Accuracy of visual inspection with acetic acid to detect cervical cancer precursors among HIV-infected women in Kenya.

Visual inspection with acetic acid (VIA) is becoming a more widely recommended and implemented screening tool for cervical cancer prevention programs in low-resource settings. Many of these settings have a high prevalence of HIV-infected women. We carried out a cross-sectional validation study to define the sensitivity, specificity and predictive values of VIA among HIV-infected women. Women enrolled in HIV care at the Family AIDS Care and Education Services clinic in Kisumu, Kenya, were recruited for participation. All participants underwent VIA followed by colposcopy performed by a second blinded clinician. At colposcopy, lesions suspicious for cervical intraepithelial neoplasia 2 or greater (CIN2+) were biopsied. Disease status was determined by final histopathologic diagnosis in women who underwent biopsies. A satisfactory colposcopy with no lesions was considered a negative result. From October 2010 to June 2012, 1,432 women underwent VIA and colposcopy. A total of 514 (35.7%) women had a positive VIA, and 179 (12.2%) had CIN2+ confirmed by colposcopically directed biopsy. Sensitivity, specificity, positive and negative predictive values of VIA for CIN2+ were 86.6, 71.6, 30.3 and 97.4%, respectively. Specificity, but not sensitivity, increased with older age. Among older women, sensitivity was affected by CD4+ count and use of antiretroviral therapy. Although they are impacted by age and immune status, test characteristics for VIA among HIV-infected women are similar to what has been reported for general populations. Recommendations to use VIA as a screening tool should not vary by HIV status.

Risk factors for cervical precancer detection among previously unscreened HIV-infected women in Western Kenya.

HIV and cervical cancer are intersecting epidemics in many low-resource settings, yet there are few accurate estimates of the scope of this public health challenge. To understand disease prevalence and risk factors for cervical intraepithelial neoplasia 2 or greater (CIN2+), we conducted a cross-sectional study of women undergoing cervical cancer screening as part of routine HIV care in Kisumu, Kenya. Women were offered screening with visual inspection with acetic acid, followed by confirmation with colposcopy and biopsy as needed. Univariable and multivariable analyses were carried out to determine clinical and demographic predictors of prevalent CIN2+. Among 3,241 women screened, 287 (9%) had an initial diagnosis of biopsy-confirmed CIN2+. On multivariable analysis, combined oral contraceptives remained significantly associated with detection of CIN2+ among women on HAART (AOR 1.84, CI 1.20-2.82), and not on HAART (AOR 1.72, 95% CI 1.08-2.73), while use of a progesterone implant was associated with increased detection of CIN2+ (AOR 9.43, 95% CI 2.85-31.20) only among women not on HAART. CD4+ nadir over 500 cells/mm(3) was associated with reduced detection of CIN2+ (AOR 0.61, CI 0.38, 0.97) in the overall group, but current CD4+ was only associated with reduced detection of CIN2+ among women not on HAART (AOR 0.42, CI 0.22, 0.80). In conclusion, a history of less severe immunosuppression appeared to reduce the risk of CIN2+ detection, but current CD4+ count was significant only in non-HAART users. The association of CIN2+ with hormonal contraception should be explored more in prospective studies designed to better control for confounding factors.

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

OBJECTIVE: To determine the optimal strategy for cervical cancer screening in women with human immunodeficiency virus (HIV) infection by comparing two strategies: visual inspection of the cervix with acetic acid (VIA) and VIA followed immediately by visual inspection with Lugol's iodine (VIA/VILI) in women with a positive VIA result. METHODS: Data from a cervical cancer screening programme embedded in two HIV clinic sites in western Kenya were evaluated. Women at a central site underwent VIA, while women at a peripheral site underwent VIA/VILI. All women positive for cervical intraepithelial neoplasia grade 2 or worse (CIN 2+) on VIA and/or VILI had a confirmatory colposcopy, with a biopsy if necessary. Overall test positivity, positive predictive value (PPV) and the CIN 2+ detection rate were calculated for the two screening methods, with biopsy being the gold standard. FINDINGS: Between October 2007 and October 2010, 2338 women were screened with VIA and 1124 with VIA/VILI. In the VIA group, 26.4% of the women tested positive for CIN 2+; in the VIA/VILI group, 21.7% tested positive (P < 0.01). Histologically confirmed CIN 2+ was detected in 8.9% and 7.8% (P = 0.27) of women in the VIA and VIA/VILI groups, respectively. The PPV of VIA for biopsy-confirmed CIN 2+ in a single round of screening was 35.2%, compared with 38.2% for VIA/VILI (P = 0.41). CONCLUSION: The absence of any differences between VIA and VIA/VILI in detection rates or PPV for CIN 2+ suggests that VIA, an easy testing procedure, can be used alone as a cervical cancer screening strategy in low-income settings.

Cervical cancer precursors and hormonal contraceptive use in HIV-positive women: application of a causal model and semi-parametric estimation methods.

OBJECTIVE: To demonstrate the application of causal inference methods to observational data in the obstetrics and gynecology field, particularly causal modeling and semi-parametric estimation. BACKGROUND: Human immunodeficiency virus (HIV)-positive women are at increased risk for cervical cancer and its treatable precursors. Determining whether potential risk factors such as hormonal contraception are true causes is critical for informing public health strategies as longevity increases among HIV-positive women in developing countries. METHODS: We developed a causal model of the factors related to combined oral contraceptive (COC) use and cervical intraepithelial neoplasia 2 or greater (CIN2+) and modified the model to fit the observed data, drawn from women in a cervical cancer screening program at HIV clinics in Kenya. Assumptions required for substantiation of a causal relationship were assessed. We estimated the population-level association using semi-parametric methods: g-computation, inverse probability of treatment weighting, and targeted maximum likelihood estimation. RESULTS: We identified 2 plausible causal paths from COC use to CIN2+: via HPV infection and via increased disease progression. Study data enabled estimation of the latter only with strong assumptions of no unmeasured confounding. Of 2,519 women under 50 screened per protocol, 219 (8.7%) were diagnosed with CIN2+. Marginal modeling suggested a 2.9% (95% confidence interval 0.1%, 6.9%) increase in prevalence of CIN2+ if all women under 50 were exposed to COC; the significance of this association was sensitive to method of estimation and exposure misclassification. CONCLUSION: Use of causal modeling enabled clear representation of the causal relationship of interest and the assumptions required to estimate that relationship from the observed data. Semi-parametric estimation methods provided flexibility and reduced reliance on correct model form. Although selected results suggest an increased prevalence of CIN2+ associated with COC, evidence is insufficient to conclude causality. Priority areas for future studies to better satisfy causal criteria are identified.