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