Validation of Cervical Cancer Screening Methods in HIV Positive Women from Johannesburg South Africa

Abstract

BackgroundHIV-infected women are at increased risk for developing cervical cancer. Women living in resource-limited countries are especially at risk due to poor access to cervical cancer screening and treatment. We evaluated three cervical cancer screening methods to detect cervical intraepithelial neoplasia grade 2 and above (CIN 2+) in HIV-infected women in South Africa; Pap smear, visual inspection with 5% acetic acid (VIA) and human papillomavirus detection (HPV).MethodsHIV-infected women aged 18–65 were recruited in Johannesburg. A cross-sectional study evaluating three screening methods for the detection of the histologically-defined gold standard CIN-2 + was performed. Women were screened for cervical abnormalities with the Digene HC2 assay (HPV), Pap smear and VIA. VIA was performed by clinic nurses, digital photographs taken and then later reviewed by specialist physicians. The sensitivity, specificity and predictive valves for CIN-2 + were calculated using maximum likelihood estimators.Results1,202 HIV-infected women participated, with a median age of 38 years and CD4 counts of 394 cells/mm3. One third of women had a high grade lesion on cytology. VIA and HPV were positive in 45% and 61% of women respectively. Estimated sensitivity/specificity for HPV, Pap smear and VIA for CIN 2+ was 92%/51.4%, 75.8%/83.4% and 65.4/68.5% (nurse reading), respectively. Sensitivities were similar, and specificities appeared significantly lower for the HPV test, cytology and VIA among women with CD4 counts ≤200 cells/mm3 as compared to CD4 counts >350 cells/mm3.ConclusionsAlthough HPV was the most sensitive screening method for detecting CIN 2+, it was less specific than conventional cytology and VIA with digital imaging review. Screening programs may need to be individualized in context of the resources and capacity in each area.

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

“…The high rates of HPV positivity and high-grade cervical lesions observed in SA are very similar to those recently reported from HIV-1-infected women in this country. 33 When focusing on the 13 hr-HPV types targeted by HC2, prevalence of hr-HPV infection detected by INNOLiPA was higher than that detected by HC2 (70% vs 52%). This observation confirms the higher analytical sensitivity of INNO-LiPA.…”

Estimating the burden of cervical disease among HIV-infected women accessing screening services in South Africa: A model-based analysis

“…disease) probability estimates were obtained from a previous study conducted among HIV-infected women in Johannesburg. [12] Specifically, the probabilities of NILM, CIN1, CIN2, CIN3 and ICC were assumed to be 0. Second, we modelled the programme-wide burden of cervical disease, estimating the frequencies of NILM, CIN1, CIN2, CIN3 and ICC expected among all HIV-infected women accessing services through our programme (N=75 358) but for whom individuallevel information was not available.…”

“…We used the probability of NILM, ASCUS, LSIL, ASC-H, HSIL and cytology suspicious for ICC observed in our programmatic database to model the expected frequency of each Pap smear finding. We then calculated the expected number of NILM, CIN1, CIN2, CIN3 and ICC cases using the parameter estimates from our published work, [12] as described above. Sensitivity analyses were conducted to provide low and high estimates of disease burden using the lower and upper bounds of the 95% CIs for NILM, ASCUS, LSIL, ASC-H, HSIL and cytology suspicious for ICC derived from programmatic data.…”

“…† Probabilities of NILM, CIN1, CIN2 and CIN3 for each cytological diagnosis are based on data previously published by our team. [12] ‡ Owing to the lack of robust data for HIV-infected women in our setting, probabilities of CIN3 and ICC are estimated as 0.500 for cytology results suspicious for ICC.…”

A comparison of two visual inspection methods for cervical cancer screening among HIV-infected women in Kenya

“…Factors associated with HIV infection, including the prevalence of cervical lesions, their size and character and the concomitant presence of genital infections can influence the PPV of VIA or VIA/VILI and affect the overall impact and cost of a screening programme. 10,11 In fact, a wide range of PPVs has been reported for visual screening tests performed in populations of HIV-infected women, [12][13][14] making it difficult to estimate disease prevalence and plan for the costs and resources necessary for programme implementation.…”