Infectious disease control as part of prevention of cancer in developing countries
Infectious disease control aspart of prevention of cancer indeveloping countries.“Insight Thursday”ADB, Manila07 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-incomecountries;BUT• Huge information bias in LIC&MIC:– Detection: screening tools availability (qualitative,geographical, financial)– Recording&reporting: medical information systemavailability and performance
Cancer: burden of disease andeconomic development• Developing countries • Developed countries70% of casesworldwide
Cancer: burden of disease andcervix uteri and liver cancerCERVIX UTERILIVERHepatitis C
Cancer: burden of disease andgenderFemaleMaleLess developedcountriesMore developedcountries
Source: IARC, WHO 2008Summary statistics (2008)MORE DEVELOPED REGIONS Male Female Both sexesPopulation (thousands) 597346 632734 1230081Number of new cancer cases (thousands) 2964,2 2591,1 5555,3Age-standardised rate (W) 299,2 226,3 255,8Risk of getting cancer before age 75 (%) 30 22,1 25,7Number of cancer deaths (thousands) 1522,4 1222,5 2744,8Age-standardised rate (W) 143,1 87,2 111,1Risk of dying from cancer before age 75 (%) 14,9 9,1 11,85-year prevalent cases, adult population (thousands) 7756,1 7505,9 15262Proportion (per 100,000) 1575,1 1408,1 1488,35 most frequent cancers (ranking defined by total numberof cases)Prostate Breast ColorectumLung Colorectum LungColorectum Lung BreastBladder Corpus uteri ProstateStomach Stomach StomachSummary statistics (2008)LESS DEVELOPED REGIONS Male Female Both sexesPopulation (thousands) 2817219 2725980 5543200Number of new cancer cases (thousands) 3653,6 3453,6 7107,3Age-standardised rate (W) 159,1 137,2 146,8Risk of getting cancer before age 75 (%) 16,9 13,9 15,3Number of cancer deaths (thousands) 2697,3 2122,7 4820Age-standardised rate (W) 118,4 84,8 100,6Risk of dying from cancer before age 75 (%) 12,6 8,9 10,75-year prevalent cases, adult population (thousands) 5758,7 7782,4 13541,1Proportion (per 100,000) 293,5 403,4 3485 most frequent cancers (ranking defined by total number ofcases)Lung Breast LungStomach Cervix uteri StomachLiver Lung BreastColorectum Stomach LiverOesophagus Colorectum ColorectumCancer: burden of disease andeconomic development – summary.
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 istherefore theoritically also affordable in resources-limitedsetting):– Tobacco use– Alcohol use– Dietary factors– Physical inactivity– Obesity• But other environmental carcinogenetic exposures aredifficult to detect:– physical (UVA)– chemical (benzopyrenes, aflatoxins)– biological (HPV, hepatitisB, HIV, …)
Screening+prevention+earlytreatment= better outcomes• Death rate increases for liver,pancreas, uterus and skinmelanoma• Growing number of HPV-relatedcancers• Poor HPV vaccination coveragelevels: 48.7% girls from 13 to 17of age received at least 1 dose,and only 32% the recommended3-dose series• USA: “Report to the Nation”shows U.S. cancer death ratescontinue to drop (lung, colon,rectum, female beast and prostate)
Cancer and infections• Infectious agents are responsible for almost 22% of cancer deaths in thedeveloping 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 cervicalcancer (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 collaborationprospective 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, Testicularcancer– 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 from12.4 million in 2006 to 33.5 million in 2010• People are at risk of infection due to agricultural, domesticand recreational activities which expose them to infestedwater. Construction workers can be exposed (hydropowerdam construction, f.i.)• Risk factor of bladder cancer in Middle-east and Africa (Egypt:bladder cancer is the most common cancer among male, and27% 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: helicobacterpylori and stomach cancer.• Stomach cancer is mainly associated with dietary factors (presence ofnitrites), tobacco use.• Helicobacter pylori infection is quite common (30% of adults), and mostof the carriers will not develop any stomach cancer. However, they aremore at risk of developing stomach ulcers.• It seems that it is the association of H. pylori infection associated with adiet 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 womenin developing countries: 260 000 deaths in 2005, of whichabout 80% occurred in developing countries.• USA: cervical cancer incidence rates were higher amongwomen 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 thepopulation.• More than 100 serotypes, among which 13 (to date) canlead to cancers (especially 16, 18, 31, 33, 45).
HPV infection screening andprevention• 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 trainednurses and midwives. (Saxena U, Sauvaget C, Sankaranarayanan R. Evidence-basedscreening, early diagnosis and treatment strategy of cervical cancer for national policy in low- resourcecountries: 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 schedulesfor boys and girls as early as 9 years old in developed countries (3injections; 1500P or 2150P/dosis at ADB medical center)• But: « Access to vaccination for underserved populations bothin 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 inThailand” (Termrungruanglert W, Havanond P, Khemapech N, Lertmaharit S, Pongpanich S, KhorprasertC, Taneepanichskul S. Cost and effectiveness evaluation of prophylactic HPV vaccine in developingcountries. Value Health. 2012 Jan-Feb;15(1 Suppl):S29-34.)
Viral hepatitis and liver cancer• Hepatitis B (DNA virus):– Two billion people worldwide havebeen infected with the virus– Kills about 600 000 people die everyyear (chronic infection/cirrhosis;hepatitis fulminans)– 50 to 100 times more infectious thanHIV.– 10% of patients will becomechronically infected, and half of thosewill develop liver cancer– Mainly sexual and blood-bornetransmition (perinatal, IDUs, unsafeblood transfusion); occupationalhazard for healthcare workers;– Hepatitis B vaccine is 95% effective inpreventing infection and its chronicconsequences, and is the first vaccineagainst a major human cancer.– Prevention: neonatal contamination,blood safety/infection control, safeinjections/tatooing/acupuncture;protected sex• Hepatitis C (RNA virus):– About 150 million people arechronically infected with hepatitis Cvirus;– Kills more than 350 000 people dieevery year (severe liver diseasesincluding cancer).– Once contaminated: 15 to 35% ofspontaneous healing/ 65 to 85% ofchronic hepatitis 20% to cirrhosis 1 to 4%/year of liver cancer– Blood-borne disease. STD? IDUs– Worldwide distribution, but espaciallyfrequent in Egypt, Pakistan andChina, due to unsafe injections– No vaccine– Curable with antiviral therapy– Prevention: blood safety, safeinjections, limitation of BT andinjections (good medical practices),safe tatooing/acupuncture, piercings;protected sex2 very different types of viruses, but both are major risk factors of hepatocarcinoma
HIV and cancer• For AIDS-defining cancers, HAART reduces the risk ofdeveloping such cancers.• However, the risk of having a cancer increases with lifeexpectancy as a consequence of HAART’s efficacy.• Non AIDS-defining cancer become the major burdencancer fo HIV-infected patients (lung, liver, anal,colorectal, Hodgkin’s disease).• Together with HAART, there is a need to review thescreening process of these cancers in this specificpopulation, and how to implement it.
Conclusions1. The boundaries between non-communicable and communicable diseasesare not so clear.2. Several cancers are clearly due to an exposure to a pathogen, essentiallyviruses.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 excision4. Most of these measures can be implemented in poor-resources settingcountries.5. Several measures require better health financing, primary healthcarefacilities, 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 HPVimmunization in limited-reources setting. GAVI now provides HPV vaccineat USD5/dose in poor-resources countries and - for WCD 2013 - providedHPV 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 adeath sentence”Professor Ian OlverChief Executive Officer, Cancer Council Australia MB BS, MD, PhD,CMin, FRACP, MRACMA, FAChPM… but not in every country, and for everyone inmost of the countries, as a matter of inequality inhealth financing, accessibility to healthcare, qualityof care, healthcare workers availability and training,…Poor-resources setting countries:Double burden of diseases – communicable andnon-communicable – but the overall burden ismore than the sum of its parts, and the sum of thebudgets is probably less than the minimumrequired to tackle even one of them.