burden of disease professor xavier bosch institut català d’oncologia barcelona, spain
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Burden of Burden of DiseaseDisease
Professor Xavier BoschInstitut Català d’Oncologia
Barcelona, Spain
The HPV Infections of the Genital Tract
• The most common genital infection worldwide• Sexually transmitted• Clinically silent and self limiting most of the times• Some women remain persistent carriers of the
viral infection and become at high risk of progression to precancer and cancer of the cervix, vulva, vagina and anal canal
• May cause cancers in the penis and anal canal in HPV infected men
• Cancers at other sites
Prof Xavier Bosch
GLOBAL 10.4% (10.2-10.7)
Africa 22.1% (20.9-23.4)
America 13.0% (12.4-13.5)
Europe 8.1% (7.8-8.4)
Asia 7.9 % (7.5-8.4)
HPV DNA Prevalence in 160,000 Women With Normal Cytology
(Adjusted Model)
Prof Xavier Bosch
De Sanjose et al. 2007, The Lancet
0
5
10
15
20
25
30
< 25 25-34 35-44 45-54 > 54AGE GROUP
AfricaCS. America
Asia
N. AmericaEurope
Age-Specific HPV Prevalence in Women with Normal Cytology
By Continent
Prof Xavier Bosch
De Sanjose et al. 2007, The Lancet
Developed Countries Developing Countries
Site
ATTRIB TO HPV (%)
Total Cancers
Attrib to HPV
% All Cancer
Total Cancers
Attrib to HPV
% All Cancer
Cervix 100 83,400 83,400 1.7% 409,400409,4
007.0%
Penis 40 5,200 2,100 0.0% 21,100 8,400 0.1%
Vulva, Vagina
40 18,300 7,300 0.1% 21,700 8,700 0.1%
Anus 90 14,500 13,100 0.3% 15,90014,30
00.2%
Mouth 3 91,200 2,700 0.1% 183,100 5,500 0.1%
Orophar 12 24,400 2,900 0.1% 27,700 3,300 0.1%
All Sites 5,016,1
00111,50
02.2%
5,827,500
449,600
7.7%Parkin M et al. Int J Cancer 2006
HPV Infection-Attributable Cancer In 2002
Prof Xavier Bosch
Globocan 2002
Africa
3,9
4,2
4,3
4,6
4,9
6,2
23,4
29,3
0 10 20 30 40 50 60 70
CERVIX UTERI
BREAST
LIVER
STOMACH
KAPOSI SARCOMA
OVARY
COLON/RECTUM
NH LYMPHOMA
Incidence
3,0
3,2
3,7
4,3
4,6
6,2
16,2
23,1
0 10 20 30 40 50 60 70
CERVIX UTERI
BREAST
LIVER
STOMACH
KAPOSI SARCOMA
COLON/RECTUM
OESOPHAGUS
OVARY
Mortality
Prof Xavier Bosch
The Seven Most Frequent Cancers in Women: Incidence and Mortality
Five Most Common Cancersin Women in Africa
Africa 1st 2nd 3rd 4th 5th
Eastern CERVIX 42.7
BREAST
19.5
KAPOSI SRC.
9.5
LIVER
8.6
OESOPHAGUS
8.0
Middle CERVIX
28.0
BREAST
16.5
LIVER
13.4
STOMACH
12.6
KAPOSI SRC.
8.6
Northern
BREAST
23.2
CERVIX
12.1
COLON & RECTUM
4.0
BLADDER
3.6
LEUKAEMIA
2.7
Southern
CERVIX
38.2
BREAST
33.4
COLON & RECTUM
8.9
OESOPHAGUS
7.0
LUNG
6.9
Western CERVIX
29.3
BREAST
27.8
LIVER
5.6
OVARY .
4.6
STOMACH
3.6
Prof Xavier Bosch
Globocan 2002
< 87.3*
< 16.1
< 32.6
< 9.2
< 26.2
N. AMERICA14,670
C-S. AMERICA71,862
AFRICA78,897
ASIA265,884
EUROPE59,931
(*per 100,000)
Estimated Number of Cases of Cervical Cancer (2002)
Prof Xavier Bosch
Globocan 2002
INCIDENCE – CASES
MORTALITY - DEATHS
1,6641,354
27162178
17261391
2181751550
1247
284229
AlgeriaLibya
Egypt
Sudan
Tunisia
Morocco
Prof Xavier Bosch
<25.1
Incidence of Cervix uteri cancer : ASR
<29.3 <33.6 <42.7 <68.6
Globocan 2002
Incidence and Mortality of Cervical Cancer in Northern Africa
Region - 81586574
Syria11811855
Region - 81934151
Incidence and Mortality of Cervical Cancer in the Middle East
Iraq252252129
Saudi Arabia271271143
Yemen370370206
Kuwait553
Qatar343417
Iran1,1181,118581 Afganistan
511511254
Pakistan2,9622,9621,605
Arab Emirates737336
Oman464625
INCIDENCE – CASES
MORTALITY - DEATHS
Globocan 2002
Turkey13641364726
ALGERIAALGERIA0 10 20 30
BREAST
CERVIX UTERI
COL/RECTUM
N-HODGKINLYMPHOMA
OVARY
23.5
15.6
5.0
3.4
3.7
0 5 10 15 20 25
EGYPTEGYPT
BREAST
CERVIX
BLADDER
LEUKEMIA
LIVER
24.2
9.7
7.0
3.3
3.3
0 10 20 30
MOROCCOMOROCCO
22.5BREAST
CERVIX
COL/RECTUM
N-HODGKINLYMPHOMA
OVARY
13.2
5.5
3.4
3.5
NORTHERN AFRICANORTHERN AFRICA
COL/RECTUM
LIBYALIBYA0 5 10 15 20 25
BREAST
CERVIX
BLADDER
LEUKEMIA
23.4
11.9
4.1
2.7
3.7
Prof Xavier Bosch
Globocan 2002
Africa, Americas excluding Northern America, Asia excluding
Japan, and Oceania excluding Australia and New Zealand
Source: 2005 estimates. United Nations, Population Division. World Population Prospects-the 2004 revision. New York, 2005.
Prof Xavier Bosch
Developing RegionsProjections
Women 25-64 yrs
All Women
1000
2000
3000
4000
Girls 10-14 yrs
Women 15-24 yrs
100
200
300
400
500
600
19
50
19
55
19
60
19
65
19
70
19
75
19
80
19
85
19
90
19
95
20
00
20
05
20
10
20
15
20
20
20
25
20
30
20
35
20
40
20
45
20
50
0
Num
ber
of w
omen
(in
mill
ions
)
Girls 10-14 years. Population Prospects300
0
50
100
150
200
250
195019
5519
6019
6519
7019
7519
8019
8519
9019
9520
0020
0520
1020
1520
2020
2520
3020
3520
4020
4520
50
Developing RegionsDeveloped Regions
Num
ber
of g
irls
(in m
illio
ns)
Prof Xavier Bosch
Source: 2005 estimates. United Nations, Population Division. World Population Prospects-the 2004 revision. New York, 2005.
0
500
1000
1500
2000
2500
3000
195019
5519
6019
6519
7019
7519
8019
8519
9019
9520
0020
0520
1020
1520
2020
2520
3020
3520
4020
4520
50
Developing RegionsDeveloped Regions
Num
ber
of w
omen
(in
mill
ions
)
Prof Xavier Bosch
Women 15 years. Population Prospects
Source: 2005 estimates. United Nations, Population Division. World Population Prospects-the 2004 revision. New York, 2005.
Projected number of cervical cancer
cases in Northern Africa will increase
by 15%
*Projections assume that rates estimated for 2002 continue into the future
20022020*
(% CHANGE)2020*
(% BURDEN)
AFRICA 78897121962
(55%)100%
Eastern 33903 50680 (49%) 42%
Middle 8201 13944 (71%) 10%
Northern 8175 8846 (15%) 7%
Southern 7698 8846 (15%) 7%
Western 20919 33678 (61%) 28%
Predicted Number of Cervical Cancer Cases in 2020 , by Africa, Area and Age
Prof Xavier Bosch
Globocan 2002
INC
IDE
NC
E R
AT
E P
ER
100
,000
Prof Xavier Bosch
Globocan 2002
Age-Specific Incidence of Cervical Cancer in Africa and the World
0
20
40
60
80
100
120
140
160
0-14 15-44 45-54 55-64 65+World Eastern Africa Middle Africa
Northern Africa Southern Africa Western Africa
The Role Of HPV In Cervical CancerCausality Established
Prof Xavier Bosch
96.2
90 91 92 93 94 95 96 97 98 99 100
Africa
Sub-Saharan Africa
North Africa
C-S. America
S. Asia
Europe / N. America
Total
97.8
95.1
95.7
94.7
96.7
96.2
HPV POSITIVE (%)
HPV DNA Prevalence in Cervical Cancer Specimens
Using GP5+/6+ PCR By Region
Prof Xavier Bosch
Adapted From Muñoz N, et.al. Int J Cancer 2004
Africa
Sub-Saharan
Northern
C-s. America
S. Asia
Total
0 10 20 30 40 50 60 70 80 90 100
FALSE NEGATIVES
POOR SPECIMENHPV TEST
squamous(N=2281)
adeno/mixed(N = 196)
HPV Positive (%)
Europa &N. America
HPV DNA Prevalence in Cervical Cancerby Histology
Prof Xavier Bosch
Muñoz N, Et Al. Int J CancerCastellsagué X, et al., J Natl Cancer Inst
*OR ADJUSTED BY COUNTRY AND AGE-GROUP OR* (LOGARITHM)
Squamous Control
0 10 20 30 40 50 60 70 80 90 100 0.1
1 10 100 1200
OR* (95% CI)
94.115.9Overall 90.0 (71.3-113.5)
97.017.3Brazil 177.0 (65.5-478.3)
96.933.3
Mali97.1
21.6113.7 (42.3-305.3)
98.119.8
208.1 (46.4-932.8)
Philippines 96.49.2
96.515.7
Thailand 163.5 (82.0-325.9)
95.317.7
Peru 115.9 (48.6-276.4)
82.46.5
Spain 67.4 (30.3-149.8)
78.416.9Colombia 18.4 ( 9.4-36.0)
96.027.7India 64.1 (28.1-146.3)
Algeria 12.492.4
110.1 (45.1-268.9)
Morocco
Paraguay
109.2 (10.6-1119.0)
276.8 (139.7-548.3)
%
Prevalence of HPV DNA and or by CountrySquamous Cell Carcinoma
Prof Xavier Bosch
Vaccine HPV Monograph, 2006
OR* (LOGARITHM)
84.87 (1.9 to + )
36.71 (5.6 to + )
OR (95% CI)
100.0
94.4
100.0
92.3
85.7
92.0
90.9
92.3
93.0
12.4
17.3
27.7
21.6
19.8
17.7
9.2
15.7
16.5
0 10 20 30 40 50 60 80 90 100 0.1
1 10 100 1000
76.23 (8.6 to 672.4)
35.82 (4.0 to 318.0)
55.34 (11.6 to 263.6)
112.70 (30.8 to 412.0)
111.40 (24.5 to 507.1)
81.27 (42.0 to 157.1)
79.55 (12.2 to + )
70
Overall
Brazil
Philippines
Thailand
Peru
India
Algeria
Morocco
Paraguay
*OR ADJUSTED BY COUNTRY AND AGE-GROUP%
Prevalence of HPV DNA and or by CountryAdenocarcinoma
Prof Xavier Bosch
Adenosquamous Control
Vaccine HPV Monograph, 2006
Association of HPV and Cervical Cancer in Rabat, Morocco
Cases 214 Controls 203
Odds Ratio (95%CI)HPV DNA Number % Number %
Negative 10 5.4 147 79.5 1.00
Positive 17694.
6 38 20.5 61.65 (29.24-129.99)
16 12667.
7 8 4.3 201.60 (76.31-532.59)
18 15 8.1 2 1.1 93.02 (18.09-478.35)
31, 35, 35 7 3.8 2 1.1 39.27(6.82-225.94)
45 9 4.8 3 1.6 54.84 (12.08-248.87)
Prof Xavier Bosch
N Chaouki, FX Bosch, N Muñoz, Int J Cancer 1998
OR*
7.5
HPV XHPV 16-18
HPV 68HPV 11HPV 6
HPV 73HPV 59HPV 35HPV 56HPV 51HPV 33HPV 58HPV 52HPV 31HPV 45
HPV 18
HPV 16
0.1 100 1,0001
281.9
222.5
157.9124.9190.691.3573.488.370.362205.8164.53.6
44.4
146.2
26.1
OR
*OR adjusted by country and age
HPV Type Specific Odds Ratios for Cervical Carcinoma
Prof Xavier Bosch
Vaccine HPV Monograph, 2006
0
5
10
15
20
25
0.0 4.5 15.0 27.0 39.0 51.0 63.0 75.0 87.0 99.0 111.0 119.5
FOLLOW-UP TIME (MONTHS)
CU
MU
LA
TIV
E I
NC
IDE
NC
E R
AT
E O
F C
IN 3
(%
)
HPV16+
HPV18+/HPV16-
HPV+/HPV16-/HPV18-
HPV-
Khan et al. JNCI, 2005
Cumulative Incidence of CIN 3+ 13,000 Women Over a Ten Year Period
(As a Function of a Single HPV Test Result at Enrolment)
Prof Xavier Bosch
0 20 40 60 80 100
16 53.518 17.245 6.731 2.933 2.652 2.358 2.235 1.459 1.356 1.251 1.039 0.768 0.673 0.582 0.3
Other 1.2X 4.4
53.5% 70.7% 77.4% 80.3% 82.9% 85.2% 87.4% 88.8%
HPV type
Munoz N et al. Int J Cancer 2004
Type-Specific HPV Prevalence in Cervical Cancer Cases (All world regions combined)
Prof Xavier Bosch
HPV 16 HPV 16
HPV 18 HPV 18
HPV 45 HPV 33
HPV 31 HPV 45
HPV 33 HPV 31
HPV 52 HPV 58
HPV 58 HPV 52
HPV 35 HPV 35Muñoz N., Bosch FX., et al. Int J Cancer 2004
Smith J., et al. In PressBosch X., et al In Preparation
HPV 16
HPV 18
HPV 45
HPV 33
HPV 31
HPV 52
HPV 58
IARC POOLED META-ANALYSIS
1
2
3
4
5
6
7
8
HPV TT
HPV 35
Prof Xavier Bosch
The 8 Most Common HPV Types in Cervical Cancer - World
Epidemiological Conclusions
• MENA generates an estimated number of 15,000 new cases of cervical cancer per year
• All cervical cancer cases are related to persistent HPV infections. HPV 16 & 18 account for 70% of cases worldwide
• Rates of cervical cancer are lower than world averages
• However cervical cancer remains the second most common cancer in women in MENA
• Predictions are that these numbers might increase by 15% in the next decade
Prof Xavier Bosch