CANCER AND INFECTIOUS DISEASES: PREVENTION AS A PATHWAY TO CONTROL

Dr. Rasha SalamaM.SC, PhD in Public Health

Suez Canal University

CANCER - GLOBAL BURDEN A major public health concern

Recognized globally as one of the leading chronic non-communicable diseases, imposing strain on the public and on existing health systems.

The impacts of cancer are multiple and far reaching, affecting people of both gender, all ages, and nationalities

13% of annual global mortality

Contribute to over 7.9 million deaths each year and this figure may projected to nearly 10 million unless the problem is addressed urgently.

CANCERS AND INFECTIOUS AGENTS

The most important advance in oncology ever is the understanding that most cancers have specific causes, and that these causes may be identified, leading potentially to control.

The causes of some cancers are infectious agents. The proposal that cancers are caused by infectious agents has had a very up and down history: today we can be certain that many cancers have aetiologies with infectious agents as necessary factors.

WORLDWIDE, AN ESTIMATED 17.8% OF NEOPLASMS ARE ASSOCIATED WITH INFECTIONS; THIS PERCENTAGE RANGES FROM LESS THAN 10% IN HIGH-INCOME COUNTRIES TO 25% IN AFRICAN COUNTRIES.

GLOBAL BURDEN: NEOPLASMS -ASSOCIATED WITH INFECTIONS

Global burden of cancers attributable to infections in 2008: a review and synthetic analysis – lancet 2008

GLOBAL BURDEN: NEOPLASMS -ASSOCIATED WITH INFECTIONS GENDER DISTRIBUTION

INFECTIONS: THE PERCENTAGE CONTRIBUTION

INFECTIONS: THE PERCENTAGE CONTRIBUTION …..

www.thelancet.com/oncology Published online May 9, 2012 DOI:10.1016/S1470-2045(12)70137-7

MECHANISM Viruses may contribute to

the development of human tumors by different mechanisms: indirectly by inducing

immunosuppression or by modifying the host cell genome without persistence of viral DNA;

directly by inducing oncoproteins or by altering the expression of host cell proteins at the site of viral DNA integration.

INFECTION & CANCER …….

Cancer of the cervix and hepatocellular carcinoma account for about 80 percent of virus-linked cancers.

www.thelancet.com/oncology Published online May 9, 2012 DOI:10.1016/S1470-2045(12)70137-7

THE INTERNATIONAL AGENCY FOR RESEARCH ON CANCER HAS CLASSIFIED THE FOLLOWING INFECTIOUS AGENTS AS CARCINOGENIC OR PROBABLY CARCINOGENIC—THAT IS, AS CAUSING OR CONTRIBUTING TO CANCER DEVELOPMENT—IN HUMANS

Infectious Agent Associated Cancers

viruses

Epstein-Barr virus (EBV) Burkitt lymphoma- Hodgkin lymphomaNon-Hodgkin lymphoma - Nasopharyngeal carcinomaNK/T-cell lymphoma

Hepatitis B virus (HBV) Hepatocellular carcinoma (a type of liver cancer)

Hepatitis C virus (HCV) Hepatocellular carcinoma - Non-Hodgkin lymphoma

Human papillomavirus types 16, 18, and others (HPV)

Anal cancer - Cervical cancer - Oral cancer - Penile cancerOropharyngeal cancer (cancer of the base of the tongue, tonsils, or upper throat)Vaginal cancer - Vulvar cancer

Human immunodeficiency virus 1 (HIV 1) A variety of immunosuppression-related cancersAnal cancer - Cervical cancerConjunctiva cancer - Hodgkin lymphomaKaposi sarcoma - Non-Hodgkin lymphoma

Human T-cell lymphotropic virus 1 (HTLV 1) Adult T-cell leukemia/lymphoma

Kaposi sarcoma herpesvirus/ human herpesvirus 8 (KSHV/HHV 8)

Kaposi sarcomaPrimary effusion lymphoma

Other infectious agents

Helicobacter pylori (bacterium) Gastric cancer

Liver flukes (parasite) Cholangiocarcinoma

Schistosomes (parasite) Bladder cancer

CHRONIC BACTERIAL INFECTIONS AND CANCER

MAIN INFECTIOUS AGENTS INVOLVED IN CANCER

Looking world wide we can now point at the main infectious agents involved in cancer:

Human papillomavirus (HPV), recognized as the primary cause of cervical carcinoma;

Hepatitis B and C viruses (HBV and HCV), certainly contribute to hepatocellular carcinoma; and

Helicobacter pylori, which most certainly contributes to gastric carcinoma.

These four examples probably account for a fifth or more of cancer globally.

EVIDENCE: In 1997, the World Health Organization estimated

that up to 84% of cases of some cancers are attributable to viruses, bacteria, and parasites and that more than 1.5 million (15%) new cases each year could be avoided by preventing the infectious disease associated with them

In 1994, the International Agency for Research on Cancer concluded that infection of humans with H. pylori is causally associated with the risk of developing adenocarcinoma of the stomach. H. pylori is also associated with two less common forms of cancer, non-Hodgkin lymphoma and mucosa-associated lymphoid tissue lymphomas of the stomach

EVIDENCE (CONT.) Another landmark study, published in June,

1997, shows that a 12-year nationwide vaccination program against hepatitis B virus in Taiwan resulted in a significant reduction in the number of cases of childhood liver cancer.

The infectious origin of carcinoma of the cervix has long been suspected, because known risk factors for the disease are linked to sexual activity (105). Recent evidence indicates that human papillomavirus (HPV) types 16 and 18 are definitely carcinogenic in humans, Types 31 and 33 are classified as probably carcinogenic

TRUE CANCER CONTROL

“aspires to prevent cancer, to detect cancer at an early stage, and to treat and hopefully cure the disease in those who are diagnosed, and to increase the survival and the quality of life in those who develop it.”

Primary prevention is the most cost-effective form of cancer control.

Prevention means eliminating exposure to the environmental causes of cancer

Promotion of healthy lifestyles could reduce as many as one third of cancers worldwide.

PREVENTION AND CONTROL EFFORTS

Population-based education and awareness campaigns are urgently required to increase screening rates for at-risk individuals and to facilitate early diagnosis and prompt treatment, thereby reducing morbidity and improving survival.

Note: What women think about Cervical cancer

APPROACHES TO CONTROLLINGINFECTION-RELATED CANCERS

Attempts to reduce infection-related cancers should involve efforts to prevent infection and control ongoing disease processes.

Using knowledge of infectious disease processes in cancer causation will further help in guiding intervention, and the benefit must go beyond individual cases to have impacts on the population.

APPROACHES TO CONTROLLINGINFECTION-RELATED CANCERS - SOME EVIDENCE

VACCINE APPROACH

There are two approaches to vaccination, one aiming at prevention of infection (prophylactic) and the other aiming at prevention of disease development following infection (therapeutic).

ANTIBACTERIAL APPROACH

A prototype of an anti bacterial approach to cancer prevention is treatment of helicobacter pylori (H pylori). It is over two decades since the discovery of H pylori as the cause of gastric ulcers and cancer. Early H pylori eradication is known to lead to decreased risk of gastric cancer in patients with peptic ulcer diseases

Effective treatment with antibiotics in combination with good hygiene could decrease gastric cancers.

ANTIVIRAL APPROACH

Currently several antiviral drugs are in use in the treatment of chronic HBV infection worldwide

Antiviral therapies have been shown to delay progression of cirrhosis and lower the incidence of HCC, thus improving long-term survival.

(another example: AIDS associated malignancies is a major complication associated with AIDS patients upon immunosuppression who pose markedly increased risk of developing cancers. Through antiretrovirals therapy (ARV), the malignant complications due to HIV-1 infection have decreased in developed countries.

CERVICAL CANCER BURDEN WORLDWIDE

Every 2 minutes a woman dies of cervical cancer.1

Every minute a woman is diagnosed with cervical cancer.1

New cases per year: ~ 500,000New cases per year: ~ 500,000

Deaths per year: ~ 270,000 Deaths per year: ~ 270,000

NA + Europe

Africa

Asia

Latina

36,000

62,00033,000

143,000

75,000

79,00072,000

266,000

80% in developing countries = 2nd cause of cancer death in women

Every one hour the Middle East loses a woman for cervical cancer.2

1-Ferlay J, et al. GLOBOCAN 2002 Cancer Incidence, Mortality and Prevalence Worldwide. IARC CancerBase; Lyon, 20042Parkin M, Bray F, Ferlay J, Pisani P. Global Cancer Statistics, 2002. CA Cancer J Clin 2005; 55:74–108.

GOVERNMENT OF DUBAI- DUBAI HEALTH AUTHORITYDUBAI CENTRAL CANCER REGISTRY CERVICAL CANCER STATISTICAL REVIEW 2010-2011

The total Number of Cervical Cancer cases registered during the period 2010-2011 were 38 cases,

HPV cancersHighest burden in cervical cancer

Adapted from Parkin DM, Bray F. Vaccine. 2006;24 Suppl 3:S11-25

HPV related cancer in women527,100 cases WW/year

25

HPV related cancer in men33,800 cases WW/year

90% of HPV cancer in women are cervical cancers

HPV and Cervical Cancer

HPV infection is common – skin/skin contact in genital mucosa

50-80% of sexually active women will acquire an HPV infection in their lifetime

50% of the HPV infection will be oncogenic

Natural infection does not reliably protect against subsequent infection: ~50% of women develop no measurable antibody response after HPV infection 1–2 When detectable, serum antibody levels are relatively low

Wallboomers JM et al. J. pathol 1999; 189:12-9Ferlay J et al. Globocan 2002. IARC 2004; Yang BH et al. Int J Cancer 2004; 109: 418–24; Sankaranarayanan R et al. WHO Bulletin 2001; 79: 954–62;

Baseman JG et al. J Clin Virol 2005; 32 Suppl 1; S1624; Brown DR et al. J Infect Dis 2005; 191: 182–92Bosch FX et al. J Natl Cancer Inst Monogr 2003; 313;

CERVICAL CANCER INTERVENTIONS FOR PREVENTION

HPV VACCINES

HPV, is related to cervical cancer . HPV vaccines are highly effective in preventing infection and precancerous lesions in women, and the quadrivalent vaccine has an extended efficacy to a number of conditions such as genital warts in men and women and precancerous anal lesions in men.

Other HPV-related cancers that potentially can benefit from this vaccine include oropharyngeal cancers and HPV-related penile cancers. The focus is already turning to these other cancers in developed countries, where cervical screening is effective, causing re-evaluation of male HPV immunisation.

HBV VACCINES Vaccination against HBV, the cause of chronic

liver diseases such as liver cancer, is a prototype of the former approach. It has already been shown to be very successful and a leading example of a new direction for controlling cancers

Since its introduction there has been a marked reduction in chronic liver disease including hepatocellular carcinoma.

HBV vaccination is already serving as a model for the global control of another important viral cause of cancer

EVEN BREAST CANCER The most common cancer worldwide among women is

breast cancer. The initiation, promotion, and progression of this cancer result from both internal and external factors. The International Agency for Research on Cancer stated that members of the herpesvirus, polyomavirus, papillomavirus, and retrovirus families definitely associate with breast cancer.

It is apparent that more effort needs to be devoted to assessing the role of these viruses in carcinogenesis, by characterizing additional confounding and synergistic effects of carcinogenic factors.

It is proposed that preventing and treating infections may eliminate certain types of cancers.

Review : Role of viruses in the development of breast cancer

Kenneth Alibek12, Ainur Kakpenova1*, Assel Mussabekova1, Marzhan Sypabekova1 and Nargis Karatayeva1

Infectious Agents and Cancer 2013, 8:32

CANCER CONTROL STRATEGY: THE GOAL…..

Reducing incidence of cancer in the country

Detection of cancer at earliest possible time

Providing equitable access to care

Enhancing patient quality of life

Ensuring high quality of cancer control services

International standards of best practice

Stimulating high-quality research on all aspects of cancer control

CANCER CONTROL STRATEGY

The development and implementation of a cancer control strategy is the most effective means of reducing the incidence and impact of cancer, and improving the quality of life of those living with cancer.

Focus on the entire cancer care continuum :

Key to Reducing Cancer Burden

REFERENCES WHO, 2002, National cancer control programs, Policies and

managerial guidelines, 2nd edition

National cancer forum: A Strategy for Cancer Control in Ireland, 2006.

Cancer control policy in Australia: Australia and New Zealand Health Policy 2006, 3:12

Canadian Strategy for Cancer Control: A provincial cancer control policy framework, 2010

WHA57.17 2004, WHO global strategy on diet, Physical Activity and Health.

Review : Role of viruses in the development of breast cancer Kenneth Alibek12, Ainur Kakpenova1*, Assel Mussabekova1, Marzhan Sypabekova1 and Nargis Karatayeva1 - Infectious Agents and Cancer 2013, 8:32

An analysis of the health status of the United Arab Emirates: the ‘Big 4’ public health issues. Institute of Public Health, College of Medicine and Health Sciences, United Arab Emirates University, School of Public Health, Loma Linda University, California, Dubai Health Authority, Dubai, United Arab Emirates – 5 Feb 2013

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