Comparison of natural histories of human papillomavirus detected by clinician- and self-sampling

Abstract

New strategies for cervical cancer screening include human papillomavirus (HPV) DNA testing. Using self-testing methods would increase access to testing in both developed and developing countries. The purpose of this study was to compare time-to-clearance of specific HPV types between clinician-collected-lavage (CC-L) and self-collected (SC) sampling in a single cohort. CC-L and SC samples were obtained every 4 months at alternate 2-month windows from 537 women. Eighteen high-risk (HR) HPV and 4 low-risk (LR) HPV were examined. Proportional hazards model was used to compare time-to-clearance between methods for combined HR and for 13 specific HPV types. Prentice-Wilcoxon test was used for within-subject paired comparison. In the independent analysis for combined HR and LR types, no differences were found. For specific types, time-to-clearance for all HPV types examined between CC-L and SC samples was similar except for HPV 66 which showed a trend to clear slower by SC (p = 0.09). When comparing methods in the same woman, time-to-clearance was similar for all types except for HPV 16 which showed a trend to clear slower by CC-L means (p = 0.08). When we examined pattern of clearance among the CC-L samples, the fastest types to clear were HPV 6, 18, 66, 84 and 39 and the slowest were HPV 62, 68, 59 and 16. These patterns of fast and slow were similar for SC samples. Our findings suggest using SC vaginal swabs would observe similar natural histories of HPV compared to studies using CC-L specimens making self-testing feasible for repeated HPV DNA detection.

Figure 1. Cartoon shows the design of sample collection with the collection of self-swabs (SC) flanking the clinician-collected lavage (CC-L) samples at 2-month intervals

Cartoon also depicts the 3 approaches to the time-to-clearance analyses. The first approach compared methods independently of each other—all women were included whether they did or did not have the same HPV type by SC and CC-L. Figure 2 and 3A reflect approach 1. The second approach compared methods in the same women—only women with the same HPV type in both the CC-L and flanking SC were included. Figure 3B reflects approach 2. The third approach compared specific HPV types within each method allowing the observation of which types cleared fastest or slowest within each method. Figure 4 reflects approach 3.

Figure 2. Comparison of type-specific time-to-clearance for 18 HR-HPV types combined and 4 LR HPV types combined between self-collected (black line) and clinician-collected lavage (gray line) samples

X-axis is in days and Y-axis is proportion remaining positive. Figure reflects the curves inclusive of all women. P-values are comparison of all 18 HR HPV types (including probable HR types) and all 4 LR HPV types between methods using Cox Proportional Hazards Model adjusting for within-subject variance, age, and prevalence.

Figure 3. Comparison of type-specific time-to-clearance between self-collected (black line) and clinician-collected lavage (gray line) samples

X-axis is in days and Y-axis is proportion remaining positive. Column A reflects curves inclusive of all women. P values are comparison of type-specific time-to-clearance using Cox Proportional Hazards Model adjusting for within-subject variance, age, and prevalence. Column B reflects curves for women who were initially positive by CC-L. Comparison in time-to-clearance is between sampling methods: SC vs CC-L for the same woman. P values are comparison of type-specific time-to-clearance using paired Prentice-Wilcoxon. Number of subjects for each HPV type and rates of clearance are given in Table 3.

Figure 3. Comparison of type-specific time-to-clearance between self-collected (black line) and clinician-collected lavage (gray line) samples

X-axis is in days and Y-axis is proportion remaining positive. Column A reflects curves inclusive of all women. P values are comparison of type-specific time-to-clearance using Cox Proportional Hazards Model adjusting for within-subject variance, age, and prevalence. Column B reflects curves for women who were initially positive by CC-L. Comparison in time-to-clearance is between sampling methods: SC vs CC-L for the same woman. P values are comparison of type-specific time-to-clearance using paired Prentice-Wilcoxon. Number of subjects for each HPV type and rates of clearance are given in Table 3.

Figure 4. Comparison of HPV type-specific clearance among clinician-collected lavage samples and self-collected samples

See Table 3 for clearance rates and Table 4 for statistical comparison.