Etiology and epidemiology of malignant tumours –

Methods for cancer prevention and screening

Csaba Polgár

National Institute of Oncology, Budapest

Semmelweis University, Department of Oncology

Etiology of malignant tumours

• Multifactorial etiology

• Environmental factors – chemical and physical factors (80-90%)

• Infections – Viral, bacterial oncogenesis (5-10%)

• Hereditary tumours (< 5%)

Chemical and physical factors – Carcinogenic agents

(n=984)

• Group 1: carcinogenic to humans (n=118; tobacco, asbest, alcohol, UV, solar and

ionizing radiation, outdoor air pollution, oral contraceptives, processed meat)

• Group 2/A: probably carcinogenic to humans (n=75; bitumens, DDT, anabolic,

steroids, red meat)

• Group 2/B: possibly carcinogenic to humans (n=288; phenobarbital, chloroform,

coffee, glass fiber, gasoline, diesel fuel, carbon black, lead, chrome, nickel)

• Group 3: not classifiable as to its carcinogenicity to humans (n=503; caffeine,

tea, PVC, printing ink, magnetic & electric fields, paracetamol, diazempam)

• Group 4: probably not carcinogenic to humans (n=1; caprolactam)

Group 1 carcinogenic chemical agents

• Policyclic aromatic carbohydrogens (combustion products)• tobacco smoke, smut, exhausted gas, urban outdoor air

• Aromatic amines

• production of aniline-dye, plant-protecting agents, plastic materials

• Nitroze-amines• tobacco smoke, rubber and war industry

• Aflatoxines (mushroom toxine)

• Not classified, other agents

• arsenic compounds, chrome, nickel, mustard gas, plant alkaloids etc.

• processed meat (2015)

Carcinogenic physical factors

• Ionising radiation (physical-chemical-biologic phases DNA-damage)

• Non-ionising radiations

• UV (melanoma, skin squamous and basal cell cancers)

• Mikrowave & radiofrequency radiation (Group 2/B, gliomas?)

• Very low frequency electromagnetic field (0-300 Hz) (Group 2/B, leukemia?)

• Asbestos, quartz, talc (powders, fibres, crystals)

Carcinogenic viral, bacterial, and worm infections (5-10%)

Virus/Bacteria/Germ Type Increased cancer risk

Human papilloma virus (HPV) 16,18,6,11…31,33,35,39,45,51,

52,56,58,59,68,73,82

cervix, anal, bladder, head&neck

ca.

Hepatitis B virus (HBV) B, C (far-east) hepatocellular ca.

Human polyoma virus BK, JC childhood neuroblastoma

Human herpes virus EBV, CMV, KS nasophyarynx, Burkitt-lymphoma.

lethal midline granuloma,

Kaposi sarcoma

Exogen retrovirus HTLV-1, HTLV-2 T-cell leukemia

Hepatitis C virus HCV lymphoma, aplastic anaemia,

cirrhosis, hepatocellular ca.

Human immunodeficiency virus HIV-1 cancer risk increased indirectly by

primary immunosuppresion

Helicobacter pylori bacteria gastric cc.

Schistosomas worms: S. haematobium, S.

japonicum,

bladder, liver, colorectal, gastric ca.

Hereditary tumours (< 5%)

• Aquired, sporadic tumours (> 95%):

Mutations in somatic cells caused by cumulated environmental effects

• Hereditary tumours (< 5%):

Hereditary germ-cell mutations + aquired somatic mutations

• Cancer itself is NOT hereditary!

• There is only a hereditary higher propensity for developing cancer!

Cancer is caused by DNA-mutations

Cancer (at cellular level) is a genetic disease

Hereditary cancer syndromes (< 5%)

Mainly based on the inactivation tumour supressor genes

Syndrome Affected gene Tumours

Hereditary breast cancer BRCA1, BRCA2 breast, ovary, prostate, pancreas

Hereditary retinoblastoma RB1 retinoblastoma, osteosarcoma

Wilms-tumour WT1 Wilms-tumour

Fam. adenomatosus polyposis APC GI, brain, thyroid gland, retina

Lynch MLH1; MSH2,6; PMS1-2 stb. non polyposus colorectal ca.

Peutz-Jeghers STK11/LKB1 GI, breast, ovary, endometrial,

testicular, pancreatic ca.

Ataxia teleangiectasia ATM lymphoma, leukemia, breast,

suprarenal gland

Li-Fraumeni TP53 sarcoma, breast, breast, leukemia

Multiplex Endokrin Neoplasia 1 MEN1 insulinoma, gastrinoma,

hypophyseal & parathyroid glands

Xeroderma pigmentosum XPA, XPB, XPC, XPD, XPE stb. melanoma, basalioma

von Hippel-Lindau VHL clear cell renal ca., phaeochromo-

cytoma, retinal angioma

Significance of cancer morbidity and mortality –

Hungarian data

• ≈ 75.000 new cancer cases/year 2030: ≈ 100.000 new cases/year

• 1 out of 3 men/women will develop cancer during his/her life-time

• 2nd. most frequent cause of death

• 1 out of 4 deaths (25%) is caused by cancer

• Cancer burden is a global challenge for the public health systems

Cancer incidence in Hungary (2007-2014)

(male & female)

Tumour siteIncidence by year

2007 2008 2009 2010 2011 2012 2013 2014

Skin (non-melanoma) (C44) 10939 12011 12070 11319 14375 14079 14629 16421

1 Lung (C33-C34) 11176 11892 11263 10564 11947 11333 11304 11654

2 Colorectal (C18-C21) 9401 10004 9543 9545 10673 10584 10664 10684

3 Breast (C50) 6694 7070 6992 6711 7939 7927 7919 8049

4 Prostate (C61) 3288 3790 3645 3635 4352 4028 4648 4558

5 Lymphoproliferative (C81-95) 3625 3822 3812 3688 4046 4477 4287 4360

6 Oral cavity (C00-C14) 3905 3950 3653 3599 3956 3742 3759 3786

7 Bladder (C67) 2697 3064 2873 2789 3182 3315 3300 3548

8 Kidney (C64-C66 és C68) 2282 2492 2399 2402 2735 2728 2814 2885

9 Stomach (C16) 2501 2672 2442 2243 2559 2437 2433 2298

ALL : 77541 84144 80745 78014 90879 89993 91089 95034

ALL (wo C44): 66606 72136 68676 66666 76504 75914 76460 78613

Tumour siteIncidence by year

2007 2008 2009 2010 2011 2012 2013 2014

Skin (non-melanoma (C44) 4 824 5 334 5 447 5 072 6 382 6392 6693 7360

1 Lung (C33-C34) 7086 7587 7160 6634 7341 6929 6731 6979

2 Colorectal (C18-C21) 5046 5422 5086 5172 5731 5698 5871 5782

3 Prostate (C61) 3288 3790 3645 3635 4 352 4028 4648 4558

4 Oral cavity (C00-C14) 2995 2979 2740 2707 2 904 2763 2697 2704

5 Bladder (C67) 1901 2133 2013 1921 2 157 2277 2256 2411

6 Lymphoproliferative (C81-95) 1778 1949 1861 1843 1 980 2248 2145 2183

7 Kidney (C64-C66 és C68) 1339 1460 1334 1352 1 562 1618 1609 1680

8 Stomach (C16) 1445 1518 1385 1243 1 430 1348 1385 1298

10 Glottic (C32) 1067 1091 977 1127 1 091 1012 1066 1062

ALL: 39246 42926 40871 39334 45198 44766 45311 46982

ALL (wo C44): 34 422 37 592 35 424 34 262 38816 38374 38618 39622

Cancer incidence in Hungary (2007-2014)

(male)

Tumour siteIncidence by year

2007 2008 2009 2010 2011 2012 2013 2014

Skin (non-melanoma) (C44) 6111 6673 6622 6258 7 993 7687 7936 9061

1 Breast (C50) 6593 6938 6861 6610 7 767 7733 7775 7880

2 Colorectal (C18-C21) 4355 4582 4457 4373 4 942 4886 4793 4902

3 Lung (C33-C34) 4090 4305 4103 3930 4 606 4404 4573 4675

4 Lymphoproliferative (C81-95) 1847 1873 1951 1845 2 066 2229 2142 2177

5 Endometrial ca. (C54-C55) 1272 1365 1378 1299 1 648 1523 1548 1694

6 Ovary (C56) 1184 1261 1185 1104 1 410 1421 1402 1357

7 Skin melanoma (C43) 936 1085 1059 1031 1156 1239 1258 1234

8 Cervical ca. (C53) 1076 1076 981 932 1 159 1060 1121 1154

9 Stomach (C16) 1056 1154 1062 1000 1 129 1089 1048 1000

ALL: 38295 41218 39874 38680 45681 45227 45778 48052

ALL (wo C44): 32 184 34 544 33 252 32 404 37 688 37540 37842 38991

Cancer incidence in Hungary (2007-2014)

(female)

Tumour siteMortality by year

2004 2005 2006 2007 2008 2009 2010 2011 2012 2013

1 Lung (C33-C34) 8260 7571 7721 8123 8330 8453 8 648 8533 8896 8591

2 Colorectal (C18-C21) 4979 4557 4695 4779 4753 4949 4 965 5054 5084 5017

3 Breast (C50) 2285 2109 2081 2066 2141 2183 2 040 2159 2123 2194

4 Pancreas (C25) 1683 1611 1692 1747 1794 1837 1 848 1850 2003 1976

6Lymphoproliferative (C81-

95)1971 1695 1639 1695 1732 1665 1 725 1734 1688 1700

5 Stomach (C16) 1938 1722 1847 1762 1725 1824 1 626 1701 1732 1619

7 Oral cavity (C00-14) 1690 1567 1585 1581 1651 1521 1 524 1494 1536 1431

8 Prostate (C61) 1275 1077 1180 1160 1186 1193 1 209 1198 1125 1211

9 Bladder (C67) 840 775 769 850 831 831 904 923 983 899

10 Kidney (C64-C66 és C68) 772 714 764 686 712 709 829 849 784 835

ALL: 33502 30615 31283 31686 32111 32536 32 460 33274 33224 32748

Cancer mortality in Hungary (2007-2013)

(male & female)

Tumour siteMortality by year

2004 2005 2006 2007 2008 2009 2010 2011 2012 2013

1 Lung (C33-C34) 5852 5336 5400 5557 5597 5687 5 741 5558 5763 5418

2 Colorectal (C18-C21) 2718 2462 2554 2621 2563 2762 2 704 2835 2810 2865

3 Oral cavity (C00-14) 1416 1298 1339 1292 1364 1245 1 232 1213 1225 1146

4 Prostate (C61) 1275 1077 1180 1160 1186 1193 1 209 1198 1125 1211

5 Stomach (C16) 1081 984 1103 1042 981 1002 932 955 1000 942

6Lymphoprolifeartive

(C81-C95)1026 838 837 835 897 845 891 879 854 854

7 Pancreas (C25) 855 808 819 838 899 897 863 942 950 943

8 Bladder (C67) 589 559 541 588 582 605 630 655 714 637

9 Esophagus (C15) 545 495 491 557 496 530 496 467 457 522

10 Glottic (C32) 499 500 482 503 485 498 507 490 484 476

ALL: 18842 17134 17614 17760 17899 18177 18 032 18283 18279 17815

Cancer mortality in Hungary (2007-2013)

(male)

Tumour siteMortality by year

2004 2005 2006 2007 2008 2009 2010 2011 2012 2013

1 Lung (C33-C34) 2408 2235 2321 2566 2733 2766 2 907 2975 3133 3173

2 Colorectal (C18-C21) 2261 2095 2141 2158 2190 2187 2 261 2219 2274 2242

3 Breast (C50) 2285 2085 2059 2045 2108 2169 2 011 2138 2096 2167

4 Pancreas (C25) 828 803 873 909 895 940 985 908 1053 1033

5Lymphoproliferative

(C81-C95)945 857 802 860 835 820 834 855 852 831

6 Stomach (C16) 857 738 744 720 744 822 694 746 732 677

7 Ovary (C56) 666 612 610 660 687 687 675 700 700 739

8 Gall bladder (C23-C24) 560 467 465 439 428 457 420 428 434 418

9 Cervical ca. (C53) 493 416 420 424 418 396 379 414 426 405

10 Endometrial ca. (C54-55) 402 375 385 357 234 377 386 436 429 417

ALL: 14660 13481 13669 13926 14212 14359 14 428 14991 14945 14933

Cancer mortality in Hungary (2007-2013)

(female)

Cancer burden according to

financial development

High-income countries Low- and middle-income

countries

• Lung • Stomach

• Breast • Liver

• Prostate • Oral cavity

• Colorectal • Cervical ca.

Boyle P. The globalisation of cancer. Lancet 368:629-630, 2006.

1

Oral cavity 1

1

Stomach 1

Colorectal

Pancreas 1

Glottic 1

Lung 1

Prostate 10

Testis 2

Bladder

Hodgkin-disease

Nem-Hodgkin lymphoma 14

Leukemia

Esophagus

3

7

Tumour site Order among 25 countries

ALL

5-6

1

* Levy F, et al. Cancer 15:2843-2850, 2004.

Hungarian cancer mortality compared to other European countries* (males)

Cancer mortality for male population in Europe

1955-2019

All cancers - Females - Former Comecon - ASR

0

20

40

60

80

100

120

140

160

1956

-60

1960

-64

1965

-69

1970

-74

1975

-79

1980

-84

1985

-89

1990

-94

1995

-99

2000

-04

2005

-09

2010

-14

2015

-19

2020

-24

AS

R(W

)

Bulgaria

Czech/Slovak

Hungary

Poland

Romania

Actual Forecast

Cancer mortality for female population in Central Europe

1955-2019

Definition of National Cancer Control Program (NCCP):

A national cancer control program is a public health program designed to reduce the incidence and mortality

of cancer and improve the quality of life of cancer patients in a particular country or state, through the

implementation of evidence-based strategies for prevention, early detection, treatment, and palliation,

making the best use of available resources.

Hungarian NCCP (1993-)

Content (WHO recommendation):

primary prevention

secondary prevention (screening)

early diagnosis

therapy

rehabilitation

palliation – hospice

education

PR activity

participants

national oncological structure

indicators, monitoring

• legislation – new law against smoking (2012)

• public health program

Smoking: lung, oral cavity, laryngeal, oesophageal, stomach, bladder, cervix

Primary prevention

• diet: new tax – „chips tax” (2012)

• increasing tax on alcohol & tobacco (2013, 2015, 2016)

Obesity: esophageal, colorectal, breast, endometrium, kidney

• physical: ionizing irradiation, solar irradiation

• chemical: several hundreds

• biological:

Physical activities: public health program – primary schools involved (2012-)

Elimination and minimalisation of carcinogenic factors

Occupational – environmental injuries

• HPV – vaccination (supported by the government; 2014-)

22

• if effectiveness proven (specificity, sensitivity)

• if conditions provided (method, staff, equipment)

• if the target population can be screened (conditions given)

• if patients identified by screening can be treated/cured (conditions given)

• if financing provided

• localization:

• Possibility of an effective treatment

• Reality of effective treatment: breast, cervix, oral cavity, larynx, colorectal, prostate, skin

Early detection:

Early detection and screening

Screening:

Screening: in symptom- and complaint-free risk groups

Early diagnosis: patients with symptoms

• breast, cervix, colorectal (US Task Force, European Code Against Cancer)

• oral cavity, prostate, skin (considerable in Hungary)

23

Recommendations for early detection and screening

of selected cancers

Site of cancer Early diagnosis Screening in Hungary

Breast Yes Yes

Cervix Yes Yes

Colorectal Yes Yes (2017-)

Oral cavity Yes No

Nasopharynx Yes No

Larynx Yes No

Lung Yes No

Oesophagus Yes No

Stomach Yes No

Skin melanoma Yes No

Other skin cancers Yes No

Ovary Yes No

Bladder Yes No

Prostate Yes No

Retinoblastoma Yes No

Testis Yes No

Secondary prevention - Screening

Cervix : cytology (Kellner, NIO, 1950-)

cytological network (Kellner, Döbrössy, NIO, 1960-)

Cytological cervical screening (Döbrössy, Bodó, NIO, 1970-)

Public Health Program (Kertai – 1994, 2001, 2002)

Breast: HNCCP (Kásler, NIO, 1993)

Public Health Program, model screening (Kertai – 1994, 2001, 2002)

Nationwide mammography screening program (2002-)

Biennial mammography screening for women ageing 45 to 65 years

Colorectal: HNCCP (Kásler, NIO, 1993)

Public Health Program (Kertai – 1994, 2001, 2002)

Model Screenings

Debate on methodology (occult bleeding vs colonoscopy)

Occult bleeding fecal test will be implemented in 2017

Hungarian population based mammography screening –

3rd. screening cycle (2006-2007)

• Invited: 925.036

• Participated: 428.151

– Participation rate: 46.3%

• Recalled (suspicious): 23.477 5.5%

• Returned: 21.743

– Appearance rate: 92.6%

• Operated: 1.503

– Bening: 379

– Malignant: 1.124 74.8%

• DCIS: 131 11.7%

• < 15 mm: 545 48.5%

Boncz I. et al: Magyar Onkológia 2013;57:140-146.

Population based cervical cancer screening in Hungary

1981. declaration: cervical screening is an emerging

task for the health system

2003.

Initiation of a population-based cervical cancer

screening

Invited: 2 million women

Participation: 96.000 (5%)

(Kovács A . et al: Orv Hetil 148:879-885, 2007.)

Strategy for colorectal cancer screening

(1) Detection of occult fecal bleeding

(2) Colonoscopy -

tumour localisation

biopsy

polypectomy

Thank you for your kind attention!