Between September 2006 and February 2007, a total of 303 eligible, consenting HIV-infected women were enrolled. Their sociodemographic information is summarized in . VIA results were recorded for all 303 women, 84 (27.7%) were VIA positive and 219 (72.3%) were VIA negative. Cytology results revealed 150 (49.5%) women with normal cytology (including 19 with inflammatory smears), 11 (3.6%) with ASC-US, 87 (28.7%) with LSIL and 18 (5.9%) with HSIL. A total of 37/303 (12.2%) slides were reported as inadequate for evaluation. There were no statistically significant differences between demographic and clinical characteristics of women screening positive by VIA and cytology (all p > 0.05; ).
Demographic, sexual/reproductive and clinical characteristics and their distribution for the entire study population and women testing positive by VIA and cytology (ASC-US+, LSIL+ and HSIL+ cutoffs)
Colposcopic–histopathologic diagnoses have been reported previously.15
Briefly, colposcopic impressions served as a final diagnosis in 246/303 (81.2%), whereas histopathology results were available for the rest (57/303, 18.8%). Histopathology was based on LEEP results in 21/57, punch biopsy results in 34/57 and ECC in 2/57 results. The composite colposcopic–histopathologic diagnosis revealed that ICC was present in 1 (0.3%), CIN3 in 18 (5.9%), CIN2 in 31 (10.2%) and CIN1 in 33 (10.9%), whereas no CIN abnormalities were present in 220 (72.6%) of the 303 women. Sixteen women had CIN2+ colposcopic impression but were missing histopathology results (this included two women with inconclusive histopathology results and 14 women for whom no histopathology was obtained) and were excluded from the secondary analysis. Thus, of the 287 women included in the secondary analysis, ICC was present in 1 (0.3%), CIN3 in 11 (3.8%), CIN2 in 22 (7.2%), CIN1 in 33 (10.9%) and no CIN abnormalities were present in 220 (76.7%) women.
Carcinogenic HPV by HC2 assay was present in 124/297 (41.75%) women (HPV test results were unavailable in six women). A total of 19 histopathologically CIN2+ women were carcinogenic HPV negative; thus the prevalence of carcinogenic HPV-positive CIN2+ lesions was 10.23% (31/303). Additionally, carcinogenic HPV was present in 33.3% of women with normal cytology results, as well as 35.8% women with VIA negative results.
The proportion of positive and negative screening test results classified as “true” and “false” against the various disease state thresholds (reference standards) are shown in . VIA had higher sensitivity than cytology at all cytology positive cutoffs (80 vs. 60.5%, 60.5 and 20.9%, at the cytology ASCUS+, LSIL+ and HSIL+ cutoffs, respectively), although the differences reached statistical significance only between VIA and HSIL+ cytology. On the other hand, the specificity of VIA (82.6%) was higher than cytology at ASC-US+ (59.6%) and LSIL+ (64.6%) cutoffs but lower than cytology at the HSIL+ (96%) cutoff (all p < 0.01; ). The PPV for HSIL+ cutoff cytology was also higher than that of VIA and the two other cutoffs of cytology. On the other hand, the NPV of VIA was greater than cytology at all three cytology positive cutoffs. Similar trends in accuracy estimates were observed in disease states defined by women with CIN2+ with concurrent presence of carcinogenic HPV, as well as at both these thresholds after excluding women without histopathology results ().
Test positive results and measures of screening test performance (individual and in combination) at various disease state (diagnostic) thresholds among HIV-infected women in India
The simulated combinations of VIA and cytology (all three cutoffs) with an “either test positive” definition had higher sensitivity, whereas the simulated combination with a “both tests positive” definition had higher specificity among corresponding combination and individual test performance measures. The NPV for the individual tests and both their simulated combinations were uniformly higher than 85% (with many over 95%), whereas their PPV were under 54% (with most under 40%).
Among women with CD4+ cell counts <200 and <350 µL−1, VIA had higher sensitivity than cytology (all three cutoffs), whereas the specificity of HSIL+ cutoff cytology was higher than VIA or positivity on cytology at the ASC-US+ and LSIL+ cutoffs (). When compared to their counterparts with higher CD4+ cell counts, women with lower CD4+ cell counts (CD4 <200 µL−1
vs. CD4 ≥200 µL−1, and CD4 <350 µL−1
vs. CD4+ ≥350 µL−1) had higher sensitivity but lower specificity for VIA and HSIL+ cutoff-cytology, whereas lower sensitivity and specificity at the ASC-US+ and LSIL+ cutoffs on cytology ().
Range of sensitivity and specificity estimates of VIA and cytology (at three positivity cutoffs) stratified by CD4+ T-cell count thresholds (<200 and <350 µL−1) among HIV-infected women in India.
Test accuracy estimates using CIN3+ and carcinogenic HPV-positive CIN3+ were limited by few analyzable endpoints (i.e
., only n
= 19 of 303 women had CIN3+, and only n
= 15 women had carcinogenic HPV-positive CIN3+). Yet, a similar pattern of VIA having a higher sensitivity and lower specificity in comparison to HSIL+ cutoff on cytology and both higher sensitivity and higher specificity than ASC-US+ and LSIL+ cutoffs on cytology was noted at both disease positivity thresholds, before and after excluding women without histopathology results (Supporting Information