Helen KellyLondon School of Hygiene and Tropical Medicine

EUROGIN 2012 Prague July 8-11, 2012

ABSTRACT AUTHORS: KELLY H, MUZAH B, SAWADOGO B, DIDELOT M, MICHELOW P, LOMPO O, DOUTRE S, GILHAM C, VON KNORRING N, ZAN S, DELANY S, OMAR T, MEDA N, DRABO J, WEISS H, LEGOOD R, NAGOT N,

SEGONDY M, COSTES V, MAYAUD P

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Prospective Evaluation of Cervical Screening Methods in HIV positive women in Africa

(HARP Study): Baseline Results

http://www.harp-fp7.org/

• Limited knowledge on cervical intraepithelial neoplasia (CIN) in Africa and no Africa-specific guidelines (particularly for HIV+) and limited implementation of cervical cancer screening and management (Firnhaber, J Int. AIDS Soc. 2012, Denny, Vaccine 2006)

• HIV and cervical cancer– The relationship between HIV immunosuppression and

cervical cancer incidence is mostly driven by CD4 count (Hawes, J Natl Cancer Inst. 2006, Grinsztejn, Int J Infect Dis. 2009)

– The effect of antiretroviral treatment (ART) is unclear in the context of cervical cancer (Heard, AIDS 1998, Lillo, J Infect Dis. 2001)

• Recent availability of CareHPV as cervical cancer screening test in low-resource settings (Qiao, Lancet Oncol. 2008)

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Background

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HARP (HPV in Africa Research Partnership) Aim of HARP

To evaluate the diagnostic performance & cost effectiveness of cervical cancer screening methods to detect prevalent and incident CIN-2+ (at 18-months) among HIV-infected African women

HARP Study Design

South Africa & Burkina Faso

1200 HIV+ women age >25 and <50 years (excluding hysterectomy and pregnancy)

Participants enrolled in two strata based on CD4 and ART use (i) taking ART OR low CD4 count (≤350 cells/μl) (ii) not taking ART AND high CD4 count

6 monthly visits up to 18 months

Main endpoint => histology CIN2+

Methodology

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If ANY HPV DNA+,

Cytology > ASCUS or ≥ AGUS, VIA/VILI +,

Colposcopy +

careHPV/HC2 INNO-LiPA

Burkina Fason (%)

South African (%)

Number women enrolled (as of 25th June 2012) 497 553

Taking ART OR low CD4 count 352 (71%) 394 (71%)

Not taking ART AND high CD4 count 145 (29%) 159 (29%)

Number with baseline questionnaire data available 221 324

Median age (yrs) 37 35

Lifetime sexual partners ≥5 24 (11%) 120 (43%)

Ever smokers 3 (1%) 25 (12%)

Ever used hormonal contraception (oral/injectable) 102 (49%) 270 (83%)

Ever had a previous PAP 31 (14%) 161 (57%)

Ever had a previous VIA/VILI 60 (27%) 13 (5%)

Ever had been treated for a previous abnormality 5 (2%) 1 (0.4%)

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Population characteristics at baseline

Screening at baselineBurkina Faso South Africa

HR HPV 159/348 (46%) 256/366 (70%)

Cytology

Negative 252/332 (76%) 35/459 (8%)

ASCUS 10/332 (3%) 24/459 (5%)

LSIL 62/332 (19%) 274/459 (60%)

HSIL 8/332 (2%) 126/459 (27%)

VIA/VILI positive (combined) 61/220 (28%) 112/313 (36%)

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HR-HPV prevalence by CD4 count

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n=33 n=37 n=62 n=90 n=89 n=98 n=131 n=141

58%

81%

52%

77%

51%

71%

38%

62%

p-trend <0.001

HR

HPV

Pre

vale

nce

(%)

CD4 count (cells/μL)

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Cytology by CD4 count

Burkina Faso South Africa

n = 33 n = 51

CD4 count

P-trend for HSIL by CD4 count: combined sites, p< 0.003 South Africa alone < 0.006

HR-HPV prevalence by ART

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67%

43%

43%

74%

52%

67%

n = 183 n = 212 n = 42 n = 54

477 cells/μL

382 cells/μL

459 cells/μL

493 cells/μL

Burkina Fason (%)

South African (%)

Number tested by INNO-LiPA 109 277

Negative for HPV DNA 32 (29%) 51 (18%)

Low risk HPV only 19 (17%) 24 (9%)

High risk HPV 58 (53%) 202 (73%)

Multiple HR HPV infections 20/58 (34%) 98/202 (49%)

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Genotyping Results

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Most frequent HPV genotypes

12% 12%

13%

8%

11%

6%

11%10%

25%

17%

• HIV women at high risk of cervical cancer appear not to be screened effectively, even fewer treated

• Study confirms high prevalence of HR HPV types and multiple infections in this population

• Similar HR genotype distribution, with HPV 52 being equally dominant in both countries

• Immuno-suppression main driver of HR HPV and cytological abnormalities– Nadir CD4 count and CD4 threshold at ART initiation probably

important factors for HR HPV infection and cervical disease development

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Summary

• London School of Hygiene & Tropical Medicine, UK– Philippe Mayaud, Helen Weiss, Rosa Legood, Clare Gilham, Helen Kelly

• Wits Reproductive Health and HIV Institute, Wits University, Johannesburg, South Africa– Sinead Delany, Batanayi Muzah, Helen Rees, Nina von Knorring

• National Health Laboratory Service (NHLS), Johannesburg, South Africa– David Lewis, Pam Michelow, Tanvier Omar, Adrian Puren

• Centre de Recherche Internationale sur la Sante, Ouagadougou University, Ouagadougou, Burkina Faso– Joseph Drabo, Nicolas Meda, Mamadou Sawadogo, Bernard Sawadogo, Olga Lompo,

Souleymane Zan

• Centre de Recherche Biomoléculaire Pietro Annigoni (CERBA), Ouagadougou, Burkina Faso– Jaques Simpore, Florencia Djigma

• University of Montpellier 1 & INSERM U1058, France– Nicolas Nagot, Michel Segondy, Valerie Costes, Marie-Noelle Didelot-Rousseau, Sylviane

Doutre, Nicolas Leventoux, Jean Ngou

http://www.harp-fp7.org/ 13

HARP Collaborators

Additional slides

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HPV testing at baselineSouth Africa Burkina Faso

INNO-LiPA

Number tested 277* 109

HR HPV + 202 (73%) 58 (53%)

Hybrid Capture 2

Number tested 202* 239

HR HPV + 118 (58%) 101 (42%)

HR HPV+ (Combined INNO-LiPA + HC2) 256/366 (70%) 159/348 (46%)

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113 samples from South Africa tested by both methods

INNO-LiPA - INNO-LiPA +

HC2 - 28 21

HC2 + 4 60

INNO-LiPA HR HPV+ defined as + for 13 HR types as in HC2 test

HR-HPV prevalence by age group

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Most frequent HPV genotypes

South Africanumber tested = 277

HPV 52 24.6%HPV 51 13.4%HPV 16 11.9%HPV 18 10.8%HPV 35 10.8%

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Burkina Fasonumber tested= 109

HPV 52 16.5%HPV 16 11.9% HPV 35 10.1%HPV 51 8.3%HPV 18 6.4%

Cytology at baseline

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10/84 (12%) CIN2+ histology32/140 (23%) CIN2+ histology

60%