. Available: http://www.who.int/cancer/publications/cancer_contr ol_detection/en/index.html

Outline
Definitions Rationale for Cancer Screening WHO Screening Program Criteria Biases in the interpretation of Screening tests Cervical Cancer
Disease facts Screening options Diagnosis and treatment Barriers/challenges to screening Current state of screening in Bangladesh

Early Detection Programs

Aim: detect (pre-)cancer at an earlier stage (e.g. when still localized, before any spread) Rationale: earlier diagnosis and treatment
This can decrease incidence, mortality, increase survival Early detection should only be promoted and funded within a public health system if certain conditions are met (e.g. accurate pathological diagnosis and effective, affordable treatment options available and accessible

Early Detection of Cancer

Two major components to early detection: 1.Education to promote early diagnosis and treatment e.g. Cancer Awareness campaigns

2.Screening

Cancer Awareness
Early diagnosis can occur when seeking medical attention for early signs or symptoms of disease Health promotion aimed at increased awareness is not recommended when there is no evidence of improvement in survival

Early detection: screening

Screening can be defined as the application of diagnostic tests or procedures to asymptomatic people for the purpose of dividing them into two groups: those who have a condition that would benefit from early intervention and those who do not.
Wallace RB, ed. Public health and preventive medicine. 14th ed. Norwalk: Appleton & Lange, 1998:907-8

The ultimate purpose of screening is to reduce morbidity and mortality.

If improved outcomes cannot be demonstrated, the rationale for screening is lost. Early diagnosis by itself does not justify a screening program. The only justification for a screening program is early diagnosis that leads to a measurable improvement in outcome.
Wallace RB, ed. Public health and preventive medicine. 14th ed. Norwalk: Appleton & Lange, 1998:907-8

Butwho or how do I screen?!?

Types of screening programs

Systematic/organized screening Opportunistic screening

Organized Screening
The systematic application of a screening test to an asymptomatic population An organized program is used to attempt to invite all members of a target, at-risk population (can include automatic recall) Advantages & disadvantages e.g. comprehensive but costly, false +

Opportunistic Screening
The unsystematic application of screening tests used in routine health services e.g. primary care visit

Individuals are offered screening when an appropriate opportunity presents itself less expensive* from a programmatic view, but will miss many at-risk people

Importance of cancer screening

Good quality, evidence-based cancer screening programs can lead to:

incidence of invasive cancer (cervix, colorectal) mortality (cervix, colon/rectum, breast) survival * cost/resource savings reduced treatment costs) and indirectly (e.g. sick leave from work)

What makes a good screening test?

Criteria for a good screening test

Disease factors
Relatively common disease Associated with high morbidity and mortality Natural history of the disease is understood Better outcomes with early detection and treatment Treatment is available Treatment benefits outweigh disadvantages (e.g. complications, side effects) Must have asymptomatic phase detectable by test

Screening for a disease

http://www.aafp.org/afp/2001/0201/p513.html

Test factors
Good at catching all cases without missing any, and ensuring those that screen positive for the test actually do have the condition
e.g. sensitivity and specificity

Safe, cost-effective/affordable, relatively rapid and easy screening test Acceptable and accessible to target population and those providing the test

Health care system factors

Adequate capacity for diagnosis, treatment and follow-up procedures for those that screen positive Clear policy guidelines and political will to support a cost-effective, sustainable screening program for the population

The REAL impact of screening

Lead time bias:
A new test diagnoses the disease earlier but does NOT affect disease outcome (e.g. death at 5 yrs) Early diagnosis falsely appears to prolong survival time

Length time bias:

Slower-growing, less aggressive/deadly disease is over-represented as screening is done intermittently and so can miss severe, rapidly progressing disease

Lead-time bias

http://en.wikipedia.org/wiki/Lead_time_bias

Length time bias

http://sph.bu.edu/otlt/lamorte/EP713/Web_Pages/EP713_Screening/EP713_Screening8.html

Evaluation of screening programs: biases and pitfalls

Voluntary nature:
Individuals volunteering for screening may be
more health-conscious, more likely to seek detection if symptoms develop, etc.

Literacy:
Those that are more literate or educated about
health issues might be more likely to access and understand screening programs and their importance

Evaluation of screening programs: biases and pitfalls

Culture:
Individuals or groups finding a screening test
more culturally appropriate or relative would be more inclined to get tested

Socioeconomic status:
More financial resources = more likely able to
afford and access screening, treatment, etc. May be more likely to attain and maintain better health status

Cervical Cancer Screening: a success story:

Cervical Cancer Screening: a success story:

http://www.cancerresearchuk.org/cancerinfo/cancerstats/types/cervix/mortality/uk-cervical-cancer-mortalitystatistics#trends

Cervical Cancer

In some regions still the most common cancer in women. Risk factors:
Infection with HPV early onset of sexual activity increasing age, low SES multiple partners

Symptoms:
None early on in disease Advanced stages: abnormal vaginal discharge or bleeding

Figure 1: Worldwide age-standardized annual incidence (per 100 000) of cervical cancer (all ages). Reproduced with permission from Elsevier (Vaccine 2006;24[Suppl 3]:1125).13

Cervical Cancer
Prevention:
Primary prevention with HPV vaccine Secondary prevention through regular screening

Diagnosis:
Colposcopy, biopsy

Treatment:
Cryotherapy LEEP hysterectomy

Screening tests available

Pap test (Cytology)
scrape cells from cervix, smear on a slide and examine with microscope

HPV-DNA test
collect cells from cervix (like Pap) and test them for HPV DNA for high risk strains Done usually in combination with Pap test

Screening tests available

Visual inspection with acetic acid (VIA)
application of 3-5% dilute acetic acid using a cotton swab examination of cervix after one minute microscope not needed

VILI
Similar to VIA but using Lugols iodine

Accuracy of tests
Test Pap test HPV-DNA Sensitivity 55-80% 84-100% Specificity 86-100% 90%

VIA
VILI

62-80%*
53-92%*

77-84%*
78-85%*

Cost-effectiveness

Screening Tests
Test Cytology Advantages
-Gets sample of cells, thus more accurate

Disadvantages
-Screen & treat model not applicable -Requires high level of training -expensive -wide range of specificity and sensitivity

VIA

-Immediate result: screen and treat model applicable better access -Range of health workers can be trained to use it (LIC) -inexpensive -higher sensitivity than VIA -same as VIA for results and users

VILI

- Low specificity

HPV-DNA

- Can be combined with cytology or VIA to increase sensitivity and specificity

-Expensive -Not same day results

Diagnostic Tests
Colposcopy +/- biopsy
Requires training in use Requires referral system for positive results Requires more than one visit due to waiting for biopsy results Usually only available in tertiary care centres (access issue)

Treatment
Cryotherapy
easy to use Low cost

LEEP
Feasibility and safety of use by non-MD health workers proven Requires working electricity Better efficacy than cryotherapy among HIV positive women

Hysterectomy
Need for tertiary care and referral Requires coordination of care

Barriers to Screening
Competing health needs
High burden of diseases other than cancer Shrinking public health budgets

Limited human and financial resources Poorly developed healthcare services

Limited and under-resourced primary care facilities in developing countries

Barriers to Screening
Women are uninformed and disempowered
Lack of education (and health literacy) Status to men (subservient) Minimal access to money in the family

War and civil strife Widespread poverty Cultural attitudes

Barriers to Screening
Nature of the screening test
Infrastructure required to do the test and analyze it Communication of results Development of appropriate referral system for positive test results Cost Training of HCWs to do screening, diagnosis and treatment

Screening in low-resource settings requires:

Screening, diagnosis and treatment provision on-site or good clinic access to all Low cost, low technology screening test that can lead to immediate treatment of abnormalities Wide coverage of at-risk women Appropriate educational programmes for women and HCWs to ensure high uptake Built-in mechanism for evaluation of programme

Screen and treat approach

One visit screen and treat approach studied
Use of VIA +/- HPV DNA, colposcopy and biopsy, and cryotherapy when indicated 25% relative reduction in cervical cancer incidence Safety and feasibility assessed in India and Thailand

WHO paper Aug 2012

Prevention of cervical cancer through screening using visual inspection with acetic acid (VIA) and treatment with cryotherapy. A demonstration project in six African countries: Malawi, Madagascar, Nigeria, Uganda, the United Republic of Tanzania, and Zambia

Training took place at the Department of Obstetrics and Gynecology, University of Zimbabwe, Harare. Technical support was provided for data management by the APHRC and IARC. Between September 2005 and May 2009, nearly 20 000 women aged 30-50 were screened with

VIA, 10.1% of which were VIA positive. Almost 90% of VIA-positive cases were eligible for cryotherapy. 63% received cryotherapy within 1 week of their screen, and the single-visit approach was successful for 39.1%. The report highlights successes and limitations, both of which inform their policy recommendations, including: that each MOH develop, update and review their strategies for cervical cancer control based on national guidelines and WHO standards; that implementation should include health education along with adequate funding at all levels through to district healthcare facilities; and that the programs should be linked to sexual and reproductive health as well as other NCD prevention and care.

Cervical Cancer Screening in Bangladesh

Pilot Program
August 2004 to December 2005 Purpose: assess feasibility of training health workers and using this method within existing governmental infrastructure Partners:
Government of Bangladesh UNFPA (United Nations Population Fund) Bangabandhu Sheikh Mujib Medical University

Pilot Program
Location: 16 of 64 districts in 6 division of the country randomly selected among districts with Maternal and Child Welfare Centres Trained:
Master trainers trained senior staff nurses, paramedics and doctors 15 days at BSMMU learning VIA and colposcopy in small groups

References

Ahmed T, Ashrafunnessa KS, Rahman J. 2008. Development of a visual inspection programme for cervical cancer prevention in Bangladesh. Reproductive Health Matters, 16(32): 78-85. Ansink AC, Tolhurst R, Haque R, Saha S, Datta S, van der Broek NR. 2008. Cervical cancer in Bangladesh: community perception of cervical cancer and cervical cancer screening. Transactions of the Royal Society of Tropical Medicine and Hygiene , 102: 499-505. Denny L, Quinn M, Sankaranarayanan R. 2006. Chapter 8: Screening for cervical cancer in developing countries. Vaccine 24S3: S3/71-S3/77. Goldie, S.J., Gaffikin, L., Goldhaber-Fiebert, J.D., Gordillo-Tobar, A., Levin, C., Mahe, C., and Wright, T.C. (2005). Cost-effectiveness of cervical cancer screening in five developing countries. N Engl J Med, 353(20):2158-68. Huchko MJ, Maloba M, Bukusi EA. 2010. Safety of the loop electrosurgical excision procedure performed by clinical officers in an HIV primary care setting. International Journal of Gynecology Obstetrics . 111(1); 89-90. Sankaranarayanan R, Bhatla N, Gravitt PE, Basu P, Esmy PO, Ashrafunnessa KS, Ariyaratne Y, Shah A, Nene BM. 2008. Human Papillomavirus Infection and Cervical Cancer Prevention in India, Bangladesh, Sri Lanka and Nepal. Vaccine 26S: M43-M52. WHO/ICO Information Centre on HPV and Cervical Cancer (HPV Information Centre). Human Papillomavirus and Related Cancers in Bangladesh. Summary Report 2010. [Date accessed]. Available at www.who.int/hpvcentre.