Pam Michelow

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/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. 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

OBJECTIVE 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. STUDY DESIGN In a cohort of 148 women, HPV DNA testing was performed with the Roche HPV genotyping test (Branchburg, New Jersey, U.S.A). Papanicolaou smears were performed by standard cytology utilizing 2001 Bethesda reporting guidelines. RESULTS The average age and CD4 count of the participants was 35 years and 255 cells per mm3, respectively. Fifty-four percent had abnormal Papanicolaou smears; 66% of the abnormal cytology was low grade changes, with 33% assessed as having high grade changes. HPV DNA was found in 95% of the 148 subjects assessed, with 83% having 1 or more HPV oncogenic types. Common oncogenic types were 16, 35, 53 and 18. When HPV results were stratified by CD4, there was a significant risk of an oncogenic HPV type in women with CD4 <200. Significant odds ratios for high grade lesions were seen in HPV types 16, 35, 51, 66, 69 and 73. CONCLUSION The results of HPV typing illustrate the diverse range of oncogenic HPV and high prevalence of oncogenic type. These results highlight the need for improved access to Papanicolaou smear screening for this population.

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

The 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.

Review of Human Immunodeficiency Virus (HIV) and squamous lesions of the uterine cervix

With heterosexual transmission becoming the primary mode of transmission, more women are being infected with Human Immunodeficiency Virus (HIV). Accrued data from around the world indicate that these HIV‐infected women exhibit higher rates of persistent HPV infection with multiple oncogenic viruses, more abnormal Pap tests, more prevalent cervical intraepithelial neoplasia (CIN) lesions, and aggressive invasive cervical cancer compared with their HIV‐negative counterparts. In countries where HAART was introduced more than a decade ago, HPV‐related disease is increasing among ageing HIV‐positive women. The high rate of cervical disease seen in HIV‐positive women has prompted recommendations for more aggressive surveillance. The best strategy to screen HIV‐infected women, particularly in resource‐poor nations, remains challenging. This article reviews the collective literature regarding HIV and squamous lesions of the cervix and highlights these key issues. Diagn. Cytopathol. 2011;39:65–72.

A Review of the Cytomorphology of Epstein-Barr Virus-Associated Malignancies.

The Epstein-Barr virus (EBV) is a member of the herpes family of viruses and is very common in humans. EBV is most often associated with infectious mononucleosis. However, it is estimated that 1% of tumors including lymphoproliferative, epithelial and mesenchymal are linked to EBV infection. EBV has a tropism for certain epithelial cells, lymphocytes and myocytes. Like other herpesviruses, EBV has both lytic and latent phases of infection. In the latent form, EBV-encoded genes ensure the survival of the viral genome, allowing it to circumvent the host’s immune surveillance by limited expression of viral proteins and carries with it the risk of neoplastic transformation. Cytologists are likely to encounter EBV-associated malignancies in cytology material but unlike other herpesviruses, EBV does not evoke a viral cytopathic effect. The manifestation of EBV-related tumors is also often variable depending upon the patient’s immune status. Therefore, knowledge of the patient’s EBV status and immune competence (e.g. HIV-infection or transplant-related immunosuppression) combined with the cytomorphology and results of ancillary studies are often all required to make a diagnosis of EBV-associated malignancy. This review discusses the unique cytomorphology and ancillary studies required to diagnose EBV-related neoplasms.

The status of cervical cytology in Swaziland, Southern Africa: a descriptive study.

Background: Cancer of the cervix is the most common cancer in women in Swaziland where most women never undergo cervical screening. The extremely high prevalence of HIV/AIDS in Swaziland complicates the management of preinvasive and invasive cervical cancer. The purpose of this study was to assess the current status of cervical cytology in Swaziland, its strengths and limitations. Methods: The study is a retrospective review of 12,188 conventional cervical smears received by the Central Public Health Laboratory in Swaziland from June 2004 to May 2006. Results: Review of results showed very high rates of cytologic abnormalities with 43.2% of smears screened reported as abnormal. The percentages of abnormalities were as follows: atypical squamous cells of undermined significance (ASC-US), 19.8%; atypical squamous cells, cannot exclude HSILs (ASC-H), 8.8%; low-grade squamous intraepithelial lesions (LSIL), 9.0%; high-grade squamous intraepithelial lesions (HSIL), 4.6%; squamous cell carcinomas, 0.5%; atypical endocervical cells, 0.6%; and atypical endometrial cells, 0.4%. Just over 5% of smears were inadequate. The highest rates of HSILs and invasive squamous carcinoma occurred in women aged 50–59 years. Conclusions: This study underscores the need to reduce the incidence of cervical cancer and its precursor lesions in Swaziland women. Based on studies of human papillomavirus (HPV) types in other Southern African countries, current HPV vaccines would reduce the incidence and mortality from cervical cancer in the future, but cervical screening would still be required, both for women already infected with the HPV and for HPV subtypes not covered by current vaccines. The most cost-effective combination of screening modalities such as visual inspection, HPV DNA testing, and cytology should be investigated. Cervical cancer reduction needs to be managed within the greater framework of the HIV/AIDS epidemic.

Costs and cost effectiveness of three approaches for cervical cancer screening among HIV-positive women in Johannesburg, South Africa

Background South 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. Methods Method 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. Results VIA was least costly in both scenarios. In the higher volume scenario, the average cost per procedure was US

Cytologic Features of Hidradenoma in Fine Needle Aspiration Biopsies

3.67 for VIA, US

Evaluation of a cervicography-based program to ensure quality of visual inspection of the cervix in HIV-infected women in Johannesburg, South Africa

8.17 for Pap and US

Fine needle aspiration of breast masses in HIV-infected patients: results from a large series.

54.34 for HPV DNA. Colposcopic biopsies cost on average US