Burden of HPV associated
diseases in Latin America
MEXICO
May 2008
F. Xavier Bosch
Institut Catalá d’Oncología
HPV: LIKELY TO BE THE NUMBER 2 HUMAN
CARCINOGEN (AFTER TOBACCO)
à 5% OF HUMAN CANCER
à 10% OF CANCER IN WOMEN
à 15% OF CANCER IN WOMEN IN
DEVELOPING COUNTRIES
WORLDWIDE ESTIMATES ON THE BURDEN OF HPV &
RELATED GENITAL DISEASES
Cervical Cancers
0.5
million
10 million
Genital
Warts
30
million
30
million
Screen detected only
High-grade
Cervical Lesions
Low-grade
Cervical Lesions
300 million
HPV infection - no abnormality
The burden of
HPV infections in women
HPV DNA PREVALENCE IN
150.000 WOMEN WITH NORMAL CITOLOGY
ADJUSTED MODEL
GLOBAL
10.4% (10.2-10.7)
AFRICA
22.1 % (20.9-23.4)
AMERICA North
Central-South
11.3 % (10.6 – 12.1)
20.4 % (19.3 – 21.4)
EUROPE
8.1 % (7.8-8.4)
ASIA
7.9 % (7.5-8.4)
De Sanjose et al Lancet 2007
ETIOLOGICAL EVIDENCE
ON THE EPIDEMIOLOGY OF HPV AND CERVICAL CANCER
HPV IS A NECESSARY CAUSE
§ PREVALENCE: Under adequate materials and testing systems HPV DNA is
always present in cervical cancer
§ CASE-CONTROL: The relative risk is high, consistent worldwide and includes
both major histological types
§ COHORT STUDIES: The absolute risk of progression to cervical pre-cancer is
high following persistent HPV infection.
§ INTERVENTION PRIMARY: HPV 16 & 18 vaccines reduced the incidence of
CIN 2/3 (projected to cervical cancer)
§ INTERVENTION SECONDARY: HPV screening reduced the incidence of CIN
3+ (projected to cervical cancer)
IARC MONOGRAPH: SCREENING FOR CERVICAL CANCER 2005 & 2007
The burden of
HPV – RELATED CANCER
in women
HPV related cancers in women
530 000 new cases per year
• Cervical
• Vulvar
95-98% of the cases
• Vagina
65-90 % of the cases
• Anal
80 + % of the cases (both sexes)
30-35 % of the cases
• Oral / Larynx
23-24% of the cases (both sexes)
• Oro-pharynx 30-35-72%... (both sexes)
• Other conjunctiva. ungueal bed… anecdotal
HPV-attributable cancers in women
Estimates 2002
SITE
TOTAL
cancers
%
HPV
Attributable
to HPV
Attributable
to HPV 16/18
% of
HPV
16/18
Cervix
492,800
100
492,800
344,900
70
Vulva,
Vagina
40,000
40
16,000
12,800
80
Anus
15,900
90
14,300
13,100
92
Oropharynx
9,600
11
(60 +)
1,100
1,000
91
Mouth
98,400
3
(25 +)
2,900
2,800
97
10.4
527,100
374,600
TOTAL
5.060.700
Adapted from D. M. Parkin, F. Bray, Vaccine 24 Suppl 3, S11 (2006).
RANKING OF WORLD’S COUNTRIES
ON INCIDENCE RATES OF CERVICAL CANCER
WOMEN ALL AGES BY DEVELOPMENT LEVEL
Less developed regions
More developed regions
N countries
%
N countries
%
1st
58
45.7 %
0
0.0 %
2nd
46
36.2 %
4
9.1 %
3rd
7
6.0 %
4
9.1 %
4th
6
5.0 %
3
6.8 %
5th
2
1.6 %
7
15.9 %
6 or +
8
6.3 %
26
59.1 %
TOTAL
127
44
GLOBOCAN 2002
RANKING
RANKING OF WORLD’S COUNTRIES
ON INCIDENCE RATES OF CERVICAL CANCER
WOMEN AGED 15-44 BY DEVELOPMENT LEVEL
Less developed regions
More developed regions
N countries
%
N countries
%
1st
58
45.7 %
1
2.3 %
2nd
49
38.6 %
27
61.4 %
3rd
7
5.5 %
13
29.5 %
4th
2
1.6 %
3
6.8 %
5th
2
1.6 %
0
0.0 %
6 or +
9
7.2 %
0
0.0 %
TOTAL
127
44
GLOBOCAN 2002
RANKING
The Morelos HPV study
ICO Study
Male factor studies
Vaccination trials
Mexican-Us Border study
Guatemala
Case control study
IARC Prevalence Survey
Honduras
ICO study
NCI Case Control
ICO study
Rivas screening project
Nicaragua
ICO study
Venezuela
The Guanacaste project
NCI Case Control
The Ludwig-McGill cohort
Vaccination trials
The Latin American Screening Study
(LAMS)
NCI Case Control
Colombia
IARC Case Control
The Bogotá Cohort
ICO study
IARC Case Control
Vaccination trials
IARC Prevalence Survey
NCI Case Control
ICO study
IARC Case Control
Vaccination trials
ICO study
Paraguay
The TATI Project
IARC Case Control
Vaccination trials
The Latin American Screening Study
(LAMS)
Chile
IARC prevalence Survey
IARC prevalence Survey
ICO study
ICO study
SELECTED HPV RESEARCH PROJECTS IN AMERICA LATINA
Argentina
ICO study
Brazil
Panamá
Peru
Costa
Rica
Vaccination trials
ESTIMATED NUMBER OF CERVICAL CANCER CASES in
2002 : 490.000
N. AMERICA
14,670
EUROPE
59,931
ASIA
265,884
C-S. AMERICA
71,862
< 87.3
AFRICA
78,897
< 32.6
< 26.2
< 16.2
Age-adjusted incidence rates per 100,000 women per year
< 9.3
MOST COMMON CANCERS IN WOMEN :
INCIDENCE & MORTALITY
Central & South America
Incidence
Mortality
40,3
BREAST
29,2
CERVIX
13,2
COLON/RECTO
13,9
CERVIX
13,6
PULMÓN
7,4
7,0
PULMÓN
7,6
COLON/RECTO
OVARIO
7,3
HÍGADO
6,4
PÁNCREAS
CORPUS
0
10
20
8,7
ESTÓMAGO
11,4
ESTÓMAGO
BREAST
30
40
50
60
70
0
5,1
4,2
10
20
30
40
50
60
GLOBOCAN 2002
RANKING OF COUNTRIES IN
LATIN AMERICA ON INCIDENCE
RATES OF CERVICAL CANCER
WOMEN ALL AGES
RANKING
N countries
%
1st
14
50.0%
2nd
12
42.9%
3rd
1
3.6%
4th
1
3.6%
5th
0
0.0%
6 or +
0
0.0%
RANKING OF COUNTRIES IN
LATIN AMERICA ON INCIDENCE
RATES OF CERVICAL CANCER
WOMEN ALL AGES
RANKING
N countries
%
1st
14
50.0%
2nd
12
42.9%
3rd
1
3.6%
4th
1
3.6%
5th
0
0.0%
6 or +
0
0.0%
RANKING OF COUNTRIES IN
LATIN AMERICA ON INCIDENCE
RATES OF CERVICAL CANCER
WOMEN ALL AGES
RANKING
N countries
%
1st
14
50.0%
2nd
12
42.9%
3rd
1
3.6%
4th
1*
3.6%
5th
0
0.0%
6 or +
0
0.0%
*Puerto rico
Time trends in target populations
& predicted impact on
HPV related cancers in women
(all other things being equal)
Worldwide Female population
Developed regions
85+
80-84
75-79
70-74
65-69
60-64
55-59
50-54
45-49
40-44
35-39
30-34
25-29
20-24
15-19
10-14
5-9
Under 5
14M
17M
23M
26M
31M
31M
39M
43M
45M
46M
44M
43M
41M
41M
40M
36M
33M
32M
Developing regions
9M
16M
30M
44M
58M
70M
90M
80% of
cervical cancer
118M
134M
161M
186M
200M
206M
230M
254M
258M
260M
269M
Population Source: 2005 estimates. United Nations, Population Division. World Population Prospects-the 2004 revision. New York, 2005.
Women 15 + years. Population prospects
Number of women (in millions)
3000
Developing Regions
Developed Regions
2500
2000
1500
1000
500
19
50
19
55
19
60
19
65
19
7
19 0
75
19
8
19 0
8
19 5
9
19 0
9
20 5
0
20 0
05
20
1
20 0
1
20 5
20
20
2
20 5
30
20
35
20
40
20
45
20
50
0
Source: 2005 estimates. United Nations, Population Division. World Population Prospects-the 2004 revision. New York, 2005.
PREDICTED NUMBER OF CASES OF CERVICAL CANCER IN
2020 : THE AMERICAS BY AREA
2002
2020* (%
CHANGE)
2020*
(%BURDEN)
WORLD
493.243
702.746 (42%)
América
86.532
122.162 (41%)
100%
Central
17.165
29.794 (74%)
24%
Sur
48.328
74.785 (55%)
61%
Norte
14.670
18.112 (23%)
15%
Caribe
6.369
8.685 (36%)
7%
* Projections asume constant rates in the interval at the 2002 estimates
THE RELEVANCE OF VIRAL TYPE IN
CERVICAL (and other genital) CARCINOMA :
Present and future vaccine composition
Understanding cross protection
Management protocols in HPV based screening
PRELIMINARY RESULTS
•
•
•
•
•
Vulvar cancer
Cases: 312
Mean age: 72.1
Range:
49.2 - 77.4
Histology
– SCC:
69 %
– Warty.basaloid: 21 %
– Other:
10 %
• HPV DNA: 27.9 %
• HPV 16: 52.9 % of the HPV+
•
•
•
•
•
Vaginal cancer
Cases: 99
Mean age: 60.9
Range: 41.4 - 70.0
Histology
– SCC:
98 %
• HPV DNA: 78.8 %
• HPV 16: 51.3 % of the HPV+
HPV TYPE DISTRIBUTION IN VULVAR AND VAGINAL
CANCERS
VULVA
VAGINA
VULVA
VAGINA
HPV Type
N
%
N
%
HPV Type
N
%
N
%
16
46
52,9
40
51,3
39/68/73
0
0.0
2
2.6
HPV X
9
10,3
4
5,1
31
1
1.1
4
5.1
45
6
6,9
2
2,6
44
1
1.1
0
0.0
18
4
4,6
2
2,6
68
1
1.1
1
1.3
6
2
2,3
1
1,3
51
1
1.1
6
7.7
33
3
3,4
2
2.6
66
1
1.1
0
0.0
52
3
3.4
2
2.6
11,39
1
1.1
0
0.0
35
2
2.3
1
1.3
16,68
0
0.0
1
1.3
39
1
1.1
4
5.1
16,56
0
0.0
1
1.3
56
2
2.3
1
1.3
33,45,6
0
0.0
1
1.3
58
2
2.3
3
3.8
16,6,39/68/73
1
1.1
0
0.0
HPV DNA PREVALENCE & TYPE SPECIFIC
RELATIVE FREQUENCY
IN CANCERS OF THE PENIS AND THE ANAL CANAL
HPV
TYPE
PENILE
(n=1152)
ANAL
Range of studies
HPV
47.3 %
(46-100%)
80-95 %
16
68.2 %
(60-100%)
80 %
18
34.1 %
5-8% %
Smith et al 2007. IARC monograph
HPV DNA PREVALENCE & TYPE SPECIFIC
RELATIVE FREQUENCY
IN CANCERS OF THE HEAD & NECK
HPV
TYPE
ORAL
(N= 2.642)
OROPHARYNX
(N= 969)
LARYNX
(N= 1.435)
HPV
23.5 %
35.6 %
24.0 %
16
68.2 %
86.7 %
69.2 %
18
34.1 %
2.8 %
17.0 %
< 1%
< 1%
< 1%
ANY
OTHER
Kreimer et al 2005
Non cancerous HPV related Lesions
Genital warts & Recurrent Respiratory
papilomatosis linked to HPV 6 and 11
(limited information from latin ameica)
EPIDEMIOLOGY of
GENITAL WARTS. Cohort study
§ Of 31 cases, 84% tested positive for hpv 6 or11
§ Median time to progression after infection was
2,9 months (ci 0–5,7 years)
§ Median time to resolution with treatment was
5,9 months (ci 3,9 - 8,0 meses)
§ Social and psicological problems are relevant
WINER RL ET AL. J INFECT DIS. 2005;191:731-738.
§ In women exposed to HPV 6 or 11, the cumulative
incidence of GW was of 66.2% (ci 52.8-79.2) at month 36
Number of partners and % of ever GW
The Copenhagen survey: Ever GW 17%
14
1% of the sexually
active population?
GW %
10
11,6
8,3
8
6
5,5
3,9
4
2
1
1,9
0
1-2
3-4
5-9
10-14
15-39
Number of partners
40+
MUNK C ET AL. SEX TRANSM DIS. 1997;24:567-572.
12
Selected characteristics with regard to
sexual habits and genital warts in the 4
Nordic countries in Europe
Characteristic
Self-reported history of genital warts
% (95% CI)
Lifetime no. of sex partners,
mean (range)
Age at first diagnosis of genital warts,
mean (range)
Genital warts during the last 12 months,
% (95% CI)
Denmark
Iceland
10.1
12.0
(9.7–10.5) (11.5–12.6)
Norway
Sweden
9.5
11.3
(9.0–9.9) (10.8–11.8)
8.4
(0–500)
8.8
(0–100)
7.4
(0–100)
8.6
(0–450)
21.9
(6–45)
21.3
(14–43)
22.7
(3–45)
21.9
(14–44)
1.3
(1.2–1.5)
1.9
(1.7–2.1)
1.1
(1.0–1.3)
1.0
(0.9–1.2)
Kjaer 2007 JID
Estimated cumulative incidence of selfreported clinically diagnosed genital warts
Estimated cumulative incidence of self-reported clinically diagnosed genital warts, by country and birth
cohort. The cumulative incidence of having had genital warts up to a certain age was estimated on the
basis of information on age at first diagnosis of genital warts.
Kjaer 2007 JID
Laryngeal Papillomatosis
Glikman (2005) New Eng J Med
Laryngeal Papillomatosis
Description of clinical entity
• Benign growths of respiratory tract in juveniles and adults
• Caused largely by HPV 6 and HPV 11
• In infants is generally attributed to exposure to genital
warts in the birth canal . About 1/500 births to mothers with
genital HPV ultimately develop symptomatic disease
• Adult-onset disease is considered to be a rare
consequence of HPV transmission during oral intercourse
• Many patients require multiple surgeries, more severe
prognosis for HPV 11-related, 1-3% die of the disease.
• Deaths to respiratory obstruction are largely unreported
Conclusions : HPV related cancers in the
latin america & the caribbean region
• Cervical cancer is a public health and a cancer control
priority in the latin American region
• HPV 16 & 18 are responsible of 70% of cervical cancer
cases followed by HPV 45, 31 y 33
• These HPV types are also responsible for a significant
fraction of vulvar cancer (40%), vaginal cancer (80%),
penile cancer (40%), anal cancer (80%) and cancers of
the oral cavity (25%) and the oropharynx (35%)
• There are no significant differences in the HPV type
implication in cancer across countries in the region nor
over time
Implications : Cancer Preventive options in the
Latin America & the Caribbean region
• Current HPV 16 & 18 vaccines have the potential
to prevent some 70% of the cervical cancer
cases, some 50% of the precursor lesions, and a
significant fraction of all other cancers of the
genital and oral tracts in women.
• Screening should continue / expand for both
vaccinated and non vaccinated women
• Should male vaccination be implemented, herdprotection against female cancers is a possibility
and significant reductions in penile, anal and
oral/oropharyngeal cancers in man could follow
LA PREVENCIÓN DEL CÁNCER CERVICAL
EN TIEMPOS DEL VPH
Es la segunda oportunidad
sobre la tierra
ICO INTERNATIONAL SURVEY PARTICIPANTS IN
LATIN-AMERICA
ARGENTINA
BRASIL
CHILE
Silvio Alejandro Tatti, Susana Vighi (Hospital
de Clínicas “José de San Martín”, Universidad
de Buenos Aires, Sociedad Argentina de
Patología)
Marcus Aurelho de Lima, Sérgio Enrique de
Almeida (Hospital Hélio Angotti, PATMED)
Rodrigo Prado (Centro de Oncología
Preventiva, Universidad de Chile); Ximena
Rodríguez (Departamento de Anatomía
Patológica, Hospital San José, Santiago)
COLOMBIA
GUATEMALA
HONDURAS
Luis E. Bravo, Luz Stella García, Titto Collazos
(Hospital Universitario del Valle); Hector J.
Posso (Liga Contra el Cáncer de Bogotá);
Gustavo A. Hernández, Carlos E. Pinzón
(Instituto Nacional de Cancerología,
Bogotá); Gloria Inés Sánchez (Universidad de
Antioquia)
Edgar Kestler, Luis Lombardi, Victor Argueta,
Obdulia Salic (Centro de Investigación
Epidemiológica en Salud Sexual y
Reproductiva – CIESAR, Hospital General San
Juan de Dios - HGSJDD); Walter Guerra
(Instituto Nacional del Cáncer – INCAN);
Hesler Morales (Instituto Guatemalteco de
Seguridad Social - IGSS, Instituto Nacional del
Cáncer - INCAN); Sergio Marroquín, Victor
Argueta (Hospital General San Juan de Dios –
HGSJDD)
Annabelle Ferrera (Universidad Nacional
Autónoma de Honduras)
MEXICO
PARAGUAY
VENEZUELA
Patricia Alonso, Gustavo Lastra, Alma Karina
Olivares Montano (Hospital General de
México)
Elena Kasamatsu, Francisco Perrota (Instituto
de Investigaciones en Ciencias de la Salud –
UNA)
Enrique López Loyo (Sociedad Venezolana
de Patología); Victoria García de Barriola,
Mirian Naranjo de Gómez, Adayza
Figueredo, Janira Navarro (Instituto
Anatomopatológico de la Universidad
Central de Venezuela)
PERU
Carlos Santos, Eduardo Cáceres, Henry
Gómez, Juvenal Sánchez, Carlos Vallejos
(Instituto Especializado de Enfermedades
Neoplásicas)
GRACIAS POR SU ATENCIÓN
AGE
-SPECIFIC HPV PREVALENCE AMONG WOMEN
AGE-SPECIFIC
WITH NORMAL CITOLOGY
Adjusted
NORTH
AMERICA
AFRICA
CENTRAL
& SOUTH
AMERICA
EUROPE
ASIA
30
20
10
Age group
<2
25 5
-3
35 4
-4
45 4
-5
4
>5
4
<2
25 5
-3
35 4
-4
45 4
-5
4
>5
4
4
>5
<2
25 5
-3
35 4
-4
45 4
-5
4
<2
25 5
-3
35 4
-4
45 4
-5
4
>5
4
>5
4
0
<2
25 5
-3
35 4
-4
45 4
-5
4
Prevalence of HPV (%)
40
WORLD: HPV type distribution
Women with normal cytology
World
16
2.5
18
0.9
31
0.7
58
0.6
52
0.6
33
0.6
51
0.5
56
0.4
35
0.4
42
0.4
0
1
2
3
4
.
De Sanjosé et al. 2007 Lancet Infect Dis
WHO/ICO Information Centre on HPV and Cervical Cancer
www.who.int/hpvcentre
ESTIMATED ANUAL INCIDENCE: 40.000 CASES OF
VULVAR AND VAGINAL CANCERS
Developed regions
Developing regions
DEVELOPED COUNTRIES:
15.700 Vulvar cancer
4.200 Vaginal cancer
DEVELOPING COUNTRIES:
§ 11.100 Vulvar cancer
§
9.000 Vaginal cancer
RRP by age at diagnosis
250
womens
277 women
330 men
607 total
150
100
50
16 10
0
<=10
10 a 20
JORRP
28
51
40
35
17
20 a 30
30 a 40
Age at diagnosis
16
40 a 50
7
19
>= 50
CORTESÍA DE BILL STERN, RRPF
200
men
193
175
RANKING OF LATIN AMERICA’S COUNTRIES
ON INCIDENCE RATES OF CERVICAL CANCER
RANKING
N countries
%
1st
14
50.0%
2nd
12
42.9%
3rd
1
3.6%
4th
1
3.6%
5th
0
0.0%
6 or +
0
0.0%
0
