Admire Chikandiwa

Epidemiology of High-risk Human Papillomavirus and Cervical Lesions in African women living with HIV/AIDS: Effect of Anti-Retroviral Therapy.

Objective: To describe the effect of antiretroviral therapy (ART) and HIV-related factors on high-risk human papillomavirus (HR-HPV) and high-grade cervical intraepithelial neoplasia lesions (CIN2+) among women living with HIV/AIDS (WLHA) in sub-Saharan Africa. Design: Prospective cohort of WLHA in Ouagadougou, Burkina Faso (BF) and Johannesburg, South Africa (SA). Recruitment was stratified by ART status. Methods: At baseline and endline (median 16 months), cervical samples, and biopsies were analyzed for HPV genotyping (InnoLiPA) and by histology. Logistic regression was used to estimate associations of ART and HIV-related factors with HR-HPV and CIN2+ outcomes, and all results presented are adjusted for baseline CD4+ cell count. Results: Among 1238 enrolled WLHA (BF = 615; SA = 623), HR-HPV prevalence was 59.1% in BF and 79.1% in SA. CIN2+ prevalence was 5.8% in BF and 22.5% in SA. Compared with long-duration ART users (>2 years), HR-HPV prevalence was higher among short-duration ART users [⩽2 years; adjusted prevalence ratio (aPR) = 1.24, 95% confidence interval (CI) 1.04–1.47] in BF, and CIN2+ prevalence was higher among short-duration ART users [adjusted odds ratio (aOR) = 1.99, 95% CI 1.12–3.54) and ART-naive participants (aOR = 1.87, 95% CI 1.11–3.17) in SA. Among 963 (77.8%) women seen at endline, HR-HPV persistence was 41.1% in BF and 30.2% in SA; CIN2+ incidence over 16-months was 1.2% in BF and 5.8% in SA. HR-HPV persistence was associated with being ART-naive in BF (aPR = 1.89, 95% CI 1.26–2.83), and with short-duration ART use (aPR = 1.78, 95% CI 1.11–2.86) and HIV-1 plasma viral load at least 1000 copies/ml (aPR = 2.87, 95% CI 1.63–5.05) in SA. CIN2+ incidence was reduced among women on ART in SA (aOR = 0.39, 95% CI 0.15–1.01). Conclusion: Prolonged and effective ART is important in controlling HR-HPV and the development of CIN2+.

Comparison of Analytical and Clinical Performances of the Digene HC2 HPV DNA Assay and the INNO-LiPA HPV Genotyping Assay for Detecting High-Risk HPV Infection and Cervical Neoplasia Among HIV-Positive African Women.

Objectives:To compare the Hybrid Capture 2 human papillomaviruses (HPV) DNA assay (HC2) and the INNO-LiPA HPV Genotyping Extra assay (INNO-LiPA) for cervical cancer screening in HIV-1–infected African women. Design:The tests were compared for agreement in detecting high-risk HPV (hr-HPV) and performance to detect squamous intraepithelial lesions (SIL), by cytology, and cervical intraepithelial neoplasia, by histology, in cervical samples from 1224 women in Burkina Faso (N = 604) and South Africa (N = 620). Results:When considering the 13 hr-HPV types detected by HC2, 634 (51.8%) and 849 (69.4%) samples were positive by HC2 and INNO-LiPA, respectively. Agreement between assays was 73.9% [adjusted kappa coefficient value, 0.44 (95% confidence interval: 0.43 to 0.53)]. Agreement improved with analysis restricted to women with high-grade cervical lesions [adjusted kappa coefficient value, 0.83 (95% confidence interval: 0.74 to 0.91)]. The prevalence of hr-HPV, as determined by HC2 and INNO-LiPA, was 34.5% and 54.5%, respectively, in samples with normal cytology, 48.0% and 68.0%, respectively, in samples with atypical squamous cells of undetermined significance, 51.8% and 75.2%, respectively, in samples with low-grade SIL, and 86.3% and 89.8%, respectively, in samples with high-grade SIL/atypical squamous cells that cannot exclude HSIL. Sensitivity, specificity, positive, and negative predictive values for the diagnosis of histological high-grade lesions (CIN2+) were 88.8%, 55.2%, 24.7% and 96.7%, and 92.5%, 35.1%, 19.1% and 96.6% for HC2 and INNO-LiPA, respectively. Conclusions:HC2 has lower analytical sensitivity but higher specificity than INNO-LiPA for diagnosing high-grade lesions; the 2 tests presented a comparable clinical sensitivity. HC2 might be suitable for cervical cancer screening in HIV-1–infected African women, but its use in resource-limited settings merits to be further evaluated in comparison with other prevention strategies.

Performance of careHPV for detecting high-grade cervical intraepithelial neoplasia among women living with HIV-1 in Burkina Faso and South Africa: HARP study.

Background:The careHPV assay is a test for high-risk (HR) human papillomaviruses (HPV) detection designed to be affordable in resource-poor settings. We evaluated the performance of careHPV screening among 1052 women living with HIV/AIDS included in the HARP (HPV in Africa Research Partnership) study in Burkina Faso (BF) and South Africa (SA).Methods:Cervical samples were tested for HR-HPV by the careHPV and the INNO-LiPA HPV genotyping Extra assays. All women had Pap smear testing, visual inspection with acetic acid/Lugol’s iodine (VIA/VILI) and colposcopy. Cervical biopsies were obtained for participants who were HR-HPV DNA positive by careHPV or who had abnormalities detected on cytology, VIA/VILI or colposcopy.Results:Overall, 45.1% of women had a positive careHPV test (46.5% in BF, 43.8% in SA). The careHPV positivity rate increased with the grade of cytological lesions. Sensitivity and specificity of careHPV for the diagnosis of CIN2+ (n=60, both countries combined) were 93.3% (95% confidence interval (CI): 83.8–98.2) and 57.9% (95% CI: 54.5–61.2), respectively. Specificity increased with CD4 count. careHPV had a similar clinical sensitivity but higher specificity than the INNO-LiPA assay for detection of CIN2+.Conclusions:Our results suggest that careHPV testing is a reliable tool for cervical cancer screening in HIV-1-infected women in sub-Saharan Africa.

Associations of Human Papillomavirus (HPV) genotypes with high-grade cervical neoplasia (CIN2+) in a cohort of women living with HIV in Burkina Faso and South Africa.

Objective To describe associations of high-risk human papillomavirus (HR-HPV) with high-grade cervical intraepithelial neoplasia (CIN2+) in women living with HIV (WLHIV) in Burkina Faso (BF) and South Africa (SA). Methods Prospective cohort of WLHIV attending HIV outpatient clinics and treatment centres. Recruitment was stratified by ART status. Cervical HPV genotyping using INNO-LiPA and histological assessment of 4-quadrant cervical biopsies at enrolment and 16 months later. Results Among women with CIN2+ at baseline, the prevalence of any HR-HPV genotypes included in the bi/quadrivalent (HPV16/18) or nonavalent (HPV16/18/31/35/45/52/58) HPV vaccines ranged from 37% to 90%. HPV58 was most strongly associated with CIN2+ (aOR = 5.40, 95%CI: 2.77–10.53). At 16-months follow-up, persistence of any HR-HPV was strongly associated with incident CIN2+ (aOR = 7.90, 95%CI: 3.11–20.07), as was persistence of HPV16/18 (aOR = 5.25, 95%CI: 2.14–12.91) and the additional HR types in the nonavalent vaccine (aOR = 3.23, 95%CI: 1.23–8.54). Conclusion HR-HPV persistence is very common among African WLHIV and is linked to incident CIN2+. HPV vaccines could prevent between 37–90% of CIN2+ among African WLHIV.

Cervical intraepithelial neoplasia (CIN) in African women living with HIV: role and effect of rigorous histopathological review by a panel of pathologists in the HARP study endpoint determination

AIMS To analyse the effect of the expert end-point committee (EPC) review on histological endpoint classification of cervical intraepithelial neoplasia (CIN). Methods A cohort of women living with HIV were recruited in Burkina Faso (BF) and South Africa (SA) and followed over 18 months. Four-quadrant cervical biopsies were obtained in women with abnormalities detected by at least one screening test. A central review by a panel of five pathologists was organised at baseline and at endline. Results At baseline the prevalence of high-grade CIN (CIN2+) was 5.1% (28/554) in BF and 23.3% (134/574) in SA by local diagnosis, and 5.8% (32/554) in BF and 22.5% (129/574) in SA by the EPC. At endline the prevalence of CIN2+ was 2.3% (11/483) in BF and 9.4% (47/501) in SA by local diagnosis, and 1.4% (7/483) in BF and 10.2% (51/501) in SA by EPC. The prevalence of borderline CIN1/2 cases was 2.8% (32/1128) and 0.8% (8/984) at baseline and endline. Overall agreement between local diagnosis and final diagnosis for distinguishing CIN2+ from ≤CIN1 was 91.2% (κ=0.82) and 88.9% (κ=0.71) for BF at baseline and endline, and 92.7% (κ=0.79) and 98.7% (κ=0.97) for SA at baseline and endline. Among the CIN1/2 cases, 12 (37.5%) were graded up to CIN2 and 20 (62.5%) were graded down to CIN1 at baseline, and 3 (37.5%) were graded up to CIN2 and 5 (62.5%) were graded down to CIN1 at endline. Conclusions This study highlights the importance of a centralised rigorous re-reading with exchange of experiences among pathologists from different settings.

Human Papillomavirus Serology Among Women Living With HIV: Type-Specific Seroprevalence, Seroconversion, and Risk of Cervical Reinfection

Background Human papillomavirus (HPV) serodynamics following infection has never been evaluated prospectively among women living with HIV (WLHIV). We determined HPV seroprevalence, seroconversion, and cervical HPV-DNA acquisition among WLHIV. Methods Prospective study of 604 WLHIV in Johannesburg, South Africa aged 25-50 years. At baseline and 16 months (endline), HPV type-specific antibodies (HPV6/11/16/18/31/33/35/39/45/52/56/58/59/68/73) were measured using HPV-pseudovirions and cervical HPV-DNA genotypes using INNO-LiPA. Results Seroprevalence of any-HPV was 93.2% and simultaneous seropositivity for HPV types of the bivalent (HPV16/18), quadrivalent (HPV6/11/16/18), and nonavalent (HPV6/11/16/18/31/33/45/52/58) vaccines were 21.4%, 10.9%, and 2.8%. Among 219 women with cervical HPV-DNA, same-type seronegative and without high-grade cervical intraepithelial neoplasia at baseline, 51 (23.3%) had type-specific seroconversion at endline. Risk of type-specific seroconversion was higher among recent antiretroviral therapy users (ART ≤2 years vs ART naive: adjusted OR [aOR] = 2.39; 95% CI, 1.02-5.62), and lower among women with low CD4+ at endline (≤350 vs >350 cells/mm3: aOR = 0.51; 95% CI, 0.24-1.07). Risk of cervical HPV-DNA acquisition was lower in women seropositive for HPV18, 35, and 58 at baseline. Conclusion WLHIV have evidence of seroconversion in response to baseline HPV-DNA, dependent on CD4+ count and ART. Baseline HPV seropositivity confers limited protection against some HPV types.

Prevalence, incidence and correlates of low risk HPV infection and anogenital warts in a cohort of women living with HIV in Burkina Faso and South Africa.

Objective To report the prevalence and incidence of low-risk human papillomavirus infection (LR-HPV) and anogenital warts (AGW) among women living with HIV (WLHIV) in Burkina Faso (BF) and South Africa (SA), and to explore HIV-related factors associated with these outcomes. Methods We enrolled 1238 WLHIV (BF = 615; SA = 623) aged 25–50 years and followed them at three time points (6, 12 and 16 months) after enrolment. Presence of AGW was assessed during gynaecological examination. Cervico-vaginal swabs for enrolment and month 16 follow-up visits were tested for HPV infection by Inno-LiPA® genotyping. Logistic regression was used to assess risk factors for prevalent infection or AGW. Cox regression was used to assess risk factors for incident AGW. Results Women in SA were more likely than those in BF to have prevalent LR-HPV infection (BF: 27.1% vs. SA: 40.9%; p<0.001) and incident LR-HPV infection (BF: 25.8% vs. SA: 31.6%, p = 0.05). Prevalence of persistent LR-HPV was similar in the two countries (BF: 33.3% vs. SA: 30.4%; p = 0.54), as were prevalence and incidence of AGW (Prevalence: BF: 7.5% vs. SA: 5.7%; p = 0.21; Incidence: BF: 2.47 vs. SA: 2.33 per 100 person-years; p = 0.41). HPV6 was associated with incident AGW (BF: adjusted Hazard Ratio (aHR) = 4.88; 95%CI: 1.36–17.45; SA: aHR = 5.02; 95%CI: 1.40–17.99). Prevalent LR-HPV (BF: adjusted Odds Ratio [aOR = 1.86]; 95%CI: 1.01–3.41; SA: aOR = 1.75; 95%CI: 0.88–3.48); persistent LR-HPV (BF: aOR = 1.92; 95%CI: 0.44–8.44; SA: aOR = 2.81; 95%CI: 1.07–7.41) and prevalent AGW (BF: aOR = 1.53; 95%CI: 0.61–3.87; SA: aOR = 4.11; 95%CI: 1.20–14.10) were each associated with low CD4+ counts (i.e. <200 vs. >500 cells/μL). Duration of ART and HIV plasma viral load were not associated with any LR-HPV infection or AGW outcomes. Conclusion LR-HPV infection and AGW are common in WLHIV in sub-Saharan Africa. Type-specific HPV vaccines and effective ART with immunological reconstitution could reduce the burden of AGW in this population.

Oropharyngeal HPV infection: prevalence and sampling methods among HIV-infected men in South Africa.

Worldwide, 96,000 cases of oropharyngeal cancer (OPC) occurred in 2012. Human papillomavirus (HPV) is a risk factor for OPC. Data on oropharyngeal HPV infection are limited. There is no consensus on the best sampling method for detecting the infection. We describe the prevalence of oropharyngeal HPV infection among HIV-infected men and compare the performance of oral rinses and swabs in detecting oropharyngeal HPV infection. Paired oral rinses and swabs for 181 men were tested for HPV DNA using the Roche Linear Array. Performance was determined by the number of infections detected and the percentage of samples with adequate DNA extraction. Agreement between sampling methods was assessed by the kappa statistic. Prevalence of oropharyngeal HPV infection with rinse samples was 1.8% (three infections) and 0.6% (one infection) with swabs (p = 0.06). Adequate cellular DNA extraction was more likely with rinse (93.4%) than swab samples (89.0%, p = 0.05). There was moderate agreement between the methods (kappa = 0.49). The prevalence of oropharyngeal HPV DNA infection among this predominantly heterosexual sample of men living with HIV was low and consistent with the infrequent oral sex practices. Oral rinse performed better than oral swab in detecting oropharyngeal HPV DNA infection and might contribute to screening for OPCs.

Temporal trends in the epidemiology of cervical cancer in South Africa (1994-2012): Cervical cancer epidemiology in South Africa

Cervical cancer (CC) is the leading cause of cancer death among female South Africans (SA). Improved access to reproductive health services following multi‐ethnic democracy in 1994, HIV epidemic, and the initiation of CC population‐based screening in early 2000s have influenced the epidemiology of CC in SA. We therefore evaluated the trends in CC age‐standardised incidence (ASIR) (1994–2009) and mortality rates (ASMR) (2004–2012) using data from the South African National Cancer Registry and the Statistics South Africa, respectively. Five‐year relative survival rates and average per cent change (AAPC) stratified by ethnicity and age‐groups was determined. The average annual CC cases and mortalities were 4,694 (75,099 cases/16 years) and 2,789 (25,101 deaths/9 years), respectively. The ASIR was 22.1/100,000 in 1994 and 23.3/100,000 in 2009, with an average annual decline in incidence of 0.9% per annum (AAPC = −0.9%, p‐value < 0.001). The ASMR decreased slightly by 0.6% per annum from 13.9/100,000 in 2004 to 13.1/100,000 in 2012 (AAPC = −0.6%, p‐value < 0.001). In 2012, ASMR was 5.8‐fold higher in Blacks than in Whites. The 5‐year survival rates were higher in Whites and Indians/Asians (60–80%) than in Blacks and Coloureds (40–50%). The incidence rate increased (AAPC range: 1.1–3.1%, p‐value < 0.001) among young women (25–34 years) from 2000 to 2009. Despite interventions, there were minimal changes in overall epidemiology of CC in SA but there were increased CC rates among young women and ethnic disparities in CC burden. A review of the CC national policy and directed CC prevention and treatment are required to positively impact the burden of CC in SA.

Performances du test careHPV pour le dépistage des lésions cervicales chez les femmes séropositives pour le VIH en Afrique subsaharienne

Introduction – objectifs Le test careHPV (Qiagen) est un test de detection de l’ADN des HPV a haut risque (HR-HPV) base sur l’hybridation d’un cocktail de sondes ciblant 14 HR-HPV (types 16, 18, 31, 33, 35, 39, 45, 51, 52, 56, 58, 59, 66, et 68). Ce test a ete concu pour etre plus simple d’utilisation que le test HC2 et d’un cout plus abordable pour les pays a faible niveau de ressources. L’objectif de cette etude est d’evaluer les performances de careHPV pour le depistage des lesions cervicales de haut grade dans une population de femmes VIH+ en Afrique sub-saharienne. Population d’etude et methodes L’etude a ete realisee chez 1 052 femmes VIH+ enrolees dans l’etude HARP (HPV in Africa Research Partnership) : 492 au Burkina Faso (BF) et 560 en Afrique du Sud (AS). La detection des HR-HPV a 18 mois de suivi etait realisee par careHPV et la detection et genotypage des HPV par le test INNO-LiPA HPV genotyping Extra (Fujirebio). Toutes les participantes ont beneficie d’une inspection visuelle a l’acide acetique/Lugol, d’une cytologie cervicale et d’une colposcopie. Les femmes presentant un test careHPV positif, et/ou une anomalie a l’inspection visuelle, la cytologie ou la colposcopie ont eu une biopsie 4 quadrants et sur les lesions colposcopiquement observables pour analyse histologique. Resultats La prevalence de HR-HPV etait de 45,1 % par careHPV (BF : 46,5 %, AS : 43,8 %) et de 70,0 % par INNO-LiPA (BF : 67,9 %, AS : 72,0 %). La concordance entre careHPV et INNO-LiPA etait globalement de 62.5 %, mais etait de 93,5 % pour les femmes presentant une lesion histologique de haut grade (CIN2+). Un total de 62 (6,7 %) CIN2+ ont ete diagnostiquees : 10 (2,3 %) au BF et 52 (10,7 %) en AS. Les valeurs respectives de sensibilite, specificite, valeur predictive positive et valeur predictive negative etaient de 93,6 %, 58,2 %, 13,8 % et 99,2 % pour careHPV et de 96,8 %, 32,1 %, 9,2 % et 99,3 % pour INNO-LiPA. Conclusion La sensibilite analytique de careHPV est moins elevee que celle de INNO-LiPA mais les deux tests presentent une sensibilite et une valeur predictive negative similaires pour le diagnostic des CIN2+, avec une specificite plus elevee pour careHPV. Le test careHPV represente un outil bien adapte au depistage du cancer du col chez les femmes africaines infectees par le VIH.