Cervical Cancer and HIV: Interactions and Interventions

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

2

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

3

Globocan 2008—Most Frequent Cancers in Women in Africa*

Breast

Cervix

Liver

Colorectal

NHL

Kaposi's S.

0 20000 40000 60000 80000 100000

92,613

80,419

16,947

15,822

15,348

12,305

DeathsCases

*www.iarc.fr/globocan2008

4

Additional Burden in Africa: HIV/AIDS

HIV incidence in Africa (UNAIDS 2010)

Cervical cancer incidence in Africa (Globocan 2008, IARC)

5

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

6

Source: Palefsky. Curr Opin Oncol 2003.

+++++ +/-

7

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: Sensitivity of 80% (range 79–82%) Specificity of 92% (range 91–92%) Positive predictive value of 10%

Cluster-randomized trial in India (Lancet 2007;370:398): 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

8

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.

9

Target for Screening and Flow Pattern

VIA30–50 Years

HIV-Positive—at Any AgeFP/MNCH, OPD, Gyn, ART Clinic

Negative Positive

Follow-Up 3–5 Years(HIV-)

Follow-Up 1 Year (HIV+)

Treat Immediately Cryotherapy

Refer/Treat with LEEP

Repeat VIA after 1 Year

10

VIA by Total and HIV-Infected Women and Treatment Rates

Country

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)

Setting Time

Period

Guyana 19,934/8%

2,529(13%)

258 (16%)

1,813 (84%)

HIV CareGeneral 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 CareC&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

Burkina Faso 10,982/4%

965 (9%)

104 (22%)

508 (65%)

OPD 9/10–8/13

11

Cervical Cancer VIA Screening and Treatment Outcomes for 3 Countries, January 2009–March 2012*

Returned for cryotherapy after

previously postponing

42 (52%) Côte d’Ivoire186 (55%) Guyana6 (18%) Tanzania

Lost to cryotherapy treatment


*Côte d’Ivoire began in October 2009 and Tanzania began in April 2010.

Suspect cancer cases detected and referred50 (0.7%) Côte d’Ivoire

108 (0.5%) Guyana 178 (2%) Tanzania

VIA screen positive*519 (7%) Côte d’Ivoire2,529 (13%) Guyana532 (7%) Tanzania

VIA screen negative6969 (92%) Côte d’Ivoire

17,297 (87%) Guyana6,739 (90%) Tanzania

New women screened7,538 Côte d’Ivoire

19,934 Guyana7,449 Tanzania

Referred for large lesions


Treated with cryotherapy on same day as screening (SVA)

279 (78%) Côte d’Ivoire1,813 (84%) Guyana416 (92%) Tanzania

LEEP performed

45 (28%) Côte d’Ivoire239 (63%) Guyana

6 (7%) Tanzania

Lost to advanced care follow-up


Cryotherapy treatment postponed


12

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.

13

Lessons Learned

Promote country ownership Implement sustainable, organized screening for scale-up Conduct monitoring and assessment Build capacity Maintain quality of care

14

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?

15

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.

16

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

Cervical Cancer and HIV: Interactions and Interventions

Documents

Transcript of Cervical Cancer and HIV: Interactions and Interventions