Review of HIV-Related Cytopathology

Exfoliative and aspiration cytologies play a major role in the management of patients with human immunodeficiency virus infection. Common cytology samples include cervicovaginal and anal Papanicolaou tests, fine needle aspirations, respiratory specimens, body fluids, Tzanck preparations, and touch preparations from brain specimens. While the cytopathologists need to be aware of specific infections and neoplasms likely to be encountered in this setting, they should be aware of the current shift in the pattern of human immunodeficiency virus-related diseases, as human immunodeficiency virus patients are living longer with highly active antiretroviral therapy and suffering fewer opportunistic infections with better antimicrobial prophylaxis. There is a rise in nonhuman immunodeficiency virus-defining cancers (e.g., anal cancer, Hodgkin's lymphoma) and entities (e.g., gynecomastia) from drug-related side effects. Given that fine needle aspiration is a valuable, noninvasive, and cost-effective tool, it is frequently employed in the evaluation and diagnosis of human immunodeficiency virus-related diseases. Anal Papanicolaou tests are also increasing as a result of enhanced screening of human immunodeficiency virus-positive patients for cancer. This paper covers the broad spectrum of disease entities likely to be encountered with human immunodeficiency virus-related cytopathology

Costs and Cost Effectiveness of Three Approaches for Cervical Cancer Screening among HIV-Positive Women in Johannesburg, South Africa

BackgroundSouth Africa has high rates of HIV and HPV and high incidence and mortality from cervical cancer. However, cervical cancer is largely preventable when early screening and treatment are available. We estimate the costs and cost-effectiveness of conventional cytology (Pap), visual inspection with acetic acid (VIA) and HPV DNA testing for detecting cases of CIN2+ among HIV-infected women currently taking antiretroviral treatment at a public HIV clinic in Johannesburg, South Africa.MethodsMethod effectiveness was derived from a validation study completed at the clinic. Costs were estimated from the provider perspective using micro-costing between June 2013-April 2014. Capital costs were annualized using a discount rate of 3%. Two different service volume scenarios were considered. Threshold analysis was used to explore the potential for reducing the cost of HPV DNA testing.ResultsVIA was least costly in both scenarios. In the higher volume scenario, the average cost per procedure was US$3.67 for VIA, US$ 8.17 for Pap and US$54.34 for HPV DNA. Colposcopic biopsies cost on average US$ 67.71 per procedure. VIA was least sensitive but most cost-effective at US$17.05 per true CIN2+ case detected. The cost per case detected for Pap testing was US$ 130.63 using a conventional definition for positive results and US$187.52 using a more conservative definition. HPV DNA testing was US$ 320.09 per case detected. Colposcopic biopsy costs largely drove the total and per case costs. A 71% reduction in HPV DNA screening costs would make it competitive with the conservative Pap definition.ConclusionsWomen need access to services which meet their needs and address the burden of cervical dysplasia and cancer in this region. Although most cost-effective, VIA may require more frequent screening due to low sensitivity, an important consideration for an HIV-positive population with increased risk for disease progression

Injectable and oral contraception and the incidence and progression of cervical disease in HIV-infected women in South Africa

Few data exist regarding the effect of hormonal contraception (HC) on incidence and progression of cervical disease (e.g., cervical dysplasia, squamous intraepithelial lesions, cervical intraepithelial neoplasia) in HIV-infected African women

Prospective One Year follow up of HIV infected women screened for cervical cancer using visual inspection with acetic acid, cytology and human papillomavirus testing in Johannesburg, South Africa

BACKGROUND: Cervical cancer is the most common cancer in Sub-Saharan Africa. There are little of HIV-infected women one-year after screening using visual inspection with acetic acid (VIA), HPV or cytology in sub-Saharan Africa. METHODS: HIV-infected women in Johannesburg South Africa were screened one year later by Pap smear, VIA and human papillomavirus (HPV) testing. Women qualified for the 12 month follow-up visit if they had a negative or cervical intra-epithelial neoplasia (CIN) 1 results at the baseline visit. Modified Poisson regression was used to analyse associations between patient baseline characteristics and progression. RESULTS: A total of 688 of 1,202 enrolled at baseline study who were CIN-2+ negative and qualified for a 12 month follow-up visit. Progression to CIN-2+ was higher in women with positive VIA results (12.6%; 24/191) than those VIA-negative (4.4%; 19/432). HPV-positive women at baseline were more likely to progress to CIN-2+ (12.3%; 36/293) than those HPV-negative (2.1%; 7/329). Cytology-positive women at baseline were more likely to progress to CIN-2+ (9.6%; 37/384) than cytology-negative women (2.5%; 6/237). Approximately 10% (10.4%; 39/376) of women with CIN 1 at baseline progressed to CIN 2+. Women who were VIA or HPV positive at baseline were more likely to progress aIRR 1.85, CI 95% (1.46 to 2.36), aIRR 1.41 CI 95% (1.14 to 1.75) respectively. CONCLUSION: Progression to CIN-2+ in HIV-infected women is significant when measured by baseline positive VIA, HPV or Pap and yearly screening by any method should be considered in this population if possible

Highly active antiretroviral therapy and cervical dysplasia in HIV-positive women in South Africa

BackgroundThe risk of squamous intra-epithelial lesions (SIL) is higher in HIV-positive women. As these women begin to live longer due to highly active antiretroviral therapy (HAART), their risk of cervical cancer may increase. Few data exist regarding the effect of HAART on the incidence and progression of SIL in HIV-positive African women. The aim of this study was to evaluate the effect of HAART on the incidence and progression of SIL in HIV-positive women in South Africa.MethodsA prospective observational study of HIV-seropositive women was conducted over 5 years in an HIV treatment clinic in Johannesburg, South Africa. The participants consisted of 601 women on and off HAART who had repeat Pap smears greater than 6 months apart. The effect of HAART use on incidence and progression rates of SIL was determined using multivariate Poisson regression to obtain incidence rate ratios (IRRs), adjusted for age, CD4 count and other potential confounders.ResultsMedian follow-up time was 445 days (inter-quartile range 383, 671). The crude rate of incidence of any SIL was 15.9 episodes (95% confidence limit (CL) 12.7, 19.9) per 100 person-years; the crude rate of all progression of cervical dysplasia among women was 13.5 episodes (95% CL 11.3, 16.1) per 100 person-years. HAART use was associated with a robust reduction in the rate of incidence and progression of cervical lesions, adjusted IRR=0.55 (95% CL 0.37, 0.80). Sensitivity analyses confirmed this main association held for incidence and progression when they were considered separately, and that the result was not dependent on the length of HAART exposure.ConclusionHAART use was associated with a reduction in the rate of both incidence and progression of cervical lesions among HIV-positive women

Association between cervical dysplasia and human papillomavirus in HIV seropositive women from Johannesburg South Africa

ObjectiveTo examine the association between CD4 counts, HPV infection and the risk of cervical neoplasia among HIV-seropositive women.MethodsA cross-sectional observational study was conducted among 1,010 HIV-seropositive women using cytology-based Pap smears. HPV DNA testing using Linear Array genotyping assay (Roche) was carried out in a subset of 191 patients. Multivariable-adjusted prevalence ratios (mPR) and 95% confidence intervals (CIs) were estimated with log-binomial regression.ResultsAmong 1,010 HIV-seropositive women, the prevalence of AGC/ASCUS, LSIL and HSIL or greater was 8.3, 23.5 and 18.0%, respectively. The risk of cervical lesions was higher with CD4500/mm3. HPV types 16 (41.7%) and HPV 56 (22.2%) were the most common types in HSIL cases. Women with CD4 levels<200/mm3 had a higher prevalence of HPV types 16 (p<0.01) and 66 (p=0.04). No statistical relationship between cervical lesions and HAART use was found.ConclusionThe burden of HPV infection and HSIL was high and correlated with HIV-induced immunosuppression. HPV 16 was the most common type in HSIL and increased in prevalence with greater immune suppression. Prophylactic HPV 16 vaccination could prevent approximately 40% of HSIL cases. Strengthening screening programs is imperative in this population

Validation of cervical cancer screening methods in HIV positive women from Johannesburg South Africa

BACKGROUND: HIV-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). METHODS: HIV-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. RESULTS: 1,202 HIV-infected women participated, with a median age of 38 years and CD4 counts of 394 cells/mm 3 . 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/mm 3 as compared to CD4 counts >350 cells/mm 3 . CONCLUSIONS: Although 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

Diverse and High Prevalence of Human Papillomavirus Associated with a Significant High Rate of Cervical Dysplasia in Human Immunodeficiency Virus–Infected Women in Johannesburg, South Africa

To evaluate the epidemiology of the human papillomavirus (HPV) type and correlate it with the Papanicolaou smears in human immunodeficiency virus–seropositive women in Johannesburg, South Africa

Evaluation of a Cervicography-Based Program to Ensure Quality of Visual Inspection of the Cervix in HIV-Infected Women in Johannesburg, South Africa

Quality assurance with cervicography and specialist review significantly improved the sensitivity of visual inspection with acetic acid to detect cervical intraepithelial neoplasia grade 2 or worse.AbstractObjectiveTo determine whether a quality assurance (QA) program using digital cervicography improved the performance of a visual inspection with acetic acid (VIA) to detect cervical intraepithelial neoplasia grade 2 or worse (CIN 2+) in HIV-infected women in Johannesburg, South Africa.Materials and MethodsVisual inspection with acetic acid was performed among HIV-infected women, aged 18 to 65 years, in Johannesburg, South Africa. Nurses received 2 weeks of training on the VIA procedure. The VIA interpretation was performed in real time. The VIA results were then photographed using a retail available digital camera. A gynecologist and medical officer reviewed the VIA digital images within 2 weeks of the procedure. Colposcopic biopsy was performed on all women with positive VIA and 25% negative VIA results. Sensitivity and specificity of VIA for the detection of CIN 2+ were compared between the nurses and physicians at the beginning and at the end of the study.ResultsPositive VIA results were found in 541 (45%) of the 1,202 participating women. The sensitivity of VIA to predict CIN 2+ was improved from 65% to 75% (p = .001) with the addition of digital cervicography and specialist review. There was no statistical difference in the sensitivity of the VIA readings when comparing the first 600 participants to the final 593 participants between the nurses (p = .613) and physicians (p = .624).ConclusionsQuality assurance performed by specialists using digital cervicography improved the sensitivity of VIA. There was no difference in sensitivity in interpreting VIA between the beginning and the end of the study. Quality assurance should form a cornerstone of any VIA program to improve sensitivity in detecting CIN 2+ lesions