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Infectious disease control as
part of prevention of cancer in
developing countries.
“Insight Thursday”
ADB, Manila
07 February 2013
Cancer: burden of disease.
• 7.6 million deaths (around 13% of all deaths)
in 2008. (WHO, 2012);
• three quarters in low- and middle-income
countries;
BUT
• Huge information bias in LIC&MIC:
– Detection: screening tools availability (qualitative,
geographical, financial)
– Recording&reporting: medical information system
availability and performance
Cancer: burden of disease and
economic development
• Developing countries • Developed countries
70% of cases
worldwide
Cancer: burden of disease and
cervix uteri and liver cancer
CERVIX UTERI
LIVERHepatitis C
Cancer: burden of disease and
gender
Female
Male
Less developed
countries
More developed
countries
Source: IARC, WHO 2008
Summary statistics (2008)
MORE DEVELOPED REGIONS Male Female Both sexes
Population (thousands) 597346 632734 1230081
Number of new cancer cases (thousands) 2964,2 2591,1 5555,3
Age-standardised rate (W) 299,2 226,3 255,8
Risk of getting cancer before age 75 (%) 30 22,1 25,7
Number of cancer deaths (thousands) 1522,4 1222,5 2744,8
Age-standardised rate (W) 143,1 87,2 111,1
Risk of dying from cancer before age 75 (%) 14,9 9,1 11,8
5-year prevalent cases, adult population (thousands) 7756,1 7505,9 15262
Proportion (per 100,000) 1575,1 1408,1 1488,3
5 most frequent cancers (ranking defined by total number
of cases)
Prostate Breast Colorectum
Lung Colorectum Lung
Colorectum Lung Breast
Bladder Corpus uteri Prostate
Stomach Stomach Stomach
Summary statistics (2008)
LESS DEVELOPED REGIONS Male Female Both sexes
Population (thousands) 2817219 2725980 5543200
Number of new cancer cases (thousands) 3653,6 3453,6 7107,3
Age-standardised rate (W) 159,1 137,2 146,8
Risk of getting cancer before age 75 (%) 16,9 13,9 15,3
Number of cancer deaths (thousands) 2697,3 2122,7 4820
Age-standardised rate (W) 118,4 84,8 100,6
Risk of dying from cancer before age 75 (%) 12,6 8,9 10,7
5-year prevalent cases, adult population (thousands) 5758,7 7782,4 13541,1
Proportion (per 100,000) 293,5 403,4 348
5 most frequent cancers (ranking defined by total number of
cases)
Lung Breast Lung
Stomach Cervix uteri Stomach
Liver Lung Breast
Colorectum Stomach Liver
Oesophagus Colorectum Colorectum
Cancer: burden of disease and
economic development – summary.
Prevention, screening, infection
Lung Breast Lung
Stomach Cervix uteri Stomach
Liver Lung Breast
Colorectum Stomach Liver
Oesophagus Colorectum Colorectum
Prostate Breast Colorectum
Lung Colorectum Lung
Colorectum Lung Breast
Bladder Corpus uteri Prostate
Stomach Stomach Stomach
LIC/MIC HIC
femalefemalemale maleall all
screenable preventable infection
Cancer prevention efficacy
• About 40% of all cancer deaths can be prevented.
• Principle: to lower the exposure to specific risk factors.
• It is usually not a matter of cutting-edge technology (and is
therefore theoritically also affordable in resources-limited
setting):
– Tobacco use
– Alcohol use
– Dietary factors
– Physical inactivity
– Obesity
• But other environmental carcinogenetic exposures are
difficult to detect:
– physical (UVA)
– chemical (benzopyrenes, aflatoxins)
– biological (HPV, hepatitisB, HIV, …)
Screening+prevention+early
treatment= better outcomes
• Death rate increases for liver,
pancreas, uterus and skin
melanoma
• Growing number of HPV-related
cancers
• Poor HPV vaccination coverage
levels: 48.7% girls from 13 to 17
of age received at least 1 dose,
and only 32% the recommended
3-dose series
• USA: “Report to the Nation”
shows U.S. cancer death rates
continue to drop (lung, colon,
rectum, female beast and prostate)
Cancer and infections
• Infectious agents are responsible for almost 22% of cancer deaths in the
developing world and 6% in industrialized countries (WHO,
http://www.who.int/cancer/prevention/en/ accessed 01 Feb.2013)
• Virus
– HVP: cervix uteri, penile, vaginal, anal cancers
– HIV:
• AIDS-defining cancers: Kaposi’s sarcoma, Non-Hodgkin lymphoma, Invasive cervical
cancer (higher risk of ICC , increasing with immunosuppression level, in Abraham AG et al.,
Invasive cervical cancer risk among HIV-infected women: A North American multi-cohort collaboration
prospective study. J Acquir Immune Defic Syndr. 2012 Dec 18.)
• Non-AIDS-defining cancers: Anal cancer, Hodgkin disease (Hodgkin lymphoma),
Melanoma skin cancer, Liver cancer, Lung cancer, Mouth and throat cancers, Testicular
cancer
– Hepatitis B and C: liver cancer (hepatocarcinoma)
– EBV: cofactor of nasopharynx cancer
– HHV 8: Kaposi’s sarcoma
– HTLV: leukemia
• Bacterias: helicobacter pylori ?
• Parasites:
– Schistosomiasis: bladder cancer
– Flukes (Opistorchis viverrini, Clonorchis sinensis): cholangiocarcinoma (Thailand,
Philippines)
NTD and Cancer: schistosomiasis
• The number of people treated for schistosomiasis rose from
12.4 million in 2006 to 33.5 million in 2010
• People are at risk of infection due to agricultural, domestic
and recreational activities which expose them to infested
water. Construction workers can be exposed (hydropower
dam construction, f.i.)
• Risk factor of bladder cancer in Middle-east and Africa (Egypt:
bladder cancer is the most common cancer among male, and
27% of them are related to S. infection).
• Prevention: improved sanitation, elimination of the snails
(reservoir of parasites), avoid skin contact with infested water
Bacteria and cancer: helicobacter
pylori and stomach cancer.
• Stomach cancer is mainly associated with dietary factors (presence of
nitrites), tobacco use.
• Helicobacter pylori infection is quite common (30% of adults), and most
of the carriers will not develop any stomach cancer. However, they are
more at risk of developing stomach ulcers.
• It seems that it is the association of H. pylori infection associated with a
diet rich in nitrites that represents a higher risk of stomach cancer.
• Screening of H. pylori infection with a direct test during a gastroscopy,
and by detecting blood circulating antibodies.
• Prevention: diet, (treatment of H. Pylori infection with antibiotics ?)
• Screening not accessible in limited-resources setting.
HPV and cervix uteri cancer
• Cervix cancer is caused by Human Papilloma Viruses.
• Most common cancer (just after breast) affecting women
in developing countries: 260 000 deaths in 2005, of which
about 80% occurred in developing countries.
• USA: cervical cancer incidence rates were higher among
women living in low versus high socioeconomic areas.
• HPV infection is related to other cancers (anal, penile,
vulvar, oropharynx) and to anal/genital warts.
• The most common STI, affecting 3 to 5% of the
population.
• More than 100 serotypes, among which 13 (to date) can
lead to cancers (especially 16, 18, 31, 33, 45).
HPV infection screening and
prevention
• Screening: PAP smear and HPV DNA detection
• Routine screening in developed countries
• Evidence of cost-effectivenes in developing countries, including
"screen-and-treat" approach, achieved in a single visit, by trained
nurses and midwives. (Saxena U, Sauvaget C, Sankaranarayanan R. Evidence-based
screening, early diagnosis and treatment strategy of cervical cancer for national policy in low- resource
countries: example of India. Asian Pac J Cancer Prev. 2012;13(4):1699-703.)
• Prevention: STI prevention and vaccination
• HPV immunization is included in regular HPV immunization schedules
for boys and girls as early as 9 years old in developed countries (3
injections; 1500P or 2150P/dosis at ADB medical center)
• But: « Access to vaccination for underserved populations both
in developed and resource-poor nations remains an issue”
(Darus CJ, Mueller JJ. Development and impact of human papillomavirus vaccines. Clin Obstet Gynecol.
2013 Mar;56(1):10-6.).
• “Nationwide coverage of HPV vaccination in girls is likely to be cost-effective in
Thailand” (Termrungruanglert W, Havanond P, Khemapech N, Lertmaharit S, Pongpanich S, Khorprasert
C, Taneepanichskul S. Cost and effectiveness evaluation of prophylactic HPV vaccine in developing
countries. Value Health. 2012 Jan-Feb;15(1 Suppl):S29-34.)
Viral hepatitis and liver cancer
• Hepatitis B (DNA virus):
– Two billion people worldwide have
been infected with the virus
– Kills about 600 000 people die every
year (chronic infection/cirrhosis;
hepatitis fulminans)
– 50 to 100 times more infectious than
HIV.
– 10% of patients will become
chronically infected, and half of those
will develop liver cancer
– Mainly sexual and blood-borne
transmition (perinatal, IDUs, unsafe
blood transfusion); occupational
hazard for healthcare workers;
– Hepatitis B vaccine is 95% effective in
preventing infection and its chronic
consequences, and is the first vaccine
against a major human cancer.
– Prevention: neonatal contamination,
blood safety/infection control, safe
injections/tatooing/acupuncture;
protected sex
• Hepatitis C (RNA virus):
– About 150 million people are
chronically infected with hepatitis C
virus;
– Kills more than 350 000 people die
every year (severe liver diseases
including cancer).
– Once contaminated: 15 to 35% of
spontaneous healing/ 65 to 85% of
chronic hepatitis  20% to cirrhosis
 1 to 4%/year of liver cancer
– Blood-borne disease. STD? IDUs
– Worldwide distribution, but espacially
frequent in Egypt, Pakistan and
China, due to unsafe injections
– No vaccine
– Curable with antiviral therapy
– Prevention: blood safety, safe
injections, limitation of BT and
injections (good medical practices),
safe tatooing/acupuncture, piercings;
protected sex
2 very different types of viruses, but both are major risk factors of hepatocarcinoma
Hepatitis B and immunization
coverage
HIV and cancer
• For AIDS-defining cancers, HAART reduces the risk of
developing such cancers.
• However, the risk of having a cancer increases with life
expectancy as a consequence of HAART’s efficacy.
• Non AIDS-defining cancer become the major burden
cancer fo HIV-infected patients (lung, liver, anal,
colorectal, Hodgkin’s disease).
• Together with HAART, there is a need to review the
screening process of these cancers in this specific
population, and how to implement it.
Conclusions
1. The boundaries between non-communicable and communicable diseases
are not so clear.
2. Several cancers are clearly due to an exposure to a pathogen, essentially
viruses.
3. Prevention of such cancers consists of:
• Prevention of contact/contamination: blood safety, infection control,
protected sex
• Prevention of infection: passive or active immunization
• Treatment of infection: antivirals, precancerous lesion excision
4. Most of these measures can be implemented in poor-resources setting
countries.
5. Several measures require better health financing, primary healthcare
facilities, simplified and cost-effective procedures (cervix cancer and
« screen and treat »), health education, training of healthcare workers.
6. The succes story of hepatitis B will certainly be replicated with HPV
immunization in limited-reources setting. GAVI now provides HPV vaccine
at USD5/dose in poor-resources countries and - for WCD 2013 - provided
HPV vaccine to 180,000 girls in 8 developing countries (Ghana, Kenya,
Lao PDR, Madagascar, Malawi, Sierra Leone, Tanzania)
Hope for everyone ?
“No magic bullet but cancer is no longer a
death sentence”
Professor Ian Olver
Chief Executive Officer, Cancer Council Australia MB BS, MD, PhD,
CMin, FRACP, MRACMA, FAChPM
… but not in every country, and for everyone in
most of the countries, as a matter of inequality in
health financing, accessibility to healthcare, quality
of care, healthcare workers availability and training,
…
Poor-resources setting countries:
Double burden of diseases – communicable and
non-communicable – but the overall burden is
more than the sum of its parts, and the sum of the
budgets is probably less than the minimum
required to tackle even one of them.

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Infectious disease control as part of prevention of cancer in developing countries

  • 1. Infectious disease control as part of prevention of cancer in developing countries. “Insight Thursday” ADB, Manila 07 February 2013
  • 2. Cancer: burden of disease. • 7.6 million deaths (around 13% of all deaths) in 2008. (WHO, 2012); • three quarters in low- and middle-income countries; BUT • Huge information bias in LIC&MIC: – Detection: screening tools availability (qualitative, geographical, financial) – Recording&reporting: medical information system availability and performance
  • 3. Cancer: burden of disease and economic development • Developing countries • Developed countries 70% of cases worldwide
  • 4. Cancer: burden of disease and cervix uteri and liver cancer CERVIX UTERI LIVERHepatitis C
  • 5. Cancer: burden of disease and gender Female Male Less developed countries More developed countries
  • 6. Source: IARC, WHO 2008 Summary statistics (2008) MORE DEVELOPED REGIONS Male Female Both sexes Population (thousands) 597346 632734 1230081 Number of new cancer cases (thousands) 2964,2 2591,1 5555,3 Age-standardised rate (W) 299,2 226,3 255,8 Risk of getting cancer before age 75 (%) 30 22,1 25,7 Number of cancer deaths (thousands) 1522,4 1222,5 2744,8 Age-standardised rate (W) 143,1 87,2 111,1 Risk of dying from cancer before age 75 (%) 14,9 9,1 11,8 5-year prevalent cases, adult population (thousands) 7756,1 7505,9 15262 Proportion (per 100,000) 1575,1 1408,1 1488,3 5 most frequent cancers (ranking defined by total number of cases) Prostate Breast Colorectum Lung Colorectum Lung Colorectum Lung Breast Bladder Corpus uteri Prostate Stomach Stomach Stomach Summary statistics (2008) LESS DEVELOPED REGIONS Male Female Both sexes Population (thousands) 2817219 2725980 5543200 Number of new cancer cases (thousands) 3653,6 3453,6 7107,3 Age-standardised rate (W) 159,1 137,2 146,8 Risk of getting cancer before age 75 (%) 16,9 13,9 15,3 Number of cancer deaths (thousands) 2697,3 2122,7 4820 Age-standardised rate (W) 118,4 84,8 100,6 Risk of dying from cancer before age 75 (%) 12,6 8,9 10,7 5-year prevalent cases, adult population (thousands) 5758,7 7782,4 13541,1 Proportion (per 100,000) 293,5 403,4 348 5 most frequent cancers (ranking defined by total number of cases) Lung Breast Lung Stomach Cervix uteri Stomach Liver Lung Breast Colorectum Stomach Liver Oesophagus Colorectum Colorectum Cancer: burden of disease and economic development – summary.
  • 7. Prevention, screening, infection Lung Breast Lung Stomach Cervix uteri Stomach Liver Lung Breast Colorectum Stomach Liver Oesophagus Colorectum Colorectum Prostate Breast Colorectum Lung Colorectum Lung Colorectum Lung Breast Bladder Corpus uteri Prostate Stomach Stomach Stomach LIC/MIC HIC femalefemalemale maleall all screenable preventable infection
  • 8. Cancer prevention efficacy • About 40% of all cancer deaths can be prevented. • Principle: to lower the exposure to specific risk factors. • It is usually not a matter of cutting-edge technology (and is therefore theoritically also affordable in resources-limited setting): – Tobacco use – Alcohol use – Dietary factors – Physical inactivity – Obesity • But other environmental carcinogenetic exposures are difficult to detect: – physical (UVA) – chemical (benzopyrenes, aflatoxins) – biological (HPV, hepatitisB, HIV, …)
  • 9. Screening+prevention+early treatment= better outcomes • Death rate increases for liver, pancreas, uterus and skin melanoma • Growing number of HPV-related cancers • Poor HPV vaccination coverage levels: 48.7% girls from 13 to 17 of age received at least 1 dose, and only 32% the recommended 3-dose series • USA: “Report to the Nation” shows U.S. cancer death rates continue to drop (lung, colon, rectum, female beast and prostate)
  • 10. Cancer and infections • Infectious agents are responsible for almost 22% of cancer deaths in the developing world and 6% in industrialized countries (WHO, http://www.who.int/cancer/prevention/en/ accessed 01 Feb.2013) • Virus – HVP: cervix uteri, penile, vaginal, anal cancers – HIV: • AIDS-defining cancers: Kaposi’s sarcoma, Non-Hodgkin lymphoma, Invasive cervical cancer (higher risk of ICC , increasing with immunosuppression level, in Abraham AG et al., Invasive cervical cancer risk among HIV-infected women: A North American multi-cohort collaboration prospective study. J Acquir Immune Defic Syndr. 2012 Dec 18.) • Non-AIDS-defining cancers: Anal cancer, Hodgkin disease (Hodgkin lymphoma), Melanoma skin cancer, Liver cancer, Lung cancer, Mouth and throat cancers, Testicular cancer – Hepatitis B and C: liver cancer (hepatocarcinoma) – EBV: cofactor of nasopharynx cancer – HHV 8: Kaposi’s sarcoma – HTLV: leukemia • Bacterias: helicobacter pylori ? • Parasites: – Schistosomiasis: bladder cancer – Flukes (Opistorchis viverrini, Clonorchis sinensis): cholangiocarcinoma (Thailand, Philippines)
  • 11. NTD and Cancer: schistosomiasis • The number of people treated for schistosomiasis rose from 12.4 million in 2006 to 33.5 million in 2010 • People are at risk of infection due to agricultural, domestic and recreational activities which expose them to infested water. Construction workers can be exposed (hydropower dam construction, f.i.) • Risk factor of bladder cancer in Middle-east and Africa (Egypt: bladder cancer is the most common cancer among male, and 27% of them are related to S. infection). • Prevention: improved sanitation, elimination of the snails (reservoir of parasites), avoid skin contact with infested water
  • 12. Bacteria and cancer: helicobacter pylori and stomach cancer. • Stomach cancer is mainly associated with dietary factors (presence of nitrites), tobacco use. • Helicobacter pylori infection is quite common (30% of adults), and most of the carriers will not develop any stomach cancer. However, they are more at risk of developing stomach ulcers. • It seems that it is the association of H. pylori infection associated with a diet rich in nitrites that represents a higher risk of stomach cancer. • Screening of H. pylori infection with a direct test during a gastroscopy, and by detecting blood circulating antibodies. • Prevention: diet, (treatment of H. Pylori infection with antibiotics ?) • Screening not accessible in limited-resources setting.
  • 13. HPV and cervix uteri cancer • Cervix cancer is caused by Human Papilloma Viruses. • Most common cancer (just after breast) affecting women in developing countries: 260 000 deaths in 2005, of which about 80% occurred in developing countries. • USA: cervical cancer incidence rates were higher among women living in low versus high socioeconomic areas. • HPV infection is related to other cancers (anal, penile, vulvar, oropharynx) and to anal/genital warts. • The most common STI, affecting 3 to 5% of the population. • More than 100 serotypes, among which 13 (to date) can lead to cancers (especially 16, 18, 31, 33, 45).
  • 14. HPV infection screening and prevention • Screening: PAP smear and HPV DNA detection • Routine screening in developed countries • Evidence of cost-effectivenes in developing countries, including "screen-and-treat" approach, achieved in a single visit, by trained nurses and midwives. (Saxena U, Sauvaget C, Sankaranarayanan R. Evidence-based screening, early diagnosis and treatment strategy of cervical cancer for national policy in low- resource countries: example of India. Asian Pac J Cancer Prev. 2012;13(4):1699-703.) • Prevention: STI prevention and vaccination • HPV immunization is included in regular HPV immunization schedules for boys and girls as early as 9 years old in developed countries (3 injections; 1500P or 2150P/dosis at ADB medical center) • But: « Access to vaccination for underserved populations both in developed and resource-poor nations remains an issue” (Darus CJ, Mueller JJ. Development and impact of human papillomavirus vaccines. Clin Obstet Gynecol. 2013 Mar;56(1):10-6.). • “Nationwide coverage of HPV vaccination in girls is likely to be cost-effective in Thailand” (Termrungruanglert W, Havanond P, Khemapech N, Lertmaharit S, Pongpanich S, Khorprasert C, Taneepanichskul S. Cost and effectiveness evaluation of prophylactic HPV vaccine in developing countries. Value Health. 2012 Jan-Feb;15(1 Suppl):S29-34.)
  • 15. Viral hepatitis and liver cancer • Hepatitis B (DNA virus): – Two billion people worldwide have been infected with the virus – Kills about 600 000 people die every year (chronic infection/cirrhosis; hepatitis fulminans) – 50 to 100 times more infectious than HIV. – 10% of patients will become chronically infected, and half of those will develop liver cancer – Mainly sexual and blood-borne transmition (perinatal, IDUs, unsafe blood transfusion); occupational hazard for healthcare workers; – Hepatitis B vaccine is 95% effective in preventing infection and its chronic consequences, and is the first vaccine against a major human cancer. – Prevention: neonatal contamination, blood safety/infection control, safe injections/tatooing/acupuncture; protected sex • Hepatitis C (RNA virus): – About 150 million people are chronically infected with hepatitis C virus; – Kills more than 350 000 people die every year (severe liver diseases including cancer). – Once contaminated: 15 to 35% of spontaneous healing/ 65 to 85% of chronic hepatitis  20% to cirrhosis  1 to 4%/year of liver cancer – Blood-borne disease. STD? IDUs – Worldwide distribution, but espacially frequent in Egypt, Pakistan and China, due to unsafe injections – No vaccine – Curable with antiviral therapy – Prevention: blood safety, safe injections, limitation of BT and injections (good medical practices), safe tatooing/acupuncture, piercings; protected sex 2 very different types of viruses, but both are major risk factors of hepatocarcinoma
  • 16. Hepatitis B and immunization coverage
  • 17. HIV and cancer • For AIDS-defining cancers, HAART reduces the risk of developing such cancers. • However, the risk of having a cancer increases with life expectancy as a consequence of HAART’s efficacy. • Non AIDS-defining cancer become the major burden cancer fo HIV-infected patients (lung, liver, anal, colorectal, Hodgkin’s disease). • Together with HAART, there is a need to review the screening process of these cancers in this specific population, and how to implement it.
  • 18. Conclusions 1. The boundaries between non-communicable and communicable diseases are not so clear. 2. Several cancers are clearly due to an exposure to a pathogen, essentially viruses. 3. Prevention of such cancers consists of: • Prevention of contact/contamination: blood safety, infection control, protected sex • Prevention of infection: passive or active immunization • Treatment of infection: antivirals, precancerous lesion excision 4. Most of these measures can be implemented in poor-resources setting countries. 5. Several measures require better health financing, primary healthcare facilities, simplified and cost-effective procedures (cervix cancer and « screen and treat »), health education, training of healthcare workers. 6. The succes story of hepatitis B will certainly be replicated with HPV immunization in limited-reources setting. GAVI now provides HPV vaccine at USD5/dose in poor-resources countries and - for WCD 2013 - provided HPV vaccine to 180,000 girls in 8 developing countries (Ghana, Kenya, Lao PDR, Madagascar, Malawi, Sierra Leone, Tanzania)
  • 19. Hope for everyone ? “No magic bullet but cancer is no longer a death sentence” Professor Ian Olver Chief Executive Officer, Cancer Council Australia MB BS, MD, PhD, CMin, FRACP, MRACMA, FAChPM … but not in every country, and for everyone in most of the countries, as a matter of inequality in health financing, accessibility to healthcare, quality of care, healthcare workers availability and training, … Poor-resources setting countries: Double burden of diseases – communicable and non-communicable – but the overall burden is more than the sum of its parts, and the sum of the budgets is probably less than the minimum required to tackle even one of them.