Transcript Powerpoint
Cervical Cancer and HIV:
Interactions and Interventions
Jean R. Anderson, M.D.
Jhpiego, an affiliate of Johns Hopkins University
The Johns Hopkins University School of Medicine
Cervical Cancer
Latest data on cervical cancer incidence and
mortality (GLOBOCAN 2008, IARC*):
Globally 529,512 cases diagnosed per year:
– 86% of all cases (n=453,032) in developing world
Globally 274,967 deaths:
– 88% of all deaths (n=241,818) in developing world
Mortality to incidence ratio:
Developed countries: 36–43%
Developing countries: 54–80%
*www.iarc.fr/globocan2008
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Globocan 2008—Most Frequent Cancers in
Women in Africa*
Kaposi's S.
12,305
NHL
15,348
Colorectal
15,822
Liver
Deaths
Cases
16,947
Cervix
80,419
Breast
92,613
0
20000
40000
60000
80000
100000
*www.iarc.fr/globocan2008
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Additional Burden in Africa: HIV/AIDS
HIV incidence in Africa
Cervical cancer incidence in Africa
(UNAIDS 2010)
(Globocan 2008, IARC)
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HIV and Cervical Cancer
Studies have shown that among HIV-positive women, there is a
consistently higher incidence of:
Human papillomavirus (HPV) infection
Persistent HPV infection with high-risk types
Infection with multiple types of HPV
Cervical cancer precursors (cervical intraepithelial neoplasia [CIN] or
squamous intraepithelial lesion [SIL])
Cervical dysplasia tends to involve a larger area of the cervix in the
setting of HIV infection
Cancer registry linkage studies have shown significant increase in
cervical cancer, particularly where women live longer due to access
to ART
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+++
++
+/-
Source: Palefsky. Curr Opin Oncol 2003.
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Alternatives to Cytology: Visual Inspection
with Acetic Acid (VIA)
Meta-analysis of 26 studies (Int J Gynecol Obstet 2011;113:14) in which VIA was
performed on asymptomatic women who underwent confirmatory testing with a
disease threshold of CIN 2 plus reported:
Cluster-randomized trial in India (Lancet 2007;370:398):
Sensitivity of 80% (range 79–82%)
Specificity of 92% (range 91–92%)
Positive predictive value of 10%
31,343 screened with VIA vs. 30,958 controls, 30–59 years old, 7-year follow-up
VIA-positive received colposcopy/biopsy and cryotherapy at same visit with colposcopy
impression low-grade SIL/high-grade SIL
VIA associated with 24% reduction in cervical cancer (Stage II or worse) incidence and 35%
reduction in cervical cancer mortality
Safe, feasible and acceptable in multiple studies
Can be done by trained nurses/midwives
Inexpensive
Allows treatment at same visit
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Alternatives To Cytology: HPV Testing
Cluster randomized trial in India
4 arms: HPV (hybrid capture), VIA, cytology, standard of
care (no screening); >2,700 women 30–59 years in each
arm with 8-year follow-up
Positive results: colposcopy/biopsy, treatment
(cryotherapy or loop electrosurgical excision procedure
[LEEP])
HPV testing associated with approximately 50%
reduction in detection of advanced cervical cancer and
cervical cancer deaths vs controls; no significant
difference for VIA, cytology
Source: NEJM 2009;360:1385.
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Target for Screening and Flow Pattern
VIA
30–50 Years
HIV-Positive—at Any Age
FP/MNCH, OPD, Gyn, ART Clinic
Positive
Negative
Follow-Up 3–5 Years
(HIV-)
Follow-Up 1 Year
(HIV+)
Treat Immediately
Cryotherapy
Refer/Treat
with LEEP
Repeat VIA after
1 Year
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VIA by Total and HIV-Infected Women and
Treatment Rates
Total No. of
New Women
Screened
with VIA/
% Who Were
HIV+
Total No. (%)
of Women
Who Were
VIA+
No. (%) of
HIV+ Women
Who Were
VIA+
No. (%) of
Women VIA+
Treated with
Cryo on the
Same Day
(Single Visit
Approach)
Guyana
19,934/
8%
2,529
(13%)
258
(16%)
1,813
(84%)
HIV Care
General
Medical
Clinic
1/09–
3/12
Côte d’Ivoire
14,338/
66%
960
(7%)
810
(9%)
460
(74%)
HIV Care
10/09–
9/13
Tanzania
26,065/
28%
2,021
(8%)
884
(12%)
1,660
(94%)
HIV Care
C&T
4/10–
9/13
Mozambique
72,818/
NA
4,990
(6.8%)
897
(17.9%)
3,333
(66.7%)
Family
Planning
4/11–
9/13
Zambia
(preliminary
results)
386/
13%
23
(6%)
4
(8%)
19
(100%)
DOD
9/13
10,982/
4%
965
(9%)
104
(22%)
508
(65%)
OPD
9/10–
10
8/13
Country
Burkina Faso
Setting
Time
Period
Cervical Cancer VIA Screening and Treatment Outcomes
for 3 Countries, January 2009–March 2012*
New women screened
7,538 Côte d’Ivoire
19,934 Guyana
7,449 Tanzania
Suspect cancer cases
detected and referred
50 (0.7%) Côte d’Ivoire
108 (0.5%) Guyana
178 (2%) Tanzania
VIA screen positive*
519 (7%) Côte d’Ivoire
2,529 (13%) Guyana
532 (7%) Tanzania
VIA screen negative
6969 (92%) Côte d’Ivoire
17,297 (87%) Guyana
6,739 (90%) Tanzania
Referred for large lesions
Treated with cryotherapy on same
day as screening (SVA)
Cryotherapy treatment
postponed
279 (78%) Côte d’Ivoire
1,813 (84%) Guyana
416 (92%) Tanzania
81 (23%) Côte d’Ivoire
336 (16%) Guyana
34 (8%) Tanzania
159 (31%) Côte d’Ivoire
381 (15%) Guyana
82 (15%) Tanzania
LEEP performed
45 (28%) Côte d’Ivoire
239 (63%) Guyana
6 (7%) Tanzania
Lost to advanced care
follow-up
114 (72%) Côte d’Ivoire
142 (37%) Guyana
76 (93%) Tanzania
Returned for
cryotherapy after
previously postponing
42 (52%) Côte d’Ivoire
186 (55%) Guyana
6 (18%) Tanzania
Lost to cryotherapy
treatment
39 (48%) Côte d’Ivoire
150 (45%) Guyana
28 (82%) Tanzania
*Côte d’Ivoire began in October 2009 and Tanzania began in April 2010.
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Initial Results from a Multi-Country Cervical Cancer
Screening Program for HIV-Infected Women
Summary of study:
VIA/SVA for cervical cancer prevention in Côte d’Ivoire (n=7,538),
Guyana (n=19,934) and Tanzania (n=7,449)
Services provided by trained nurses/midwives at HIV care and treatment
sites and general health facilities
Key results:
In all 3 countries, HIV-positive women were more likely to be VIA-positive
than HIV-negative/unknown women
In all 3 countries, HIV-positive women who were VIA-positive were more
likely to have large lesions (occupying >75% cervix) and therefore
ineligible for cryotherapy
85% of eligible women had same-day treatment with cryotherapy; of
those who postponed, 48% did not return for treatment
Source: Anderson J, Lu E, Wysong M, Kibwana S,
Estep D, Varallo J, Toure K, Giattas M, for Jhpiego.
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Lessons Learned
Promote country ownership
Implement sustainable, organized screening for scale-up
Conduct monitoring and assessment
Build capacity
Maintain quality of care
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Research Priorities
What are the optimal screening strategies for cervical
cancer precursors in setting of HIV?
Potential role of self-collection
Role of HPV-DNA testing
What are the optimal treatment methods for cervical
cancer precursors in setting of HIV?
Does screening or treatment effectiveness vary by
CD4/CD4 nadir or ART status?
What are the determinants of recurrence and what are
best strategies to identify recurrences?
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Research Priorities (cont.)
How can recurrences be prevented?
What is the role of male circumcision in cervical cancer
prevention (and programmatic implications)?
What are effects of treatment (cryotherapy vs. LEEP,
others?) on HIV shedding and what are the
determinants?
What are the most effective strategies to incorporate
cervical screening and treatment into HIV care?
Models of integration
Systems issues
Quality control: training, pathology, etc.
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Summary
Cervical cancer is a leading cause of morbidity and
mortality in limited-resource countries
HIV infection is associated with higher incidence of
cervical cancer and its precursors and this association
persists in the era of effective ART
Alternatives to cytology, such as VIA, are critical to
ensure adequate coverage and appropriate interventions
for cervical cancer screening and prevention in the
setting of HIV, but several key research questions
remain
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