Clinical Performance Validation of 4 Point-of-Care Cervical Cancer Screening Tests in HIV-Infected Women in Zambia.

OBJECTIVES: We sought to determine the clinical performance of visual inspection with acetic acid (VIA), digital cervicography (DC), Xpert human papillomavirus (HPV), and OncoE6 for cervical cancer screening in an HIV-infected population. MATERIALS AND METHODS: HIV-infected women 18 years or older were included in this cross-sectional validation study conducted in Lusaka, Zambia. The screening tests were compared against a histological gold standard. We calculated sensitivity, specificity, positive and negative predictive values, positive and negative likelihood ratios, and odds ratios using cervical intraepithelial neoplasia grade 2 or worse (CIN 2+) and grade 3 or worse (CIN 3+) thresholds. RESULTS: Between January and June 2015, a total of 200 women were enrolled. Fifteen percent were screen positive by VIA, 20% by DC, 47% by Xpert HPV, and 6% by OncoE6. Using a CIN 2+ threshold, the sensitivity and specificity of VIA were 48% (95% CI = 30%-67%) and 92% (95% CI = 86%-95%), respectively. Similarly, the sensitivity and specificity of DC were 59% (95% CI = 41%-76%) and 88% (95% CI = 82%-93%), respectively. The sensitivity and specificity of Xpert HPV were 88% (95% CI = 71%-97%) and 60% (95% CI = 52%-68%), respectively. Finally, the sensitivity and specificity of OncoE6 were 31% (95% CI = 16%-50%) and 99% (95% CI = 97%-100%), respectively. CONCLUSIONS: VIA and DC displayed moderate sensitivity and high specificity. Xpert HPV performed equivalently to currently approved HPV DNA tests, with high sensitivity and moderate specificity. OncoE6 displayed excellent specificity but low sensitivity. These results confirm an important role for VIA, DC, and Xpert HPV in screen-and-treat cervical cancer prevention in low- and middle-income countries, such as Zambia.

The burden of cervical pre-cancer and cancer in HIV positive women in Zambia: a modeling study.

BACKGROUND: HIV infection is associated with a higher incidence of precancerous cervical lesions and their progression to invasive cervical cancer (ICC). Zambia is a global epicenter of HIV and ICC, yet the overall burden of cervical pre-cancer [cervical intraepithelial neoplasia 3 (CIN3)] and ICC among its HIV positive adult female population is unknown. The objective of this study was to determine the burden of cervical disease among HIV positive women in Zambia by estimating the number with CIN3 and ICC. METHODS: We conducted a cross-sectional study among 309 HIV positive women attending screening in Lusaka (Zambia's most populated province) to measure the cervical disease burden by visual inspection with acetic acid enhanced by digital cervicography (DC), cytology, and histology. We then used estimates of the prevalence of CIN3 and ICC from the cross-sectional study and Spectrum model-based estimates for HIV infection among Zambian women to estimate the burden of CIN3 and ICC among HIV positive women nationally. RESULTS: Over half (52 %) of the study participants screened positive by DC, while 45 % had cytologic evidence of high grade squamous intraepithelial lesions (SIL) or worse. Histopathologic evaluation revealed that 20 % of women had evidence of CIN2 or worse, 11 % had CIN3 or worse, and 2 % had ICC. Using the Spectrum model, we therefore estimate that 34,051 HIV positive women in Zambia have CIN3 and 7,297 have ICC. CONCLUSIONS: The DC, cytology, and histology results revealed a large cervical disease burden in this previously unscreened HIV positive population. This very large burden indicates that continued scale-up of cervical cancer screening and treatment is urgently needed.

Identification of human papillomaviruses from formalin-fixed, paraffin-embedded pre-cancer and invasive cervical cancer specimens in Zambia: a cross-sectional study.

BACKGROUND: The most common human papillomavirus (HPV) genotypes isolated from cervical cancer in select African countries are HPV-16, HPV-18, HPV-35, and HPV-45, but the most common genotypes in Zambia are unknown. The overall objective of this study was to assess the potential impact of current HPV vaccines in preventing cervical cancer in Zambia, by determining the combined prevalence of HPV-16 and/or HPV-18 in invasive cervical cancer (ICC) and high-grade pre-cancer [cervical intraepithelial neoplasia 2 or 3 (CIN2/3)] cases. FINDINGS: We compared DNA extraction techniques to determine which assay performs well in the Zambian context, where unbuffered formalin is used to fix specimens. We then tested specimens with the Abbott RealTime High-Risk HPV test to estimate the prevalence of HPV-16/18 in formalin-fixed, paraffin-embedded ICC and CIN2/3 specimens. DNA extraction using heat (without xylene) was more successful than xylene-based extraction. Over 80% of specimens tested using heat extraction and the Abbott RealTime HPV test were positive for HPV. HPV-16 and/or HPV-18 were identified in 65/93 (69.9%) ICC specimens positive for HPV and in 38/65 (58.5%) CIN2/3 specimens positive for HPV. CONCLUSIONS: To our knowledge this is the first report to identify HPV genotypes in cervical cancers in Zambia. A combined HPV-16/18 prevalence of 69.9% in ICC specimens suggests that current vaccines will be highly protective against cervical cancer in Zambia.

The Effect of Cryotherapy on Human Papillomavirus Clearance Among HIV-Positive Women in Lusaka, Zambia.

OBJECTIVE: We sought to investigate the progression of human papillomaviruses (HPV) infection in HIV-positive women after cryotherapy. METHODS: We examined changes in detection of high-risk HPV (hrHPV) cervical infections among HIV-infected women over a 12-week period after cryotherapy using stored specimens from a cohort study conducted between June 2009 and March 2011 in Lusaka, Zambia. Samples from visits at baseline and weeks 4, 8, and 12 were tested using the Roche Linear Array assay. RESULTS: A total of 89 women were included in the analysis. The median age was 32 years (interquartile range [IQR], 28-36 years). The median CD4+ cell count was 350 cells/µL (IQR, 214-470 cells/µL), and 66% of women were receiving antiretroviral therapy. At baseline, the prevalence of hrHPV was 91% (95% confidence interval [CI], 83%-95%). HPV45 was the most common HPV type, present in (30%) women, followed by HPV16 (27%), HPV18 (27%), HPV51 (20%), and HPV58 (22%). Among women with valid results both at baseline and 12 weeks, 25% (17/67) cleared their initial hrHPV infection within 12 weeks of treatment, although 65% (11/17) had new hrHPV types detected. CONCLUSIONS: Cryotherapy led to clearance of 25% of hrHPV infections within 12 weeks of treatment. However, hrHPV infection remained persistent in most women, and new hrHPV types were detected often, explaining the high rate of persistence and recurrence of cervical disease in this population. Continued efforts to scale up HPV vaccination and cervical screening should remain a priority in high HIV burden settings such as Zambia.

Clinical performance of digital cervicography and cytology for cervical cancer screening in HIV-infected women in Lusaka, Zambia.

Although there is a growing literature on the clinical performance of visual inspection with acetic acid in HIV-infected women, to the best of our knowledge, none have studied visual inspection with acetic acid enhanced by digital cervicography. We estimated clinical performance of cervicography and cytology to detect cervical intraepithelial neoplasia grade 2 or worse. Sensitivity and specificity of cervicography were 84% [95% confidence interval (CI): 72 to 91) and 58% (95% CI: 52 to 64). At the high-grade squamous intraepithelial lesion or worse cutoff for cytology, sensitivity and specificity were 61% (95% CI: 48 to 72) and 58% (95% CI: 52 to 64). In our study, cervicography seems to be as good as cytology in HIV-infected women.